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# Annalen der Physik, 29 June 2011

Relativity, thermodynamics and entropic forces
Charles T. Ridgely∗1
1

Thienes Engineering, Inc., La Mirada, CA 90638

Received 21 January 2011, accepted 10 June 2011 Key words Entropic force, lapse function, relativity, information theory. A recent assertion that inertial and gravitational forces are entropic forces is discussed. A more conventional approach is stressed herein, whereby entropy is treated as a result of relative motion between observers in different frames of reference. It is demonstrated that the entropy associated with inertial and gravitational forces is dependent upon the well known lapse function of general relativity. An interpretation of the temperature and entropy of an accelerating body is then developed, and used to relate the entropic force to Newton’s second law of motion. The entropic force is also derived in general coordinates. An expression of the gravitational entropy of in-falling matter is then derived by way of Schwarzschild coordinates. As a ﬁnal consideration, the entropy of a weakly gravitating matter distribution is shown to be proportional to the self-energy and the stress-energy-momentum content of the matter distribution.

1

Introduction

One of the longest standing questions in physics certainly has been by what means does ordinary matter resist acceleration, as expressed by way of Newton’s second law of motion, F= d (mv). dt (1)

In an attempt to provide an answer to this question, E. Verlinde [1] has proposed that gravitational and inertial forces are caused by changes in the information associated with the positions and movements of material bodies [1]. According to the information proposal, space may be viewed as being comprised of a continuum of holographic membranes or screens that store information about the positions and movements of particles. As a particle approaches such a screen, the particle inﬂuences, and in essence merges with the information contained in the screen, causing a change in the entropy S associated with the information on the screen. The entropy change ∆S and temperature T of the screen give rise to an “entropic force” on the particle expressed as [1] F = T S. (2)

According to Verlinde [1], (2) is the underlying origin of inertial and gravitational forces. At present, there appears to be precious little in the way of discussion of (2) falling outside the paradigm espoused in [1]. Although (2) can be derived with respect to gravitational and inertial forces, certainly there is no reason to view entropy as the underlying cause of such forces. Indeed, as shown herein, the entropy in (2) can just as well be viewed as a result of the relative motion between various observers in space-time. Likewise, the temperature in (2) can be treated as simply the temperature of a body subjected to an external force. In the next section, the entropy change of a material body undergoing uniform acceleration in Minkowski space-time is derived. The body is treated as a closed thermodynamic system, which is subjected to an external force by a stationary heat engine. Although the heat engine operates between hot and cold heat

Corresponding author

E-mail: charles@ridgely.ws, Phone: +1 714 494 3346, Fax: +1 714 521 4173
Pre-peer reviewed copy DOI: 10.1002/andp.201100013

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Charles T. Ridgely: Relativity, thermodynamics and entropic forces

reservoirs, the internal energy of the body is assumed to remain unchanged during the acceleration. The entropy change of the body is then expressed in terms of the relativistic change in total energy of the body. Carrying this out leads to an expression of the entropy change in terms of a lapse function, which is well known to express the quantity of proper time that elapses per unit of coordinate time [2]. The change in entropy is then expressed in the limit of inﬁnitesimal displacement, leading to (2), but suggesting a different interpretation of the temperature and entropy than given in [1]. It is proposed that the entropy and temperature are to be associated with the body itself rather than the holographic screens in space-time [1]. Moreover, it is pointed out that the dependence of the entropy on the lapse function tells us that the entropy is simply due to the relative motion between the body and non-accelerating observers in ﬂat space-time. The section closes with a derivation of the connection between the entropic inertial force and Newton’s second law of motion, (1). Section 3 is devoted to deriving the entropic force in general coordinates. The section begins with a derivation of the change in entropy of a test body based on the change in the total energy of the body at two locations in an arbitrary coordinate system. A general expression of the entropic force is then obtained upon limiting the entropy change to inﬁnitesimal displacement. Next, the entropy of a test body in Schwarzschild coordinates is considered. The resulting expression indicates that the entropy of in-falling matter decreases as the gravitational force performs positive work. It is pointed out that the second law of thermodynamics requires the entropy of the gravitational ﬁeld to increase as matter is drawn in and captured. In section 4, the gravitational entropy derived in section 3 is used to demonstrate that the entropy of a weakly gravitating distribution of matter is proportional to the total proper stress-energy-momentum content and gravitational self-energy of the matter distribution. Although the gravitational source in question is not a black hole, the resulting expression of the entropy agrees in principle with black hole mechanics. It is pointed out that were the matter distribution the size of a star which later collapsed into a black hole, the gravitational entropy would then be associated with the event horizon of the black hole [3]-[6].

2

Entropic Inertial Force

As mentioned in the introduction, the information proposal asserts that gravitational and inertial forces are entropic forces caused by changes in information stored in space that is associated with the positions and movements of material bodies [1]. According to general relativity, however, gravitational and inertial forces are manifestations of space-time geometry [7]-[15]. As shown in [16], the force on a body in arbitrary coordinates, due either to the body’s own acceleration or to being held ﬁxed in position outside a large gravitational source, is given by F = U0 γ −1 γ (3)

where U0 is the total proper energy of the body, and γ −1 is the “lapse function,” or “gravitational redshift factor,” which expresses the quantity of proper time that elapses per unit of coordinate time [2]. For the sake of brevity, the term “lapse function” is used herein casually in reference to both γ and γ −1 . As shown below, the entropy of an observer subjected to an external force is intimately related to the lapse function. Let a material body be a closed thermodynamic system situated in ﬂat, Minkowski space-time. Nearby is a non-accelerating observer that uses a heat engine to apply an external force to the body such that the body accelerates uniformly over a distance ∆x. According to the non-accelerating observer, the total relativistic change in energy of the body during the acceleration can be associated with a change in the thermodynamic state of the body. Let us suppose the initial state of the body, say state A, coincides with the beginning of the distance ∆x, and the ﬁnal state of the body, state B, coincides with the end of ∆x. The change in entropy of the body over ∆x can then be determined by using the familiar expression
B

S(B) − S(A) =
A

dQ T

(4)
Pre-peer reviewed copy DOI: 10.1002/andp.201100013

Pre-peer reviewed copy DOI: 10.1002/andp.201100013

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where Q is heat energy, and T is temperature. According to the ﬁrst law of thermodynamics, the heat energy dQ entering or leaving the body is given by dQ = dE + dW , where dE is the change in internal energy, and dW is the work performed on or by the body. Although the heat engine operates between its own hot and cold heat reservoirs as it produces a force on the body, let us assume the internal energy of the body remains unchanged during the acceleration. Thus, we may put dE = 0 and hold T constant in (4). Moreover, since the heat engine does positive work on the body, the work performed by the body is negative. Under these conditions, the ﬁrst law of thermodynamics reduces to dQ = −dW . Using this in (4) and noting that the change in total energy of the body can be expressed as dU = dW gives ∆S = − 1 T
B

dU.
A

(5)

According to the non-accelerating observer, the total energy of the body at any point along the path from state A to state B can be expressed as U (γ) = U0 γ, where U0 is the total proper energy associated with the body, and γ is the lapse function discussed in the introduction. Using this in (5) puts the entropy change of the moving body in the form ∆S = − U0 T
B

dγ = −
A

U0 (γB − γA ) . T

(6)

Thus, the entropy change of the body is proportional to the change in the lapse function occurring between state A and state B. As discussed above, the change in entropy ∆S occurs over the distance ∆x. With this in mind, let us take the limit of (6) with respect to ∆x → 0. Carrying out the limit on both sides of (6) leads directly to S=− U0 T γ. (7)

Upon using (3) to express the force on the moving body as F = U0 γ, it is straightforward to see that (7) can then be recast in the form F = −T S. (8)

Equation (8) is equivalent to the entropic force given by (2), with the exception of a minus sign. With (8) in hand, the next order of business is to determine the entropy S and temperature T so as to relate (8) and (1). It will be recalled that T was held constant in the derivation of (8). Determining ∆S, however, is easily carried out by returning to (6) and noting that for the case of weak acceleration over the distance ∆x, we may put [17, 18] ∆γ ≈ a∆x c2 (9)

where a is the proper acceleration of the body. Substituting (9) into (6) and using the expression U0 = m0 c2 leads to m0 a ∆S ≈ − ∆x (10) T where m0 is the proper inertial mass due to all forms of internal stress-energy-momentum associated with the accelerating body. Equation (10) used in conjunction with (8) leads directly to Newton’s second law of motion, (1). It will be noted that (10) indicates that for any given temperature, the entropy of the accelerating body decreases as positive work is performed on the body. At the same time, however, the entropy of the heat engine increases as it performs positive work to accelerate the body, which we may denote by ∆She > 0. It is conceptually straightforward to see that the net effect of applying the force to the body is an increase
Pre-peer reviewed copy DOI: 10.1002/andp.201100013

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Charles T. Ridgely: Relativity, thermodynamics and entropic forces

in the entropy of the universe, given by ∆(She + S) > 0, as we should expect by way of the second law of thermodynamics. Equations (6) and (7) suggest a different interpretation than that put forth in [1]. According to Verlinde [1], the entropy change ∆S and the temperature T are characteristics of the holographic screens comprising space. Upon inspecting (6), however, it is straightforward to see that the entropy depends not only on the lapse function, but also on the mass and temperature of the body, as well. The dependence on the mass and temperature of the body suggests that the entropy is to be associated with the body itself rather than any particular feature of space-time, such as the holographic screens proposed in [1]. Moreover, the dependence on the lapse function indicates that the entropy of the body is simply due to the relative motion between the body and the non-accelerating observer in ﬂat space-time. Thus, (3) and (8) provide us with a choice. Forces can be equivalently expressed either by way of the lapse function and (3) or in terms of the temperature and entropy of the moving body by way of (8).

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Entropy in General Coordinates

In the previous section, the entropic inertial force was derived by use of the lapse function for a body accelerating in ﬂat, Minkowski space-time. Let us now consider the entropic force in a general system of coordinates. Consider an observer within an enclosed vessel that is relatively small, such as an elevator car or telephone booth. An external force operates on the vessel such that the observer possesses weight and can stand at one end of the vessel. Ignoring any tidal effects, the observer might conclude that the vessel is suspended from a tether near a gravitational source, or that the vessel is accelerating uniformly in Minkowski space-time. In either case, the local reference frame of the observer appears characterized by the effects of acceleration. Suppose the observer measures the weight of a test body at the ceiling of the vessel, say wall A, and then carries out the same measurement at the ﬂoor of the vessel, wall B. According to the observer, the total energy of the body changes from wall A to wall B. This change in energy can be associated with a change in the thermodynamic state of the test body. Assuming the temperature T of the test body remains constant, the observer can use (4) to determine the change in entropy of the test body occurring between these two states. Let us suppose that the energy of the test body at wall A is simply UA = U0 , where U0 is the total proper energy associated with the body according to the observer in the vessel. Relative to wall A, the −1 energy of the body at wall B is UB = U0 γA γB where γA and γB express the quantity of proper time that elapses at walls A and B, respectively, per unit of coordinate time [2]. The energy of the body between walls A and B is thus expressible relative to wall A as U (γ) = U0 γA γ −1 . According to (4), the entropy change of the test body in moving from wall A to wall B is ∆S = − U0 γA T
B

γ −2 dγ = −
A

U0 −1 γ (γB − γA ) . T B

(11)

Upon inspecting (11), it is straightforward to see that ∆S → 0 when γA → γB . Equation (11) underscores the interpretation of the entropy S given in the previous section. Whereas γ expresses the condition of the coordinate system in the local reference frame of the test body, ∆S is the relativistic entropy change of the test body due to the differentiability of γ. Let us suppose that the path of travel of the test body in moving from state A to state B is along an interval ∆xi in which the superscript denotes the i−coordinate direction. Taking the limit of (11) with respect to ∆xi → 0 as (γB , γA ) → γ, and then rearranging a bit leads to U0 −1 γ γ. (12) T Upon comparing (12) and (3), it is straightforward to see that the numerator on the right-hand side of (12) is just the force on the test body due to the general coordinate system [2, 16]. Using (3) puts the entropic S=−
Pre-peer reviewed copy DOI: 10.1002/andp.201100013

Pre-peer reviewed copy DOI: 10.1002/andp.201100013

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force on the test body in the form F = −T S (13)

which at ﬁrst sight appears to be identical to (8), derived in ﬂat space-time. It must be kept in mind, however, that the gradient operator in general coordinates assumes the form [19] → −gi g ij ∂j (14)

where gi is a general basis vector pointing in the i−coordinate direction, g ij is the inverse metric tensor, and Latin indices are carried over the values (1, 2, 3). The minus sign is included in (14) due to our choice of sign convention, (+, −, −, −). Expanding the gradient operator in (13) by way of (14) expresses the entropic force in terms of general coordinates as F = gi g ij T ∂j S. (15)

Thus, the force on a body in general coordiantes can be expressed either by way of the lapse function and energy content of the body in (3) or by way of the temperature and entropy of the body in (13) and (15). It is illustrative to consider the entropy of a test body held ﬁxed in position outside a large, spherically symmetric source of mass M . This is most easily carried out by expressing (12) in Schwarzschild coordinates. The lapse function in Schwarzschild coordinates is γ −1 = (1 + 2φ/c2 )1/2 , where φ = −GM/r is the ﬁeld potential at a radial distance r from the center of the gravitational source [2]. Using (14) and the Schwarzschild lapse function in (12) leads to ∆Sm = m 2 γ ∆φ T (16)

where m is the proper mass of the test body, and the subscript on Sm denotes the entropy associated with the test body. Noting that the ﬁeld potential φ is negative relative to distant, star-ﬁxed observers, (16) indicates that the entropy of the test body will decrease if the body is released and allowed to free-fall toward the gravitational source. Although the motion of the body is due to space-time curvature near the gravitational source, approaching this problem by way of a classical, Newtonian standpoint, the gravitational force can be said to perform positive work on the body. With the second law of thermodynamics in mind, it seems reasonable that while the gravitational force performs positive work on the test body, the entropy of the gravitational ﬁeld must increase according to ∆Sg ≥ − m 2 γ ∆φ T (17)

where the subscript on Sg denotes the entropy associated with the gravitational ﬁeld, and it should be understood that the minus sign is included simply because φ is negative relative to distant observers, as mentioned above. Combining (16) and (17) suggests that the total entropy change of the universe due to the test body gravitating toward the gravitational source is ∆ (Sg + Sm ) ≥ 0, as required by the second law of thermodynamics.

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Entropy of a Weakly-Gravitating Matter Distribution

As a ﬁnal thought, it is interesting to consider that while entropy is very well known to be associated with black holes [3]-[6], (17) indicates that entropy can also be associated with weak-ﬁeld, Newtonian gravitation, as well. In an attempt to demonstrate this, let us use a classical approach analogous to that used to derive the electrostatic self-energy of a charge distribution. Suppose a dispersed gas of material particles occupies a vast region of space. Classically speaking, the particles may be said to be inﬁnitely far from one another. Given time, however, pairs of the particles
Pre-peer reviewed copy DOI: 10.1002/andp.201100013

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Charles T. Ridgely: Relativity, thermodynamics and entropic forces

gravitate toward one another and bind together, forming a volume distribution of matter. As the number of bound particles increases, so too does the total entropy of the resulting gravitational ﬁeld. Let us use (11) to determine the total entropy of the matter distribution. Our ﬁrst step is to recast (11) relative to distant, star-ﬁxed observers. This amounts to putting γA → 1 and γB → γ, and noting that the entropy of the gravitational ﬁeld may be expressed as ∆Sg ≥ −∆Sm . Carrying this out in (11) gives ∆Sg ≥ U (γ − 1) Tg (18)

where we have put Tg = T γ, and U is the total mass-energy associated with an individual particle of matter. Equation (18) expresses the change in entropy of the particle in moving from a region where γA = 1 to the region where γB = γ. The rightmost term in (18) suggests that when γA = 1 there is a certain initial entropy contribution associated with the mass-energy of each particle, expressible as Sm = U/Tg . Moreover, with respect to black holes, we know that as matter is absorbed into a black hole, the total entropy of the hole increases according to T δS = δ M c2 [6]. We should expect a similar phenomenon with the ideal matter distribution considered here. Based on this, it seems reasonable to include contributions to (18) due to the stress-energy-momentum of the constituent particles, as well. Furthermore, for the sake of simplicity let us deﬁne a new ﬁeld potential given by λ = γ − 1. Putting everything together, we may recast (18) for N -many gravitating particles as 1 ∆Sg ≥ 2Tg
N N

Ui
i=1
j=1 j=i

1 λj + Tg

N

Ui
i=1

(19)

where the rightmost term is the entropy due to the stress-energy-momentum of all the particles, and the factor of 1/2 is included in the ﬁrst term to account for duplicate pairs of particles in the sum. Equation (19) can be simpliﬁed upon noticing that the sum over λj in the ﬁrst term is just the total ﬁeld potential λ (Pi ) at the position Pi of Ui . Using this observation puts (19) in the form ∆Sg ≥ 1 2Tg
N

Ui λ (Pi ) +
i=1

1 Tg

N

Ui .
i=1

(20)

Upon generalizing to the case of a continuous volume distribution of matter, (20) can be expressed as ∆Sg (x) ≥ 1 2Tg u (x ) λ (x ) d3 x + 1 Tg u (x ) d3 x (21)

where u (x ) is the mass energy-density of the matter distribution, λ (x ) is the ﬁeld potential, and primed quantities are taken over the volume of the matter distribution. For the special case of a weakly gravitating matter distribution, we may express the lapse function as γ (x ) ≈ 1 − φ (x ) /c2 in which φ (x ) is the gravitational ﬁeld potential. Using this expression for the lapse function gives λ (x ) ≈ −φ (x ) /c2 , which puts (21) in the form ∆Sg (x) ≥ − 1 2Tg ρ (x ) φ (x ) d3 x + c2 Tg ρ (x ) d3 x (22)

where ρ (x ) is the mass-density of the matter distribution, and the expression u (x ) = c2 ρ (x ) has been used. It is straightforward to see that the ﬁrst integral on the right-hand side of (22) is just the gravitational self-energy Us of the matter distribution. Taking this into account and integrating the second term puts (22) into the very simple form Sg ≥ Us mc2 + Tg Tg (23)
Pre-peer reviewed copy DOI: 10.1002/andp.201100013

Pre-peer reviewed copy DOI: 10.1002/andp.201100013

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where m is to be interpreted as the total gravitational mass due to all sources of energy associated with the particles, including internal stresses, momentum, and any thermodynamic phenomena that may be present, as well. Equation (23) suggests that the total gravitational entropy increases in proportion to both the self-energy used in assembling all the constituent particles of the matter distribution as well as the total stress-energy-momentum content of the particles comprising the matter distribution. Considering that gravitational self-energy is well known to be a source of gravitation, it seems reasonable to recast (23) in the form Sg ≥ M c2 Tg (24)

where M is the total gravitational mass associated with all forms of stress-energy-momentum, including the gravitational self-energy of the matter distribution. Although the matter distribution considered here is not a black hole, and thus has no event horizon, (24) −1 agrees in principle with the expression Tg = ∂Sg /∂M c2 familiar to black hole mechanics [4]. It is interesting to consider that while M and Tg are the mass and temperature of the matter distribution, the left-hand side of (24) is the entropy associated with the gravitational ﬁeld, not the matter distribution itself. Were this idealistic group of particles allowed to assume the characteristics of a star that later collapsed into a black hole, it is straightforward to see that the entropy given by (24) would then be associated with the event horizon of the black hole, as is well known in the literature [3]-[6].

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Discussion and Conclusions

Verlinde’s information proposal asserts that space may be viewed as being comprised of a continuum of holographic membranes or screens which, when possessing a temperature and an entropy change, are the underlying origin of inertial and gravitational forces [1]. Herein, entropic forces were considered from the standpoint of conventional thermodynamics and relativity. The approach presented in the preceding sections demonstrates that the entropic force associated with gravitation and inertia is intimately related to the well known lapse function of general relativity [2]. The relationship between the entropy and the lapse function prompted a different interpretation of the temperature and entropy than that presented in [1]. The temperature appearing in the expression of the entropic force was herein treated as the temperature of a material body undergoing motion, and thus was held constant. The entropy was found to be directly proportional to the lapse function. In the case of uniform acceleration, the entropy was found to be due to the relative motion between the moving body and a non-accelerating observer in ﬂat space-time. In the case of gravitation, the entropy was determined to be due to the coordinate system in the local frame of the moving body. It is interesting to note that whereas the lapse function depends only on the characteristics of space-time in the local reference frame of the moving body, the entropy is proportional to the lapse function as well as the mass and temperature of the body. As pointed out in section 2, the dependence on the mass and temperature of the body indicates that the entropy is to be associated with the body itself rather than being somehow associated with space-time as proposed in [1]. At the same time, the dependence on the lapse function indicates that the entropy of the body arises simply due to the relative motion between the body and other observers in space-time. In section 2, the ﬁrst and second laws of thermodynamics were applied to a body undergoing uniform acceleration due to an external force applied by a heat engine. This conventional approach led directly to an expression of the entropic force identical to that proposed in [1], with the exception of a minus sign. The minus sign made it clear that the entropy of the accelerating body decreases as the heat engine performs positive work on the body. At the same time, the entropy of the heat engine increases. It was concluded that the net effect of applying the force to accelerate the body is an increase in the entropy of the universe, in agreement with the second law of thermodynamics. Section 3 was devoted to deriving the entropic force in general coordinates. This was carried out by determining the entropy change of a test body due to the change in the lapse function occurring between two
Pre-peer reviewed copy DOI: 10.1002/andp.201100013

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Charles T. Ridgely: Relativity, thermodynamics and entropic forces

different locations in the coordinate system. Limiting the entropy to inﬁnitesimal displacement produced an expression of the entropic force in general coordinates. The entropy of a test body held ﬁxed near a large gravitational source was then derived by way of Schwarzschild coordinates. The resulting expression made it clear that the entropy of in-falling matter decreases as the gravitational force performs positive work. In closing, it was pointed out that the second law of thermodynamics requires the entropy of the gravitational ﬁeld to increase as matter is drawn in and captured. In section 4, an idealistic derivation was used to demonstrate that the entropy of a weakly gravitating distribution of matter is proportional to the total stress-energy-momentum content and gravitational self-energy of the matter distribution. The resulting expression indicates that as the size of the matter distribution grows, so too does its total gravitational entropy. In closing, it was pointed out that were this idealistic matter distribution a black hole, the entropy would be associated with the event horizon of the black hole as is well known in the literature [3]-[6].

References
[1] Verlinde E 2010 On the origin of gravity and the laws of Newton arXiv:1001.0785v1 [hep-th] <http://arxiv.org/PS_cache/arxiv/pdf/1001/1001.0785v1.pdf> [2] Thorne K, Price R and Macdonald D 1986 Black Holes: The Membrane Paradigm (New Haven: Yale University) p 13, 67 [3] Bardeen J, Carter B and Hawking S 1973 The four laws of black hole mechanics Commun. Math. Phys. 31 p 161 [4] Bekenstein J 1973 Black holes and entropy Phys. Rev. D. 7 p 2333 [5] Wald R 1993 Black hole entropy is the Noether charge Phys. Rev. D. 48 p R3427 [6] Davies P, Ford L and Page D 1986 Gravitational entropy: Beyond the black hole Phys. Rev. D. 34 p 1700 [7] Weinberg S 1972 Gravitation and Cosmology: Principles and Applications of the General Theory of Relativity (New York: Wiley) p 126, 147 [8] Bergmann P 1976 Introduction to the Theory of Relativity (New York: Dover) p 160, 198 [9] Kenyon I 1990 General Relativity (New York: Oxford) p 63 [10] Jonsson R 2005 Visualizing curved spacetime Am. J. Phys. 73 248 [11] M¨ ller H, Peters A and Chu S 2010 A precision measurement of the gravitational redshift by the interference of u matter waves Nature 463 926 [12] Einstein A 1988 The Meaning of Relativity, Including the Relativistic Theory of the Non-Symmetric Field 5th edn (New Jersey: Princeton University Press) p 79 [13] Born M 1965 Einstein’s Theory of Relativity (New York: Dover) p 339 [14] Schutz B 1990 A First Course in General Relativity (New York: Cambridge) p 125 [15] Ohanian H and Rufﬁni R 1994 Gravitation and Spacetime 2nd edn (New York: Norton) p 163 [16] Ridgely C 2010 Forces in general relativity Eur. J. Phys. 31 949 [17] Misner C, Thorne K and Wheeler J 1973 Gravitation (New York: Freeman) p 331 [18] Desloge E 1990 Relativistic motion of a free particle in a uniform gravitational ﬁeld Int. J. Theor. Phys. 29 p 193 [19] Jonsson R 2006 An intuitive approach to inertial forces and the centrifugal force paradox in general relativity Am. J. Phys. 74 p 905

Pre-peer reviewed copy DOI: 10.1002/andp.201100013