bluuebunny/crossref_metadata_2025 huggingface dataset:
The mother‐litter relationship in developmental rat studies: Cannibalism vs caring
Authors: DeSantis Darlene T. , Schmaltz Leonard W.
Published: January 2005

This incidence of cannibalism was studied in a series of developmental studies (on neonatal lesions, prenatal stress, prenatal surgery, unoperated controls) in which rats were manipulated during either the prenatal or early postnatal periods. Cannibalism during the preweaning period occurred in from 0 to 33% of the litters, dependig on the treatment group. It was found in most cases, however, that mothers who cannibalized were also good caretakers of their remaining pups. The same litters were also involved in preweaning tests of mother‐young interactions to determine if experimental treatments altered the maternal‐filial relationshi. It was found that as early as postnatal Day 4, nursing episodes were predominantly pup‐initiated in the lesioned litters but mother‐initiated in control litters.
Neonatal sex‐steroid hormones and muscular strength of boys and girls in the first three years
Authors: Jacklin Carol Nagy , Maccoby Eleanor E. , Doering Charles H. , King David R.
Published: January 2005

Five sex‐steroid hormones were assayed in umbilical cord blood. Strength was assessd in children in three samples at several ages from birth to 33 months. At defferent ages, differents strength measures were tatken, viz., at birth, prone head responses; at 3 months, leg strength; from 6 to 33 months, grip strength. Boys had higher average strength scores than girls but the sex differences were small and did not increase or decrease over the age period studied. Across‐age strength scores showed a significant relation to androstenedione and a significant interaction of sexc and progesterone. Both boys and girls with higher strength scores had lower androstenedione. Girls with high cord blood progesterone showed low strength with boys with high progesterone showed high strength. There were no sex differences in androstenedione or progesterone level. The androstenedione finding did not replicate across samples but the Progesterone × sex interaction was replicated in all three sample. No relationship was found between strength and other hormones assayed: Tstosterone, estradiol, and estrone.
Conditioning of aversion to an odor paired with peripheral shock in the developing rat
Authors: Kucharski David , Spear Norman E.
Published: January 2005

Four experiments examined an apparent inability to associate, or severe deficiency in associating, an odor and a footshock during the first 2 weeks of life in the rat, a cue‐to‐consequence relationship that had formerly seemed age‐dependent. With a particular classical conditioning procedure, however, significiant conditioning occurred on postnatal Days 6 and 10 with relatively few conditioning trials; the procedure employed an odor explicitly unpaired with footshock (CS−), as well as an odor paired with footshock (CS+) (Experiment I). Experiment II assessed the contribution of a CS− exposure in the conditioning of rats 8, 15, or 50 days of age. For 8‐day‐olds, exposure to both the CS+ and CS− resulted in conditioned aversion to the CS+ after eight but not one conditioning trials, but neither 1 nor eight trials with only a CS+ produced conditioning. For 15‐ and 50‐day‐olds, conditioning to the CS+ odor was significant after one trial with, but not without, a specific CS− with eight trials, however, conditioning was significant with or without the specific CS−. It was verified with the 50‐day‐olds in Experiment III that aversion to the CS+ was conditioned with a single trial only if a CS− had been presented, with a slight trend toward superior conditioning if the CS− preceded rather than followed the CS+ during conditioning. Experiment IV tested the hypothesis that exposure to the distinctive CS− odor sensitzes the animal to the specific properties of the CS+ odor. Fifteen and 50‐day‐old rats were given one conditioning trial with a CS+ odor that was either unaccompanied by a CS− or that was presented with a CS− odor in the same context as the CS+ or in a different context. For both 15− and 50‐day‐old rats, conditioning to the CS+ occurred only for animals given the CS− in the same context as the CS+, indicating that the hypothesis should be rejected. The results generally indicate rapid and substantial odor‐footshock conditioning in rats as young as 6 days of age, with CS‐exposure established as perhaps especially significant for conditioning early in life, but important for rats of all ages tested, from infancy to adulthood.
Influence of neonatal handling on blood pressure, locomotor activity, and preweanling heart rate in spontaneously hypertensive and Wistar Kyoto rats
Authors: Tucker Diane C. , Johnson Alan Kim
Published: January 2005

This experiment tested the hypothesis that increased stimulation early in development would (a) alter developmental changes in heart rate and behavioral reactivity and (b) affect the level at which blood pressure was regulated in adulthood. For this purpose, the effects of daily handling and maternal separation (3 min per day) on both behavioral and cardiovascular measures were examined in spontaneously hypertensive (SHR) and normotensive control Wistar Kyoto (WKY) rats. Prior to weaning, elevated heart rates in pups handled during the first postnatal week were most pronounced among 4‐week‐old prehypertensive SHR pups. Early handling affected behavior observed during openfield testing similarly in young adult rats of the SHR and WKY strains (e.g., increased locomotor activity on the first day of testing). In female rats of the WKY strain, early handling resulted in a lower baseline blood pressure; the blood pressure; the blood pressure of SHR rats was not affected by increased stimulation in infancy. Examination of longitudinal data yielded no support for a direct association between behavioral reactivity or preweaning heart rate and high blood pressure. These findings demonstrate the influence of both early environmental conditions and genetic factors on maturation within the cardiovascular system and suggest that genetic models of pathological conditions may provide a productive means of examining environmentally shaped aspects of individual differences in physiological regulation.
Home odor preferences in young hares (Lepus capensis syriacus): Effects of age and role of maternal presence
Authors: Stavy M. , Goldblatt A. , Terkel J.
Published: January 2005

The odor preferences of mother‐reared and hand‐reared young hares between 1–30 days of age were studied. Subjects were exposed daily to three choice tests in which the following pairs of odors were presented: home cage odor (HCO)‐neutral odor (NO); HCO‐strange cage odor (SCO); SCO‐NO. All young strongly preferred their HCO over SCO throughout the 30‐day period. HCO was preferred over NO until the age of 20 days, while avoidance of SCO was shown during the first 10 or 20 days. The same experiment conducted on postweaned hares (31–50 days of age) revealed a strong preference for SCO over both HCO and NO.

These findings may be interpreted with respect to the natural history of the hare and its unusual mother‐young relationship, which, in the wild, is limited to a single daily meeting for nursing. It is suggested that the highly precocial hare recognizes and prefers its home odor independently of any maternal contribution to that odor, possibly relying on odor cues from its own body to return to its nursing site. Other possible advantages of these olfactory preferences, including predation avoidance and facilitation of social relationships, are discussed.
The organization and stability of sleep states in fullterm, preterm, and small‐for‐gestational‐age infants: A comparative study
Authors: Watt Jan E. , Strongman K. T.
Published: January 2005

Sleep state organization in the neonatal period was compared for groups of fullterm, preterm, and small‐for‐gestational‐age infants. Preterm and small‐for‐gestational‐age groups were found to have greater rates of state change than the fullterm group, and maternal perception of the infants was found to be negatively correlated to rates of state change in the preterm infants. Small‐for‐gestational‐age infants had more active sleep without rapid eye movements than fullterm or preterm infants. The findings are discussed with regard to implications for CNS organization and possible early identification of infants at risk of developmental problems.
Perinatal dietary supplementation with a commercial soy lecithin preparation: Effects on behavior and brain biochemistry in the developing rat
Authors: Bell J. M. , Slotkin T. A.
Published: January 2005

Rats exposed perinatally to dietary commercial soy lecithin preparation (SLP) showed alterations in sensorimotor development and brain cell maturation. Latencies for righting responses (measured on postnatal Days 1–4) and negative queotaxis (measured on postnatal Days 5–8) were shorter in the SLP treated animals. This pattern was accompanied by specific alterations in cerebellar development; biochemical markers for cellular maturation indicated a compression of the ontogenetic time course, as assessed by ornithine decarboxylase (ODC) activity, and levels of nucleic acids and proteins. In contrast, cellular development in the cerebral cortex indicated a generalized slowing of the time course of maturation and a deficit in the number of cells which persisted into adulthood. Behavioral abnormalities also did not disappear in adulthood, as morphine analgesia was markedly reduced in the SLP group. These results indicate that exposure of the fetus and neonate to dietary SLP during development leads to regionally specific alterations in brain cell maturation associated with disruption or behavioral patterns.
Maternal behavior in rats and the effects of neonatal progestins given to the pups
Authors: Birke Lynda I. A. , Sadler Dawn
Published: January 2005

This paper reports changes in maternal behavior of rats following progestin treatment of the neonates. There have been recent reports that hormonial treatment of pups can alter maternal behavior, particularly licking of pups, and that such effects might have implication for the later development of those pups. Accordingly, the major objective of the experiments described was to test the hypothesis that the effects of neonatal progestins on later behavioral development that we have previously described (Birke & Sadler, 1983; 1984) might in part be mediated by changes in maternal behavior. This was done by investigating the behavior of dams, including pup‐directed behavior, following the hormone treatments that we have used previously. In the first experiment, medroxyprogesterone acetate (MPA), given via maternal milk, was found to increase rates of pup licking by dams. In the second experiment, anogenital licking was increased to litters containing pups that had received either MPA or progesterone by direct injection. No significant changes in licking following pup treatment with the antiserum to progesterone were observed, however. The results are discussed in relation to our previous work on progestin effects on later behavior, and in relation to the suggestion that hormonal effects on sexually dimorphic behaviors might, at least partly, be mediated through interactions with the mother during the neonatal period.
Maturation of olfactory exploration in golden hamsters
Authors: Schoenfeld Thomas A. , Corwin James V.
Published: January 2005

Following placement into a test cage filled with pine shavings, a litter of 7–8 golden hamster pups (aged 3–18 days postnatal: P3‐18) initially displays a period of locomotion which ends reliably in huddling. The latency to establish a huddle (i.e., the duration of locomotion) is significantly longer in the presence of novel odors (fresh or lemon shavings) than more familiar odors (slightly soiled fresh or lemon shavings) but only in pups aged P12 or older. Pups aged P9 or younger do not locomote differentially in the presence of novel or familiar odors. This age difference represents the emergence of olfactory exploration in hamsters between P9 and P12. Exploration of novel odors interferes with initial attempts to establish a single huddle site by a litter, but does not preclude the ultimate aggregation of all pups at a single site as guided by conspecific odors and possibly thermotactile cues as well. Such shifts in the control of behavior by non‐nest and nest‐related, conspecific stimuli correspond well with the first occurrence of nest exits at P11‐12 (e.g., Dieterlen, 1959) coupled with the persistent return of hamster pups to the maternal nest for as long as it is maintained (Rowell, 1961).
An experimental study on developmental changes of maternal discrimination of infants in crab‐eating monkeys (Macaca fascicularis)
Authors: Negayama Koichi , Honjo Shigeo
Published: January 2005

Individually reared mother‐infant dyads of crab‐eating monkeys (Macaca fascicularis) were observed cross‐sectionally in their mother‐infant relationship. In infants aged from 0 to 5.0 months, rather drastic changes were found both at 0.5–1.0 and 2.0–3.0 months of age. For an explanation of these changes, developmental processes of discrimination between mother and infant were analyzed cross‐sectionally by exchanging mother‐infant combinations. The results indicated that the first 0.5 months postpartum was characterized as a behaviorally nondiscriminating stage where nipple discrimination by infants was the only exception. The latter half of the first month was the beginning of a nonaggressive discrimination stage by mothers, indicated by lipsmacking and sniffing and in infants by clinging. When infants reached the age of 2.0–3.0 months, the mothers' nonaggressive discimination with lipsmacking decreased, and her aggressive discrimination of alien infants increased. In addition to maternal visual discrimination of infants' physical appearances, differences in infants' odor and/or their method of nipple contact were suggested to affect the mothers' differential behaviors.
Postnatal locomotion development in a neurological mutant of rolling mouse nagoya
Authors: Tamaki Yoshitaka , Oda Sen‐Ichi , Kameyama Yoshiro , Kameyama Yoshiro
Published: January 2005

Postural control skills and quadrupedal locomotor pattern in infant rolling mice, a neurological mutant, were observed in the following situations: hindlimb support when suspended, rope descent, narrow path traverse, quadrupedal locomotion on an inclined corridor, and swimming behavior when entirely submerged. Until the second week of age, rolling mice developed primitive responses similar to, or somewhat slower than, their unaffected littermates, but failed to show mature adaptive and coordinated movements from Days 16–18 onward in hinblimb support and rope descent tests. The gait was broadbased and they frequently lurched, rolled over on the side in the narrow‐path and incline situations. Also, swimming behavior was extremely clumsy with varying degrees of disturbed rhythm and inconsistent movement of hindlimb paddling. These findings might result from an immature development of hindlimb muscle tonus control system and distortion of smooth and orderly sequence of hindlimb muscular contractions which characterize skillful quadrupedal locomotion.
Development of auditory localization in dogs: Single source and precedence effect sounds
Authors: Ashmead Daniel H. , Clifton Rachel K. , Reese Ellen P.
Published: January 2005

The development of auditory localization in dogs was investigated in a litter of 12 pups. Behavioral auditory localization consisted of orienting responses to dog vocalizations presented from loudspeakers 90 degrees to each side. Sounds were presented in two configurations, single source (only one loudspeaker) and precedence effect (both loudspeakers, with one slightly leading the other). Localization began around 16 days after birth, for single‐source sounds. This is consistent with previous observations and with findings on dogs' auditory neural development. Single‐source sounds were localized earlier during development than precedence‐effect sounds. This ordering resembles findings on human infants and can be related to neuroanatomical investigations of mammalian brain structures mediating single source versus precedence effect localization.
Postural and lateral asymmetries in the ontogeny of handedness during infancy
Authors: Michel George F. , Harkins Debra A.
Published: January 2005

Ten newborn infants who preferred to lie with their heads turned rightward and ten who preferred to lie with their heads turned leftward had their hand‐use preferences for reaching assessed at 8 different ages during the period 12–74 weeks postpartum. Eighteen infants maintained stable hand‐use preferences throughout this period and the direction of their neonatal head orientation preference predicted the hand they preferred to use. The neonatal head‐turn preference was maintained through the first 2 months and induced lateral asymmetries in visual regard and motor control of the hands. These lateral asymmetries are plausible contributors to mechanisms linking neonatal headturn preference to infant hand‐use preference. Thus, the dextral bias in handedness may be derived, in part, from the rightward bias in neonatal head‐turn preference.
Play profiles of captive adult orangutans: A developmental perspective
Authors: Zucker Evan L. , Dennon M. Beth , Puleo Stephanie G. , Maple Terry L.
Published: January 2005

The social play of 6 adult orangutan heterosexual dyads was observed, and the frequencies of the component behaviors extracted. Frequencies were converted to proportions of total play outputs for each individual and for each age/sex class, and then compared to the proportions observed for the social play of juvenile and adolescent orangutans. Adult play was more stationary, and contact maintaining, in style than was the play of younger orangutans. For the females, rolling and grabbing comprised similar proportions of the play repertoires, whereas for males, slapping and biting were developmentally consistent. For adult males, little chasing was observed, although this behavior was prominant in the play of immature males. These developmental changes in orangutan social play are addressed with respect to the natural history and ecology of orangutans, the refinement of communication skills, and the influences of captivity on social play.
Long‐term effects of prenatal stress on HPA axis activity in juvenile rhesus monkeys
Authors: Clarke A. S. , Wittwer D. J. , Abbott D. H. , Schneider M. L.
Published: January 2005

The effect of stress to the pregnant mother on hormonal responses of the offspring to stressful events was investigated in juvenile rhesus monkeys. Six pregnant monkeys were repeatedly removed from their home cages and exposed to unpredictable noise during mid‐ to late gestation (Days 90–145 postconception), while six undisturbed pregnant mothers served as controls. Blood samples were collected from the juvenile offspring under anesthesia on four occasions and assayed for ACTH and cortisol. In a second experiment, blood samples were collected from the awake offspring under a baseline and four progressively stressful conditions. Offspring of stressed mothers showed higher ACTH and cortisol levels than control offspring at all four anesthesia samples and at a nonanesthesized home cage baseline. Prenatally stressed offspring also showed higher ACTH values in all four stress conditions. Cortisol values were similar for the two groups under the stress conditions. The disparity between the two groups in the relationship between ACTH and cortisol was greatest in the most stressful condition, suggesting regulatory differences between the two groups. These results indicate that offspring of primate mothers stressed during pregnancy show enhanced HPA axis responsivity to stressors later in life, and concur with rodent findings indicating that prenatal stress may have long‐term effects on HPA axis regulation. © 1994 John Wiley & Sons, Inc.
Tonic immobility and high‐intensity calls in a precocial chick as a function of age, diet, and time of day
Authors: Hill Wendy L. , Fleming Tara M. , Shrier Eric M.
Published: January 2005

Tonic immobility (TI) and high‐intensity vocalizations are two antipredator behaviors employed by domestic chicks (Gallus gallus) which vary in their function and the proximate mechanisms that govern them. In the present study, we sought to determine the influence of age (3 or 10 days old), diet (control or tryptophan‐free), and time of testing (A.M. or P.M.) on the duration of TI and the number of calls produced in domestic chicks. Older chicks remained immobile significantly longer than younger chicks as did subjects on the control diet or those tested at night. However, 3‐day‐old chicks had significantly shorter TI durations only when tested in the A.M.: TI did not differ between age groups when subjects were tested in the P.M. Three‐day‐olds called significantly more than 10‐day‐olds when given the control diet and when tested in the P.M. but vocalization frequencies did not differ between age groups during the A.M. testing or when given the tryptophan‐free diet (T‐). Vocalization rate (calls/TI duration), however, was significantly greater during the A.M. testing. These results emphasize the importance of considering circadian rhythms and behavioral development. Furthermore, an integrative view of the proximate mechanisms and adaptive functions of TI and high‐intensity vocalizations is presented.©1994 John Wiley & Sons, Inc.
Effects of physiological state on oral habituation in developing rats: Cellular and extracellular dehydration
Authors: Swithers Susan E.
Published: January 2005

Hydrational state has been demonstrated to influence intake of various solutions in young rat pups. For instance, both cellular and extracellular dehydration produce an enhancement of intake in pups tested at 6 days of age. However, the behavioral mechanisms that result in increased intake following manipulations of hydrational state have been less extensively studied. The impact of hydrational state on behavioral responsiveness in young rat pups was examined by assessing the pattern of responding to a series of repeated oral infusions of diet. Pups were tested at 6, 12, or 18 days of age following either acute cellular dehydration produced by injection of 1 M NaCl or acute extracellular dehydration produced by injection of 10% polyethylene glycol (PEG). Oral responsiveness to a series of 30 brief infusions of one of four taste solutions (water, 10% sucrose, 0.135 M NaCl, or 1 M NaCl) was measured. Each infusion lasted 3 s and there was 1 min between infusions. The pattern of oral responding to solutions was affected by the developmental age of the pup, the hydrational state of the pup, and the solution offered, with the largest effects of dehydration observed in the youngest animals. In all conditions except one, pups habituated to repeated infusions. The exception was the failure of extracellularly dehydrated 6‐day‐old pups to display habituation to oral infusions of sucrose. These results suggest that, although intake is enhanced by both cellular and extracellular dehydration in very young pups, the behavioral changes responsible for the enhancement of intake after cellular dehydration are different from the behavioral changes resulting from extracellular dehydration. This dissociation of behavioral effects of dehydration in young pups demonstrates that intake measures alone may obscure subtle differences in behavior and argues for the utility of dissection of behavioral components in understanding the neural and physiological control of behavior. © 1995 John Wiley & Sons, Inc.
Total cortisol, free cortisol, and growth hormone associated with brief social separation experiences in young macaques
Authors: Laudenslager Mark L. , Boccia Maria L. , Berger Christy L. , Gennaro‐Ruggles Mary M. , McFerran Britta , Reite Martin L.
Published: January 2005

Many behavioral, immunological, and physiological consequences of brief maternal separation in bonnet (Macaca radiata) and pigtail monkeys (Macaca nemistrina) have been documented. However, the impact of social separation on plasma cortisol and growth hormone is unknown for these particular species. In the present study, the behavioral and endocrinological consequences of a 2‐week maternal separation in socially housed infant bonnet and pigtail monkeys were followed. In seven pairs (separated and matched control) of bonnet and six pairs of pigtail infants, plasma was obtained under baseline, separated, and reunion conditions twice weekly for the duration of the study. Blood samples were obtained from both infants of the pair in approximately 10 min. Plasma total cortisol, free cortisol, and growth hormone were measured in these samples. Focal animal behavioral observations were made on all subjects twice daily throughout the study period. In both species, total cortisol and free cortisol rose immediately following maternal separation in comparison to the matched nonseparated controls and returned to basal levels (e.g., that of matched non‐separted controls) following reunion with the mother. In contrast, plasma growth hormone rose only in the pigtail infants over a time course that peaked around the time of reunion. Multiple regression techniques indicated for the first week of separation, in the separated but not control subjects, that mean plasma free and total cortisol was positively related to distress behaviors (vocalization and postural slouch) observed during this week and negatively related to social behaviors (play and proximity to others) noted during the same period. In contrast, plasma growth hormone was related to both species and sex of the subjects but unrelated to behavioral variables. © 1995 John Wiley & Sons, Inc.
Testosterone‐induced shortening of the storage phase of song development in birds interferes with vocal learning
Authors: Whaling C. S. , Nelson D. A. , Marler P.
Published: January 2005

Bird song is a complex, learned behavior. Vocal learning in sparrows involves several different processes that occur in a distinct temporal pattern over the course of the first year of life. Songs are acquired without practice during a sensitive period within the first 3 months of life and rehearsal of the acquired song does not begin until 7 or 8 months of age. The function of the storage period between song acquisition and production is not known. We set out to investigate its significance by administering testosterone, known to stimulate production of adult song, to birds at 100 days of age after song acquisition was completed but some 5 months prior to normal song onset. Most testosterone‐treated birds produced abnormal songs resembling those of males raised in acoustic isolation suggesting that, in sparrows, events occurring during the storage phase play a significant role in vocal learning. © 1995 John Wiley & Sons, Inc.
Molecular mechanics of organic halides. III. Fluorinated olefins
Authors: Meyer A. Y.
Published: January 2005

A molecular mechanical force field for fluorinated ethylenes and propylenes is described. The field computes geometries, dipole moments, and energy differences between isomers and rotamers. Component analysis indicates that “classical” strains alone (skeletal, nonbonded, electrostatic) cannot account for energy relationships. The discussion is supplemented by a semiempirical quantum chemical comparison of cis‐ and trans‐FCHCHF and of gauche‐ and anti‐FCH2CH2F.
An ab initio study of the geometry, harmonic and anharmonic force fields, and fundamental vibrational frequencies of cis‐ and trans‐ thiolformic acid
Authors: Bock Charles W. , Trachtman Mendel , George Philip
Published: January 2005

The geometry, harmonic and anharmonic force fields, and fundamental vibrational frequencies of cis‐ and trans‐thiolformic acid are studied ab initio in the 4‐31G basis set. An extensive comparison is made between changes in diagonal and off‐diagonal quadratic and cubic force constants and diagonal stretching quartic constants in going from the chain to the ring structure in thiolformic acid and formic acid. The changes in the force constants are indicative of a much weaker interaction in the trans conformer between SH and OC, compared with O–H and OC, in keeping with the weaker hydrogenbonding property of the SH group in general.
The torsional potential function for n‐butane
Authors: Allinger N. L. , Profeta S.
Published: January 2005

The energies of four different conformations for n‐butane were calculated by the ab initio method using an STO‐3G basis set. Fully relaxed molecular geometries obtained from molecular mechanics (MM2) were used. The two energy minima [anti (C2h), gauche (C2)] and the two maxima (C2, C2v) had the following relative energies: 0.0, 0.88, 3.56, 5.99 kcal/mole. These are approximate Hartree–Fock numbers. It is estimated that inclusion of electron correlation in the calculation would lower the last number to about 5.1 kcal/mole while leaving the first three values essentially unchanged.
The barrier to internal rotation in Ge2H6
Authors: Hinchliffe Alan
Published: January 2005

High‐quality SCF‐MO calculations yield a barrier to internal rotation of 1.70 kJ mole−1 for Ge2H6. A new contraction scheme is reported for Dunning's larger Ge basis set. Geometry optimization, although carried out, is unimportant in this particular calculation. Wavefunctions and properties are reported for GeH4 and the staggered and eclipsed conformers of Ge2H6. The magnitude of the calculated barrier is more physically reasonable than those deduced from experimental data. Comparisons are made across the two series X2H6 and CH3XH3.
The computational application of the Cahn–Ingold–Prelog rules 1 and 2
Authors: Meyer Edgar F.
Published: January 2005

Cahn–Ingold–Prelog (CIP) rules 1 and 2 (material differences) have been expressed in the formal logic of a high‐level computer language (FORTRAN IV) on a laboratory minicomputer (PDP 11/40) by the program CHIRAL. An oversight in the CIP formalism in the treatment of rings was treated on an ad hoc basis; the problem has been expressed simply in terms of elementary graph theory in a way consistent with and similar to chemical notation. An example of the operation of CHIRAL is provided and the internal procedures discussed.
A method for constrained energy minimization of macromolecules
Authors: Van Gunsteren W. F. , Karplus M.
Published: January 2005

Two algorithms for the local energy minimization of the structure of macromolecules in the presence of constraints are proposed. They are a combination of the method of steepest descents and the method of conjugate gradients with the procedure SHAKE, by which distance constraints can be satisfied. The two algorithms are tested by applying them to a small protein, the bovine pancreatic trypsin inhibitor (BPTI), and compared with the penalty function method for conserving constraints. The efficiency of the proposed methods depends on the level of interdependence of the constraints. For bond‐length constraints, the use of SHAKE is superior to the penalty function method. However, when bond‐angle constraints are included, SHAKE is more efficient only if the curvature of the penalty function is considerably greater than that of the potential function being minimized. The results indicate that with bond‐length constraints the minimization behavior is similar to that without constraints. However, the simultaneous application of bond‐length and bond‐angle constraints appears to confine the molecule to a very limited part of configuration space, very different from the part covered by an unconstrained minimization. This conclusion calls into question energy minimizations of protein systems in which only the dihedral angles are allowed to vary.
Systematic synthesis design. 8. Generation of reaction sequences
Authors: Hendrickson James B. , Braun‐Keller Elaine
Published: January 2005

The numerical description of functionality allows a rigorous generation of all reactions from one structure (or partial structure) to another. The minimum number of steps required can be calculated and this “reaction distance” used to guide computer generation of sequences to converge on the target structure. A computer algorithm is described for efficient generation of all shortest synthetic routes between two given molecules as starting material and product. The program is seen as a prototype of a complete synthesis design program.
Properties of strong hydrogen‐bonded systems. II. Ab initioSCF‐MO study of the hydrogen bond between nitric acid and ammonia
Authors: Latajka Z. , Szczçśniak M. M. , Ratajczak H. , Orville‐Thomas W. J.
Published: January 2005

The hydrogen‐bonded complex between nitric acid and ammonia molecules has been studied by the ab initio molecular orbital method using the 4‐31G basis set. The calculated interaction energy for the complex (ΔE = −91.4 kJ mole−1) indicates that one is dealing with the strongest “nonionic” H‐bonded complex considered hitherto by theoretical methods. Other properties of the hydrogen‐bonded complex such as geometrical parameters, dipole moment, amount of charge transfer, and stretching force constants of the OH and (OH)… N bonds are calculated and discussed.
Conformational stability and flexibility of the ala dipeptide in free space and water: Monte Carlo computer simulation studies
Authors: Ravishanker G. , Mezei M. , Beveridge D. L.
Published: January 2005

Monte Carlo determinations of the intramolecular thermodynamics of the Ala dipeptide in the C7, C5, αR, and PII conformations are reported. The calculations are carried out in the quasiharmonic approximation, with intramolecular entropies determined from the covariance matrix of the atomic displacements. The free energy of transition from C7 to C5, αR, and PII are found to be endergonic and dominated by the intrinsic energy of disrupting the intramolecular hydrogen bond in the C7 conformation. These results are combined with previous estimates of the free energy of hydration of the Ala dipeptide in water computed from liquid state Monte Carlo simulations using the probability ratio method. The net free energy of C7, αR, and PII are found to be similar, and it is thus reasonable to expect that all three forms are thermally populated at ambient temperature. The intermolecular carbonyl‐water hydrogen bond in C5, αR, and PII competes successfully with the intramolecular NH…︁OC interaction in C7.
Energy‐optimized GTO basis sets for LCAO Calculations. A Gradient Approach
Authors: Faegri Knut , Almlof Jan
Published: January 2005

The use of gradient techniques for the development of energy‐optimized basis sets has been investigated. The region where the energy surface is approximately quadratic with a positive definite Hessian is found to be very small for large basis sets. However, scaled Newton‐Raphson methods prove quite effective even when the starting point is outside this region. The analytic calculation of the Hessian is found to be most efficient in terms of computing time.
MINDO/3 Study of the Rearrangement of 1‐Methylcyclohexyl Cation to 1,2‐Dimethylcyclopentyl Cation
Authors: Viruela‐Martín P. M. , Nebot‐Gil I. , Tomás F. , Viruela‐Martín R.
Published: January 2005

The rearrangement of the 1‐methylcyclohexyl cation to the 1,2‐dimethylcyclopentyl cation has been studied by MINDO/3 calculations, as an application of the branching mechanism model for cycloalkanes. Possible intermediates and transition states have been characterized by diagonalization of their Hessian matrixes. Two nonequivalent pathways, α and β scissions, are relatively close in energy. The calculated transition states are almost equivalent in energy to those found for cyclohexyl cation. Hence, the energy barriers are higher for the rearrangement of the 1‐methyl than for cyclohexyl cation, because the former is less stable than the latter.
Substituent Effects on the Low‐Lying Singlet and Triplet States of Methylene
Authors: Farrǵs Jaume , Olivella Santiago , Solé Albert , Vilarrasa Jaume
Published: January 2005

The relative energies of the three lower‐lying singlet states (here called Sa, Sb, and Sc for the sake of generality) and the lowest triplet state of CHX and CX2 carbenes (in which X = Li, BeH, BH2, NH2, OH, or F) are evaluated by means of the semiempirical MNDO method as well as, for some species, by means of ab initio calculations at the 6‐31G, MP3/6‐31G, and MP3/6‐31G* levels. Calculations for CH(CN) and C(CN)2 are also reported. In spite of the known MNDO overestimation of the stability of the σ1π1 configurations of methylene, this method turns out to be satisfactory for most carbenes reported here. Emphasis is put on the appearance of the plots of the ΔH values vs. the carbene bond angles for the different states and on the seldom considered Sb states (1B1 for C2v carbenes). A carbene classification is proposed on the basis of the form of these plots. For carbenes with π‐acceptor substituents such as those of “type IA”, open‐shell, diradical configurations are predicted for the lowest singlet states, so that no significant structural differences should be expected between their lowest singlet and triplet states. On the other hand, for carbenes with strong π‐donor substituents, either “type ID” or “IID”, the closed‐shell singlets appear to be the ground states, and the singlet and triplet behaviors should be much more clearly distinguishable.
Transfer‐Matrix Method for Subgraph Enumeration: Applications to Polypyrene Fusenes
Authors: Klein D. J. , Hite G. E. , Schmalz T. G.
Published: January 2005

A frequently encountered problem in chemical applications is that of a weighted enumeration (or summation over) a class of extended subgraphs of a given system graph, which might represent a chemical structure. Some aspects of a powerful transfer‐matrix method are described for treating such graphtheoretic weighted enumeration problems. This method is seen to be particularly amenable for system graphs which are long in one direction and narrow in transverse directions. When the system graph is uniform (i.e., translationally symmetric) along one extended direction, asymptotic results can be readily extracted.

A second point of emphasis here is that the weighted enumeration problems of the type studied here naturally arise in computing matrix elements over cluster expanded wave functions, though most applications so far framed in the literature differ from this. Size consistency and size‐extensivity aspects of this application are noted in terms of the transfer‐matrix approach.

Polypyrene fusene strips of varying lengths are considered as applications of the transfer‐matrix methods for two weighted enumeration problems. Different graph‐theoretic problems are noted to arise for low‐order cluster expanded wave functions, such as in fact occur in both the Herndon‐Simpson and the Pauling‐Wheland resonance theories. For higher‐order wave function ansätze the graph‐theoretic problems would simply have more complicated weights and transfer matrices, which for the present examples are very small (i.e., 2 by 2 and 3 by 3).
Conformational Dynamics of 9,9‐Dimethyl‐1,5‐Dihetero‐Spiro [5.5] Undecanes by Molecular Mechanics Calculations: A Three‐Dimensional Topological Approach
Authors: Iratçabal P. , Liotard D.
Published: January 2005

The dynamic behavior of 9,9‐dimethyl‐1,5‐dihetero‐spiro [5.5] undecanes is investigated by molecular mechanics calculations. A topological approach is taken which leads to a model consistent with the available NMR data. A three‐dimensional representation of the conformational potential energy surface is given.
Empirical energy functions for energy minimization and dynamics of nucleic acids
Authors: Nilsson Lennart , Karplus Martin
Published: January 2005

An improved empirical energy function for energy minimization and dynamics calculations of nucleic acids is developed and evaluated by an examination of its representation of both static and dynamic properties of model systems. Among the properties studied and used for parameter optimization are base pairing interactions, sugar and phosphate energy surfaces, small crystal heats of sublimation, base, phosphate and sugar analogue vibration spectra, and the overall behavior of a DNA hexamer duplex in vacuum molecular dynamics simulations. The results obtained are compared with those from two other energy functions that have been used recently for nucleic acids. Parameters for two energy functions are given; one includes heavy atoms and only polar hydrogens and the other includes all atoms.
The Computer System G R A P H: A Useful Tool in Chemical Graph Theory
Authors: Cvetković Dragos̆ , Gutman Ivan
Published: January 2005

The interactive programming system GRAPH, implemented at the Faculty of Electrical Engineering in Belgrade, is described. This system has been designed to treat a great variety of problems of graph theory. In the present article we point out the applicability of the system GRAPH in chemical investigations and illustrate it by two examples.
Computer Simulation of Metabolic Transformation
Authors: Tinker John F. , Gelernter Herbert
Published: January 2005

SYNCHEM2 is a large knowledge‐based domain‐specific heuristic problem solving system that applies the methodology of artificial intelligence to the problem domain of synthetic organic chemistry. The program may be used for both synthetic and retrosynthetic exploration of the reaction transform space. We describe some experiments that might lead to the development of a special purpose version of the program for the investigation and prediction of environmental and metabolic processes undergone by chemicals that are released into the biosphere or directly ingested. The test system was used to predict the metabolites of three molecules of considerable biochemical interest, benzo[a]pyrene (known to be metabolically transformed into an active carcinogen), paramethyl substituted phenylalanine (which undergoes the NIH‐shift when metabolized), and haloperidol (an important and widely used neuroleptic). In the case of the benzo[a]pyrene, the program predicted all of the known metabolites, as well as several others. All of the 11 compounds predicted as metabolites of 4‐methylphenylalanine, which included the major known metabolite that exhibits the NIH‐shift, were reasonable. Contained among the predicted metabolic pathways for haloperidol was a credible explanation for the occurrence of a known haloperidol metabolite derived from a substituted phenylacetic acid, but for which no intermediates have been isolated. The program was able to bridge the problem space between haloperidol and the derived hippuric acid by using an unsuspected, but metabolically sound pinacol rearrangement.
On the importance of size‐consistency corrections in semiempirical MNDOC calculations
Authors: Cremer Dieter , Thiel Walter
Published: January 2005

Energies obtained by configuration interaction calculations including all double excitations with regard to the Hartree‐Fock reference determinant can empirically be corrected to size consistency using either the Langhoff‐Davidson (LD) formula or a formula suggested by Pople, Seeger, and Krishnan (PSK). Semiempirical MNDOC calculations suggest that for molecular systems with a large number of electrons and important correlation effects the PSK correction is superior to the LD correction.
Converged calculations of rotational energy transfer in HFHF collisions
Authors: Schwenke David W. , Truhlar Donald G.
Published: January 2005

We have performed large‐scale close coupling calculations of rotational‐to‐rotational energy transfer in HFHF collisions for the realistic potential energy surface of Brobjer and Murrell. We employ up to 525 angular terms in the expansion of the potential and up to 440 coupled channels in the rotational‐orbital basis set. The results for zero total angular momentum are well converged for relative translational energies up to over 0.6 eV, and they show extensive rotational excitation.
Time step error in diffusion Monte Carlo simulations: An empirical study
Authors: Rothstein Stuart M. , Patil Narayan , Vrbik Jan
Published: January 2005

Diffusion Monte Carlo (DMC) is a random walk computational method for solving the ground‐state Schrödinger equation for atoms or molecules. One obtains a biased simulated energy which is used to estimate the exact energy, where the bias increases with the time step used in the simulation. We present six new DMC algorithms, all of which have the same theoretical justification. Yet, when applied to the LiH and H2 molecules, the algorithms give results with markedly different error. Furthermore, algorithms which exhibit a small error when applied to one molecule show significantly greater error for the other. The explanation for these results relates to sampling of configuration space in the neighborhood of the nuclei. We investigate this issue hoping that our results will aid in the design of more efficient DMC algorithms.
Theoretical study of the addition of hydrogen halides to olefins: A comparison between (HCl)2 and (HF)2 additions to ethylene
Authors: Clavero Carmen , Duran Miquel , Lledós Agustí , Ventura Oscar N. , Bertrán Juan
Published: January 2005

The addition of HCl and (HCl)2 to ethylene is theoretically studied by means of ab initio SCF techniques using the 3‐21G basis set. A statistical thermodynamics analysis is also carried out. When a comparison is made with the HF and (HF)2 additions to ethylene, the general fact of the catalytic action of the second HX molecule in the (HX)2 complex is revealed. The behavior of HF, however, is very different from that of HCl, since in the former case the driving force in the termolecular transition state is the bonding between fluorine and carbon, while in the latter case the driving force is the bonding between carbon and hydrogen, as generally accepted for electrophilic reactions. The use of density plots of the transition states on the plane of the cycle allows us to conclude that, while both HF and HCl termolecular transition states are hexacyclic, the bimolecular transition state of the HCl addition is bicentric and not tetracentric as previously reported.
Innate degree of freedom of a graph
Authors: Klein D. J. , Randić M.
Published: January 2005

For a Kekulé structure we consider the smallest number of placements of double bonds such that the full Kekulé structure on the given parent graph is fully determined. These numbers for each Kekulé structure of the parent graph sum to a novel structural invariant F, called the degree of freedom of the graph. Some qualitative characteristics are identified, and it is noted that apparently it behaves differently from a couple of other invariants related to Kekulé structures.
Ab initio study of the He(1S)‐Li2(X̃, 1∑) interaction by the SCF and MP2 methods
Authors: Matías M. A. , Varandas A. J. C.
Published: January 2005

Ab initio electronic structure calculations have been carried out for the He(1S)‐Li2 (X̃, 1∑) interaction both by the single‐configuration SCF and correlated second‐order MP2 methods using an extended basis set. From these calculations, an estimate of the isotropic (V0) and first two anisotropic (V2 and V4) terms of the He‐Li2 potential surface has been obtained. An assessment of the leading induced‐dipole‐induced‐dipole dispersion energy is presented from the MP2 energies. Where possible, a comparison is made with previous unpublished ab initio calculations by Staemmler and Stahl using the CEPA method.
Improvement of the hydrogen bonding correction to MNDO for calculations of biochemical interest
Authors: Goldblum Amiram
Published: January 2005

Recent suggestions for correcting HAcceptor interactions within MNDO, together with results of crystallographic analysis, were used to modify this SCF semiempirical calculation for multiple hydrogen bonded associations. Thermodynamic profiles for model systems of biochemical interest such as H2OH2O, hydration of neutral and charged molecules, dimerizations and proton transfers show the advantages of this method. Its treatment of charges, bonding, geometries, energetics and vibrational frequencies is shown to be comparable to ab initio calculations with various basis sets. However, basic MNDO deficiencies and criteria applied for H‐bonding result in some too high barriers for proton transfers.