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The abc-conjecture is applied to various questions involving the number of distinct fields , as we vary over integers n.

We have prepared a series of potent, dual inhibitors of the prenyl transferases farnesyl protein transferase (FPTase) and geranyl-geranyl protein transferase I (GGPTase). The compounds were shown to possess potent activity against both enzymes in cell culture. Mechanistic analysis has shown that the compounds are CAAX competitive for FPTase inhibition but geranyl-geranyl pyrophosphate (GGPP) competitive for GGPTase inhibiton.

This paper deals with generalizations of Hilbert's irreducibility theorem. The classical Hilbert irreducibility theorem states that for any cover f of the projective line defined over a number field k, there exist infinitely many k-rational points on the projective line such that the fiber of f over P is irreducible over k. In this paper, we consider similar statements about algebraic points of higher degree on curves of any genus. We prove that Hilbert's irreducibility theorem admits a natural generalization to rational points on an elliptic curve and thus, via a theorem of Abramovich and Harris, to points of degree 3 or less on any curve. We also present examples that show that this generalization does not hold for points of degree 4 or more. These examples come from an earlier geometric construction of Debarre and Fahlaoui; some additional necessary facts about this construction can be found in the appendix provided by Debarre. We exhibit a connection between these irreducibility questions and the sharpness of Vojta's inequality for algebraic points on curves. In particular, we show that Vojta's inequality is not sharp for the algebraic points arising in our examples.

Let OK be any domain with field of fractions K . Let F(x, y) ∈ OK [x, y] be a homogeneous polynomial of degree n, coprime to y, and assumed to have unit content (i.e., the coefficients of F generate the unit ideal in OK ). Assume that gcd(n, char(K )) = 1. Let h ∈ OK and assume that the polynomial hzn − F(x, y) is irreducible in K[x, y, z]. We denote by X F,h/K the nonsingular complete model of the projective plane curve CF,h/K defined by the equation hzn − F(x, y) = 0. We shall assume in this article that g(X F,h) ≥ 2. When K is a number field, Mordell’s Conjecture (now Faltings’ Theorem) implies that |X F,h(K )| < ∞. Caporaso, Harris, and Mazur ([CHM, 1.1]) have shown that if Lang’s conjecture for varieties of general type is true, then for any number field K , the size |X(K )| of the set of K -rational points of any curve X/K of genus g(X) ≥ 2 can be bounded by a constant depending only on g(X). Prior to the paper [CHM], Mazur and others had asked whether |X(K )| can be bounded by a constant depending only on g(X) and the Mordell-Weil rank of X/K over K (that is, the rank of the group J(K ) of K -rational points of the jacobian J/K of X/K ). These farreaching questions are totally open. As we shall recall in Sect. 1, the method of Chabauty-Coleman sometimes yields a bound for |X F,h(K )| depending only on g(X F,h) when it is known in advance that the Mordell-Weil rank of X F,h/K is small. Unfortunately, the Chabauty-Coleman method does not yield a bound for |X F,h(K )| independent of the coefficients of hzn − F(x, y) for all curves of the form X F,h . It does, however, produce such a nice bound for the number of primitive integral solutions of F(x, y) = h, as we now explain. Let K = Q and OK = Z. A classical Thue equation is an equation F(x, y) = h where F(x, 1) does not have repeated roots. Thue showed in 1909 that such an equation has finitely many solutions (x, y) ∈ Z2 if n ≥ 3.

Using methods of p-adic analysis, we obtain effective bounds for the length of the orbit of a preperiodic subvariety Y⊂ X under the action of an etale endomorphism of X. As a corollary of our result, we obtain effective bounds for the size of torsion of any semiabelian variety over a finitely generated field of characteristic 0. Our method allows us to show that any finitely generated torsion subgroup of Aut(X) is finite. This yields a different proof of Burnside’s problem for automorphisms of quasiprojective varieties X defined over a field of characteristic 0.

Let $\varphi: {\mathbb P}^1 \longrightarrow {\mathbb P}^1$ be a rational map of degree greater than one defined over a number field $k$. For each prime ${\mathfrak p}$ of good reduction for $\varphi$, we let $\varphi_{\mathfrak p}$ denote the reduction of $\varphi$ modulo ${\mathfrak p}$. A random map heuristic suggests that for large ${\mathfrak p}$, the proportion of periodic points of $\varphi_{\mathfrak p}$ in ${\mathbb P}^1({\mathfrak o}_k/{\mathfrak p})$ should be small. We show that this is indeed the case for many rational functions $\varphi$., Comment: 23 pages

This paper deals with upper bounds on arithmetic discriminants of algebraic points on curves over number fields. It is shown, via a result of Zhang, that the arithmetic discriminants of algebraic points that are not pullbacks of rational points on the projective line are smaller than the arithmetic discriminants of families of linearly equivalent algebraic points. It is also shown that bounds on the arithmetic discriminant yield information about how the fields of definition k(P) and k(f(P)) differ when P is an algebraic point on a curve C and f : C --C' is a nonconstant morphism of curves. In particular, it is demonstrated that k(P) 74 k(f(P)), with at most finitely many exceptions, whenever the degrees of P and f are sufficiently small, relative to the difference between the genera g(C) and g(C'). The paper concludes with a detailed analysis of the arithmetic discriminants of quadratic points on bi-elliptic curves of genus 2. Let C be a curve defined over a number field k, and let X be a regular model for C over the ring of integers R of k. In [V 3], Vojta proves that, for any c > 0, all points P E C(k) of bounded degree satisfy the inequality (0.0.1) hK(P) < da(P) + EhA(P) + 0(1), where A is any ample divisor on C, hA and hK are Weil heights associated with A and the canonical divisor K, respectively, and da(P) is the arithmetic discriminant of P. The arithmetic discriminant depends on the choice of a regular model X; it is defined as (Hp.(Wx/B+HP)) [k(P) : k] where Hp is the arithmetic curve on X corresponding to P and Wx/B is the sheaf of relative differentials of X over B = Spec R. The difference between arithmetic discriminants derived from different regular models is always bounded. Hence, (0.0.1) is not affected by one's choice of a regular model. The arithmetic discriminant is related to d(P), the normalized field discriminant of the field of definition of P, which is defined as d(P) '_ log IN|Dk(p)/k [k(P): ] One may obtain da(P) by adding to d(P) terms corresponding to singularities of Hp at finite places and v-adic distances between the conjugates of P at infinite places v (see [V 2, Section 3]). The precise nature of the relationship between Received by the editors November 30, 1999 and, in revised form, February 25, 2000. 2000 Mathematics Subject Classification. Primary 11G30, 11J25. ()2001 American Mathematical Society

This paper addresses questions involving the sharpness of Vojta's conjecture and Vojta's inequality for algebraic points on curves over number fields. It is shown that one may choose the approximation term mS(D,! ) in such a way that Vojta's inequality is sharp in Theorem 2.3. Partial results are obtained for the more difficult problem of showing that Vojta's conjecture is sharp when the approximation term is not included (that is, when D = 0). In Theorem 3.7, it is demonstrated that Vojta's conjecture is the best possible with D = 0 for quadratic points on hyperelliptic curves. It is also shown, in Theorem 4.8, that Vojta's conjecture is sharp with D = 0 on a curve C over a number field when an analogous statement holds for the curve obtained by extending the base field of C to a certain function field. Mathematics Subject Classifications (1991): 11G30, 11J68.

As part of an ongoing effort to prepare therapeutically useful orally active thrombin inhibitors, we have synthesized a series of compounds that utilize nonbasic groups in the P1 position. The work is based on our previously reported lead structure, compound 1, which was discovered via a resin-based approach to varying P1. By minimizing the size and lipophilicity of the P3 group and by incorporating hydrogen-bonding groups on the N-terminus or on the 2-position of the P1 aromatic ring, we have prepared a number of derivatives in this series that exhibit subnanomolar enzyme potency combined with good in vivo antithrombotic and bioavailability profiles. The oxyacetic amide compound 14b exhibited the best overall profile of in vitro and in vivo activity, and crystallographic studies indicate a unique mode of binding in the thrombin active site.

A novel, nonpeptidyl thrombin inhibitor, L-636,619 (1), was identified via topological similarity searching over the Merck Corporate Sample Database. X-ray crystallographic studies determined the geometry for ligand binding to the enzyme. Chemical modification of the P1 and P3 segments of the ligand resulted in enhanced potency and improvement in the chemical stability of the lead. Analog 9 proved to be the most interesting lead from this structurally novel series.

As part of an effort to prepare efficacious and orally bioavailable analogs of the previously reported thrombin inhibitors 1a,b, we have synthesized a series of compounds that utilize 3,3-disubstituted propionic acid derivatives as P 3 ligands. By removing the N-terminal amino group, the general oral bioavailability of this class of compounds was enhanced without excessively increasing the lipophilicity of the compounds. The overall properties of the molecules could be drastically altered depending on the nature of the groups substituted onto the 3-position of the P 3 propionic acid moiety. A number of the compounds exhibited good oral bioavailability in rats and dogs, and numerous compounds were efficacious in a rat FeCl 3 -induced model of arterial thrombosis. Compound 7, the 3,3-diphenylpropionic acid derivative, showed the best overall profile of in vivo and in vitro activity. Molecular modeling studies suggest that these compounds bind in the thrombin active site in a manner essentially identical to that previously reported for compound 1a.

In an effort to prepare orally bioavailable analogs of our previously reported thrombin inhibitor 1, we have synthesized a series of compounds that utilize the unique amino acid D-dicyclohexylalanine as a P3 ligand. The resulting compounds are extremely potent and selective thrombin inhibitors, and the N-terminal Boc derivative 8 exhibited excellent oral bioavailability and pharmacokinetics in both rats and dogs. The des-Boc analog 6 was not orally bioavailable in rats. The high level of oral bioavailability observed with 8 appears to be a direct function of its increased lipophilicity versus other close analogs. Although increased lipophilicity may serve to increase the oral absorption of tripeptide thrombin inhibitors, it also appears to have detrimental effects on the antithrombotic properties observed with the compounds. Compound 6 performed extremely well in our in vivo antithrombotic assay, while the much more lipophilic but essentially equipotent analog 8 performed poorly. We have found that in general with this series of thrombin inhibitors as well as with other unreported series, increased lipophilicity and the associated increases in plasma protein binding have detrimental effects on 2X APTT values and subsequent performance in in vivo antithrombotic models.

Let X be a smooth curve defined over the algebraic numbers, let a,b be algebraic numbers, and let f_l(x) be an algebraic family of rational maps indexed by all l in X. We study whether there exist infinitely many l in X such that both a and b are preperiodic for f_l. In particular we show that if P,Q are polynomials over the algebraic numbers such that deg(P) >= 2+deg(Q), and there exists l such that a is periodic for P(x)/Q(x) + l, but b is not preperiodic for P(x)/Q(x) + l, then there exist at most finitely many l such that both a and b are preperiodic for P(x)/Q(x)+l. We also prove a similar result for certain two-dimensional families of endomorphisms of P^2., 30 pages

As part of an ongoing effort to prepare novel non-nucleoside inhibitors of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT), a series of 4-(arylethynyl)-6-chloro-4-cyclopropyl-3,4-dihydroquinazolin -2(1H)-ones 4aa-l has been prepared. Target compounds 4a-e were synthesized via addition of various 1-lithio-2-(aryl)alkyne nucleophiles to a 1-protected-4-cyclopropylquinazolin-2(1H)-one (7), followed by deprotection. The 3-methyl compound 4aa was prepared in an analogous manner, with the 3-alkylation performed prior to deprotection. Alternatively, the target compounds 4f-l were prepared by addition of 1-lithio-2-(trimethylsilyl)acetylene to 7, followed by deprotection and subsequent palladium-catalyzed coupling with various aryl halides. By incorporating an aryl group onto the end of the 4-acetylene functionality, the requirement for a metabolically labile 3-methyl group on the dihydroquinazolinone nucleus has been eliminated. A number of the target compounds were shown to be potent inhibitors of HIV-1 RT. Compound 4a, which had exhibited the most favorable overall biological profile, was resolved via a four-step procedure to provide the enantiomers 13a and 13b. Compound 13a having the (-)-4(S) configuration was shown to be the active enantiomer and was selected as a candidate for further investigation.

If K is a number field and \(\varphi: {\mathcal{P}}_{K}^{1}\rightarrow {\mathcal{P}}_{K}^{1}\) is a rational map of degree d > 1, then at each place v of K, one can associate to φ a generalized Mahler measure for polynomials F ∈ K[t]. These Mahler measures give rise to a formula for the canonical height h φ(β) of an element \(\beta\in \overline{K}\); this formula generalizes Mahler’s formula for the usual Weil height h(β). In this paper, we use Diophantine approximation to show that the generalized Mahler measure of a polynomial F at a place v can be computed by averaging log | F | v over the periodic points of φ.

Let K be a number field, let $${\varphi \in K(t)}$$ be a rational map of degree at least 2, and let $${\alpha, \beta \in K}$$ . We show that if α is not in the forward orbit of β, then there is a positive proportion of primes $${\mathfrak{p}}$$ of K such that $${\alpha {\rm mod} \mathfrak{p}}$$ is not in the forward orbit of $${\beta {\rm mod} \mathfrak{p}}$$ . Moreover, we show that a similar result holds for several maps and several points. We also present heuristic and numerical evidence that a higher dimensional analog of this result is unlikely to be true if we replace α by a hypersurface, such as the ramification locus of a morphism $${\varphi: \mathbb{P}^{n} \to \mathbb{P}^{n}}$$ .

Conditions for facile solution-phase amide conjugation of amine-modified siRNA with a diverse set of carboxylic acid partners using the coupling reagent HATU are described. These conditions eliminate the need for isolated activated esters and allow for rapid access to conjugates with a wide range of lipophilicity and functionality in good yield.

We provide a family of counterexamples to a first formulation of the dynamical Manin-Mumford conjecture. We propose a revision of this conjecture and prove it for arbitrary subvarieties of abelian varieties under the action of endomorphisms of abelian varieties and for lines under the action of diagonal endomorphisms of P × P.

Studies were conducted to investigate mutation pathways among subtypes A, B, and C of human immunodeficiency virus type 1 (HIV-1) during resistance selection with nonnucleoside reverse transcriptase inhibitors (NNRTIs) in cell culture under low-multiplicity of infection (MOI) conditions. The results showed that distinct pathways were selected by different virus subtypes under increasing selective pressure of NNRTIs. F227C and Y181C were the major mutations selected by MK-4965 in subtype A and C viruses during resistance selection. With efavirenz (EFV), F227C and V106M were the major mutations responsible for viral breakthrough in subtype A viruses, whereas a single pathway (G190A/V106M) accounted for mutation development in subtype C viruses. Y181C was the dominant mutation in the resistance selection with etravirine (ETV) in subtype A, and E138K/H221Y were the mutations detected in the breakthrough viruses from subtype C viruses with ETV. In subtype B viruses, on the other hand, known NNRTI-associated mutations (e.g., Y181C, P236L, L100I, V179D, and K103N) were selected by the NNRTIs. The susceptibility of the subtype A and B mutant viruses to NNRTIs was determined in order to gain insight into the potential mechanisms of mutation development. Collectively, these results suggest that minor differences may exist in conformation of the residues within the NNRTI binding pocket (NNRTIBP) of reverse transcriptase (RT) among the three subtypes of viruses. Thus, the interactions between NNRTIs and the residues in the NNRTIBPs of different subtypes may not be identical, leading to distinct mutation pathways during resistance selection in cell culture.

The palladium catalyzed coupling of allylic acetates with carbon nucleophiles generates urethane protected trans-allylic amines with exceptionally high stereoselectivity.

Biaryl ethers were recently reported as potent NNRTIs. Herein, we disclose a detailed effort to modify the previously reported compound 1. We have designed and synthesized a series of novel pyrazole derivatives as a surrogate for pyrazolopyridine motif that were potent inhibitors of HIV-1 RT with nanomolar intrinsic activity on the WT and key mutant enzymes and potent antiviral activity in infected cells.

A series of HIV-1 protease inhibitors containing a novel hydroxyethyl secondary amine transition state isostere has been synthesized. The compounds exhibit a strong preference for the (R) stereochemistry at the transition state hydroxyl group. Molecular modeling studies with the prototype compound 11 have provided important insights into the structural requirements for good inhibitor-active site binding interaction. N-Terminal extension of 11 into the P2-P3 region led to the discovery of 19, the most potent enzyme inhibitor in the series (IC50 = 5.4 nM). 19 was shown to have potent antiviral activity in cultured MT-4 human T-lymphoid cells. Comparison of analogs of 19 with analogs of 1 (Ro31-8959) demonstrates that considerably different structure-activity relationships exist between these two subclasses of hydroxyethylamine HIV-protease inhibitors.

By tethering of a polar hydrophilic group to the P1 or P1' substituent of a Phe-based hydroxyethylene isostere, the antiviral potency of a series of HIV protease inhibitors was improved. The optimum enhancement of anti-HIV activity was observed with the 4-morpholinylethoxy substituent. The substituent effect is consistent with a model derived from inhibitor docked in the crystal structure of the native enzyme. An X-ray crystal structure of the inhibited enzyme determined to 2.25 A verifies the modeling predictions.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been shown to be a key component of highly active antiretroviral therapy (HAART). The use of NNRTIs has become part of standard combination antiviral therapies producing clinical outcomes with efficacy comparable to other antiviral regimens. There is, however, a critical issue with the emergence of clinical resistance, and a need has arisen for novel NNRTIs with a broad spectrum of activity against key HIV-1 RT mutations. Using a combination of traditional medicinal chemistry/SAR analyses, crystallography, and molecular modeling, we have designed and synthesized a series of novel, highly potent NNRTIs that possess broad spectrum antiviral activity and good pharmacokinetic profiles. Further refinement of key compounds in this series to optimize physical properties and pharmacokinetics has resulted in the identification of 8e (MK-4965), which has high levels of potency against wild-type and key mutant viruses, excellent oral bioavailability and overall pharmacokinetics, and a clean ancillary profile.

We study the orbits of a polynomial f in C[X], namely the sets {e,f(e),f(f(e)),...} with e in C. We prove that if nonlinear complex polynomials f and g have orbits with infinite intersection, then f and g have a common iterate. More generally, we describe the intersection of any line in C^d with a d-tuple of orbits of nonlinear polynomials, and we formulate a question which generalizes both this result and the Mordell--Lang conjecture., Comment: 27 pages

For any elements b,c of a number field K, let G(b,c) denote the backwards orbit of b under the map f_c: C-->C given by f_c(x)=x^2+c. We prove an upper bound on the number of elements of G(b,c) whose degree over K is at most some constant B. This bound depends only on b, [K:Q], and B, and is valid for all b outside an explicit finite set. We also show that, for any N>3 and any b in K outside a finite set, there are only finitely many pairs of complex numbers (y,c) for which [K(y,c):K], 15 pages; very minor changes from v1

The palladium catalyzed coupling of allylic acetates with carbon nucleophiles generates urethane protected trans-allylic amines with exceptionally high stereoselectivity.

We prove a dynamical version of the Mordell-Lang conjecture in the context of Drinfeld modules. We use analytic methods similar to the ones employed by Skolem, Chabauty, and Coleman for studying diophantine equations., 13 pages

We prove that if nonlinear complex polynomials of the same degree have orbits with infinite intersection, then the polynomials have a common iterate. We also prove a special case of a conjectured dynamical analogue of the Mordell-Lang conjecture., Comment: 19 pages; to appear in Inventiones Mathematicae; in this version we modified the exposition in view of the referee's comments

Study of surface representations of the inhibitor-bound thrombin P-1 pocket revealed a lipophilic recess in this pocket which is not occupied by any known inhibitor. Solid-phase synthesis was used to generate benzylamides of D-diphenylAlaPro by aminolysis of Boc dipeptide Kaiser resin. The resulting amides inhibited thrombin in the range IC50 = 3-13,000 nM, and the structure-activity relationships and molecular modeling suggest a unique fit of the benzyl side chain into P-1 with the meta substituent occupying the recess.

The Mahler measure formula expresses the height of an algebraic number as the integral of the log of the absolute value of its minimal polynomial on the unit circle. The height is in fact the canonical height associated to the monomial maps xn. We show in this work that for any rational map ϕ(x) the canonical height of an algebraic number with respect to ϕ can be expressed as the integral of the log of its equation against the invariant Brolin-Lyubich measure associated to ϕ, with additional adelic terms at finite places of bad reduction. We give a complete proof of this theorem using integral models for each iterate of ϕ. In the last chapter on equidistribution and Julia sets we give a survey of results obtained by P. Autissier, M. Baker, R. Rumely and ourselves. In particular our results, when combined with techniques of diophantine approximation, will allow us to compute the integrals in the generalized Mahler formula by averaging on periodic points.

We show that if f: X --> Y is a finite, separable morphism of smooth curves defined over a finite field F_q, where q is larger than an explicit constant depending only on the degree of f and the genus of X, then f maps X(F_q) surjectively onto Y(F_q) if and only if f maps X(F_q) injectively into Y(F_q). Surprisingly, the bounds on q for these two implications have different orders of magnitude. The main tools used in our proof are the Chebotarev density theorem for covers of curves over finite fields, the Castelnuovo genus inequality, and ideas from Galois theory., 19 pages; various minor changes to previous version. To appear in International Mathematics Research Notices

Psycho~ogical experiments often require the presentanon of pictures or other complex graphics as stimuli, and also require control over the time and order of their presentation. If a Macintosh computer is used as a laborato~ d~vice, construction of virtually any graphic or pictO~lallmage, as well as text, can be accomplished easily With an.y of several programs that create paint files (e.g., MacPamt, HyperCard, FuIlPaint). If one can then write a computer program that will select a given paint file and present it on the computer screen, the basic ingredients for laboratory use and control of graphic stimuli become available. In this paper, we describe a Pascal function useful for presenting any paint image on the screen, and illustrate its possible use. GETMACPAINT (see Appendix, Lines 15-68) is a boolean function with two arguments: the name of a paint file and the memory location of a bitmap area to which the file contents are to be transferred. It uses the local function GoodFile (Lines 29-37) to test if the file to be opened is a paint file, and the local function FileError (Lines 23-28) to handle errors that may occur when various file-handling procedures are called. Ifany errors occur, GETMACPAINT is exited with a value of "false." GETMACPAINT's statement part uses a set of nested "if' statements that perform the following tasks unless a file-handling or a memory-allocation error occurs. I. Use GoodFile to verify that the file name (parameter fNAME) to be opened is a paint file (Line 40); 2. Open the paint file fName using FSOPEN (Line 41); 3. Find the end of the file (using GETEOF, Line 43) and establish a starting position (MacPaint's first allocation block, 512 bytes, does not contain any part of the picture); 4. Use SETFPOS to locate the point in the file at which reading begins and allocate a data structure to hold the data and a pointer to it (Lines 46-49); 5. Read the file row by row into the bitmap using UNP~CKBITS (Lines 50-60; MacPaint bytes are packed but bitmap bytes are not, so unpacking is necessary); 6. Set the value of the function to "true" and dispose of the file-reading pointer using DISPOSPTR (Lines 61-62); 7. Close the file using FSCLOSE (Line 66).

Summary A method of data analysis is described in which the determination of exact probabilities associated with randomized mean differences between two independent samples may be programmed on a small computer. Application of the enumerative and probabilistic features of this method to specific randomization test analyses performed by other investigators revealed the presence of errors in several previously published reports.

Summary Bilateral ablations of dorsolateral frontal granular cortex were performed in four monkeys prior to the 35th postnatal day and in three monkeys at 3 years of age. Subsequent testing procedures involved the learning of a color discrimination, a series of delayed response tests and a delayed alternation task. No differences were found between early- and late-frontals in learning the color problem. All animals were equally impaired in delayed alternation performance. Delayed response testing revealed a marked superiority for early-frontals, relative to the performances of later-frontals. Differential delayed response performances of the two frontal groups were not due to differences in either surface lesion or retrograde thalamic degeneration. It was concluded that either a compensatory neural reorganization or a progressive cerebral maturation might account for the sparing of delayed response capacity in the early frontal preparations.

Under suitable hypotheses, we prove a dynamical version of the Mordell–Lang conjecture for subvarieties of quasiprojective varieties X, endowed with the action of a morphism Φ:X→X. We also prove a version of the Mordell–Lang conjecture that holds for any endomorphism of a semiabelian variety. We use an analytic method based on the technique of Skolem, Mahler, and Lech, along with results of Herman and Yoccoz from nonarchimedean dynamics.

Combined bilateral lesions of frontal granular cortex and caudate nucleus were produced in 7 monkeys between the 2nd and 56th postnatal day. When comparisons were made with 4 monkeys which had previously sustained bilateral resections of frontal granular cortex alone at comparable ages, it was found that the frontal-caudates, in contrast to the frontals, displayed failure to thrive, somato-motor and growth deficiencies, postoperative seizures and later cognitive impairments. When tested at the 7th postoperative month, 2 of the 3 surviving frontal-caudates could not perform a delayed response task beyond a minimal (0 sec) delay interval. It was concluded that early reflexive and somato-motor function is principally mediated by subcortical systems but that some degree of representation also exists at cortical levels. In contrast to neocortex, the caudate nucleus appears to be involved in a neural system responsible for the retention of delayed response capacity following early brain injury.

Summary Twenty adult female rhesus monkeys (Macaca mulatta) were divided into 4 treatment groups of 5 subjects each; nonlesioned-nontrained (NLNT), nonlesioned-trained (NLT), lesioned-nontrained (LNT), and lesioned-trained (LT). All lesions were bilateral ablations of dorsolateral frontal cortex. The training consisted of color discrimination and delayed alternation. AChE activity was determined for 19 brain regions in each subject. Significant changes in AChE activity due to the lesion were found in orbital cortex, caudate nucleus and pons while training procedures produced significant changes only in the orbital cortex. The 3 brain areas in which significant AChE changes were found bear a close anatomical and functional relationship to the lesioned prefrontal cortex.