Volume changes correlate with entropies and enthalpies in the formation of nucleic acid homoduplexes: Differential hydration of A and B conformations

We have used a combination of densimetric, calorimetric, and uv absorption techniques to obtain a complete thermodynamic characterization for the formation of nucleic acid homoduplexes of known sequence and conformation. The volume change ΔV accompanying the formation of four duplexes was interpreted to reflect changes in hydration based on the electrostriction phenomenon. In 10 mM sodium phosphate buffer at pH 7, the magnitude of the measured ΔV's ranged from ?2.0 to +7.2 ml/mol base pair and followed the order of poly(rA) · poly(dT) ～ poly(dA) · poly(dT) < poly(rA) · poly(dU) ～ poly(rA) · poly(rU). Inclusion of 100 mM NaCl in the same buffer gave the range of ?17.4 to ?2.3 mL/mol base pair and the following order: poly(dA) · poly(dT) < poly(rA) · poly(dT) < poly(rA) · poly(rU) ～ poly(rA) ～ polyr(dU). Standard thermodynamic profiles of forming these duplexes from their corresponding complementary single strands indicated similar free energies that resulted from the compensation of favorable enthalpies with unfavorable entropies along with a similar counterion uptake at both ionic strengths. The differences in these compensating effects of entropy and enthalpy correlated very well with the volume change measurements in a manner suggesting that the homoduplexes in the B conformation are more hydrated than are those in the A conformation. Moreover, the increased thermal stability of these homoduplexes resulted from an increase in the salt concentration corresponding to larger hydration levels as reflected by the ΔV results. © 1993 John Wiley & Sons, Inc.     

On using network RAM as a non‐volatile buffer

File systems and databases usually make several synchronous disk write accesses in order to make sure that the disk always has a consistent view of their data, so that it can be recovered in the case of a system crash. Since synchronous disk operations are slow, some systems choose to employ asynchronous disk write operations that improve performance at the cost of low reliability: in case of a system crash all data that have not yet been written to disk are lost. In this paper we describe a softwarebased NonVolatile RAM system that achieves the high performance of asynchronous write operations without sacrificing the reliability of synchronous write operations. Our system takes a set of volatile main memories residing in independent workstations and transforms it into a nonvolatile memory buffer – much like RAIDS do with magnetic disks. It then uses this nonvolatile buffer as an intermediate storage space in order to acknowledge synchronous write operations before actually writing the data to magnetic disk, but after writing the data to (intermediate) stable storage. We demonstrate the performance advantages of our system using both simulation and experimental evaluation.     

Neural network-based segmentation and classification system for automated grading of histologic sections of bladder carcinoma

OBJECTIVE: To develop an image analysis system for automated nuclear segmentation and classification of histologic bladder sections employing quantitative nuclear features. STUDY DESIGN: Ninety-two cases were classified into three classes by experienced pathologists according to the WHO grading system: 18 cases as grade 1, 45 as grade 2, and 29 as grade 3. Nuclear segmentation was performed by means of an artificial neural network (ANN)-based pixel classification algorithm, and each case was represented by 36 nuclei features. Automated grading of bladder tumor histologic sections was performed by an ANN classifier implemented in a two-stage hierarchic tree. RESULTS: On average, 95% of the nuclei were correctly detected. At the first stage of the hierarchic tree, classifier performance in discriminating between cases of grade 1 and 2 and cases of grade 3 was 89%. At the second stage, 79% of grade 1 cases were correctly distinguished from grade 2 cases. CONCLUSION: The proposed image analysis system provides the means to reduce subjectivity in grading bladder tumors and may contribute to more accurate diagnosis and prognosis since it relies on nuclear features, the value of which has been confirmed.     

Suspensory locomotion of Lagothrix lagothricha and Ateles belzebuth in Yasuní National Park,Ecuador

A comparative field study of the locomotion of woolly monkeys (Lagothrix lagothricha) and spider monkeys (Ateles belzebuth) in undisturbed rainforest of northeastern Ecuador reveals substantial differences in their use of suspensory modes. Ateles performed both more brachiation (by forelimbs and tail, with trunk rotation), and forelimb swing (similar to brachiation, but without trunk rotation) than Lagothrix. In contrast, in Lagothrix 20% of suspensory movement was by pronograde forelimb swing, which resembles forelimb swing except that the body is held in a pronograde orientation due to the tail and/or feet intermittently grasping behind the trailing forelimb. Ateles never exhibited this mode. Both brachiation and forelimb swing by Ateles were more dynamic than in Lagothrix, consisting of higher proportions of full-stride bouts (versus single-step). Both species used smaller supports for suspensory than for quadrupedal locomotion, and Ateles used both smaller and larger supports for suspension than did Lagothrix. Analysis of support inclination shows that both species tended to perform more above-support movement on horizontal supports and more below-support (suspensory) movement from oblique supports. Our attempt to elucidate the aspects of canopy structure that favor suspension suggests the need for additional kinds of observational data, focusing on the "immediate structural context" of positional events.     

Time accelerated Monte Carlo simulations of biological networks using the binomial tau-leap method

SUMMARY: Developing a quantitative understanding of intracellular networks requires simulations and computational analyses. However, traditional differential equation modeling tools are often inadequate due to the stochasticity of intracellular reaction networks that can potentially influence the phenotypic characteristics. Unfortunately, stochastic simulations are computationally too intense for most biological systems. Herein, we have utilized the recently developed binomial tau-leap method to carry out stochastic simulations of the epidermal growth factor receptor induced mitogen activated protein kinase cascade. Results indicate that the binomial tau-leap method is computationally 100-1000 times more efficient than the exact stochastic simulation algorithm of Gillespie. Furthermore, the binomial tau-leap method avoids negative populations and accurately captures the species populations along with their fluctuations despite the large difference in their size. AVAILABILITY: http://www.dion.che.udel.edu/multiscale/Introduction.html. Fortran 90 code available for academic use by email. SUPPLEMENTARY INFORMATION: Details about the binomial tau-leap algorithm, software and a manual are available at the above website.     

A functional multivariate analysis of Mesopithecus (Primates: Colobinae) humeri from the Turolian of Greece

The genus Mesopithecus is well represented in the late Miocene of Greece by several recognized species. The present paper investigates functional aspects of the humeri of Mesopithecus delsoni/pentelicus, M. pentelicus and M. aff. pentelicus of several Turolian sites from central and northern Greece, using multivariate approaches. For these purposes, we selected significant humeral functional features, which were represented by 23 linear dimensions and three angles on 14 fossil humeri and 104 humeri from 10 genera and 22 species of extant African and Asian Colobines. All size-adjusted measurements were examined through a principal components analysis, followed by a discriminant function analysis, and a canonical variates analysis. All analyses revealed that the selected characters were able to discriminate between extant colobine genera. Functional groups, such as arboreal walking/climbing, arboreal walking/suspensory and semi-terrestrial walking, were set apart from a central cluster formed by the arboreal walking and arboreal walking/terrestrial groups. This cluster also grouped the three studied Mesopithecus species, which were mainly classified as arboreal walkers with significant terrestrial activities. These observations match with paleoenvironmental reconstructions and the suggested opportunistic feeding habits. Moreover, the overall arboreal/terrestrial locomotor tendencies of these fossil forms are discussed in relation to their earlier migration from Africa and later dispersal to eastern and southern Asia.     

Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment

Dexamethasone (Dexa) is a widely used glucocorticoid to treat inflammatory diseases; however, a multitude of undesired effects have been reported to arise from this treatment including osteoporosis, obesity, and in children decreased longitudinal bone growth. We and others have previously shown that glucocorticoids induce apoptosis in growth plate chondrocytes. Here, we hypothesized that Bax, a pro-apoptotic member of the Bcl-2 family, plays a key role in Dexa-induced chondrocyte apoptosis and bone growth impairment. Indeed, experiments in the human HCS-2/8 chondrocytic cell line demonstrated that silencing of Bax expression using small-interfering (si) RNA efficiently blocked Dexa-induced apoptosis. Furthermore, ablation of Bax in female mice protected against Dexa-induced bone growth impairment. Finally, Bax activation by Dexa was confirmed in human growth plate cartilage specimens cultured ex vivo. Our findings could therefore open the door for new therapeutic approaches to prevent glucocorticoid-induced bone growth impairment through specific targeting of Bax.     

Positional behavior of Siberian chipmunks (Tamias sibiricus) in captivity

Arboreal and semi-arboreal mammals have remarkably diverse positional behavior and associated morpho-functional adaptations related to the three-dimensional nature of their arboreal habitat. In this context, we investigated the positional behavior of captive Siberian chipmunks (Tamias sibiricus), small bodied semi-arboreal sciurids, in an aviary-type wire-mesh cage containing both terrestrial and arboreal supports. We sampled four adult individuals during a five-month period using focal animal sampling every 30 s. Results showed that animals preferred 8–10 cm horizontal supports and always avoided vertical supports. Locomotion occurred on both terrestrial and 8–10 cm arboreal supports whereas postural behavior occurred primarily on 8–10 cm arboreal supports. Quadrupedal walk dominated during locomotion, and occurred primarily on terrestrial horizontal supports, as is observed for other squirrels. The predominance of quadrupedal locomotion is consistent with the postcranial morphology of chipmunks. In contrast, clawed locomotion occurred on wire mesh and on >13 cm arboreal vertical supports. Finally, pronograde and orthograde sitting, both on 8–10 cm arboreal supports and on terrestrial supports, were the predominant postures, implying general predisposition to selection of stable postures on stable supports for food item manipulation and ingestion.     

Seasonal variation in the positional behavior of red howling monkeys (Alouatta seniculus)

Recent studies on the positional behavior of primates reveal that significant seasonal variation occurs in both locomotion and postures that is related to changes in diet and foraging techniques. Howling monkeys (genusAlouatta), which also have a seasonally varied diet, are predicted to have correspondingly varied positional behaviors. Two groups of red howling monkeys were studied in a primary rain forest in French Guinana during the dry and wet seasons. During the dry season, when howler diet is based mainly on leaves, howlers traveled more frequently by quadrupedal walking on large supports, a mode of progression that is probably inexpensive energetically and relatively stable. During feeding, quadrupedal and tripedal stand contributed considerably, a posture probably associated with the equal distribution of leaves within a tree crown. In contrast, during the wet season, when fruit was abundant, howlers fed very frequently by sitting on large supports, probably because fruit consumption required more time for special manipulation. However, most seasonal changes in feeding postures, and in travel and feeding locomotion, were difficult to associate directly with dietary shifts. These behavioral changes may be more highly correlated with slight modifications in microhabitat use (horizontal and vertical daily ranges, similar and alternative arboreal pathways) that are not considered in this paper.