Viscoelasticity near the gel-point: a molecular dynamics study

We report on extensive molecular dynamics simulations on systems of soft spheres of functionality f, i.e. particles that are capable of bonding irreversibly with a maximum of f other particles. These bonds are randomly distributed throughout the system and imposed with probability p. At a critical concentration of bonds, p_c approximately equal to 0.2488 for f=6, a gel is formed and the shear viscosity \eta diverges according to \eta ~ (p_c-p)^{-s}. We find s is approximately 0.7 in agreement with some experiments and with a recent theoretical prediction based on Rouse dynamics of phantom chains. The diffusion constant decreases as the gel point is approached but does not display a well-defined power law.Comment: 4 pages, 4 figure

Acute Infection and Subsequent Subclinical Reactivation of Herpes Simplex Virus 2 after Vaginal Inoculation of Rhesus Macaques.

Herpes simplex virus 2 (HSV-2) is a common sexually transmitted infection with a highly variable clinical course. Many infections quickly become subclinical, with episodes of spontaneous virus reactivation. To study host-HSV-2 interactions, an animal model of subclinical HSV-2 infection is needed. In an effort to develop a relevant model, rhesus macaques (RM) were inoculated intravaginally with two or three HSV-2 strains (186, 333, and/or G) at a total dose of 1 × 107 PFU of HSV-2 per animal. Infectious HSV-2 and HSV-2 DNA were consistently shed in vaginal swabs for the first 7 to 14 days after each inoculation. Proteins associated with wound healing, innate immunity, and inflammation were significantly increased in cervical secretions immediately after HSV-2 inoculation. There was histologic evidence of acute herpesvirus pathology, including acantholysis in the squamous epithelium and ballooning degeneration of and intranuclear inclusion bodies in epithelial cells, with HSV antigen in mucosal epithelial cells and keratinocytes. Further, an intense inflammatory infiltrate was found in the cervix and vulva. Evidence of latent infection and reactivation was demonstrated by the detection of spontaneous HSV-2 shedding post-acute inoculation (102 to 103 DNA copies/swab) in 80% of RM. Further, HSV-2 DNA was detected in ganglia in most necropsied animals. HSV-2-specifc T-cell responses were detected in all animals, although antibodies to HSV-2 were detected in only 30% of the animals. Thus, HSV-2 infection of RM recapitulates many of the key features of subclinical HSV-2 infection in women but seems to be more limited, as virus shedding was undetectable more than 40 days after the last virus inoculation.IMPORTANCE Herpes simplex virus 2 (HSV-2) infects nearly 500 million persons globally, with an estimated 21 million incident cases each year, making it one of the most common sexually transmitted infections (STIs). HSV-2 is associated with increased human immunodeficiency virus type 1 (HIV-1) acquisition, and this risk does not decline with the use of antiherpes drugs. As initial acquisition of both HIV and HSV-2 infections is subclinical, study of the initial molecular interactions of the two agents requires an animal model. We found that HSV-2 can infect RM after vaginal inoculation, establish latency in the nervous system, and spontaneously reactivate; these features mimic some of the key features of HSV-2 infection in women. RM may provide an animal model to develop strategies to prevent HSV-2 acquisition and reactivation

Linking Metabolic QTLs with Network and cis-eQTLs Controlling Biosynthetic Pathways

Phenotypic variation between individuals of a species is often under quantitative genetic control. Genomic analysis of gene expression polymorphisms between individuals is rapidly gaining popularity as a way to query the underlying mechanistic causes of variation between individuals. However, there is little direct evidence of a linkage between global gene expression polymorphisms and phenotypic consequences. In this report, we have mapped quantitative trait loci (QTLs)–controlling glucosinolate content in a population of 403 Arabidopsis Bay × Sha recombinant inbred lines, 211 of which were previously used to identify expression QTLs controlling the transcript levels of biosynthetic genes. In a comparative study, we have directly tested two plant biosynthetic pathways for association between polymorphisms controlling biosynthetic gene transcripts and the resulting metabolites within the Arabidopsis Bay × Sha recombinant inbred line population. In this analysis, all loci controlling expression variation also affected the accumulation of the resulting metabolites. In addition, epistasis was detected more frequently for metabolic traits compared to transcript traits, even when both traits showed similar distributions. An analysis of candidate genes for QTL-controlling networks of transcripts and metabolites suggested that the controlling factors are a mix of enzymes and regulatory factors. This analysis showed that regulatory connections can feedback from metabolism to transcripts. Surprisingly, the most likely major regulator of both transcript level for nearly the entire pathway and aliphatic glucosinolate accumulation is variation in the last enzyme in the biosynthetic pathway, AOP2. This suggests that natural variation in transcripts may significantly impact phenotypic variation, but that natural variation in metabolites or their enzymatic loci can feed back to affect the transcripts

Construction of the free energy landscape by the density functional theory

On the basis of the density functional theory, we give a clear definition of the free energy landscape. To show the usefulness of the definition, we construct the free energy landscape for rearrangement of atoms in an FCC crystal of hard spheres. In this description, the cooperatively rearranging region (CRR) is clealy related to the hard spheres involved in the saddle between two adjacent basins. A new concept of the simultaneously rearranging region (SRR) emerges naturally as spheres defined by the difference between two adjacent basins. We show that the SRR and the CRR can be determined explicitly from the free energylandscape.Comment: 11 pages, 3 figures, submitted to J. Chem. Phy

Shear viscosity of a crosslinked polymer melt

We investigate the static shear viscosity on the sol side of the vulcanization transition within a minimal mesoscopic model for the Rouse-dynamics of a randomly crosslinked melt of phantom polymers. We derive an exact relation between the viscosity and the resistances measured in a corresponding random resistor network. This enables us to calculate the viscosity exactly for an ensemble of crosslinks without correlations. The viscosity diverges logarithmically as the critical point is approached. For a more realistic ensemble of crosslinks amenable to the scaling description of percolation, we prove the scaling relation $k=\phi-\beta$ between the critical exponent $k$ of the viscosity, the thermal exponent $\beta$ associated with the gel fraction and the crossover exponent $\phi$ of a random resistor network.Comment: 8 pages, uses Europhysics Letters style; Revisions: results extende

Preparation of an ion with the highest calculated proton affinity: ortho-diethynylbenzene dianion

Owing to the increased proton affinity that results from additional negative charges, multiply-charged anions have been proposed as one route to prepare and access a range of new and powerful superbases . Paradoxically, while the additional electrons in polyanions increase basicity they serve to diminish the electron binding energy and thus, it had been thought, hinder experimental synthesis. We report the synthesis and isolation of the ortho-diethynylbenzene dianion (ortho-DEB2−) and present observations of this novel species undergoing gas-phase proton-abstraction reactions. Using a theoretical model based on Marcus-Hush theory, we attribute the stability of ortho-DEB2− to the presence of a barrier that prevents spontaneous electron detachment. The proton affinity of 1843 kJ mol−1 calculated for this dianion superbase using high-level quantum chemistry calculations significantly exceeds that of the lithium monoxide anion, the most basic system previously prepared. The ortho-diethynylbenzene dianion is therefore the strongest base that has been experimentally observed to date

The role of mutation rate variation and genetic diversity in the architecture of human disease

Background We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have already been identified. Results Consistent with our predictions we find that genes associated with Mendelian and complex disease are substantially longer than non-disease genes. However, we find that both Mendelian and complex disease genes are found in regions of the genome with relatively low mutation rates, as inferred from intron divergence between humans and chimpanzees, and they are predicted to have similar rates of non-synonymous mutation as other genes. Finally, we find that disease genes are in regions of significantly elevated genetic diversity, even when variation in the rate of mutation is controlled for. The effect is small nevertheless. Conclusions Our results suggest that gene length contributes to whether a gene is associated with disease. However, the mutation rate and the genetic architecture of the locus appear to play only a minor role in determining whether a gene is associated with disease

Critical Dynamics of Gelation

Shear relaxation and dynamic density fluctuations are studied within a Rouse model, generalized to include the effects of permanent random crosslinks. We derive an exact correspondence between the static shear viscosity and the resistance of a random resistor network. This relation allows us to compute the static shear viscosity exactly for uncorrelated crosslinks. For more general percolation models, which are amenable to a scaling description, it yields the scaling relation $k=\phi-\beta$ for the critical exponent of the shear viscosity. Here $\beta$ is the thermal exponent for the gel fraction and $\phi$ is the crossover exponent of the resistor network. The results on the shear viscosity are also used in deriving upper and lower bounds on the incoherent scattering function in the long-time limit, thereby corroborating previous results.Comment: 34 pages, 2 figures (revtex, amssymb); revised version (minor changes