This article presents new symbolic solutions for the problem of pore elasticity and pore pressure. These techniques are based on the classic theoretical approach proposed by M. A. Biot [1]. The new symbolic solutions differ from the well-known approximations of the functions proposed for the 2D pore elasticity problem. Both new symbolic and numerical solutions are then applied to solve problems arising in offshore design technology, specifically dealing with the penetration of a gravity-based rig installed in the Arctic region of the North Sea of Russia. All symbolic approaches are based on solutions of the linear problem of the pore elasticity for homogeneous soil. The new symbolic solutions are compared with Biot’s solutions.

The main purpose of this article is to derive new symbolic solutions for the classic problem of pore elasticity set up in [1]. Approximate solutions proposed by Biot have been widely used to solve various linear initial-boundary problems involving pore elasticity. But more accurate solutions of the problem are still of interest.

In offshore technology, a practical example deals with the penetration of huge oil rigs into the soil of the sea bed. Such cases are usually based on solutions given by the linear theory of pore elasticity.

First, consider Biot’s problem for a rectangular load on homogeneous soil [1].

In the three-dimensional case, the depth of penetration of a rigid body into soil may be found by solving the equations

(1) |

where , , are the components of the displacements of the saturated soil in the , , directions and

(2) |

is the divergence of the displacements of the soil. The initial and boundary conditions will be given later.

The other variables are:

- , the pore pressure
- , the shear modulus of the rigid skeleton of the saturated soil
- , the Poisson coefficient of the rigid skeleton of the soil
- , the coefficient of consolidation
- , the coefficient of permeability
- , the final compressibility

As usual, define the Laplace operator:

(3) |

Consider an infinite half-space (e.g. clay) bounded by the horizontal - plane, and let the axis be directed vertically downward.

The vertical deflection of the horizontal plane is to be found when a vertical load acts on the rectangular plane at time ; the rectangular load is distributed in the strip on the surface.

Assume that water saturates the clay and may be freely filtered by the neighboring half-area, and that the water pressure on the - surface equals atmospheric pressure.

Then the original problem becomes two dimensional, with . The equations in (1) become

(4) |

Taking the Laplace transform and noting that changes the third equation, giving the system

(5) |

where is a Laplace-transformed parameter.

The boundary conditions for the 2D case (reduced for the full symmetric geometry of the body) of the pore elasticity are:

1. The displacements and pore pressure are 0 as :

(6) |

2. The pore pressure at the surface is

(7) |

3. The skeleton stress at the surface is equal to the external load given by

(8) |

4. The shear stress at the surface is 0:

(9) |

First, clear any old values of and .

Define three operators and three equations.

Consider general solutions of the system of equations (5) in the form of functions with separated variables.

Then (5) is transformed into the following system of ODEs.

(10) |

This determines the general solutions of (10).

This allows us to define the three previously unknown functions.

New forms of the symbolic solutions are presented in section 3.3.

The symbolic solutions derived in section 3.2 may be combined in the function .

(11) |

To satisfy the boundary condition (6), the coefficients and in (11) must be zero.

Here is a linear system for the unknown coefficients in .

This finds solutions for three of the coefficients.

We can express the functions in a different form using .

The other three unknown constants are found from the boundary conditions (7), (8), and (9). These conditions lead to three linear equations.

Finally, here is the system of linear equations.

It leads to the general solutions for all the coefficients of the problem of pore elasticity.

Following [1], we introduce a transformed solution for the vertical deflection of the plane.

This gives the time dependence of the vertical displacement of the saturated soil.

This is the formula for the initial distribution at the surface.

Based on [1], here is the general vertical deflection for the horizontal level of the soil.

Finally, a new symbolic solution for a rectangular load acting on the plane (with zero Poisson coefficient) is derived by integrating.

The result is a new symbolic form for problem [1].

(12) |

Originally in [1] the approximate symbolic solution was given by:

(13) |

This is the new function for practical solutions based on the exact solution derived above.

Here is the displacement of the horizontal level of the porous space under a rectangular load.

Let us consider an application of the new symbolic solution of the pore elasticity problem obtained above to the study of the penetration of the gravity rig into the sea bed. The platform Prirazlomnaya has a mass of 250,000 tons and its bottom measures (see [2]). We also define the parameters of the clay soil and sediment.

This is the average pressure of the rig on the surface of the sediment.

(14) |

Here is a plot of the rectangular load.

This plots the family of vertical displacements of the rig penetrated into clay and sediment.

For a complex load acting on the rig, the general penetration is the sum of each of the component penetrations.

(15) |

where and are the sizes of the mechanical components and living quarters of the platform.

Here is a plot of the loads on the platform from the housing and mechanical blocks.

Let the production unit have length 30 meters and suppose the distributed load is .

This shows the penetration of the platform on the sediment due to the production unit over a two-week period.

This shows the penetration of the platform, taking into account the nonuniform load distribution on the sediment, where is the side length of the square of the bottom of the rig in (15).

**Figure 1.** Here is a photo of the rig Prirazlomnaya.

Since [1] does not take account of porous pressure, here is a new symbolic solution for this case, substituting 0 for .

Following [1], here is an approximate symbolic solution for the pressure.

The explicit form of the pore pressure function is computed by taking the inverse Laplace transform.

So this is a new symbolic solution for the porous pressure for a rectangular load at the surface.

This section shows how the pore pressure changes with time and depth of the soil layer near the horizon.

This determines the distribution function of pore pressure 1.5 meters below the bottom of the gravity platform.

This shows the family of porous pressure distributions at the bottom of the gravity platform.

Obviously, the pore pressure is the load-bearing frame factor, which restrains the platform to the surface of the ground.

In this article, new symbolic solutions for the penetration of a gravity platform into soil and a determination of the porous pressure in the saturated soil are found by computer algebra techniques. These solutions improve upon earlier solutions obtained by M. Biot and give us new possibilities to apply symbolic computer applications to diverse problems in pore elasticity theory.

Both symbolic solutions are applicable to the design of offshore gravity structures installed in shallow water.

[1] | M. A. Biot, “General Theory of Three-Dimensional Consolidation,” Journal of Applied Physics, 12(2), 1941 pp. 155–164. doi:10.1063/1.1712886. |

[2] | Wikipedia. “Prirazlomnoye Field.” (Jan 12, 2015) en.wikipedia.org/wiki/Prirazlomnoye_field. |

A. N. Papusha and D. P. Gontarev, “New Symbolic Solutions of Biot’s 2D Pore Elasticity Problem,” The Mathematica Journal, 2015. dx.doi.org/doi:10.3888/tmj.17-5. |

Professor Alexander N. Papusha is the head of the Continuum Mechanics and Offshore Exploration Department at Murmansk State Technical University (MSTU). He received an M.S. in mechanics from Kiev State University in 1972 and a Ph.D. in theoretical mechanics in 1979 from the Institute of Mechanics, Ukrainian Academy of Sciences, as well as a Doctor of Sciences from the Institute of Machinery (St. Petersburg), Russian Academy of Sciences in 1999. Since 1983, he has been a full professor at MSTU.

Denis P. Gontarev is a postgraduate student in the Continuum Mechanics and Offshore Exploration Department at MSTU.

**Alexander N. Papusha**

*Continuum Mechanics and Offshore Exploration Department
Murmansk State Technical University
13, Sportyvnay
183010 Murmansk, Russia
*

**Denis P. Gontarev**

*Continuum Mechanics and Offshore Exploration Department
Murmansk State Technical University
13, Sportyvnay
183010 Murmansk, Russia
*

This article is divided into five sections: the orbit transfer problem, equations of motion, the optimal control problem, necessary conditions for the Mayer problem, and a dynamic approach to the maximal orbit transfer problem using *Mathematica*’s built-in `Manipulate` function.

The Earth-Mars orbit transfer problem is timely, given the successful flight and smooth landing of the American *Curiosity* rover on Mars.

For the orbit transfer problem, assume that:

- There is a unique center of attraction.
- Initially the spacecraft moves in a circular trajectory around the center of attraction.
- The spacecraft moves with a constant thrust from a rocket engine operating in the time interval .
- The spacecraft moves to the largest possible circular orbit around the center of attraction.
- The orbit transfer trajectory is coplanar with the two circular orbits and the center of attraction.

All these assumptions are stated in [1, p. 66]. Here is a sketch of a solution to the problem with some notation. The blue curve is the orbital transfer trajectory, while the red and green curves are the initial lower circular orbit and the final upper circular orbit.

The notation from [1, pp. 66–68], [2], or [3] is:

- is time in the given interval , which is called the horizon.
- is the radial distance from the center of attraction to the spacecraft; increases as fuel is burned; is the initial distance; is the final and maximal distance.
- is the polar angle, measured counterclockwise from the straight line connecting the center of attraction with the position of the spacecraft at .
- is the radial velocity component.
- is the tangential velocity component.
- is the thrust-direction angle; it is the control variable.
- is the initial mass of the spacecraft with propellant included; is the time-dependent mass, which decreases due to the constant fuel consumption rate .
- is the thrust, also assumed to be constant.
- is the gravitational constant.

The equations of motion of the spacecraft consistent with the above assumptions, according to [1,

p. 67] and [2], are

(1) |

(2) |

(3) |

(4) |

The associated boundary conditions are

(5) |

(6) |

(7) |

(8) |

(9) |

(10) |

The system of nonlinear differential equations (1) to (4) with the boundary value conditions (5) to (10), the control function , and the maximizing condition

(11) |

form the optimal control problem to be solved, assuming that the state functions , , , and and the control function are sufficiently smooth. Conditions (6), (7), (9), and (10) guarantee that the trajectory of the spacecraft is tangent to the two circular orbits.

The goal is to maximize , the radius of the orbit transfer at the endpoint in time, so the cost functional is determined by

(12) |

Thus the horizon is with . This is a Mayer optimal control problem (see Ch. 4 in [4]).

Since the differential equations (1) to (4) with conditions (5) to (10) and the cost functional (12) are not time dependent, the optimal control problem is equivalent to either of the following two problems:

- differential equations (1) to (4) with conditions (5) to (10), a given , and finite and arbitrary, with optimality condition to minimize
- differential equations (1) to (4) with conditions (5) to (10), a given , with the optimality condition to minimize the fuel consumption

**Theorem 1**

Under the hypotheses of Filippov’s theorem (theorem 9.2.i of [4]), the optimal control problem (1) to (4) with conditions (5) to (10) and the maximizing functional (11) and (12) has an absolute maximum in the nonempty set of admissible pairs.

For brevity, here is an abbreviated version of theorem 4.2.i in [4]: Let the Mayer problem be expressed as

(13) |

(14) |

A pair , , is said to be *admissible* (or *feasible)* provided that is absolutely continuous [5], is measurable, and and satisfy (14) a.e. Let be the class of admissible pairs . The goal is to find the minimum of the cost functional (13) over , that is, to find an element so that for all . Introduce the variables , called *multipliers*, and an auxiliary function , called the *Hamiltonian*, defined on by

(15) |

Define

Further necessary assumptions:

- There exists an element such that for all .
- is closed in .
- The set is closed in .
- .
- Notation:
- The graph of the optimal trajectory belongs to the interior of .
- does not depend on time and is a closed set.
- The endpoint of the optimal trajectory is a point of , where has a tangent variety (of some dimension , ) whose vectors are denoted by

**Theorem 2**

Assume the above eight hypotheses and let be an optimal pair for the Mayer problem (13) and (14). Then the optimal pair necessarily has the following properties:

(b) For almost any fixed (a.e.), the Hamiltonian, as a function depending only on , takes its minimum value in at the optimal strategy . This implies , (a.e).

(16) |

for every vector .

From (15) and (a) of theorem 2, the Hamiltonian and the equations for the multipliers for (1) to (4) are

(17) |

(18) |

(19) |

(20) |

(21) |

From (21) and (18), and thus (17) to (20) become

(22) |

(23) |

(24) |

Furthermore, from (b) in theorem 2,

Thus the control function is determined by the multipliers and

Based on (4), note that the polar angle is determined by and .

From the transversality relation (d) in theorem 2 (i.e. equation (16)),

(25) |

This yields a system of six nonlinear differential equations (1), (2), (3), (22), (23), and (24) in the variables , , , , , and with six bilocal conditions (5), (6), (7), (9), (10), and (25).

As mentioned earlier, the variables and follow.

The next section implements a dynamical approach to the maximal orbit transfer problem.

The function `MaximalRadiusOrbitTransfer` dynamically shows the maximal radius orbit transfer between two coplanar circular orbits so that their centers are located at a single center of attraction. Here `thrust` is the constant thrust of the engine, `dmr` is the decreasing mass rate due to the constant propellant flow rate, `b` is the final time, `m0` is the initial mass of the spacecraft including the propellant, `μ` is the gravitational constant, `r0` is the initial radius, `u0` is the initial radial velocity, `ub` is the final radial velocity, `v0` is the initial tangential velocity, and `k` is the number of thrust vectors.

Clearly the problem is nonlinear and, to the author’s knowledge, no closed-form solution has been found. The possibility of obtaining a solution through a numerical method remains, as implied by theorem 1. The accuracy of the results depends sensitively on the initial values. The `Method` option is needed for *Mathematica* 9 or lower; for faster processing, remove it in *Mathematica* 10 or higher.

A similar picture can be found on the front cover and on pages 1–2 of [6].

The author expresses his deep gratitude to Prof. Dr., Dr. H. C., Heiner H. Gonska of the University of Duisburg-Essen, Faculty of Mathematics, located in Duisburg, Germany, for his kind invitation and warm hospitality. The invitation was funded by a grant from the Center of Excellence for Applications of Mathematics supported by DAAD. The author also thanks Aida Viziru for her rapid and professional help.

[1] | A. E. Bryson and Y.-C. Ho, Applied Optimal Control: Optimization, Estimation, and Control, New York: Halsted Press, 1975. |

[2] | S. Alfano and J. D. Thorne, Constant-Thrust Orbit-Raising Transfer Charts, Report PL-TR-93-1010, July 1993. www.dtic.mil/dtic/tr/fulltext/u2/a269088.pdf. |

[3] | S. Alfano and J. D. Thorne, “Circle-to-Circle Constant-Thrust Orbit Raising,” The Journal of the Astronautical Sciences, 42(1), 1994 pp. 35–45. www.centerforspace.com/downloads/files/pubs/JAS.V42.N01.pdf. |

[4] | L. Cesari, Optimization—Theory and Applications, Problems with Ordinary Differential Equations, Applications of Mathematics, Vol. 17, New York: Springer, 1983. |

[5] | M. Mureşan, A Concrete Approach to Classical Analysis, New York: Springer, 2009. |

[6] | R. Vinter, Optimal Control, Systems & Control: Foundations & Applications, Boston: Birkhäuser, 2000. |

M. Mureşan, “On the Maximal Orbit Transfer Problem,” The Mathematica Journal, 2015. dx.doi.org/doi:10.3888/tmj.17-4. |

Marian Mureşan is affiliated with Babeş-Bolyai University, Faculty of Mathematics and Computer Science, in Cluj-Napoca, Romania. He is interested in analysis, calculus of variations, optimal control, and nonsmooth analysis.

**Marian ****Mureşan**

*Babe*ş*-Bolyai University
Faculty of Mathematics and Computer Science
1, M. Kog*

Romania

A formal, axiomatic conceptualization of buffering action—generally applicable to any physical, chemical, or biological process—was first presented by B. M. Schmitt in 2005 [1, 2]. This article provides a series of tools designed to aid in the application of these concepts to both classical and non-classical buffering phenomena. To illustrate the utility of the approach in the biological sciences, an abstract measure of the magnitude of “genetic” buffering associated with an allele of the gene encoding the heat shock protein Hsp90 is determined.

Buffering is observed when a parameter changes less than expected in response to a given disturbance. For example, if a strong acid is added to an aqueous solution, and not all of the added ions remain free (unbound), then the solution is said to act as a buffer. While such phenomena have been observed in the physical, chemical, and biological sciences for centuries, a formal and general approach for their quantitation across distinct disciplines was not presented until recently

[1, 2].

In [1, 2], B. M. Schmitt presents a comprehensive mathematical framework for evaluating buffering action—a framework that is applicable to any scenario in which a quantity partitions between two compartments or states. While suitable for the analysis of “classical” buffering phenomena (e.g. acid-base chemistry), the formalism also provides a simple means with which to quantitate and characterize phenomena that, at first glance, seem to be outside the buffering paradigm—at least when the term is used in its traditional sense with respect to the homeostasis of physiological parameters (see [2] for several in-depth examples of the formal and general approach applied to phenomena spanning diverse disciplines).

This article provides a series of mathematical tools designed to facilitate the application of Schmitt’s paradigm to both “classical” and “non-classical” buffering phenomena. By inputting the transfer function and the buffering function , the provided code: (1) defines the four buffering parameters , , , and ; (2) provides a series of graphical outputs describing the system; and (3) calculates the buffering angle , thereby classifying the system as being moderating/amplifying/

inverting/non-inverting. Thus, the burden of computation associated with the approach is seamlessly transferred from the user to the *Mathematica* kernel.

Lastly, in order to illustrate the utility of the approach outside traditional disciplines, I use these same tools to calculate the magnitude of “genetic” buffering associated with an allele of the gene encoding the heat shock protein Hsp90. In this way, the capacity of an allele to buffer phenotypic variation is formally and quantitatively determined for the first time.

To illustrate Schmitt’s “formal and general approach,” consider a system comprised of a pair of communicating vessels (i.e. cylindrical flasks connected by a small tube). As described in [1], the total volume of liquid in the vessels, , is the sum of the two partial volumes contained in each vessel. In the specific example described below, the rightmost of the two cylindrical vessels (the “buffering” vessel) has a radius exactly two times that of the first. Thus, any fluid added to the leftmost vessel (the “transfer” vessel) will partition in a ratio of 1:4 between the transfer and buffering vessels. The partial volume present in the transfer vessel is thus one-fifth the total volume of fluid added to the system. Likewise, the partial volume present in the buffering vessel is four-fifths the total volume of fluid added to the system.

It is possible to formalize the system below by defining three functions: the transfer function , the buffering function , and the sigma function .

The transfer function defines the amount of fluid present in the transfer vessel.

Likewise, the buffering function defines the amount of fluid present in the buffering vessel.

The sigma function defines the sum of the individual functions comprising the system.

Once the functions are defined, it is possible to visualize the system by plotting the lines.

It is also possible to visualize the system (in a more intuitive manner) by creating an area plot in which the two partial volumes are indicated by the heights of the transfer and buffering areas at any given value of .

The definition of the respective functions also provides a convenient means with which to quantitate buffering action. This is accomplished in any one of four ways, using the three available differentials. The buffering coefficient measures the change in the buffering compartment relative to the total change.

The buffering ratio measures the change in the buffering compartment relative to the change in the transfer compartment.

Conversely, the transfer coefficient measures the change in the transfer compartment relative to the total change.

The transfer ratio measures the change in the transfer compartment relative to the buffering compartment.

In this simple linear example—where the cross-sectional area of the buffering vessel is constant (i.e. does not vary with fluid level)—the dimensionless values of total volumes , , , and are invariant, equal to 0.8, 4, 0.20, and .0.25, respectively.

While of great utility, the parameters and are undefined in the case of perfect buffering or perfect transfer, respectively. To address this issue, it is possible to define an alternative measure, the buffering angle , which is capable of representing any type of buffering without the introduction of discontinuities.

As described in [1], the buffering angle can be defined by first creating a three-dimensional space curve of the system.

A projection of this curve onto the - plane corresponds to the transfer function.

A projection onto the - plane corresponds to the buffering function.

A projection onto the - plane, however, generates a third curve that can be used to determine the proportions between the individual changes in the transfer and buffering functions. This is accomplished by simply measuring the angle between the axis and the line formed by joining the origin to any given point on the curve.

This calculates the buffering angle in degrees ([1], Supplement 5).

Similar to the buffering parameters, is invariant in cases of linear buffering.

It is evident from the above analysis that this methodology creates a system in which perfect buffering corresponds to an angle of 90° and perfect transfer to an angle of 0°. In fact, any type of buffering behavior (moderating/amplifying/inverting/non-inverting) can be represented continuously by a finite angle between and 135° ([1], Supplement 7).

Importantly, it is also possible—using the same logic in the reverse direction—to use this single value to unambiguously define all of the buffering parameters describing the system. This can be demonstrated by defining a variable `littleb`1 (corresponding to the buffering coefficient ) that is calculated using only the buffering angle.

This checks that and `littleb` are the same.

Similarly, the values of the remaining three buffering parameters can be calculated using only the buffering angle and shown to be equal to the corresponding parameters calculated using the relevant differentials.

Thus, the buffering angle provides a simple, powerful, single-value measure that is capable of capturing and communicating the underlying nature of the buffering relationships comprising

the system.

While the simple linear scenario described above made it possible to lay the foundation for Schmitt’s “formal and general approach,” the computational effort associated with its application was minimal. Thus, the utility of applying these methods within *Mathematica* was not fully exploited. For this reason, I next consider a more complex, nonlinear example (i.e. where the cross-sectional area of the buffering vessel is not constant). This serves the purpose of highlighting the advantages of exploiting *Mathematica*’s computational engine.

Consider a nonlinear system defined by the functions listed below.

As previously described, the buffering parameters can be determined using the relevant differentials. However, in contrast to the previous example, the computational burden associated with their calculation is no longer trivial (at least in the absence of *Mathematica)*.

Once the functions are defined and the system visualized through the creation of the corresponding line and area plots, one can clearly see that the magnitude of buffering action in this nonlinear scenario varies with fluid level (imagine a buffering vessel in the shape of an hourglass as opposed

to a cylinder).

Furthermore, unlike the linear case, it is also clear that the buffering parameters vary as a function

of .

As previously described, it is also possible to calculate the buffering angle by first creating a three-dimensional space curve of the system and then projecting this curve onto the - plane.

In this instance the buffering angle varies as a function of , with near-perfect buffering being observed at both high and low fluid levels, and minimal buffering being observed when attains a value of approximately 4.38.

As described previously, the buffering parameters can be determined using the buffering angle and are equivalent to the values calculated using the originally defined functions (compare the plots below to the plots for , , , and above).

Thus, just as in the case of a linear system, plotting over the range of the disturbance (i.e. the addition of fluid) provides a simple, single-value measure with which to grasp the inherent buffering properties of the system under consideration.

At this point it is important to note that, up to now, only the overall changes in the buffering and transfer compartments have been considered (by comparing differentials). However, in the case of nonlinear systems, it is also informative to consider the *rate* at which these values change relative to one another (by comparing derivatives). For example, in the same way that it would be important for an investor to be aware of the current price of gold, and how it has changed in previous years, months, or weeks, it would also be important for that same investor to be cognizant of the rate at which the price is changing at any given instant in time (i.e. increasing, decreasing, or stable). This is to say, the choice to sell at a given price at a given moment would be greatly influenced by knowing if the price was stable or on either an upward or a downward trend. In other words, it is not only of interest to know how a quantity *has* *changed*, but how that quantity *is changing*.

To determine the instantaneous rates of change in a buffered system, simply calculate and plot the first derivatives of the functions describing the system.

Once the functions are defined, the instantaneous buffering parameters (denoted by adding an “i” to the respective variable names) can also be calculated.

As is evident from viewing the respective plots of these functions, this analysis allows one to clearly identify the points of maximum and minimum buffering/transfer rate, as well as the points at which the buffering/transfer rates are zero.

In this way, the most critical junctures in the development of the system (over the range of the disturbance) can be quickly and easily identified.

The analysis presented in the previous sections concludes my efforts to establish the theoretical foundation of the formal and general approach, as well as its application within *Mathematica*. Next, in order to illustrate how these abstractions can be directly applied to the real world, I consider an example of non-classical buffering—namely, that of the “genetic buffering” of phenotypic variation.

In this way, the ability to exactly and formally quantitate phenomena that at first glance might be thought of as being outside the buffering paradigm is practically demonstrated.

The axiomatic foundation and abstract nature of the “formal and general approach” allows it to be readily applied to any scenario in which an arbitrary quantity partitions itself between two compartments or states. While suitable for the analysis of “classical” buffering phenomena (the homeostasis of physiological parameters), the approach is also germane to a variety of “non-classical” buffering phenomena. One such phenomenon, which up to now has been considered in only a qualitative manner, is that of “genetic” buffering. While many instances of genetic buffering have been described and characterized, a well-known and classic example of the phenomenon—revolving around the gene encoding the heat shock protein Hsp90—will be used to illustrate the real-world application of Schmitt’s paradigm.

The Hsp90 protein is an ATP-dependent molecular “chaperone” that is extensively expressed in organisms ranging from bacteria to humans. It functions to promote the proper folding of a specific subset of molecular targets referred to as its “client” proteins. Interestingly, many of Hsp90’s client proteins are involved in the process of signal transduction and modulate developmental processes [3]. For example, in the fruit fly, *Drosophila melanogaster*, mutations in the gene encoding Hsp90 result in morphological abnormalities affecting the development of the eye, legs, wings, thorax, and bristles [4].

Interestingly, the proportion of Hsp90 mutant flies exhibiting eye defects (in a line prone to such abnormalities) increases dramatically as the temperature rises. In contrast, the proportion of control flies (expressing the normal or “wild-type” version of the Hsp90 protein) also increases in response to increased temperature, but not nearly to the same degree as in the mutant flies [4]. The gene encoding the wild-type version of the Hsp90 protein is thus said to “buffer” the appearance of the defective eye trait.

It is possible to analyze these experimental results in more detail by importing the raw data (see Figure 8 in [4]) from the original publication in the form of two arrays. These two arrays, corresponding to the wild-type and mutant fly lines, relate temperature to the penetrance of the mutant phenotype (i.e. the percentage of flies in the line displaying the eye defect).

Plotting the data illustrates that the mutant line is indeed more sensitive to increasing temperature than the wild-type line.

To proceed with the application of the formal and general approach, we now create two curves that fit the data using the `FindFit` function.

With the above constants, the curves describing the behavior of the wild-type and mutant lines can be generated.

The appropriateness of the fit can then be inspected by plotting the curves together with the raw data.

With these results in hand, it is now possible to define both the buffering and transfer functions and then to visualize the system using an area plot.

As is evident from inspecting this plot, an increase in temperature translates into only a small increase in the proportion of flies with eye defects in the wild-type line. However, in the mutant line, a much more pronounced increase is observed. We can thus infer that the expression of the wild-type Hsp90 protein buffers the effect of temperature on the penetrance of the eye defect. In other words, since the “transfer” of the eye defect phenotype is greater in the mutant line, the wild-type Hsp90 protein must possess the abstract capacity of diverting or “soaking up” this disturbance (into an equally abstract buffering compartment) so that the “transfer” of the eye defect is diminished. Importantly, using the formal and general approach, we can now provide an exact quantitative measure of the buffering capacity of the wild-type allele by calculating and plotting the four buffering parameters together with the buffering angle (below).

As shown above, the buffering coefficient can be calculated to range from ~0.935 at 18 °C to ~0.822 at 32 °C. While these calculations are now trivial, the critical biological question of how to interpret these calculations is more challenging. As discussed by Schmitt ([1], Supplements 6 and 7), one way to proceed is to consider the conceptual overlap between the formal and general approach and probability theory. In essence, the buffering coefficient is analogous to a probability. In the same way that a probability measures the proportion of a part to a whole (i.e. the number of successful events to the total number of events), so does the buffering coefficient (by measuring the fractional change in the buffering compartment relative to the whole compartment). The critical realization is that both quantities are measured on a relative scale that is normalized to 1. Interpreting the graph in this way, one can say that the “probability” of buffering decreases from ~0.935 to ~0.822 from 18 °C to 32 °C.

Using similar logic, one can say that, in essence, the buffering ratio is analogous to the “odds” of buffering. In the same way that odds measure the proportion between two parts of a whole (by comparing events to non-events), so does (by comparing the fractional change in the buffering compartment to the fractional change in the transfer compartment). Again the critical realization is that both quantities are measured on a scale with equal intervals and an absolute zero. Interpreting the data in this way, one can say that the “odds” of buffering decrease from ~14.4 to ~4.6 from 18 °C to 32 °C. Similarly, one can consider and to be analogous to the “probability” of transfer and the “odds” of transfer, respectively.

Lastly, the buffering angle provides information regarding not only the magnitude of buffering but also the class of buffering behavior. As discussed by Schmitt ([1], Supplement 7), angles between 90° and 0° correspond to non-inverting moderation, with angles of 90° corresponding to perfect buffering and 0° to zero buffering. Thus, the simple inspection of the plot of reveals that the buffering capacity of wild-type Hsp90 is very strong (near perfect at ~86°) but decreases slightly with increasing temperature (to a value of ~78°). In any event—and however the data is interpreted—the analysis presented above clearly demonstrates the ease with which the buffering capacity of a genetic determinant can be formally and exactly quantified.

A formal conceptualization of genetic buffering was first put forward by famed geneticist and Nobel laureate Leland Hartwell [5, 6]. In these publications, Hartwell highlights the importance of buffering relationships in determining phenotype in outbred organisms. Subsequent research both in yeast and in the roundworm, *Caenorhabditis elegans*, has strongly supported his assumptions [7, 8]. Thus, in addition to increasing our basic understanding of genetic networks, these results also raised the theoretical question of whether or not it might be possible to provide an exact quantitative measure of a genetic determinant’s buffering activity.

As described for the first time above, Schmitt’s “formal and general approach” provides a powerful means with which to accomplish this goal. Through the calculation of the four buffering parameters , , , and and the buffering angle , it is indeed possible to provide an exact quantitative measure of the buffering activity or “power” of any genetic determinant in response to an environmental disturbance. Furthermore, the activity can be measured using either a relative scale normalized to one ( and ) or an absolute scale with equal intervals ( and ), or distilled to a single value measure , capable of describing the system in its entirety.

In conclusion, it must be noted that the application of the formal and general approach becomes practical only when used in conjunction with a sophisticated computational engine that is capable of readily analyzing the relevant data. As demonstrated in this article, *Mathematica* provides such an engine. The application of the formal and general approach using the Wolfram Language thus provides a powerful tool with which to quantitatively analyze both classical and non-classical buffering phenomena, irrespective of discipline.

[1] | B. M. Schmitt, “The Quantitation of Buffering Action I. A Formal & General Approach,” Theoretical Biology and Medical Modelling, 2(8), 2005. doi:10.1186/1742-4682-2-8. |

[2] | B. M. Schmitt, “The Quantitation of Buffering Action II. Applications of the Formal & General Approach,” Theoretical Biology and Medical Modelling, 2(9), 2005.doi:10.1186/1742-4682-2-9. |

[3] | M. Taipale, D. F. Jarosz, and S. Lindquist, “HSP90 at the Hub of Protein Homeostasis: Emerging Mechanistic Insights,” Nature Reviews Molecular Cell Biology, 11(7), 2010 pp. 515-528. doi:10.1038/nrm2918. |

[4] | S. L. Rutherford and S. Lindquist, “Hsp90 as a Capacitor for Morphological Evolution,” Nature, 396, 1998 pp. 336-342. doi:10.1038/24550. |

[5] | J. L. Hartman, B. Garvik, and L. Hartwell, “Principles for the Buffering of Genetic Variation,” Science, 291(5506), 2001 pp. 1001-1004. www.sciencemag.org/content/291/5506/1001.abstract. |

[6] | L. Hartwell, “Robust Interactions,” Science, 303(5659), 2004 pp. 774-775. doi:10.1126/science.1094731. |

[7] | A. H. Tong, G. Lesage, G. D. Bader, H. Ding, H. Xu, X. Xin, J. Young, G. F. Berriz, R. L. Brost, M. Chang, Y. Chen, X. Cheng, G. Chua, H. Friesen, D. S. Goldberg, J. Haynes, C. Humphries, G. He, S. Hussein, L. Ke, N. Krogan, Z. Li, J. N. Levinson, H. Lu, P. Ménard, C. Munyana, A. B. Parsons, O. Ryan, R. Tonikian, T. Roberts, A. M. Sdicu, J. Shapiro, B. Sheikh, B. Suter, S. L. Wong, L. V. Zhang, H. Zhu, C. G. Burd, S. Munro, C. Sander, J. Rine, J. Greenblatt, M. Peter, A. Bretscher, G. Bell, F. P. Roth, G. W. Brown, B. Andrews, H. Bussey, and C. Boone, “Global Mapping of the Yeast Genetic Interaction Network,” Science, 303(5659), 2004 pp. 808-813. doi:10.1126/science.1091317. |

[8] | B. Lehner, C. Crombie, J. Tischler, A. Fortunato, and A. G. Fraser, “Systematic Mapping of Genetic Interactions in Caenorhabditis Elegans Identifies Common Modifiers of Diverse Signaling Pathways,” Nature Genetics, 38(8), 2006 pp. 896-903. doi:10.1038/ng1844. |

J. Karagiannis, “The Quantitation of Non-classical Buffering,” The Mathematica Journal, 2015. dx.doi.org/doi:10.3888/tmj.17-3. |

Dr. Jim Karagiannis is an associate professor at the University of Western Ontario in London, Ontario, Canada. His research makes use of the model eukaryote *Schizosaccharomyces pombe* and explores the complex post-translational modifications that take place on the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II. Through an empirical examination of the informational properties and regulatory potential of the CTD, Dr. Karagiannis hopes to decipher the “programming language” used by eukaryotes to control aspects of gene expression.

**Jim Karagiannis**

*Department of Biology
The University of Western Ontario
London, ON
Canada, N6A-5B7*

This article describes the implementation of RIFA, a computational biology algorithm designed to identify the genes most directly responsible for creating differences in phenotype between two biological states, for example, tumorous liver tissue versus cirrhotic liver tissue.

With the invention of microarray technology, scientists finally had a means to measure global changes in gene expression between two biological states [1]. This has led to thousands of scientific publications describing long lists of differentially expressed genes in each scientist’s favorite experimental system. What has gradually become apparent to biologists is that having a list of differentially expressed genes, while an important first step in understanding the differences between two phenotypes (where phenotype represents the physical manifestation of one or more traits), is often not enough to identify the genes most directly responsible for driving changes in phenotype. While it is true that genes that are differentially expressed between two biological states may be important in explaining those differences, it is also possible that genes whose expression is *not* changed can also be pivotal in driving phenotypic differences.

For those unfamiliar with biology, a rough analogy may prove useful. Consider a manufacturing setting where there is a supervisor (a “boss” gene) and employees (“slave” genes) under the supervisor’s responsibility charged with manufacturing widgets (a particular phenotype, such as healthy liver tissue). A change in phenotype, such as transitioning from healthy liver tissue (manufacturing blue widgets) to cancerous liver tissue (manufacturing red widgets) can be accomplished by: (1) changing the rate that employees work (such as might happen if a supervisor shouts at the employees; this is analogous to differential expression); and/or (2) changing the instructions the supervisor is giving to employees (keeping the volume of instructions constant, but changing the information contained in the instructions; this is analogous to a mutation in the “boss” gene); and/or (3) a combination of scenarios (1) and (2). In scenario (1), there is a transition in phenotype because the employees (“slave” genes) begin working faster or slower than they have previously, which produces too many or too few gene products at the wrong time, creating a rippling effect throughout all of the manufacturing, which ends up in a different product (the red widget phenotype) being made. In this situation, the supervisor’s instructions to the employees remain constant (manufacture blue widgets) but are spoken with more (“shouting”) or less (“whispering”) volume. Scenario (1) reflects the kind of information that can be measured in microarray studies, whose sole purpose is to identify genes whose expression changes between two biological states. In scenario (2), the rate at which employees work remains constant, but they still manufacture a different-colored widget (phenotype), because the instructions they are receiving from their supervisor have changed. Differences in phenotype due to scenario (2) are rarely discovered by producing long lists of differentially expressed genes, because the primary driving force creating a change in phenotype is a change in instruction from the supervisor (such as a mutation in the “boss” gene) to the employees (“slave” genes), not a difference in the manufacturing rate of employees.

For these reasons, computational biologists have begun to develop algorithms that are better at highlighting those genes primarily responsible for driving changes in phenotype, regardless of whether those genes are differentially expressed or not. This is the purpose of the regulatory impact factor analysis (RIFA) algorithm presented here; that is, to highlight those genes most directly responsible for driving changes in phenotype. RIFA provides a computationally tractable way to detect differences in connectivity between genes in two biological states. Figure 1 illustrates the basic premise of connectivity and differences in connectivity between two biological states.

**Figure 1.** Two gene networks comprised of the same five genes (a through e) in two different biological states (phenotypes). Each vertex represents a gene, and each edge represents a connection between genes. In standard differential expression studies, each gene’s expression level

is compared to itself between the two biological states but ignores potential relationships between different genes. When even a casual observer compares the two networks above, it is immediately noticeable that the shape of each network is different, a difference driven by a change in connectedness between genes within each biological state.

Regulatory impact factor analysis (RIFA) is based on seminal work by Hudson, Reverter, and Dalrymple [2], which introduced three higher-order metrics all computed from basic information obtained in differential gene expression studies. The purpose of these metrics is to use the information present in gene expression studies to quantify the connectedness between differentially expressed genes (“slave” genes, using the analogy above) and a group of gene expression regulator genes, known as transcription factors (“boss” genes, using the analogy above). The three metrics are:

(1) |

(2) |

(3) |

Equation (1) (PIF) computes the average expression of the gene between two biological states (A and B) and multiplies that result by the differential expression of the gene between states A and B. In doing so, the magnitude of the differential expression of a gene is weighted by the overall expression level of the gene. PIF is then used to compute equation (2) (RIF4), which multiples the PIF value for each differentially expressed gene by the differential co-expression (calculated using the Spearman correlation coefficient) between each differentially expressed gene (the “slave” genes in our analogy above) and each transcriptional regulator (the “boss” genes in our analogy above) between states A and B. By summing these calculations over each differentially expressed gene, a prioritized list of the most important regulators driving changes in phenotype between states A and B can be obtained. Equation (2) is designed to provide an answer to the question, which regulator is consistently highly differentially co-expressed with the most abundant differentially expressed genes? Equation (3) (RIF5) is an alternative metric to equation (2) (RIF4), which also seeks to produce a prioritized list of the most important regulators driving phenotypic change. By multiplying the expression of each differentially expressed gene by the correlation between itself and each transcription regulator twice, once in state A and once in state B, the difference in state values can be computed and then summed over each differentially expressed gene to yield an alternative prioritized list of the most important regulators. Equation (3) is designed to answer the question, which regulator has the most altered ability to predict the abundance of differentially expressed genes? Further details of these equations are presented in [3-4], but the basic idea behind the use of these metrics in RIFA is straightforward. When gene expression data (from a well-thought-out experiment) is presented to RIFA, the algorithm can use the “echoes of sound off structures” (differential gene expression data) to triangulate the location of the “rifle shot creating the sound” (identify the master gene(s) driving the changes in phenotype).

RIFA is template driven, meaning the algorithm expects several pieces of user-defined information to be provided in a notebook cell that is used as a template for entering information. As RIFA was designed to process output from AffyDGED [5], it will be assumed the reader is familiar with AffyDGED as well. The features of RIFA are illustrated using data from a microarray study comparing gene expression profiles of tumorous liver tissue to cirrhotic liver tissue [6]. All microarray data used in this study and presented here is publicly available at NCBI’s Gene Expression Omnibus portal (www.ncbi.nlm.nih.gov/geo), using the access number GSE17548.

The template cell begins with a command to purposefully reinstall Java, for the express purpose of expanding the memory available to import large datasets into *Mathematica*.

The remainder of the template cell defines several variables requiring user input.

**1.** `timecoursedata`: This variable points to the directory containing the microarray gene expression data, in spreadsheet format, to be processed by RIFA. While this variable uses the term “timecourse” as part of its name, it is not necessary for the microarray data to be part of a time course experiment. The spreadsheet format of the data is non-negotiable and requires strict organization. To aid in instruction, a screen shot of the `timecoursedata` that will be described throughout this paper is included here (Figure 2).

**Figure 2.** Formatting of gene expression data for variable <`timecoursedata`>.

Column A contains unique transcript identification information from the microarray chip used in the study. Columns B through X contain gene expression measurement from samples (or time points) under the *same experimental condition* of the study. The columns after X contain gene expression measurements from samples (or time points) under the *same control condition* of the study. For example, in the liver study referenced above, tumor samples from multiple patients were randomly placed into six groups and compared to six groups of cirrhotic liver tissue by AffyDGED. Column B contains the gene expression measurements (transcript abundance, not differential expression) for the first group of tumor samples processed with AffyDGED, column C contains the gene expression measurements from the second group of tumor samples, and so on. In this example, the last column containing tumor (experimental condition) data is column G. Column H is the first column containing gene expression measurements from the first group of cirrhotic (control condition) tissue, column I from the second group of cirrhotic tissue, and so on. Notice how columns B and H contain output from AffyDGED’s processing of the first groups of tumor and cirrhotic tissues, respectively.

**2.** `conditiononecol`: This contains a short list defining the first and last column positions within `timecoursedata` to contain experimental condition data.

**3.** `conditiontwocol`: This contains a short list defining the first and last column positions within `timecoursedata` to contain control condition data.

**4.** `rawtranscriptionreg`: This variable points to the location of a spreadsheet file containing a list (organized into a single column) of known or suspected transcription factor genes present on the microarray chip being used. The file used here was created by parsing the biological process column of the annotation file for Affymetrix’s Human Genome U133 Plus 2.0 chip (available at www.affymetrix.com) for genes linked to the transcription process. The probeset identifiers referring to this group of genes were used to build a list of transcription factor genes.

**5.** `rawdegenes`: This link points to the spreadsheet file containing lists of differentially expressed genes (referenced by their probeset IDs, organized into columns) created by processing the experimental and control groups referenced in `timecoursedata` (above) with AffyDGED. In the liver example here, there are six columns of differentially expressed genes created by using AffyDGED to compare the six groups of tumorous livers with the six groups of cirrhotic livers.

**6.** `affyginlocation`: This variable holds the directory location for finding the Affymetrix .gin (gene information) file that provides the necessary information to annotate output from RIFA.

**7.** `savelocationroot`: This variable holds the location where the user would like the final results of the analysis to be saved.

**8.** `studyname`: This variable allows the user to name the output files generated by RIFA with study-specific information.

The first tasks completed by RIFA include the loading, parsing, and organization of raw data to facilitate downstream computation.

Upon completion of this first section of code, the transcription factor genes (the “boss” genes from the analogy above) are grouped with the differentially expressed genes (the “slave” genes from above) to facilitate calculation of each pairings’ Spearman rank correlation coefficient.

RIFA proceeds by calculating the Spearman rank correlation coefficients, which requires that each vector of gene expression measurements be tested for the presence of duplicate entries, which requires special handling to calculate Spearman rho. This is the purpose of the `tieCheck` module below. Based on the results of `tieCheck`, the code calls the `spearmanControl` module to optimize calculation of Spearman rho, taking advantage of function listability and the use of compilable expressions, where appropriate, to maximize speed.

**Caution:** Due to the sheer volume of computation that needs to be completed using the data described in this paper, the next segment of code will likely take 20-40 minutes to complete (depending on the speed of your computer) and consume roughly 28 Gb of RAM. Computations on machines with less RAM will finish but will require significant use of the hard drive, slowing computation considerably.

By pairing (and taking a sampling of) the correlations of the “boss” and “slave” genes between the tumor and cirrhotic livers, a satisfying (but not biologically surprising) pattern reveals itself (Figure 3). It is clear that there are many more strongly positive correlations between the “boss” and “slave” genes in the cirrhotic liver than the tumorous liver. This supports what biologists have known for a long time; that is, gene regulation in tumorous tissue is significantly uncoordinated.

**Figure 3.** A histogram of the Spearman rank correlation coefficients between regulator and differentially expressed genes in tumorous and cirrhotic liver biopsies.

Following the correlation calculations, RIFA calculates several important metrics, including PIF, RIF4, and RIF5 of equations (1), (2), and (3) described above.

The resulting plots (Figure 4) of PIF (equation (1)), RIF4 (equation (2)), and RIF5 (equation (3)) reveal the bidirectional nature of each of the three metrics. In other words, regardless of the metric used, and are equally influential to the underlying biology. This makes sense when one remembers that gene expression measurements, used in the calculations of the metrics above, are represented on a scale.

**Figure 4.** Histograms for each of the three primary metrics used in the RIFA algorithm. Positive and negative values should be interpreted as equally important (i.e., a gene that is fourfold down in expression is equally as likely to be important as a gene that is fourfold up in expression.)

After the metric calculations are completed, four files are exported containing all the results in file formats directly usable by *Mathematica* and Microsoft Excel. One set of files is appended with the phrase “RifSortByAvg” and contains the following information in table form, sorted by the average of RIF4 and RIF5 values.

Column 1: unique transcript (gene) IDs

Column 2: the average of RIF4 and RIF5 values

Column 3: RIF4 values

Column 4: RIF5 values

Column 5: genbank accession numbers

Column 6: gene names

Column 7: gene product information

A second set of files is appended with the phrase “sortedPIF” and contains the following information in table form, sorted by PIF values.

Column 1: unique transcript (gene) IDs

Column 2: PIF values

Column 3: genbank accession numbers

Column 4: gene names

Column 5: gene product information

As described above, the RIF4 and RIF5 results are most useful for identifying the “boss” genes and the PIF results are most useful for identifying the “slave” genes. Both the “boss” and “slave” genes can be influential in creating differences in phenotypes between two states.

The final output of RIFA is a network graph that associates the most strongly correlated, highest impact PIF scores with the highest impact RIF scores. In this graph, the top 10 most positive and negative average RIF entries, the top 10 most positive and negative RIF4 entries, and the top 10 most positive and negative RIF5 entries are linked to the phenotype of interest with red edges. In other words, the red edges highlight the “boss” genes most responsible for driving changes in phenotype. The nodes of the graph use tooltips to identify the gene represented by the node. The phenotype of interest node is abbreviated “POI.” Blue edges are used to highlight the “slave” genes most responsible and most correlated to the “boss” genes for driving changes in phenotype. In this way, the graph highlights the “slave” genes responding to the “boss” genes’ orders to change phenotype. Here, the highest 0.5% of positive and the lowest 0.5% of negative PIF scores are connected to transcription regulators (represented by RIF nodes) if they share a Spearman rho value of with the transcription regulator.

Three primary lines of evidence show that RIFA is performing to design specifications. Evidence line 1: RIFA was created to provide a *Mathematica* implementation of the regulatory impact factor algorithm originally described by Hudson et al. to highlight those genes most directly responsible for driving changes in phenotype. During development, RIFA was vetted with the original data used by these authors, to highlight the genes most responsible for driving phenotypic differences between Wagyu and Piedmontese cattle. The most prominent (and well-characterized) phenotypic difference between these breeds of cattle is the increased musculature of Piedmontese animals, which is known to be due to a mutation in the breed’s myostatin (GDF8) gene [7]. Using the author’s own data, RIFA correctly identifies GDF8 at the bottom (most negative value of ) of its RIF5 output.

Evidence line 2: The Piedmontese/Wagyu data represents the only dataset that is completely and publicly available to validate RIFA. For this reason, evidence line 1 represents the strongest line of evidence that RIFA is functioning properly, as RIFA is able to duplicate the results of Hudson et al. Even so, other gene expression datasets have been analyzed and discussed in the literature that allow for comparison to RIFA output. Please keep in mind that RIFA’s results cannot be identical to these other examples, as the full list of normalized gene expression data and the full list of transcription regulators, both necessary input to RIFA, are not publicly available. Reverter and colleagues discuss their analysis of porcine gene expression data from [8] and attempt to explain why their results do not prioritize SRY, a gene that is arguably one of the most important sex-determining genes known to science [9]. Reanalysis of this same data using normalized gene expression from AffyDGED and an alternative list of gene regulators shows that RIFA does highlight SRY as the fourth most negatively prioritized gene. While being a satisfying result, it also serves to highlight the fact that all algorithms (RIFA included) are sensitive to the quality of the input data provided to them.

Evidence line 3: Keeping in mind the discussion above, a similar reanalysis of data referenced in [10-11] shows that RIFA highlights CDK8 [12] as the 33rd most negatively prioritized gene. Hudson’s analysis of this data highlights CDK8 as the fourth most positive regulator of colon cancer. Why does RIFA rank CDK8 at position 33, while Hudson’s analysis ranks it at 4? The most reasonable explanation is that RIFA processed a transcription regulator list that included 6,685 regulators, while Hudson’s work employed a smaller regulator list of 1,292 entries. Fourth out of 1292 (4 divided by 1292) is 0.0031, while 33rd out of 6685 is 0.0049. On a percentage basis of the transcription regulator list size, RIFA’s output is nearly identical to that obtained by the original authors who developed the algorithm.

From the evidence presented, we know that RIFA is performing as expected and can begin to ask if results from other studies make biological sense. If RIFA is working correctly, it should highlight genes that have been linked to cirrhosis and/or cancer in the scientific literature. Keep in mind that not every gene likely to be linked to cirrhosis or cancer has been discovered or characterized yet—which is the value in using a program like RIFA, that is, to find new connections between genes and phenotype. A small sample of output will be reprinted for easier referencing here. Additionally, the output will be reformatted to fit within printable margins by forcing the data in each entry to occupy two or more rows of the table below.

What information is revealed in this list? First, let us obtain a list of the unique entries present in this list (a handful of entries may be prioritized by RIF4 and RIF5 metrics simultaneously, thus showing up more than once).

Do any of the results contain entries that have been linked to cirrhotic or tumorous livers in the scientific literature? Any entry that has a gene name associated with it may have information that can be investigated further.

RIFA produces a list of 29 unique gene names that can be searched for in PubMed (www.ncbi.nlm.nih.gov/pubmed). Performing a literature search for these genes in association with liver disease search terms produces the results described in Table 1.

Twenty-one of the 29 RIFA output entries with a gene name associated with them yield compelling connections between each gene and the disease phenotype search terms “liver cirrhosis,” “liver cancer,” and “cancer,” suggesting that RIFA is enriching for genes driving the phenotypic changes observed between cirrhotic and tumorous liver tissue.

The remaining eight out of 29 genes do not show evidence in the scientific literature linking them to these disease phenotypes. Explanations for this abound, but it is impossible to rule out the possibility that these genes are, in fact, linked to the disease phenotypes but have not yet been characterized by the scientific community. It is simply impossible to conclude if those eight genes are or are not linked to the disease phenotypes at this time. The same conclusion must also be admitted for the other 25 RIFA output entries that have no gene name associated with them. In other words, RIFA has identified 25 potential new “boss” genes associated with the cirrhotic to tumor transition in liver tissue. These may represent valuable new avenues of research.

To gauge the performance of RIFA, several publicly available datasets of different sizes and complexity were analyzed. The first column of Table 2 shows the series accession number for each dataset available at NCBI’s Gene Expression Omnibus. Timings were acquired running *Mathematica* 9.0.1 under Windows 7 (64 bit) using an Intel Core i5-2500K processor overclocked to 4.48Ghz. Total system memory is 32GB. All reported timings use a fresh kernel.

Table 2 reveals that small datasets can easily be processed in under one minute, while very large datasets, involving thousands of transcription regulators, differentially expressed genes, and multiple time points can take upwards of 30 minutes. RIFA’s code base utilizes functions with the `Listable` attribute whenever possible to increase speed, which places demands on the computer’s memory infrastructure, as evidenced by the sizeable memory consumption measured with large datasets.

Changes in gene expression are at the core of what distinguishes healthy tissue from diseased tissue. Part of unraveling the mystery behind disease centers on identifying those genes most directly responsible for controlling the differences in gene expression that link those differences to disease traits. RIFA’s implementation brings to the *Mathematica* user community a compelling algorithm used by biomedical researchers to intelligently prioritize the thousands of genes present in an organism and tie their behavior to specific traits of interest.

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T. D. Allen, “RIFA: A Differential Gene Connectivity Algorithm,” The Mathematica Journal, 2015. dx.doi.org/doi:10.3888/tmj.17-2. |

Todd Allen is an associate professor of biology at HACC, Lancaster. His interest in computational biology using *Mathematica* took shape during his postdoctoral research years at the University of Maryland, where he developed a custom cDNA microarray chip to study gene expression changes in the chestnut blight pathogen, *Cryphonectria parasitica*.

**Todd D. Allen, Ph.D.**

*Harrisburg Area Community College (Lancaster Campus)
East 206R
1641 Old Philadelphia Pike
Lancaster, PA 17602
*

There exists a range of explicit and approximate solutions to the cubic polynomial Rayleigh equation for the speed of surface waves across an elastic half-space. This article presents an alternative approach that uses Padé approximants to estimate the Rayleigh wave speed with five different approximations derived for two expansions about different points. Maximum relative absolute errors of between 0.34% and 0.00011% occur for the full range of the Poisson ratio from to 0.5. Even smaller errors occur when the Poisson ratio is restricted within a range of 0 to 0.5. For higher-order approximants, the derived expressions for the Rayleigh wave speed are more accurate than previously published solutions, but incur a slight cost in extra arithmetic operations, depending on the desired accuracy.

In 1885 Lord Rayleigh published his paper “On Waves Propagated along the Plane Surface of an Elastic Solid” [1] and observed that:

It is proposed to investigate the behavior of waves upon the plane surface of an infinite homogeneous isotropic elastic solid, their character being such that the disturbance is confined to a superficial region, of thickness comparable with the wave-length. …

It is not improbable that the surface waves here investigated play an important part in earthquakes, and in the collision of elastic solids.Diverging in two dimensions only, they must acquire at a great distance from the source a continually increasing preponderance.

The italicized phrase above is a supreme understatement, given the ensuing history of seismology. In any case, Rayleigh proved the theoretical existence of surface waves on an elastic half-space and showed that the speed of such waves may be calculated from the real roots of a cubic polynomial whose coefficients are all real and depend on the ratio of the S-wave velocity to the P-wave velocity, or alternatively on the Poisson ratio of the elastic half-space. He provides the solutions for harmonic waves for both incompressible and compressible half-spaces, shows the elliptic orbit of points on the surface as the wave travels across the surface, demonstrates that the motion is restricted to within approximately one wavelength of the surface, and states that the Poisson ratio may lie between 0.5 and for an elastic material. However, he does not provide explicit expressions for the Rayleigh wave speed.

It appears that the first paper that published explicit expressions for the Rayleigh wave speed for the full range of elastic material properties was by Rahman and Barber [2]. Since that time, a number of authors have sought to develop alternative analytical expressions for the Rayleigh wave speed [3-11]. It is noted that the solutions provided cannot be used indiscriminately, as care is required on occasions to choose the correct root to ensure a smooth and continuous estimate of the Rayleigh wave speed [3, 5, 7]. A parallel effort has attempted to derive approximate expressions for the Rayleigh wave speed [3, 12-18].

Complete analytical derivations were provided by [2, 4, 7, 9, 11]. Others have used computer algebra to assist in their derivations [3, 5, 6]. The original approach given in [4] contains unspecified typographical errors [5, 9]. Indeed, the recent solution given in [9] appears to have been derived earlier and independently but with typographical errors [6]. It has also been shown to be identical to the solution provided in [5]. Cardano’s formula for the roots of a cubic polynomial with real coefficients [19, 20] is used by [2, 5, 7, 9, 11], although the starting point in [9] appears to be different from the other solutions. A more recent solution appears to use Cardano’s formula (but referred to as Shengjin’s formula) [11]. As an aside, an interesting history of Cardano’s formula appears in [21].

Cardano’s formula was published in 1545, and it is perhaps surprising that no explicit solution for the Rayleigh speed was available until the Rahman and Barber publication [2]. It would appear unreasonable to expect that Rayleigh was not aware of the Cardano formula. In any case, and as just one example of prior publication of the Rayleigh wave speed, we may refer to the work in J. E. White’s book, *Underground Sound* [22]. Given without derivation, and in somewhat standard notation often associated with the use of Cardano’s formula, we find by simple algebra that White’s solution is identical to that of Rahman and Barber. It may be speculated that similar solutions were found even earlier.

The approximate expressions for the Rayleigh wave speed of surface waves have been derived by various methods, including Taylor series expansion of the Rayleigh equation [3], approximation of the Rayleigh equation to lower-degree polynomials using the Lanczos method [13], minimization of the integral of the Rayleigh equation with arbitrary coefficients using a least-squares approach [14], least-squares minimization [15, 18] given a known exact solution [5, 7], use of a bilinear function for the root and applying least squares to determine the coefficients of the bilinear function [16], and an iterative method with asymptotic quadratic convergence [17].

In this article, we follow the approach given by Liner [3], but rather than using a Taylor series expansion of the Rayleigh equation, we use Padé approximants. Padé approximants of various orders are described and their accuracy compared to the exact solution given in [7]. The complexity of the various derived solutions is assessed in terms of the number of numerical operations required to calculate the Rayleigh wave speed.

Functions may be approximated in various ways. Perhaps the best known is the Taylor series expansion, whereby a function can be expressed as an infinite series expanded around the

point as

(1) |

where is the derivative of the function evaluated at the point . It is usual to truncate the series to use the lower-order terms as an approximation to the function.

An alternative method to approximate a function is to use Padé approximants. Here the function is approximated as a rational function of two truncated polynomials expanded around the point :

(2) |

where the numerator and denominator are polynomials of degree at most and at most , respectively. The approximant is referred to as a Padé approximant of type . The approximation given in equation (2) has parameters.

The Rayleigh equation [1] for an elastic half-space is given by

(3) |

where , , is the Rayleigh wave speed, and and are the P-wave and S-wave velocities of the medium, respectively. Real roots of equation (3) represent the normalized Rayleigh wave speed, and in the case of several real roots, the smallest is taken. The Poisson ratio may be calculated to give .

The Padé approximant is found for the left-hand side of equation (3), using computer algebra to calculate the necessary coefficients [23]. Equating the numerator polynomial in equation (2) to zero yields the estimate of the normalized Rayleigh speed. Multiple solutions are possible, and these depend on the Padé approximant type, . Given that the Rayleigh equation is a cubic polynomial, the approximations are restricted to and . In particular, the following Padé approximant types are examined: , , , , and .

The five sets of Padé approximants obtained yield solutions for the value of in equation (2) with the following forms: for types , , and , the solutions are ratios of polynomials in of degree 2, 3, and 4, respectively. In each case, both the numerator and denominator polynomials have identical degree, and a general expression for them is

(4) |

for the type . For the types , and , the general expression is

(5) |

where for type and for type . The coefficient for all cases considered here, except in the single case of type for expansion about , in which case .

Like the Taylor series expansion, the Padé approximants are expansions about a given value. In the first instance, expansions were obtained around unity, following previous work [3], but after some trial and error, expansions around were found to be superior in terms of minimizing the absolute relative error across the full range of values for . It is worth repeating that the expansions are done for the ratio of the Rayleigh wave speed to the S-wave velocity squared , unlike the Taylor expansion in Liner [3] that is done about the square root of . Clearly, it is possible to seek the value around which expansions are minimized using a least-squares approach, some aspects of which are discussed below. Below are shown the results obtained for the coefficients in (4) and (5) for expansions about (suitable for the full range of Poisson’s ratio) and (suitable for non-negative Poisson’s ratio), respectively. The coefficient values were obtained using *Mathematica* 9 and are exact.

The relative absolute errors in percentages for the range of are shown below for some of the cases considered. The errors are defined as

(6) |

where and denote numerical and analytical solutions for the Rayleigh wave speed, respectively, and the analytical solution refers to that in [7].

Figure 1 shows a comparison of the exact analytical solution [7], the solution obtained using the Padé approximant , and the solution for a Taylor expansion of the Rayleigh equation given in equation (3). The solution based on the Padé approximant was for an expansion with , while the Taylor series solution was for an expansion with . The relative absolute errors for these two approximate solutions and the one provided by Liner [3] are shown in Figure 2. The Liner solution was a Taylor series expansion in the normalized Rayleigh wave speed, whereas the expansion in its square is shown in Figure 1 and labeled as “Taylor.” It is clear that both Taylor series expansions have increasing errors as increases. The solution based on the Padé approximant has larger errors than either of the Taylor expansion solutions for smaller values of but performs better for larger values of .

Figures 3 and 4 show the relative absolute errors for solutions based on the Padé approximants , and , expanded around the point . As expected, the errors are smaller for the solutions based on higher-order Padé approximants.

The following function gives an exact analytical expression for the Rayleigh wave speed [7, 10].

The function `taylorR` gives the Taylor series expansion in the square of the ratio of Rayleigh wave velocity to the S-wave velocity. (The expansion is not in the ratio alone as in the Liner Taylor series expansion given below.)

The function `padeR` calculates the Rayleigh wave speed based on using Padé approximants. Here `mdegree` is the numerator degree, `ndegree` is the denominator degree, `avalue` is the expansion point, and `root1or2` is 1 or 2, so as to ensure the smallest root is chosen. (Normally `root1or2` is 1, and an incorrect choice is obvious when overlaying the Rayleigh velocity estimate and the exact analytical Rayleigh wave velocity.)

The function `legName` is for the labels in the legend of some of the plots. `rspeed` is used to switch to one of the functions defined for the Rayleigh wave speed; they are defined in the body of the article or in the Appendix.

`plotRayleighSpeedEstimate` is a plotting function that enables comparison of the Rayleigh wave speed obtained by using two functions given in either the body of the report or in the Appendix, and also one derived from a Padé approximant (see the function `legName`). The input parameters are `rspeed1`, `rspeed2` (for the two different functions), and the Padé approximant parameters. `max` is for the full range of Poisson’s ratio and for positive Poisson’s ratio. Note that when , ; , ; , .

**Figure 1.** The normalized Rayleigh wave speed using the Padé approximant expanded around and the Taylor series expanded around . The solid curve is the analytical solution given in Vinh and Ogden [7].

We define a function for the approximation to the Rayleigh wave speed given by Liner [3]. The approximation is based on a Taylor series expansion in the ratio of the Rayleigh wave speed to the shear wave speed.

`plot3RayleighWaveSpeedRelativeError` is a plotting function for comparing the relative absolute errors for the Rayleigh speed estimates from two functions and an estimate obtained from a Padé approximant with similar inputs, described above. `ymax` is the maximum range for the relative error and is adjusted to scale the plot.

**Figure 2.** Relative absolute error for Rayleigh wave speed using the Padé approximant expanded around compared to the two Taylor series expansions, both expanded around .

`plot2RayleighWaveSpeedRelativeError` is a plotting function for comparing the relative absolute errors for the Rayleigh speed estimates obtained using two Padé approximants. The function has similar inputs described above, and here the suffix 1 or 2 refers to the given Padé approximant.

**Figure 3.** Relative absolute error for Rayleigh wave speed using the Padé approximants and expanded around .

**Figure 4.** Relative absolute error for Rayleigh wave speed using the Padé approximants and expanded around .

It is possible to generate the expressions for equations (4) and (5) based on a Padé approximant simply by squaring the Rayleigh wave speed estimate. The square roots of the full set of results given below are good estimates of the Rayleigh wave speed for different ranges of the Poisson ratio. Simple arithmetic yields the results in the forms given in equations (4) and (5).

Here are some useful and accurate expressions for the Rayleigh wave speed squared over the full range of the Poisson ratio with .

Here are some useful and accurate expressions for the Rayleigh wave speed squared over the positive range of Poisson’s ratio with .

Polynomial expressions for the Rayleigh wave speed are given in equations (4) and (5) with respective coefficients given above. These expressions have been derived using Padé approximants around and for (Poisson ratio in the range 0.5 to ) and (Poisson ratio in the range 0.5 to 0), respectively. The two expansion values ( in equations (1) and (2)) were obtained by examining the area under the relative absolute error curve for increments of between 0.5 and 1. In principle, a least-squares solution for the value of producing the minimum error would be feasible for each Padé type, but in so doing we ignore the detailed shape of the error curve across the range of values. For example, Figure 5 shows the relative absolute error for the Rayleigh wave speed based on Padé type for expansions around and . While the error is less for the expansion around for most of the range of values, we observe that for larger values of , the errors become larger and exceed those for the expansion around . This basic behavior is characteristic of the errors obtained (but not shown) using the Padé types and . It is worth noting that for non-negative Poisson’s ratio of , the errors are smaller for expansions about for the three Padé types , , and . The question arises, is it possible to expand around another value that will have smaller errors for non-negative Poisson’s ratio? Figure 6 shows the relative absolute error for the Padé type expanded about and . The error in the latter case is smaller for all values up to approximately , after which it increases beyond that for the expansion about , but not significantly. The maximum error is about the same for both cases. Once more, similar behavior is observed for the other two Padé types and .

Figure 7 shows the relative absolute errors for the Rayleigh wave speed based on using the Padé type expanded around and . The behavior of these curves is different from those shown earlier—here there is a monotonic decrease in the error for most of the full range of as it increases. The errors are one hundred times smaller than those based on the Padé type shown in Figure 6. A somewhat extraordinary reduction of a further five times (so a total of a 500-fold reduction) in relative absolute error occurs for the Rayleigh wave speed estimate based on the Padé type expanded around and shown in Figure 8.

**Figure 5.** Relative absolute error for Rayleigh wave speed using the Padé approximants expanded around the points and .

**Figure 6.** Relative absolute error for Rayleigh wave speed using the Padé approximants expanded around the points and .

**Figure 7.** Relative absolute error for Rayleigh wave speed using the Padé approximants expanded around the points and .

`plot1RayleighWaveSpeedRelativeError` is a plotting function for the relative absolute error of the Rayleigh speed obtained using a single Padé approximant. The function has similar inputs described earlier.

**Figure 8.** Relative absolute error for Rayleigh wave speed using the Padé approximant expanded around .

It is worth summarizing the various error estimates arising from the Rayleigh wave speed based on the Padé approximant types studied for the two ranges of Poisson’s ratios (Table 1). These are compared to other published estimates given in Table 2. Tables 1 and 2 show this data and also the number of arithmetic operations required to compute the value of (equation (3)), from which we estimate any given Rayleigh wave speed. The latter information shows the tradeoff between the accuracy of the Rayleigh wave speed estimate and the associated computational effort. The operations included are addition, subtraction, multiplication, division, and the taking of a root or a trigonometric function; raising to a power is taken as a series of multiplications, and the minimum number of such operations is used wherever possible. It is assumed that an analytical solution is exact, that is known, and that for each approximate solution all coefficients are known and retained as integers until the calculation commences. In the case of the exact solution based on Cardano’s formula, two different expressions exist for different values of , and in this case, the number of operations is given for each path separated by a forward slash. Functions not previously introduced in the body of the text and required to calculate the estimates in Table 2 may be found in the Appendix.

The data in Tables 1 and 2 shows that the computational effort is generally greatest for the three analytical solutions. The approximate solutions based on the Padé approximants improve their error estimates approximately tenfold as we move from Padé types to for expansions around . The number of arithmetic operations increases by about five for Padé types to , without a significant change in the number of operations as we move to Padé types and . For the Padé types expanded around and for non-negative Poisson’s ratio, we find a remarkable reduction in the errors, commencing with a thirtyfold reduction in the Padé type , followed by a twentyfold reduction as we move from Padé types to , and a further tenfold reduction in the errors as we move to Padé types to . The Padé type expanded around has a fifteenfold smaller error than either of the Taylor expansions, and with fewer operations. The methods based on least-squares solutions that minimize the area under the absolute error curves perform strongly, with a good mix of relatively small errors and a small number of arithmetic operations. It is necessary to go to the approximation based on Padé type before the error is less than that for the solutions based on least squares, but this requires more arithmetic operations.

The Rayleigh wave speed was estimated based on expansions of the Rayleigh equation by Padé approximants and equating the numerator of that representation to zero. The numerator polynomials were solved for the normalized Rayleigh wave speed and provide five distinct solutions. The solutions have varying degrees of accuracy, depending on the value about which the Rayleigh equation is expanded. Good, accurate solutions occur for the full range of Poisson’s ratio, and even more accurate solutions are found for non-negative Poisson’s ratio. It is concluded that these expressions for the Rayleigh wave speed provide a useful approximation, with a balance between accuracy and number of arithmetic operations required.

This Appendix contains a number of functions that estimate the Rayleigh wave speed, which may be used to reproduce some results for the approximate solutions found in Table 2. Other needed functions have been presented in the body of the main text.

Here is the Bergmann formula from Vinh and Malischewsky [24].

Here is the Vinh and Malischewsky [18] formula to degree 2 in Poisson’s ratio.

Here is the Vinh and Malischewsky [18] formula to degree 3 in Poisson’s ratio.

Here is the Vinh and Malischewsky [18] formula to degree 4 in Poisson’s ratio.

Here is the Rahman and Michelitsch [18] formula using the Lanczos approximation.

Here is the Li [14] formula for the full range of Poisson’s ratio.

Here is the Li [14] formula for the positive range of Poisson’s ratio.

[1] | L. Rayleigh, “On Waves Propagated along the Plane Surface of an Elastic Solid,” Proceedings of the London Mathematical Society, S1-17(1), 1885 pp. 4-11. doi:10.1112/plms/s1-17.1.4. |

[2] | M. Rahman and J. R. Barber, “Exact Expressions for the Roots of the Secular Equation for Rayleigh Waves,” Journal of Applied Mechanics, 62(1), 1995 pp. 250-252. doi:10.1115/1.2895917. |

[3] | C. L. Liner, “Rayleigh Wave Approximations,” Journal of Seismic Exploration, 3, 1994 pp. 273-281. |

[4] | D. Nkemzi, “A New Formula for the Velocity of Rayleigh Waves,” Wave Motion, 26(2), 1997 pp. 199-205. doi:10.1016/S0165-2125(97)00004-8. |

[5] | P. G. Malischewsky, “Comment to ‘A New Formula for the Velocity of Rayleigh Waves’ by D. Nkemzi [Wave Motion 26 (1997) 199-205],” Wave Motion, 31(1), 2000 pp. 93-96. doi:10.1016/S0165-2125(99)00025-6. |

[6] | H. Mechkour, “The Exact Expressions for the Roots of Rayleigh Wave Equation,” Proceedings of the 2nd International Colloquium of Mathematics in Engineering and Numerical Physics (MENP-2), Bucharest, 2002, Geometry Balkan Press, 2003 pp. 96-104. |

[7] | P. C. Vinh and R. W. Ogden, “On Formulas for the Rayleigh Wave Speed,” Wave Motion, 39(3), 2004 pp. 191-197. doi:10.1016/j.wavemoti.2003.08.004. |

[8] | P. G. Malischewsky Auning, ” A Note on Rayleigh-Wave Velocities as a Function of the Material Parameters,” Geofísica internacional, 43(3), 2004 pp. 507-509. www.geofisica.unam.mx/unid_apoyo/editorial/publicaciones/investigacion/geofisica_internacional/anteriores/2004/03/Malischewsky.pdf. |

[9] | D. W. Nkemzi, “A Simple and Explicit Algebraic Expression for the Rayleigh Wave Velocity,” Mechanical Research Communications, 35(3), 2008 pp. 201-205. doi:10.1016/j.mechrescom.2007.10.005. |

[10] | P. G. Malischewsky, “Reply to Nkemzi, D. W., ‘A Simple and Explicit Algebraic Expression for the Rayleigh Wave Velocity,’ [Mechanical Research Communications (2007), doi:10.1016/j.mechrescom.2007.10.005],” Mechanical Research Communications, 35(6), 2008 p. 428. doi:10.1016/j.mechrescom.2008.01.011. |

[11] | X.-F. Liu and Y.-H. Fan, “A New Formula for the Rayleigh Wave Velocity,” Advanced Materials Research, 452-453, 2012 pp. 233-237. |

[12] | D. Royer, “A Study of the Secular Equation for Rayleigh Waves Using the Root Locus Method,” Ultrasonics, 39(3), 2001 pp. 223-225. doi:10.1016/S0041-624X(00)00063-9. |

[13] | M. Rahman and T. Michelitsch, “A Note on the Formula for the Rayleigh Wave Speed,” Wave Motion, 43(3), 2006 pp. 272-276. doi:10.1016/j.wavemoti.2005.10.002. |

[14] | X.-F. Li, “On Approximate Analytic Expressions for the Velocity of Rayleigh Waves,” Wave Motion, 44(2), 2006 pp. 120-127. doi:10.1016/j.wavemoti.2006.07.003. |

[15] | P. C. Vinh and P. G. Malischewsky, “Explanation for Malischewsky’s Approximate Expression for the Rayleigh Wave Velocity,” Ultrasonics, 45(1-4), 2006 pp. 77-81. doi:10.1016/j.ultras.2006.07.001. |

[16] | D. Royer and D. Clorennec, “An Improved Approximation for the Rayleigh Wave Equation,” Ultrasonics, 46(1), 2007 pp. 23-24. doi:10.1016/j.ultras.2006.09.006. |

[17] | A. V. Pichugin. “Approximation of the Rayleigh Wave Speed.” (Jan 10, 2008) people.brunel.ac.uk/~mastaap/draft06rayleigh.pdf. |

[18] | P. C. Vinh and P. G. Malischewsky, “Improved Approximations of the Rayleigh Wave Velocity,” Journal of Thermoplastic Composite Materials, 21(4), 2008 pp. 337-352. doi:10.1177/0892705708089479. |

[19] | M. Abramowitz and I. A. Segun, eds., Handbook of Mathematical Functions, New York: Dover Publications, 1965. |

[20] | D. Zwillenger, ed., Standard Mathematical Tables and Formulae, 31st ed., Boca Raton: CRC Press, 2003. |

[21] | P. R. Hewitt. “Cardano’s Formulas or a Pivotal Moment in the History of Algebra.” (Apr 7, 2009) livetoad.org/Courses/Documents/bb63/Notes/cardanos_formulas.pdf. |

[22] | J. E. White, Underground Sound: Application of Seismic Waves, New York: Elsevier, 1983. |

[23] | Mathematica, Release Version 9.0, Champaign: Wolfram Research, Inc., 2013. |

[24] | P. C. Vinh and P. G. Malischewsky, “An Approach for Obtaining Approximate Formulas for the Rayleigh Wave Velocity,” Wave Motion, 44(7-8), 2007 pp. 549-562. doi:10.1016/j.wavemoti.2007.02.001. |

A. T. Spathis, “Use of Padé Approximants to Estimate the Rayleigh Wave Speed,” The Mathematica Journal, 2015. dx.doi.org/doi:10.3888/tmj.17-1. |

A. T. (Alex) Spathis works in rock mechanics and rock dynamics. He has measured the stresses in the Earth’s crust at shallow depths of tens of meters down to moderate depths of over 1000 meters. This data assists in understanding earthquakes and in the design of safe underground mines. He has formal qualifications in applied mathematics, electrical engineering, and rock mechanics, and has a Ph.D. in geophysics.

**A. T. Spathis**

*Orica Technical Centre
PO Box 196
Kurri Kurri NSW
Australia 2327*

Remarkable advances have been made in radiotherapy for cancer. Tumors inside the body that move with respiration can now be tracked during irradiation or can be irradiated at a specific phase of respiration [1]. Since radiation of these wavelengths is invisible to the human eye, it is not possible to see whether a tumor that is moving during respiration is being irradiated accurately. Therefore, simulations that use the actual respiration wave to show the tumor being irradiated are useful for training and to explain the procedure to patients.

Radiation generated by radiotherapy equipment has a dosage rate, which is defined as the strength over time. Therefore, the duration of irradiation of a tumor inside the body at a certain dose is determined by the dose rate. For tumors in the brain, head, and neck region, fixing the target area in place can prevent tumor movement during irradiation. However, with tumors of the lung or abdomen, the displacement of the organs during respiration is substantial, and the tumor moves with respiration during the irradiation time. In conventional radiotherapy, respiratory displacement of the tumor is taken into account by targeting a large radiation field. However, when a large radiation field is used, the large radiation dose delivered to the patient in one session can cause severe side effects; thus, irradiation has to be carried out over a longer period with smaller doses.

For small tumors located inside the brain, precise irradiation of a small field has been shown to enable delivery of a single large dose without adverse side effects. An attempt has been made to apply this technology to tumors of the trunk, where the most important issue is countering the respiratory movement of the tumor. One way to achieve this is to detect respiratory displacement and conduct irradiation according to the positional information. One such method is to carry out irradiation when the tumor is in position within a certain range, and another method is to track respiratory displacement during irradiation. Revolutionary advances in radiation therapy technology have enabled both these methods to be used in practice [1].

Depicting the form of irradiation of a small tumor inside the body with countermeasures against respiratory movement in a three-dimensional simulation could promote better understanding of this therapeutic method. In the simulation, a target volume is set to encompass the shape of a small tumor. The tumor moves along the vertical axis of the trunk ( axis). For irradiation, either the radiation field moves in accordance with the tumor movement, or irradiation is performed only when the tumor has completely entered the radiation field in a set respiratory phase. At the same time, the respiration wave is output and the position of the tumor on that waveform is recreated.

Respiratory displacement was sampled at a rate of 25 times/s using a pressure sensor attached to the body. The sampled data was stored in a CSV file to be read into *Mathematica*. The read-in data is shown in the output of the list plot below. In the graph, the minimum value on exhalation during free respiration was defined as 0, and the maximum value on inhalation was defined as 100.

The notebook defines 3407 triplets.

This extracts the respiration wave data and plots it.

A single malignant tumor cell generated by the effects of carcinogenic factors at several stages forms a visible tumor mass through continued monoclonal proliferation. Cell density is high in the center of the tumor and is assumed to spread out in three dimensions in a normal distribution.

This defines the 3D normal distribution of tumor morphology.

This defines the location of the tumor at a given time with a given color.

The center of the tumor moves along the axis with amplitude given by the respiratory wave and shown on the left with a red point. Think of the front of the body as the front plane (the plane parallel to the - given by ).

The patient is lying on the surface of the bed (with respect to the graph, the patient lies on the - plane with the head in the negative direction, the feet in the positive direction, and looking up in the direction). As the patient breathes, the tumor moves in the direction of the length of the body (i.e. along the axis). A tumor-tracking beam acts on the - plane set at five times the standard deviation of the tumor spread. The beam moves with the respiratory wave in the same way as the tumor.

In this situation, the beam is set to turn on when it enters a set position in the respiratory wave amplitude (“Threshold ”). On and off gating of the radiation beam is easily observable on the respiratory waveform, the % threshold value being clearly indicated.

This shows the irradiation synchronized to respiration.

Stereotactic radiotherapy was originally developed for the treatment of diseased regions inside the cranium, which do not move once fixed in position. It has been demonstrated that targeting a small lesion from multiple directions enables delivery of a large radiation dose in one session, without causing side effects to the adjacent normal tissue. To apply this technology to tumors in the trunk region, which move in conjunction with respiration, the tumor needs to be immobilized. An attempt was made to irradiate the tumors from multiple directions with minimized respiratory movement by fixing the body in position and compressing the abdomen to reduce the movement of the diaphragm to very slight movement [2, 3]. This method was shown to be safe and effective and represents a technological innovation in stereotactic irradiation of the trunk region. Having patients hold their breath during irradiation is the simplest method, which is becoming widespread—a method equivalent to stereotactic radiotherapy used for the cranium. On the other hand, irradiation conducted under free-breathing conditions is the most appropriate physiological method, but requires a mechanism for irradiating during a phase synchronized with the respiratory wave [4, 5]. Moreover, the method of irradiating the tumor while tracking its movement with respiration has presented difficulties in controlling the motion of a movable section of the irradiation equipment [6, 7]. However, recent advances in irradiation equipment and control computers have now enabled both of these methods to be utilized.

To make these complicated therapies understandable is difficult with only written descriptions and static images. We have therefore attempted to develop a dynamic simulation model based on actual respiratory wave data. This simulation model has been well received by students and medical residents and is also effective in explaining the procedure to patients.

[1] | S. B. Jiang, “Technical Aspects of Image-Guided Respiration-Gated Radiation Therapy,” Medical Dosimetry, 31(2), 2006 pp. 141-151. doi:10.1016/j.meddos.2005.12.005. |

[2] | V. M. Remouchamps, F. A.Vicini, M. B. Sharpe, L. L. Kestin, A. A. Martinez, and J. W. Wong, “Significant Reductions in Heart and Lung Doses Using Deep Inspiration Breath Hold with Active Breathing Control and Intensity-Modulated Radiation Therapy for Patients Treated with Locoregional Breast Irradiation,” International Journal of Radiation Oncology *Biology *Physics, 55(2), 2003 pp. 392-406. doi:10.1016/S0360-3016(02)04143-3. |

[3] | M. Nakamura, K. Shibuya, A. Nakamura, T. Shiinoki, Y. Matsuo, M. Nakata, A. Sawada, T. Mizowaki, and M. Hiraoka, “Interfractional Dose Variations in Intensity-Modulated Radiotherapy with Breath-Hold for Pancreatic Cancer,” International Journal of Radiation Oncology *Biology *Physics, 82(5), 2012 pp.1619-1626. doi:10.1016/j.ijrobp.2011.01.050. |

[4] | Y. Otani, I. Fukuda, N. Tsukamoto, Y. Kumazaki, H. Sekine, E. Imabayashi, O. Kawaguchi, T. Nose, T. Teshima, and T. Dokiya, “A Comparison of the Respiratory Signals Acquired by Different Respiratory Monitoring Systems Used in Respiratory Gated Radiotherapy,” Medical Physics, 37, 2010 pp. 6178-6186. doi:10.1118/1.3512798. |

[5] | S. S. Vedam, P. J. Keall, V. R. Kini, and R. Mohan, “Determining Parameters for Respiration-Gated Radiotherapy,” Medical Physics, 28, 2001 pp. 2139-2146. doi:10.1118/1.1406524. |

[6] | A. Schweikard, H. Shiomi, and J. Adler, “Respiration Tracking in Radiosurgery,” Medical Physics, 31, 2004 pp. 2738-2741. doi:10.1118/1.1774132. |

[7] | A. Schweikard, H. Shiomi, and J. Adler, “Respiration Tracking in Radiosurgery without Fiducials,” International Journal of Medical Robotics and Computer Assisted Surgery, 1(2), 2005 pp. 19-27. doi:10.1002/rcs.38. |

H. Sekine and Y. Otani, “Development of Simulation Models of Respiratory Tracking and Synchronizing for Radiotherapy,” The Mathematica Journal, 2014. dx.doi.org/doi:10.3888/tmj.16-12. |

Hiroshi Sekine is a professor in the Department of Radiology, Jikei University, School of Medicine, Tokyo. His recent research interests relate to quantitative analysis of the time-dose-fractionation relationship of radiation therapy.

Yuki Otani is a physicist in the Department of Radiation Oncology, Graduate School of Osaka University, Osaka, Japan. His recent research interests relate to exact tracking of moving tumors in the body.

**Hiroshi Sekine**

*Department of Radiology
Jikei University School of Medicine
Jikei Daisan Hospital
4-11-1, Izumi-Honcho, Komae, Tokyo,
Japan. 201-8601*

**Yuki Otani**

Department of Radiation Oncology

Graduate School of Medicine, Osaka University

2-2, Yamadaoka, Suita, Osaka,

Japan. 565-0871

*y.otani@radonc.med.osaka-u.ac.jp*

This article carries out the evaluation of nuclear-electron attraction energy integrals using Gaussian-type functions with arbitrary Cartesian angular values. As an example, we calculate the corresponding matrix for the water molecule in the STO-3G basis set.

Evaluating molecular integrals has been an active field since the middle of the last decade. Efficient algorithms have been developed and implemented in various programs. Detailed accounts of molecular integrals can be found in the references of [1]. In this article, the third in a series describing algorithms for evaluating molecular integrals, we detail the evaluation of the nuclear-electron attraction energy integrals from a more didactic point of view, following the approach of Rys, Dupuis, and King [2] as implemented in the OpenMol program [3].

The energy caused by the attraction between an electron in the region described by the overlap of the orbitals , and a nuclear of charge located at is expressed by the nuclear-electron attraction integral

(1) |

in which is an unnormalized Cartesian Gaussian primitive.

Using the Gaussian product (see, for example [1]) and defining the angular part as :

(2) |

The pole problem can be solved by the Laplace transform

(3) |

which turns the integral into

(4) |

where for now, we have ignored the factor . In the following steps, we will make certain modifications, knowing in advance that they will help simplify the expressions later on. We first reduce the upper limit of to unity by making the changes of variable (recall from the Gaussian product that ):

(5) |

and

(6) |

Replace , , and in , to get

(7) |

We now multiply by the factor :

(8) |

Again, by inserting , we get

(9) |

Having arrived at the desired form, we reinsert the value of the angular part into the expression and separate the term enclosed by the curly brackets into three components , , and :

(10) |

Defining as the function of the component inside the bracket,

(11) |

and similarly for and , we rewrite the integral as

(12) |

We will show that the integrand in the expression for is in fact an overlap between two one-dimensional Gaussians, and we may use the results that have been developed in [1]. First, we expand the exponential parts of the integrand

(13) |

regrouping in terms of and , we have

(14) |

which becomes

(15) |

where and . These definitions let us compare this equation with the result of the Appendix, in which we see that equation (15) is simply

(16) |

where

(17) |

Substituting and ,

(18) |

into equation (13), we have

(19) |

Substitute this result into the definition of to get

(20) |

The integral has the same form as a one-dimensional overlap integral where the integrand is a Gaussian function centered at with an exponential coefficient .

From the observation above, we make use of the results developed for overlap integrals in [1]. For example, for ,

(21) |

In particular, we have the transfer equations

(22) |

The and functions take similar forms. The product is a polynomial in , and if we replace , then the integral in equation (12) is

(23) |

where is the said polynomial. The integral is a combination of the Boys function (see, for example, Reference 4 of [1])

(24) |

a strictly positive and decreasing function.

Aside from the obvious choice of using *Mathematica* to evaluate the Boys function, there are several ways of evaluating the integral. In practice, most programs store pretabulated values of the function at different intervals and interpolation is done as needed (e.g. by Chebyshev polynomials). Here we use the Gauss-Chebyshev quadrature numerical integration [4]. For simplicity, we have adopted almost verbatim the F77 code in [4, p. 46].

The function `Nea` evaluates the nuclear-electron attraction integral of two Gaussian primitives; here `alpha`, `beta`, `RA`, `RB`, `LA`, and `LB` are , , , , , and as defined earlier; `RR` is the nuclear position.

As in our two earlier articles [1, 5], we use the same data for the water molecule (, , the geometry optimized at the HF/STO-3G level). The molecule lies in the - plane with Cartesian coordinates in atomic units.

In the STO-3G basis set, each atomic orbital is approximated by a sum of three Gaussians; here are their unnormalized primitive contraction coefficients and orbital exponents.

Here are the basis function origins and Cartesian angular values of the orbitals, listed in the order , , , , , , and .

Specifically, for the nuclear-electron attraction energy integral between the first primitive of the orbital of hydrogen atom 1, , the first primitive of the orbital of the oxygen atom, , and atom 1 () is

(25) |

We have

From the Gauss-Chebyshev quadrature, the integral in equation (23) yields . The nuclear-electron integral (25) is . This is calculated as follows.

We would first need the normalization factor before evaluating the nuclear-electron energy matrix.

We have provided a didactic introduction to the evaluation of nuclear-electron attraction-energy integrals involving Gaussian-type basis functions by use of recurrence relations and a numerical quadrature scheme. The results are sufficiently general so that no modification of the algorithm is needed when larger basis sets with more Gaussian primitives or primitives with larger angular momenta are employed.

Consider the Gaussian product: . Combine and expand the coefficients

to get

Let and substitute in the exponent to get

The first three terms inside the second bracket factor to , and the last two can be reduced to . The original Gaussian product is thus

Here is a verification.

If one opts to use *Mathematica*’s own incomplete gamma function , equation (24) can be defined in closed form.

Here is an example.

This is the result.

Here is a comparison with the quadrature result.

Understandably, direct use of the `Gamma` function is much faster and yields more accurate results. We thank Paul Abbott for providing the example.

[1] | M. Hô and J. M. Hernández-Pérez, “Evaluation of Gaussian Molecular Integrals I,” The Mathematica Journal, 14(3), 2012. doi:10.3888/tmj.14-3. |

[2] | J. Rys, M. Dupuis, and H. F. King, “Computation of Electron Repulsion Integrals Using the Rys Quadrature Method,” Journal of Computational Chemistry, 4(2), 1983 pp. 154-157. doi:10.1002/jcc.540040206. |

[3] | G. H. F. Diercksen and G. G. Hall, “Intelligent Software: The OpenMol Program,” Computers in Physics, 8(2), 1994 pp. 215-222. doi:10.1063/1.168520. |

[4] | J. Pérez-Jorda and E. San-Fabián, “A Simple, Efficient and More Reliable Scheme for Automatic Numerical Integration,” Computer Physics Communications, 77(1), 1993 pp. 46-56. doi:10.1016/0010-4655(93)90035-B. |

[5] | M. Hô and J. M. Hernández-Pérez, “Evaluation of Gaussian Molecular Integrals II,” The Mathematica Journal, 15(1), 2013. doi:10.3888/tmj.15-1. |

M. Hô and J. M. Hernández-Pérez, “Evaluation of Gaussian Molecular Integrals,” The Mathematica Journal, 2014. dx.doi.org/doi:10.3888/tmj.16-9. |

Minhhuy Hô received his Ph.D. in theoretical chemistry at Queen’s University, Kingston, Ontario, Canada, in 1998. He is currently a professor at the Centro de Investigaciones Químicas at the Universidad Autónoma del Estado de Morelos in Cuernavaca, Morelos, México.

Julio-Manuel Hernández-Pérez obtained his Ph.D. at the Universidad Autónoma del Estado de Morelos in 2008. He has been a professor of chemistry at the Facultad de Ciencias Químicas at the Benemérita Universidad Autónoma de Puebla since 2010.

**Minhhuy Hô**

*Universidad Autónoma del Estado de Morelos
Centro de Investigaciones Químicas
Ave. Universidad, No. 1001, Col. Chamilpa
Cuernavaca, Morelos, Mexico CP 92010
*

**Julio-Manuel Hernández-Pérez
**

Facultad de Ciencias Químicas

Ciudad Universitaria, Col. San Manuel

Puebla, Puebla, Mexico CP 72570

julio.hernandez@correo.buap.mx

This article presents a compact analytic approximation to the solution of a nonlinear partial differential equation of the diffusion type by using Bürmann’s theorem. Expanding an analytic function in powers of its derivative is shown to be a useful approach for solutions satisfying an integral relation, such as the error function and the heat integral for nonlinear heat transfer. Based on this approach, series expansions for solutions of nonlinear equations are constructed. The convergence of a Bürmann series can be enhanced by introducing basis functions depending on an additional parameter, which is determined by the boundary conditions. A nonlinear example, illustrating this enhancement, is embedded into a comprehensive presentation of Bürmann’s theorem. Besides a recursive scheme for elementary cases, a fast algorithm for multivalued Bürmann expansions and inverse functions is developed using integer partitions. The present approach facilitates the search for expansions of analytic functions superior to commonly used Taylor series and shows how to apply these expansions to nonlinear PDEs of the diffusion type.

For most nonlinear problems in physics, analytic closed-form solutions are not available. Thus the investigator initially searches for an approximate analytic solution. This approximation must be reliable enough to correctly describe the dependence of the solution on all essential parameters of the system. This article aims to show that Bürmann’s theorem can serve as a powerful tool for gaining approximations fulfilling such demands. We have chosen canonical examples [1, 2, 3] from the field of linear and nonlinear heat transfer to illustrate this technique.

A Bürmann series may be regarded as a generalized form of a Taylor series: instead of a series of powers of the independent variable , we have a series of powers of an analytic function

:

Starting at an elementary level, we present a recursive calculation scheme for the coefficients of a Bürmann series. Such a recursive formulation is easily implemented in *Mathematica* and can find the Bürmann expansion for all elementary cases. For instances where we have to deal with series expansions of in terms of powers of functions of the form

that is, functions for which the first derivatives vanish at some point of the complex plane, we approach the limits of the recursive account. To calculate such expansions using *Mathematica* efficiently, we give a generalized formulation of the coefficients of the Bürmann series, using the expansion coefficients of the reciprocal power of an analytic function :

This formulation avoids the time-consuming process of symbolic differentiation usually used. The calculation of the coefficients is based on finding all partitions of the index in terms of the frequencies of the part of ,

These sets of frequencies for the partitions are tabulated by using the function `FrobeniusSolve`.

Once the coefficients are determined by using the tabulated solutions for , the calculation of the coefficients of a generalized Bürmann series is a simple task. A special case of a Bürmann series, representing a function as a series of powers of its own derivative, is of particular importance:

Expansions of this type will be applied to functions defined by integrals. For linear and also for nonlinear processes of heat transfer, these series expansions will serve us to find valuable approximations. This is due to the fact that the integral representation for the error function leads to an expansion in fractional powers of the integrand. It turns out that a similar strategy can be applied to find approximate solutions for nonlinear cases, since these solutions obey integral equations closely related to the integral defining the error function. Finally, by introducing a free parameter, the convergence of a Bürmann expansion can be improved. The free parameter is determined by the boundary conditions. By this procedure, we find reliable analytical approximations for the heat transfer in ZnO [3], comprising only a few terms.

The common analytic solutions to these problems use Taylor series or numerical evaluations, which do not exploit the structure revealed by the integral relation fulfilled by the exact solutions. We mention here that a similar procedure can also be applied successfully to the diffusion of metal cations in a solid solvent [4].

The article is organized in such a way as to offer the formulas to the reader, together with brief remarks concerning their origin. Necessary details of deriving the formulas are displayed in the corresponding appendices.

Bürmann’s theorem [5] states that it is possible to find a convergent expansion of an analytic function as a sum of powers of another analytic function . The simplest form of such an expansion, supposed to be valid around some point in the complex plane, is given by

(1) |

or transferred to another notation, for some purposes more convenient,

(2) |

where the functions and are called the basis functions of the Bürmann series. The functions and have to fulfill certain conditions in order to guarantee the convergence of the series in (1) and (2). These conditions will be discussed later in this article. In their classic work *A Course of Modern Analysis* [5], Whittaker and Watson give a formula for the coefficient (Bürmann coefficient) of a Bürmann series. Transferred to the notation used in (1), their formula is

(3) |

This formula is widely cited by numerous authors [6, 7]. Actually determining the limit value of a higher-order derivative is a cumbersome procedure, which is shown in an example. Expanding the function in powers of around gives the following coefficients , for which CPU time increases dramatically for .

This section shows how to calculate the coefficients of the Bürmann series recursively, which is easier to handle than (3) and more efficient when translated to symbolic programs. If we use (1) and (2) to find convergent series representations of solutions to differential equations, it is important to simplify the algorithms necessary to determine the expansion coefficients.

For basis functions of the general form

(4) |

we get the recursion in terms of the representation used in (1),

(5) |

with the initial coefficient given by

(6) |

Hence, the nested expression for is

(7) |

The recursion (5) is more efficient to calculate than the expression in (3) and is easily implemented.

The Bürmann series for up to order in is calculated with .

We now show the expansion for the same problem shown in the previous section (i.e. expanding around into powers of ). It can be easily expanded to order 25 in a reasonable amount of time. This is the explicit truncated Bürmann series.

The result is validated in terms of a Taylor series. This shows that the error is at least of order 26.

Here are the coefficients as they are calculated with this procedure in their explicit analytic form, according to the definition given in (2).

A useful application of the recursion (5)-(7) to the case of the expansion of the inverse function of around follows immediately: we have and it follows that the inverse function is the Bürmann series of in powers of (see [8]). By writing

(8) |

we obtain

(9) |

The following program calculates the first three coefficients for the inverse function in general, which corresponds to the expression shown in [8].

As an example, the inverse of the sine function is expanded, and the result is displayed for order 11.

Compare it to the result of the *Mathematica* built-in function `InverseSeries` (see [9]).

If we choose the basis function to be equal to the first derivative of , we find, by using formula (5), the recursive expression and the first three coefficients:

(10) |

The idea of expanding an analytic function using its derivative as a basis function is fruitful for cases where the function is defined by an integral. It will be shown that solutions to linear and nonlinear problems of diffusion or heat transfer can be expressed as integrals. We get

To illustrate the advantage of this technique, we choose the expansion of the transcendental function . The function is defined by the integral

Using the results listed in (10) for the Bürmann coefficients, we arrive at once at the expansion around :

Here is the series to order 11.

It can be simplified.

Although the representation given by the recursive formula in (5) is more efficient in terms of CPU time compared to formula (3), there is still the restriction of using basis functions with nonvanishing first derivative at the expansion position , since appears in the denominator of the coefficients in (5)-(7). To overcome this limitation, we introduce an alternative representation of the Bürmann coefficients based on a combinatorial approach [10] that can be generalized.

Actually, the Bürmann expansions are related to Taylor series of reciprocal powers of analytic functions represented by

(11) |

The function is uniquely determined by the basis function . We will show that explicit expressions for the expansion of and the corresponding Bürmann coefficients as defined in (2) can be derived using the coefficients . The Bürmann expansion in this representation reads as

(12) |

The formula for the Bürmann coefficient in terms of the coefficients is thus given by

(13) |

The explicit formulation of generalized Bürmann series using powers of functions with derivatives, vanishing up to the order at , is given by

(14) |

and the expression for the Bürmann coefficient is

(15) |

Also, the special case of expanding the inverse function of can be derived in this general way, and one gets

(16) |

The standard case (i.e. and ) is obtained by setting in (14)-(16). By using the combinatorial approach as shown in the next subsection, one can also evaluate the coefficients in expansions resulting from the theorem of Teixeira [5], which is a generalization of Bürmann’s theorem to singular functions.

The approach is explained in more detail and demonstrated with examples coded in *Mathematica* in the following.

A partition of the positive integer is a sequence of positive integers with such that , for example, , a partition of 10 that is usually written as . The number of times a part occurs in a partition is its frequency . In the example, the parts occur with frequencies ; the example partition can be written as .

For a partition of , define the vector of frequencies, . Then

(17) |

for convenience, define

(18) |

In the example, and .

In *Mathematica*, gives all possible partitions of .

The frequencies of the parts, , can be found with .

However, `FrobeniusSolve` is slow for integers larger than about 30.

The function `PartitionsM`, based on `IntegerPartitions`, is significantly faster.

The function `PartitionsJ`, based on an undocumented but highly efficient function [11], is even faster.

According to

(19) |

the coefficients of reciprocal powers of analytic functions can be derived explicitly on the basis of combinatorics and analysis, recapitulated in appendix A. When is an integer, the coefficients are

(20) |

The case when is rational, , is relevant for Bürmann expansion with basis functions with vanishing derivatives . In that case,

(21) |

Now we show how to calculate (21) symbolically. For example, choosing the function , let us calculate .

We use the fact that the *Mathematica* functions `Times`, `Plus`, and `Total` work with empty lists.

To avoid the undefined expression , the differentiation is performed analytically first on the symbolic function . Then raising to the power of (which can be zero) is performed, and finally the symbolic function is substituted out by the function .

Here are the for the symbolic function expanded at .

Now we expand at . For convenience, define `auxf`.

While the expansion is valid for complex-valued functions, the plot shows only the real part of .

Explicit expressions for the Bürmann coefficients as they are defined in (2) can be defined with respect to the coefficients .

Again using (see appendix A), we can formulate the general expressions for Bürmann series using functions with vanishing derivatives . For instance, series of powers of functions of this type can give convergent expansions for functions that are defined by integrals, like the error function

(22) |

which plays a key role in the theory of linear and nonlinear heat transfer [1]. Defining the integrand as the basis function of a Bürmann series, as explained in (10), we will find a rapidly converging series representation of .

All the results of the previous section can be applied to get a formula for the Bürmann coefficients that is efficiently implemented in a simple function. The starting point of the derivation of this expression is a formulation of the Bürmann expansion in terms of a complex contour integral, as it is given in [5]. This approach can be found in various presentations [6, 7]. The evaluation of the integral representation of the Bürmann expansion results in

(23) |

The formula for the Bürmann coefficient in terms of the coefficients is thus

given by

(24) |

The function `fbür` shows how to apply (23) and (24) to the expansion of in powers of , the same example as presented in the first section. The series is expanded up to order 15, so that the error is at least of order 16.

For the special case of the inverse function of given by (12), in using the transformations indicated in (8),

(25) |

So the expansion of the inverse function can be expressed as

(26) |

Equation (26) is the compact formulation of a result given by Morse and Feshbach [12]. As a result of our approach, we have developed formulas for Bürmann coefficients and for the expansion coefficients of inverse functions that reveal the close relationship of these coefficients to the coefficients for reciprocal powers of an analytic function defined in (20). In the following section, we present a generalization of Bürmann’s theorem, using the solutions of equation (17).

Inspecting formulas (23) and (26), we notice that they cannot be evaluated for cases where or vanishes. This shortcoming must be overcome, for in some cases of interest we will be forced to find Bürmann series using basis functions whose first derivatives at vanish:

(27) |

To this end, define the multivalued function

(28) |

which is cast into the form

(29) |

The function in (29) can be expanded into a Taylor series with , and hence (28) fulfills the condition violated by . Thus, instead of expanding in powers of , we expand in powers of . A reformulation of the contour integral [5] results in the generalized form of Bürmann’s theorem given in (14). Actually, the introduction of the root function (28) in (14) leads to several solution branches. For real-valued functions , the use of the `Sign` and `Abs` functions in the following code extracts the correct branch of the root function for numerical purposes. For a formal proof of the equivalence of the Bürmann series and the Taylor series for , the `Sign` and `Abs` functions can be omitted.

As an example, we calculate an expansion of up to order 15 according to (14) in powers of , a basis function with a vanishing first derivative at (i.e. ):

Use this definition for the formal proof of equivalence.

Use this definition for numerical purposes, such as for plotting.

A faster convergence can be achieved by using a basis function of the form , for which the first and second derivatives vanish at the point (i.e. ).

Using formula (14), it is easy to deduce the expansion of the inverse function of an analytic function of the form

(30) |

The inverse function of comes from (14) by setting and :

(31) |

The error function

is the first example demonstrating the efficiency of Bürmann series using the first derivative as a basis function. We define the function and the basis function by

The error function will be expanded around the origin , where we find that . This expansion thus calls for the application of the generalized form of the Bürmann expansion given in (14). Hence we have to set, according to (28),

To evaluate (14), we use the following relations for the derivatives of the integrand:

The result of this calculation performed up to order nine in is

(32) |

A function calculating the expansion (32) is given below. To show that this approach is superior to a common Taylor expansion in a plot, we calculate the power series in up to order 10.

The plot shows that the series in (32) has only a small constant offset error for larger values of , whereas the Taylor expansion dramatically deviates for smaller values of , although it converges uniformly for all values of . The series in (32) converges uniformly for all and gives the exact value for the error function. The rearrangement of terms, leading to , is thus justified. Even for the lowest order, we will find a result that shows no unbounded error, unlike the Taylor series.

Due to the uniform convergence of (32), we can write:

(33) |

Using and in (33), we find . So by reordering the sums, we automatically get rid of the offset error at infinity. In fact, we can furthermore achieve a practical application of (33) by keeping only a few coefficients . For example, using only and requesting the correct slope at , one gets an approximation of the error function with a relative error smaller than 1.2%. Taking additional terms of (33) with meaningful conditions further improves the approximating series in (33), as also shown in the following plot (choosing and ).

This section applies the concept of Bürmann series to get solutions of nonlinear differential equations. After a short introduction, an example from the field of the diffusion type is presented.

In studying nonlinear ordinary differential equations, we cannot, in general, expect to find an exact solution expressible in terms of commonly used algebraic or transcendental functions. This difficulty is illustrated by the equations studied by Fujita, Lee, and Crank, which we will encounter later [13-17]. For the case of a general nonlinear second-order equation

(34) |

where denotes an analytic function of its arguments, one approach is to cast a solution into the form of a series of powers of the independent variable . Depending on the complexity of the expression on the right-hand side of the equation (34), determining the coefficients of this expansion by collecting the powers of and solving the resulting system of equations is a cumbersome procedure. Equations of the form (34) are often encountered in physics, and either their solutions can be determined numerically or their behavior is known qualitatively from experiments. Guided by this prior knowledge about the nature of , we can eventually construct or guess a function that is a more favorable base for a power series than the independent variable itself. We have to cast the representation of the solution of equation (34) into the form

and so we expand the solution using the recursive formula (5). The code below gives an expansion of the first four terms.

The free parameter occurring in will then be determined by the boundary conditions for . In the following, this kind of expansion with suitable basis functions will be applied to the solution of a problem of nonlinear heat transfer, and its convergence will be treated as far as relevant for this special case. For all the cases investigated in this article, we apply the recursive approach (7), since the structure of the chosen basis functions is relatively simple. For more sophisticated basis functions, the combinatorial formulas (12) and (14) have to be implemented in order to reduce CPU time. This may be done in future investigations.

As a canonical example, we study the partial differential equation of transient nonlinear heat transfer with temperature-dependent thermal conductivity . We demonstrate the application of Bürmann series to the practical problem of heat transfer in ZnO ceramics The half space is filled by this material, which has initial constant temperature , and the temperature as . At the surface temperature at is instantaneously raised to a constant temperature . Using the results of measurements of the thermal conductivity in ZnO [3], we can formulate the problem by writing

(35) |

Using the transformation

Kirchhoff’s transformation

and Boltzmann’s transformation

we find a nonlinear ordinary differential equation that has been extensively studied by Fujita [13-15], Lee [16, 17], and Crank [2]:

(36) |

While the first boundary condition in (35) is regular (i.e. and ), the second one is given in terms of the asymptotic expression . The equivalent value of the derivative has to be estimated, which is performed by calculating the time evolution of the total thermal energy of the semi-infinite half space [18]. The approximate value of this energy integral (in terms of an algebraic expression) is determined in appendix B, where we use the Bürmann series (10) to approximate the energy integral. The explicit expression is displayed in appendix B, equation (56), which describes the dependence of on the parameters with a relative accuracy of 0.37%.

To apply the methods developed in the preceding sections, we establish a convergent iteration scheme for equation 1 of (36). To this end, we transform this equation into an integral equation:

(37) |

The solutions for 1 of equation (36) are strictly decreasing functions of , which implies that for all positive values of we have

From this relation, we conclude that we can define a system of functions , , , … of the form

(38) |

Taking the first term of the expansion (32) of the error function, we have

(39) |

Since the system (39) converges toward the solution , a possible choice for a basis function would be . Instead of , we prefer to introduce a less complicated function that simplifies the calculations. According to (39), this function has to fulfill the following conditions:

The function can be constructed in such a way as to guarantee that all essential boundary conditions are fulfilled by :

The parameter is as yet undetermined. A useful basis for an expansion is obtained by taking

(40) |

which will lead, according to (6) and (7), to the Bürmann series calculated as follows.

Expressed in terms of , this is

(41) |

If we consider in (40) and (41) as a free parameter, we have to investigate how its choice influences the convergence of the corresponding Bürmann series. We write, using (37) and omitting the index for ,

All integrands are representable by uniformly convergent series expansions in powers of , and thus the argument is similar to the one used in proving the convergence of the system (39). Furthermore, we observe that the expansion of the exponential function converges more quickly for higher values of . Thus, as long as can be chosen to guarantee the condition

for some value , an iterative system of functions can be constructed that converges to the solution of equation 1 of (36). This fact can be exploited by determining in such a way as to assure that the approximation

assumes the correct value at infinity. So we have

(42) |

resulting in an algebraic equation of the order in with roots ,

(43) |

where satisfies the condition

(44) |

If there is a solution to equation (43) simultaneously fulfilling condition (44), we get an approximation that converges to the correct value of as . For the third-order approximation , we get from (41) and (43) the cubic equation

(45) |

The relevant real solution to this equation is

(46) |

with

(47) |

We display the explicit expression for the third-order approximation below:

(48) |

In the next two plots, we show a comparison between the approximation (48) and the exact solution found by applying `NDSolve` to 1 of (36). The value for is calculated by using the approximation given by equation 2 of (57). Note that (48) can also be inverted exactly by using common algebraic and transcendent functions. The corresponding procedure is listed below for the same parameters as given in the previous section.

This defines the cubic approximation according to (45)-(48).

For the numerically exact solution, calculated by using `NDSolve`, we impose the condition (i.e. ). This condition is equivalent to selecting a slope at the surface . Bürmann’s theorem is used a second time to find an approximation for the slope by calculating the Bürmann expansion (56) of the energy integral (see appendix B).

The plot shows the numerically exact temperature profiles (the colored curves) and the exact solution’s third-order approximation according to equation (48) (the dotted lines), in the range at .

Additionally the relative error of the third-order approximation (48) is displayed for the same profiles as shown before.

The goal of this work is to give a comprehensive presentation of Bürmann’s theorem and its application to linear and nonlinear DEs and PDEs of heat transfer, using single-valued and multivalued basis functions.

To this end, a reformulation of the formulas of the expansion coefficients of Bürmann series, based on a combinatorial viewpoint, is developed. As a result of this reformulation, an algorithm is presented, which accelerates the calculation of expansion coefficients, compared to standard methods. Using this approach, the expansion of transcendental functions in powers of their derivative is applied to the error integral, to the solution of nonlinear differential equations, and to the evaluation of the heat integral. By combining these methods, it is possible to show that the approximate solution of nonlinear problems of heat transfer can be given in terms of Bürmann expansions. Finally, it is shown that the introduction of an additional parameter in the basis function can significantly enhance the convergence of a Bürmann series. The value of this parameter can be found by solving algebraic equations that result from the boundary conditions of the problems.

The coefficients , defined by

result from elementary considerations. We write

(49) |

The power of is given by

(50) |

Rearranging equation 1 of (50) in increasing powers , we have two conditions

(51) |

Thus, collecting all powers of over all the contributions arising from all with is equivalent to imposing one single condition, replacing the conditions 1 and 2 of (51):

Since , we define :

(52) |

Using equations 1 of (49), 1 of (50), and (52) we finally arrive at the expansion

A similar result, displayed in (21), is obtained for .

We define the temperature difference and the differential equation it obeys:

(53) |

By integrating equation 2 of (53) over , we find

(54) |

Performing the transformations of Kirchhoff and Boltzmann, we arrive at the solution for :

(55) |

On the other hand, using the definition given in (54), we expand in a Bürmann series in powers

of according to (10). This leads to

(56) |

Combining (55) and (56) up to order three gives

According to the transformations in (36), we have

which leads, after some manipulations, to a quartic algebraic equation for and its solution , given by

(57) |

An approximation of (56) up to order six would lead to a sextic equation that is reducible to a cubic equation, and hence to an algebraic expression for . The approximation obtained from the first equation of (57) for is , which shows a maximum relative error of 0.37% compared to the exact value found by numerical methods (i.e. `NDSolve`) using the parameters listed in (35).

The authors wish to thank Prof. Dieter Messner, Lienz, and Dr. Hans Riedler, Graz, for their encouragement and helpful advice. Special thanks go to the editors and reviewers of *The Mathematica Journal* for their constructive suggestions and support.

[1] | H. S. Carslaw and J. C. Jaeger, Conduction of Heat in Solids, 2nd ed., Oxford: Clarendon Press, 1959 pp. 482-484. |

[2] | J. Crank, The Mathematics of Diffusion, 2nd ed., Oxford: Clarendon Press, 1975 pp. 107-110, 119-121. |

[3] | T. Olorunyolemi, A. Birnboim, Y. Carmel, O. C. Wilson Jr., I. K. Loyd, S. Smith, and R. Campbell, “Thermal Conductivity of Zinc Oxide: From Green to Sintered State,” Journal of the American Ceramic Society, 85(5), 2002 pp.1249-53.doi:10.1111/j.1151-2916.2002.tb00253.x. |

[4] | C. Wagner, “Diffusion of Lead Chloride Dissolved in Solid Silver Chloride,” Journal of Chemical Physics, 18, 1950 pp. 1227-1230. doi:10.1063/1.1747915. |

[5] | E. T. Whittaker and G. N. Watson, A Course of Modern Analysis, 4th ed., Cambridge: Cambridge University Press, 1927 pp. 128-132. |

[6] | E. W. Weisstein. “Bürmann’s Theorem” from Wolfram MathWorld—A Wolfram Web Resource. mathworld.wolfram.com/BuermannsTheorem.html. |

[7] | Wikipedia. “Lagrange Inversion Theorem.” (Oct 17, 2014) en.wikipedia.org/wiki/Lagrange_inversion_theorem. |

[8] | H. Stenlund, “Inversion Formula.” arxiv.org/abs/1008.0183. |

[9] | E. W. Weisstein, “Series Reversion” from MathWorld—A Wolfram Web Resource. mathworld.wolfram.com/SeriesReversion.html. |

[10] | L. Comtet, “Advanced Combinatorics: The Art of Finite and Infinite Expansions” (J. W. Nienhuys, trans.), D. Reidel: Dordrecht, 1974. |

[11] | E. W. Weisstein, “Faà di Bruno’s Formula” from MathWorld—A Wolfram Web Resource. mathworld.wolfram.com/FaadiBrunosFormula.html. |

[12] | P. M. Morse and H. Feshbach, Methods of Theoretical Physics, Vol. I, New York: McGraw-Hill, 1953 pp. 411-413. |

[13] | H. Fujita, “The Exact Pattern of a Concentration-Dependent Diffusion in a Semi-infinite Medium, Part I,” Textile Research Journal, 22(11), 1952 pp. 757-760. doi:10.1177/004051755202201106. |

[14] | H. Fujita, “The Exact Pattern of a Concentration-Dependent Diffusion in a Semi-infinite Medium, Part II,” Textile Research Journal, 22(12), 1952 pp. 823-827. doi:10.1177/004051755202201209. |

[15] | H. Fujita, “The Exact Pattern of a Concentration-Dependent Diffusion in a Semi-infinite Medium, Part III,” Textile Research Journal, 24(3), 1954 pp. 234-240. doi:10.1177/004051755402400304. |

[16] | C. F. Lee “On the Solution of Some Diffusion Equations with Concentration-Dependent Diffusion Coefficients—I,” Journal of the Institute of Mathematics and Its Applications (now IMA Journal of Applied Mathematics), 8(2), 1971 pp. 251-259. doi:10.1093/imamat/8.2.251. |

[17] | C. F. Lee “On the Solution of Some Diffusion Equations with Concentration-Dependent Diffusion Coefficients—II,” Journal of the Institute of Mathematics and Its Applications (now IMA Journal of Applied Mathematics), 10(2), 1972 pp. 129-133. doi:10.1093/imamat/10.2.129. |

[18] | T. R. Goodman, “Application of Integral Methods for Transient Nonlinear Heat Transfer,” in Advances in Heat Transfer, Vol. I (T. F. Irvine, Jr. and J. P. Hartnett, eds.), New York: Academic Press, 1964 pp. 51-122. |

H. M. Schöpf and P. H. Supancic, “On Bürmann’s Theorem and Its Application to Problems of Linear and Nonlinear Heat Transfer and Diffusion,” The Mathematica Journal, 2014. dx.doi.org/doi:10.3888/tmj.16-11. |

Harald Markus Schöpf was born in Lienz, Austria on May 5, 1965. He studied solid-state physics and technical physics in Graz. After two years as a research assistant at the Graz University of Technology, Austria, he moved to Siemens Matsushita (now EPCOS) in Deutschlandsberg, Austria. Now he works as a teacher in Lienz.

Peter Hans Supancic was born in Graz, Austria on September 7, 1967. He studied theoretical physics in Graz and graduated in materials science at the University of Leoben, Austria. After finishing the habilitation on functional ceramics, he became ao. Prof. at the University of Leoben.

**Harald Markus Schöpf**

*Schillerstrasse 4
A-9900 Lienz*

**Peter Hans Supancic**

Institut für Struktur- und Funktionskeramik/Montanuniversitaet Leoben

*Peter Tunner Strasse 5
A-8700 Leoben *

When my son brought home a paper from school with a grid of numbers on it, I was immediately interested. The goal: cover the puzzle with all the dominoes from the “bone pile,” making sure that each number of the puzzle is covered by the same number on a domino. Many similar puzzles can be found online and in puzzle collections: see [1, 2, 3, 4, 5] for several online resources, which are the source of some of the examples considered here.

**Figure 1.** A partially solved domino grid, with almost half of the 28 dominoes placed on the underlying puzzle grid.

Our first task is to represent the board.

Next, we need the bone pile, the list of available dominoes. In this case, the bone pile consists of all 28 dominoes from the double zero to double six, but the definition is generally valid for any non-negative number , for a total of dominoes.

Find possible locations for a given piece .

This is the workhorse of the entire solution, first dividing the puzzle into pairs along each row and looking for matches to the given pair, then repeating the process on the transposed matrix (i.e. along the columns of the original grid) and noting the locations of any matches found. The location of the pair in the partition gives the location of the first half domino in the original grid, but adding the appropriate offset gives the location of the second half domino as well, and both are included as a domino location in the list of locations found.

Now for functions to highlight the dominoes within a puzzle. The function `frameDomino` generates the options to include in the `Frame` option of `Grid`.

The function `displayPuzzle` accepts a puzzle grid (a matrix) and a domino list (a list of location pairs) and displays the puzzle grid with frames around the dominoes indicated in the list.

For example, there are two possible locations for the domino in the `m9` puzzle.

A `puzzle` object takes three arguments.

- The matrix
`m`contains the puzzle to be solved, a 2D array of integers. - The filled locations list
`filled`is a list of coordinate pairs: , where either and or and . - The bone pile
`bones`, the list of unplayed dominoes, consists of a list of pairs of integers.

The `Format` command defines how to format a puzzle: the puzzle matrix has its filled list of dominoes framed, and a tooltip shows the bone pile, if any.

This section shows examples of various puzzles; mouse over a puzzle to see the bone pile. In this puzzle, no dominoes have been played yet.

Here two pieces have been removed from the bone pile and placed on the board.

To ensure that the squares filled by already placed pieces are no longer included, make a version of the board with the affected squares blanked out.

This function finds the forced locations; only one piece can possibly go into a forced location.

Find the forced locations after two particular dominoes have been played.

The forced locations are shown empty.

- Select the pieces that fit in forced locations.
- Use
`find`to return a list of all possible locations for playable pieces, and select the pieces that have only one possible location:

In this artificial case, there are two forced locations: in each, only one piece can be placed.

The function `step` finds the forced locations and fills them in with the appropriate dominoes taken from the bone pile. Mouse over to see that these dominoes have been removed from the bone pile.

At the beginning, there are no forced locations, but there are four forced pieces: pieces that can only be placed in one location in the puzzle: , , , and . The `step` function plays all four at once.

We are ready to solve the whole puzzle. The next command prints the current state, takes one step, and repeats until the bone pile is empty.

Along the way, multiple partial solutions had to be considered when no forced locations or forced pieces were found, but in the end all but one solution were dropped because of inconsistency. The comments were left in to show the forced locations or forced pieces at each step, but now we turn them off.

There is no reason not to make a prettier display function to show the dominoes with their customary pips (or dots), rather than showing only the grid numbers. We can represent the pip positions by matrices, some of which can be easily created by built-in matrix commands. Since the pip positions of double-9 and double-6 domino sets are consistent, let us build the larger set here. (A double-12 set would require adjusting the pip positions.)

The other matrices could be built by hand or using `SparseArray` or `Table` with appropriate criteria, but it is easy to create them by addition and subtraction.

A pip will be placed on a half-domino square wherever the matrix had a 1.

The function `displayDottedPuzzle` creates a graphical display of the puzzle, optionally replacing numbers by half-domino faces for any locations listed in the “filled list,” outlining any placed dominoes in a way similar to `displayPuzzle`.

The method described here can be thought of as “human-type,” since it uses intelligently chosen criteria for deciding which step to perform and which option to try next. The criteria used can be summarized as follows:

- Seek forced locations: if any locations can take none of the available dominoes, abandon the partial solution currently being constructed; if any locations can take exactly one available domino (and not the same one), fill all of these “forced locations.”
- Else seek forced dominoes: if any of the available dominoes cannot be placed on the board, abandon the partial solution currently being constructed; if any of the available dominoes can only be placed in one location on the board, play all of these “forced dominoes.”
- Else for a minimal case, place one domino in all possible locations, making separate copies of the puzzle for each case.
- Repeat until no further changes occur.

A human can make more complicated arguments eliminating some options; for examples, see the explanations at the sites [1, 2, 3, 4, 5]. (But not all suggested solving strategies turn out to be useful. One common idea, placing the “double” dominoes first, can easily be defeated by a clever puzzle designer.) The order is arbitrary and might be modified, but is far faster than the more simplistic, brute-force method presented in the following section.

Here is a list of all possible locations of all dominoes in our original puzzle.

The number of options for the pieces varies wildly.

(You can easily verify that in this puzzle, all the double dominoes have between four and eight possible placement options, making “place doubles first” a poor strategy in this case.) Taking all possible options for all the pieces gives a very large number.

Too many cases to consider! But this method would work, theoretically: Use `Outer` to get all combinations of choices of these options and then use `Select` on those that have no overlapping dominoes. Here do only the first three dominoes.

Using the first three dominoes, there are possibilities, reduced to 19 after elimination of conflicts. Placing the first 13 dominoes involves considering 653184 cases, of which only four have no conflicts.

So the following code should work, but will take an unreasonable amount of time and memory. It is beautifully simple and short, but do not run it, as it probably would not finish in our lifetimes!

“To a hammer, everything looks like a nail.” A few years ago, I worked out an exhaustive search-and-collision detection algorithm based on a idea of a generalized odometer, and since then I have seen applications for it everywhere. It works here, too.

Create a 28-digit generalized odometer, whose digit refers to which option we are trying for the domino. All digits start as 1; incrementing the odometer does not in general occur at the right end, but at the first digit (from the left) whose domino placement conflicts with that of any previous domino. A digit “rolls over” when it is incremented past its maximum value and must be reset to 1. Whenever a digit rolls over, also increment the digit to its left, just as in a real odometer. Each odometer digit has a separate maximum determined by the number of options available for that domino. When the first digit finally rolls over, all solutions have been found. We also accelerate the procedure by sorting the domino option list in increasing length.

Notice that the first four odometer digits can only be 1; each starts at 1 and has a maximum of 1.

To see or use the parts of options specified by the odometer, we use the function `MapThread`.

Here is the program that more or less immediately returns the answer(s).

As expected, there is only one odometer reading that works; that is, only one choice of domino placements solves the puzzle. The generalized odometer method works best for situations with a large number of variables taking on values that can be calculated in advance, particularly if the possible values are the same for all variables or vary in a way that can be easily specified. Here the options have to be recomputed for each new puzzle, making it less efficient than the previous method.

A “quadrilles” puzzle [5], an idea credited to French mathematician Edouard Lucas, can be divided into blocks, each containing the same number. Since the following figure does not completely fill a rectangular array, we add empty strings.

This particular quadrille has only one solution. At each step there are a large number of forced locations or pieces, and all 28 dominoes are placed in only four iterations.

Now for a puzzle with so many different ways to solve it that one feels that almost anything will work [5]!

If a puzzle is nonrectangular or has intentional gaps in it, such as the one shown below [4], simply embed it in a larger rectangle, and indicate the gaps by empty strings.

It seems likely that the online or downloadable domino puzzle generators effectively lay out the dominoes to create a grid that is guaranteed to be solvable. But even if all puzzles presented can be solved, a number of questions spring to mind:

For given grid dimensions, how many different solutions are there? (The three methods derived above solve individual puzzles, but what if the numbers are rearranged in a given grid in all possible ways?)

For given grid dimensions, what fraction of the possible puzzles has only one solution, and in general, for all , what fraction of the puzzles has solutions? What is the largest number of solutions possible?

Bear in mind that in the sense of the functions developed here, a “solution” is a merely a list of domino locations, so different puzzles of the same dimensions can have the same solution just by permuting the underlying grid numbers or rearranging them in other valid ways. In the interest of increased clarity, define a *solution schema* as a layout of dominoes face-down on a board. Now we can talk about the number of possible distinct schemas for a given puzzle grid.

What about writing a program that generates all solution schemas for a given board, ignoring the numbers? This could be done by modifying either the function `solvePuzzle` or the function `odometerSolve`, neither of which can quite do the job as written. (Yes, I did try them on a board filled with 0 entries, but they would need to be tweaked to expect a bone pile of double-zero dominoes.)

Finally, it is interesting that the first solution method worked so well, basically following how a human would decide which domino to play next. The code for the brute-force method is the simplest, but impractical without massive parallel processing. The odometer method works well, but here not as fast as the “human” method, and in any case may not be as transparent to the reader. There is more than one way to solve a puzzle! And if you spend much time thinking about a puzzle, other methods and other questions will probably occur to you.

I thank my colleagues at Southern Adventist University who have encouraged me, the folks at Wolfram Research who have occasionally helped me, and Claryce, who has put up with me in all my most puzzling moods.

[1] | E. W. Weisstein. “Domino Tiling” from Wolfram MathWorld—A Wolfram Web Resource. mathworld.wolfram.com/DominoTiling.html. |

[2] | Domino-Games.com. “Domino Puzzles.” (Sep 4, 2014) www.domino-games.com/domino-puzzles.html. |

[3] | “Dominosa.” (Sep 4, 2014) www.puzzle-dominosa.com. |

[4] | Yoogi Games. “Domino Puzzle Puzzles.” (Sep 4, 2014) syndicate.yoogi.com/domino. |

[5] | J. Köller. “Domino Puzzles.” (Sep 4, 2014) www.mathematische-basteleien.de/dominos.htm. |

K. E. Caviness, “Three Ways to Solve Domino Grids,” The Mathematica Journal, 2014. dx.doi.org/doi:10.3888/tmj.16-10. |

Ken Caviness teaches at Southern Adventist University, a liberal arts university near Chattanooga. Since obtaining a Ph.D. in physics (relativity and nuclear physics) from the University of Massachusetts Lowell, he has taught math and physics in Rwanda, Texas, and Tennessee. His interests include both computer and human languages (including Esperanto), and he has used *Mathematica* since Version 1, both professionally and recreationally.

**Kenneth E. Caviness**

*Department of Physics & Engineering
Southern Adventist University
PO Box 370
Collegedale, TN 37315-0370*

Evaluating molecular integrals has been an active field since the middle of the last decade. Efficient algorithms have been developed and implemented in various programs. Detailed accounts of molecular integrals can be found in the references of [1]. In this article, the third in a series describing algorithms for evaluating molecular integrals, we detail the evaluation of the nuclear-electron attraction energy integrals from a more didactic point of view, following the approach of Rys, Dupuis, and King [2] as implemented in the OpenMol program [3].

The energy caused by the attraction between an electron in the region described by the overlap of the orbitals , and a nuclear of charge located at is expressed by the nuclear-electron attraction integral

(1) |

in which is an unnormalized Cartesian Gaussian primitive.

Using the Gaussian product (see, for example [1]) and defining the angular part as :

(2) |

The pole problem can be solved by the Laplace transform

(3) |

which turns the integral into

(4) |

where for now, we have ignored the factor . In the following steps, we will make certain modifications, knowing in advance that they will help simplify the expressions later on. We first reduce the upper limit of to unity by making the changes of variable (recall from the Gaussian product that ):

(5) |

and

(6) |

Replace , , and in , to get

(7) |

We now multiply by the factor :

(8) |

Again, by inserting , we get

(9) |

Having arrived at the desired form, we reinsert the value of the angular part into the expression and separate the term enclosed by the curly brackets into three components , , and :

(10) |

Defining as the function of the component inside the bracket,

(11) |

and similarly for and , we rewrite the integral as

(12) |

We will show that the integrand in the expression for is in fact an overlap between two one-dimensional Gaussians, and we may use the results that have been developed in [1]. First, we expand the exponential parts of the integrand

(13) |

regrouping in terms of and , we have

(14) |

which becomes

(15) |

where and . These definitions let us compare this equation with the result of the Appendix, in which we see that equation (15) is simply

(16) |

where

(17) |

Substituting and ,

(18) |

into equation (13), we have

(19) |

Substitute this result into the definition of to get

(20) |

The integral has the same form as a one-dimensional overlap integral where the integrand is a Gaussian function centered at with an exponential coefficient .

From the observation above, we make use of the results developed for overlap integrals in [1]. For example, for ,

(21) |

In particular, we have the transfer equations

(22) |

The and functions take similar forms. The product is a polynomial in , and if we replace , then the integral in equation (12) is

(23) |

where is the said polynomial. The integral is a combination of the Boys function (see, for example, Reference 4 of [1])

(24) |

a strictly positive and decreasing function.

Aside from the obvious choice of using *Mathematica* to evaluate the Boys function, there are several ways of evaluating the integral. In practice, most programs store pretabulated values of the function at different intervals and interpolation is done as needed (e.g. by Chebyshev polynomials). Here we use the Gauss-Chebyshev quadrature numerical integration [4]. For simplicity, we have adopted almost verbatim the F77 code in [4, p. 46].

The function `Nea` evaluates the nuclear-electron attraction integral of two Gaussian primitives; here `alpha`, `beta`, `RA`, `RB`, `LA`, and `LB` are , , , , , and as defined earlier; `RR` is the nuclear position.

As in our two earlier articles [1, 5], we use the same data for the water molecule (, , the geometry optimized at the HF/STO-3G level). The molecule lies in the - plane with Cartesian coordinates in atomic units.

In the STO-3G basis set, each atomic orbital is approximated by a sum of three Gaussians; here are their unnormalized primitive contraction coefficients and orbital exponents.

Here are the basis function origins and Cartesian angular values of the orbitals, listed in the order , , , , , , and .

Specifically, for the nuclear-electron attraction energy integral between the first primitive of the orbital of hydrogen atom 1, , the first primitive of the orbital of the oxygen atom, , and atom 1 () is

(25) |

We have

From the Gauss-Chebyshev quadrature, the integral in equation (23) yields . The nuclear-electron integral (25) is . This is calculated as follows.

We would first need the normalization factor before evaluating the nuclear-electron energy matrix.

We have provided a didactic introduction to the evaluation of nuclear-electron attraction-energy integrals involving Gaussian-type basis functions by use of recurrence relations and a numerical quadrature scheme. The results are sufficiently general so that no modification of the algorithm is needed when larger basis sets with more Gaussian primitives or primitives with larger angular momenta are employed.

Consider the Gaussian product: . Combine and expand the coefficients to get

Let and substitute in the exponent to get

The first three terms inside the second bracket factor to , and the last two can be reduced to . The original Gaussian product is thus

Here is a verification.

[1] | M. Hô and J. M. Hernández-Pérez, “Evaluation of Gaussian Molecular Integrals I,” The Mathematica Journal, 14(3), 2012. doi:10.3888/tmj.14-3. |

[2] | J. Rys, M. Dupuis, and H. F. King, “Computation of Electron Repulsion Integrals Using the Rys Quadrature Method,” Journal of Computational Chemistry, 4(2), 1983 pp. 154-157. doi:10.1002/jcc.540040206. |

[3] | G. H. F. Diercksen and G. G. Hall, “Intelligent Software: The OpenMol Program,” Computers in Physics, 8(2), 1994 pp. 215-222. doi:10.1063/1.168520. |

[4] | J. Pérez-Jorda and E. San-Fabián, “A Simple, Efficient and More Reliable Scheme for Automatic Numerical Integration,” Computer Physics Communications, 77(1), 1993 pp. 46-56. doi:10.1016/0010-4655(93)90035-B. |

[5] | M. Hô and J. M. Hernández-Pérez, “Evaluation of Gaussian Molecular Integrals II,” The Mathematica Journal, 15(1), 2013. doi:10.3888/tmj.15-1. |

M. Hô and J. M. Hernández-Pérez, “Evaluation of Gaussian Molecular Integrals,” The Mathematica Journal, 2014. dx.doi.org/doi:10.3888/tmj.16-9. |

Minhhuy Hô received his Ph.D. in theoretical chemistry at Queen’s University, Kingston, Ontario, Canada, in 1998. He is currently a professor at the Centro de Investigaciones Químicas at the Universidad Autónoma del Estado de Morelos in Cuernavaca, Morelos, México.

Julio-Manuel Hernández-Pérez obtained his Ph.D. at the Universidad Autónoma del Estado de Morelos in 2008. He has been a professor of chemistry at the Facultad de Ciencias Químicas at the Benemérita Universidad Autónoma de Puebla since 2010.

**Minhhuy Hô**

*Universidad Autónoma del Estado de Morelos
Centro de Investigaciones Químicas
Ave. Universidad, No. 1001, Col. Chamilpa
Cuernavaca, Morelos, Mexico CP 92010
*

**Julio-Manuel Hernández-Pérez
**

Facultad de Ciencias Químicas

Ciudad Universitaria, Col. San Manuel

Puebla, Puebla, Mexico CP 72570