Towards an exact factorization of the molecular wave function

An exact single-product factorisation of the molecular wave function for the timedependent Schrodinger equation is investigated by using an ansatz involving a phasefactor. By using the Frenkel variational method, we obtain the Schrodinger equations for the electronic and nuclear wave functions. The concept of a potential energy surface (PES) is retained by introducing a modified Hamiltonian as suggested earlier by Cederbaum. The parameter in the phase factor is chosen such that the equations of motion retain the physically appealing Born- Oppenheimer-like form, and is therefore unique.

The putative role of some conserved water molecules in the structure and function of human transthyretin

Human transthyretin (hTTR) is a multifunctional protein that is involved in several neurodegenerative diseases. Besides the transportation of thyroxin and vitamin A, it is also involved in the proteolysis of apolipoprotein A1 and A beta peptide. Extensive analyses of 32 high-resolution X-ray and neutron diffraction structures of hTTR followed by molecular-dynamics simulation studies using a set of 15 selected structures affirmed the presence of 44 conserved water molecules in its dimeric structure. They are found to play several important roles in the structure and function of the protein. Eight water molecules stabilize the dimeric structure through an extensive hydrogen-bonding network. The absence of some of these water molecules in highly acidic conditions (pH <= 4.0) severely affects the interfacial hydrogen-bond network, which may destabilize the native tetrameric structure, leading to its dissociation. Three pairs of conserved water molecules contribute to maintaining the geometry of the ligand-binding cavities. Some other water molecules control the orientation and dynamics of different structural elements of hTTR. This systematic study of the location, absence, networking and interactions of the conserved water molecules may shed some light on various structural and functional aspects of the protein. The present study may also provide some rational clues about the conserved water-mediated architecture and stability of hTTR.

Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions

Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice.

Protein Structure and Function: Looking through the Network of Side-Chain Interactions

Network theory has become an excellent method of choice through which biological data are smoothly integrated to gain insights into complex biological problems. Understanding protein structure, folding, and function has been an important problem, which is being extensively investigated by the network approach. Since the sequence uniquely determines the structure, this review focuses on the networks of non-covalently connected amino acid side chains in proteins. Questions in structural biology are addressed within the framework of such a formalism. While general applications are mentioned in this review, challenging problems which have demanded the attention of scientific community for a long time, such as allostery and protein folding, are considered in greater detail. Our aim has been to explore these important problems through the eyes of networks. Various methods of constructing protein structure networks (PSN) are consolidated. They include the methods based on geometry, edges weighted by different schemes, and also bipartite network of protein-nucleic acid complexes. A number of network metrics that elegantly capture the general features as well as specific features related to phenomena, such as allostery and protein model validation, are described. Additionally, an integration of network theory with ensembles of equilibrium structures of a single protein or that of a large number of structures from the data bank has been presented to perceive complex phenomena from network perspective. Finally, we discuss briefly the capabilities, limitations, and the scope for further explorations of protein structure networks.

Evolution of social behaviour in the primitively eusocial wasp Ropalidia marginata: do we need to look beyond kin selection?

Ropalidia marginata is a primitively eusocial wasp widely distributed in peninsular India. Although solitary females found a small proportion of nests, the vast majority of new nests are founded by small groups of females. In suchmultiple foundress nests, a single dominant female functions as the queen and lays eggs, while the rest function as sterile workers and care for the queen's brood. Previous attempts to understand the evolution of social behaviour and altruism in this species have employed inclusive fitness theory (kin selection) as a guiding framework. Although inclusive fitness theory is quite successful in explaining the high propensity of the wasps to found nests in groups, several features of their social organization suggest that forces other than kin selection may also have played a significant role in the evolution of this species. These features include lowering of genetic relatedness owing to polyandry and serial polygyny, nest foundation by unrelated individuals, acceptance of young non-nest-mates, a combination of well-developed nest-mate recognition and lack of intra-colony kin recognition, a combination of meek and docile queens and a decentralized self-organized work force, long reproductive queues with cryptic heir designates and conflict-free queen succession, all resulting in extreme intra-colony cooperation and inter-colony conflict.

Dissecting pi-helices: sequence, structure and function

A new procedure for the identification of regular secondary structures using a C-alpha trace has identified 659 pi-helices in 3582 protein chains, solved at high resolution. Taking advantage of this significantly expanded database of pi-helices, we have analysed the functional and structural roles of helices and determined the position-wise amino acid propensity within and around them. These helices range from 5 to 18 residues in length with the average twist and rise being 85.2 +/- 7.2 and 1.28 +/- 0.31 angstrom, respectively. A total of 546 (similar to 83%) out of 659 pi-helices occur in conjunction with alpha-helices, with 101 pi-helices being interspersed between two alpha-helices. The majority of interspersed pi-helices were found to be conserved across a large number of structures within a protein family and produce a significant bend in the overall helical segment as well as local distortions in the neighbouring a-helices. The presence of a pi-helical fragment leads to appropriate orientation of the constituent residues, so as to facilitate favourable interactions and also help in proper folding of the protein chain. In addition to intra helical 6 -> 1 N H center dot center dot center dot O hydrogen bonds, pi-helices are also stabilized by several other non-bonded interactions. pi-Helices show distinct positional residue preferences, which are different from those of a-helices.

Lack of Critical Slowing Down Suggests that Financial Meltdowns Are Not Critical Transitions, yet Rising Variability Could Signal Systemic Risk

Complex systems inspired analysis suggests a hypothesis that financial meltdowns are abrupt critical transitions that occur when the system reaches a tipping point. Theoretical and empirical studies on climatic and ecological dynamical systems have shown that approach to tipping points is preceded by a generic phenomenon called critical slowing down, i.e. an increasingly slow response of the system to perturbations. Therefore, it has been suggested that critical slowing down may be used as an early warning signal of imminent critical transitions. Whether financial markets exhibit critical slowing down prior to meltdowns remains unclear. Here, our analysis reveals that three major US (Dow Jones Index, S&P 500 and NASDAQ) and two European markets (DAX and FTSE) did not exhibit critical slowing down prior to major financial crashes over the last century. However, all markets showed strong trends of rising variability, quantified by time series variance and spectral function at low frequencies, prior to crashes. These results suggest that financial crashes are not critical transitions that occur in the vicinity of a tipping point. Using a simple model, we argue that financial crashes are likely to be stochastic transitions which can occur even when the system is far away from the tipping point. Specifically, we show that a gradually increasing strength of stochastic perturbations may have caused to abrupt transitions in the financial markets. Broadly, our results highlight the importance of stochastically driven abrupt transitions in real world scenarios. Our study offers rising variability as a precursor of financial meltdowns albeit with a limitation that they may signal false alarms.

Mutations in the nucleotide binding and hydrolysis domains of Helicobacter pylori MutS2 lead to altered biochemical activities and inactivation of its in vivo function

Background: Helicobacter pylori MutS2 (HpMutS2), an inhibitor of recombination during transformation is a non-specific nuclease with two catalytic sites, both of which are essential for its anti-recombinase activity. Although HpMutS2 belongs to a highly conserved family of ABC transporter ATPases, the role of its ATP binding and hydrolysis activities remains elusive. Results: To explore the putative role of ATP binding and hydrolysis activities of HpMutS2 we specifically generated point mutations in the nucleotide-binding Walker-A (HpMutS2-G338R) and hydrolysis Walker-B (HpMutS2-E413A) domains of the protein. Compared to wild-type protein, HpMutS2-G338R exhibited similar to 2.5-fold lower affinity for both ATP and ADP while ATP hydrolysis was reduced by similar to 3-fold. Nucleotide binding efficiencies of HpMutS2-E413A were not significantly altered; however the ATP hydrolysis was reduced by similar to 10-fold. Although mutations in the Walker-A and Walker-B motifs of HpMutS2 only partially reduced its ability to bind and hydrolyze ATP, we demonstrate that these mutants not only exhibited alterations in the conformation, DNA binding and nuclease activities of the protein but failed to complement the hyper-recombinant phenotype displayed by mutS2-disrupted strain of H. pylori. In addition, we show that the nucleotide cofactor modulates the conformation, DNA binding and nuclease activities of HpMutS2. Conclusions: These data describe a strong crosstalk between the ATPase, DNA binding, and nuclease activities of HpMutS2. Furthermore these data show that both, ATP binding and hydrolysis activities of HpMutS2 are essential for the in vivo anti-recombinase function of the protein.

Spatio-temporal Map Formation Based on a Potential Function

We revisit the problem of temporal self organization using activity diffusion based on the neural gas (NGAS) algorithm. Using a potential function formulation motivated by a spatio-temporal metric, we derive an adaptation rule for dynamic vector quantization of data. Simulations results show that our algorithm learns the input distribution and time correlation much faster compared to the static neural gas method over the same data sequence under similar training conditions.

An New Area Function for Sharp indenter Tips in Nanoindentation

A new area function is introduced and applied to a Berkovich tip in order to characterize the contact projected area between an indenter and indented material. The function can be related directly to tip-rounding, thereby having obviously physical meaning. Nanoindentation experiments are performed on a commercial Nano Indenter XPsystem. The other two area functions introduced by Oliver and Pharr and by Thurn and Cook respectively are involved in this paper for comparison. By comparison from experimental results among different area functions, the indenter tip described by the proposed area function here is very close to the experimental indenter.

Dynamic function of damage and its implications

Dynamic function of damage is the key to the problem of damage evolution of solids. In order to understand it, one must understand its mesoscopic mechanisms and macroscopic formulation. In terms of evolution equation of microdamage and damage moment, a dynamic function of damage is strictly defined. The mesoscopic mechanism underlying self-closed damage evolution law is investigated by means of double damage moments. Numerical results of damage evolution demonstrate some common features for various microdamage dynamics. Then, the dynamic function of damage is applied to inhomogeneous damage field. In this case, damage evolution rate is no longer equal to the dynamic function of damage. It is found that the criterion for damage localization is closely related to compound damage. Finally, an inversion of damage evolution to the dynamic function of damage is proposed.

A species conserving genetic algorithm for multimodal function optimization

This paper introduces a new technique called species conservation for evolving parallel subpopulations. The technique is based on the concept of dividing the population into several species according to their similarity. Each of these species is built around a dominating individual called the species seed. Species seeds found in the current generation are saved (conserved) by moving them into the next generation. Our technique has proved to be very effective in finding multiple solutions of multimodal optimization problems. We demonstrate this by applying it to a set of test problems, including some problems known to be deceptive to genetic algorithms.

Material parameter extraction in THz-TDS using a converging beam transfer function

We demonstrate a parameter extraction algorithm based on a theoretical transfer function, which takes into account a converging THz beam. Using this, we successfully extract material parameters from data obtained for a quartz sample with a THz time domain spectrometer. © 2010 IEEE.

Anaesthetic impairment of immune function is mediated via GABA(A) receptors.

BACKGROUND: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. PRINCIPAL FINDINGS: We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. SIGNIFICANCE: Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.