Wilson Loops in N=2 Super-Yang-Mills from Matrix Model

We compute the expectation value of the circular Wilson loop in N=2 supersymmetric Yang-Mills theory with N_f=2N hypermultiplets. Our results indicate that the string tension in the dual string theory scales as the logarithm of the 't Hooft coupling.Comment: 37 pages, 9 figures; v2: Numerical factors corrected, simple derivation of Wilson loop and discussion of continuation to complex lambda added; v3: instanton partition function re-analyzed in order to take into account a contribution of the hypermultiplet

Interactions in vivo between the Vif protein of HIV-1 and the precursor (Pr55GAG) of the virion nucleocapsid proteins

The abnormality of viral core structure seen in vif-defective HIV-1 grown in PBMCs has suggested a role for Vif in viral morphogenesis. Using an in vivo mammalian two-hybrid assay, the interaction between Vif and the precursor (Pr55GAG) of the virion nucleocapsid proteins has been analysed. This revealed the amino-terminal (aa 1–22) and central (aa 70–100) regions of Vif to be essential for its interaction with Pr55GAG, but deletion of the carboxy-terminal (aa 158–192) region of the protein had only a minor effect on its interaction. Initial deletion studies carried out on Pr55GAG showed that a 35-amino-acid region of the protein bridging the MA(p17)–CA(p24) junction was essential for its ability to interact with Vif. Site-directed mutagenesis of a conserved tryptophan (Trp21) near the amino terminus of Vif showed it to be important for the interaction with Pr55GAG. By contrast, mutagenesis of the highly conserved YLAL residues forming part of the BC-box motif, shown to be important in Vif promoting degradation of APOBEC3G/3F, had little or no effect on the Vif–Pr55GAG interaction

Correlators of Wilson loops and local operators from multi-matrix models and strings in AdS

We study correlation functions of Wilson loops and local operators in a subsector of N=4 SYM which preserves two supercharges. Localization arguments allow to map the problem to a calculation in bosonic two-dimensional Yang-Mills theory. In turn, this can be reduced to computing correlators in certain Gaussian multi-matrix models. We focus on the correlation function of a Wilson loop and two local operators, and solve the corresponding three-matrix model exactly in the planar limit. We compare the strong coupling behavior to string theory in AdS_5xS^5, finding precise agreement. We pay particular attention to the case in which the local operators have large R-charge J \sim sqrt{lambda} at strong coupling.Comment: 50 pages, 9 figures. v2: minor changes, references adde

The generalized cusp in ABJ(M) N = 6 Super Chern-Simons theories

We construct a generalized cusped Wilson loop operator in N = 6 super Chern-Simons-matter theories which is locally invariant under half of the supercharges. It depends on two parameters and interpolates smoothly between the 1/2 BPS line or circle and a pair of antiparallel lines, representing a natural generalization of the quark-antiquark potential in ABJ(M) theories. For particular choices of the parameters we obtain 1/6 BPS configurations that, mapped on S^2 by a conformal transformation, realize a three-dimensional analogue of the wedge DGRT Wilson loop of N = 4. The cusp couples, in addition to the gauge and scalar fields of the theory, also to the fermions in the bifundamental representation of the U(N)xU(M) gauge group and its expectation value is expressed as the holonomy of a suitable superconnection. We discuss the definition of these observables in terms of traces and the role of the boundary conditions of fermions along the loop. We perform a complete two-loop analysis, obtaining an explicit result for the generalized cusp at the second non-trivial order, from which we read off the interaction potential between heavy 1/2 BPS particles in the ABJ(M) model. Our results open the possibility to explore in the three-dimensional case the connection between localization properties and integrability, recently advocated in D = 4.Comment: 53 pages, 10 figures, added references, this is the version appeared on JHE

Dynamics of dental evolution in ornithopod dinosaurs.

Ornithopods were key herbivorous dinosaurs in Mesozoic terrestrial ecosystems, with a variety of tooth morphologies. Several clades, especially the 'duck-billed' hadrosaurids, became hugely diverse and abundant almost worldwide. Yet their evolutionary dynamics have been disputed, particularly whether they diversified in response to events in plant evolution. Here we focus on their remarkable dietary adaptations, using tooth and jaw characters to examine changes in dental disparity and evolutionary rate. Ornithopods explored different areas of dental morphospace throughout their evolution, showing a long-term expansion. There were four major evolutionary rate increases, the first among basal iguanodontians in the Middle-Late Jurassic, and the three others among the Hadrosauridae, above and below the split of their two major clades, in the middle of the Late Cretaceous. These evolutionary bursts do not correspond to times of plant diversification, including the radiation of the flowering plants, and suggest that dental innovation rather than coevolution with major plant clades was a major driver in ornithopod evolution

Developmental differences in children’s interpersonal emotion regulation

Previous research on interpersonal emotion regulation (ER) in childhood has been rather unsystematic, focusing mainly on children’s prosocial behaviour, and has been conducted in the absence of an integrative emotion theoretical framework. The present research relied on the interpersonal affect classification proposed by Niven, Totterdell, and Holman (2009) to investigate children’s use of different interpersonal ER strategies. The study drew on two samples: 180 parents of children aged between 3 and 8 years reported about a situation where their child was able to change what another person was feeling in order to make them feel better. In addition, 126 children between 3- and 8-years old answered two questions about how they could improve others’ mood. Results from both samples showed age differences in children’s use of interpersonal ER strategies. As expected, ‘affective engagement’ (i.e., focusing on the person or the problem) and ‘cognitive engagement’ (i.e., appraising the situation from a different perspective) were mainly used by 7-8 years-old, whereas ‘attention’ (i.e., distracting and valuing) was most used by 3-4 and 5-6 years-old. ‘Humor’ (i.e., laughing with the target) remained stable across the different age groups. The present research provides more information about the developmental patterns for each specific interpersonal emotion regulation strategy

Sex-specific Trans-regulatory Variation on the Drosophila melanogaster X Chromosome

The X chromosome constitutes a unique genomic environment because it is present in one copy in males, but two copies in females. This simple fact has motivated several theoretical predictions with respect to how standing genetic variation on the X chromosome should differ from the autosomes. Unmasked expression of deleterious mutations in males and a lower census size are expected to reduce variation, while allelic variants with sexually antagonistic effects, and potentially those with a sex-specific effect, could accumulate on the X chromosome and contribute to increased genetic variation. In addition, incomplete dosage compensation of the X chromosome could potentially dampen the male-specific effects of random mutations, and promote the accumulation of X-linked alleles with sexually dimorphic phenotypic effects. Here we test both the amount and the type of genetic variation on the X chromosome within a population of Drosophila melanogaster, by comparing the proportion of X linked and autosomal trans-regulatory SNPs with a sexually concordant and discordant effect on gene expression. We find that the X chromosome is depleted for SNPs with a sexually concordant effect, but hosts comparatively more SNPs with a sexually discordant effect. Interestingly, the contrasting results for SNPs with sexually concordant and discordant effects are driven by SNPs with a larger influence on expression in females than expression in males. Furthermore, the distribution of these SNPs is shifted towards regions where dosage compensation is predicted to be less complete. These results suggest that intrinsic properties of dosage compensation influence either the accumulation of different types of trans-factors and/or their propensity to accumulate mutations. Our findings document a potential mechanistic basis for sex-specific genetic variation, and identify the X as a reservoir for sexually dimorphic phenotypic variation. These results have general implications for X chromosome evolution, as well as the genetic basis of sex-specific evolutionary change

Frequency-specific hippocampal-prefrontal interactions during associative learning

Much of our knowledge of the world depends on learning associations (for example, face-name), for which the hippocampus (HPC) and prefrontal cortex (PFC) are critical. HPC-PFC interactions have rarely been studied in monkeys, whose cognitive and mnemonic abilities are akin to those of humans. We found functional differences and frequency-specific interactions between HPC and PFC of monkeys learning object pair associations, an animal model of human explicit memory. PFC spiking activity reflected learning in parallel with behavioral performance, whereas HPC neurons reflected feedback about whether trial-and-error guesses were correct or incorrect. Theta-band HPC-PFC synchrony was stronger after errors, was driven primarily by PFC to HPC directional influences and decreased with learning. In contrast, alpha/beta-band synchrony was stronger after correct trials, was driven more by HPC and increased with learning. Rapid object associative learning may occur in PFC, whereas HPC may guide neocortical plasticity by signaling success or failure via oscillatory synchrony in different frequency bands.National Institute of Mental Health (U.S.) (Conte Center Grant P50-MH094263-03)National Institute of Mental Health (U.S.) (Fellowship F32-MH081507)Picower Foundatio

Binding Modes of Peptidomimetics Designed to Inhibit STAT3

STAT3 is a transcription factor that has been found to be constitutively activated in a number of human cancers. Dimerization of STAT3 via its SH2 domain and the subsequent translocation of the dimer to the nucleus leads to transcription of anti-apoptotic genes. Prevention of the dimerization is thus an attractive strategy for inhibiting the activity of STAT3. Phosphotyrosine-based peptidomimetic inhibitors, which mimic pTyr-Xaa-Yaa-Gln motif and have strong to weak binding affinities, have been previously investigated. It is well-known that structures of protein-inhibitor complexes are important for understanding the binding interactions and designing stronger inhibitors. Experimental structures of inhibitors bound to the SH2 domain of STAT3 are, however, unavailable. In this paper we describe a computational study that combined molecular docking and molecular dynamics to model structures of 12 peptidomimetic inhibitors bound to the SH2 domain of STAT3. A detailed analysis of the modeled structures was performed to evaluate the characteristics of the binding interactions. We also estimated the binding affinities of the inhibitors by combining MMPB/GBSA-based energies and entropic cost of binding. The estimated affinities correlate strongly with the experimentally obtained affinities. Modeling results show binding modes that are consistent with limited previous modeling studies on binding interactions involving the SH2 domain and phosphotyrosine(pTyr)-based inhibitors. We also discovered a stable novel binding mode that involves deformation of two loops of the SH2 domain that subsequently bury the C-terminal end of one of the stronger inhibitors. The novel binding mode could prove useful for developing more potent inhibitors aimed at preventing dimerization of cancer target protein STAT3

Low dose cranial irradiation-induced cerebrovascular damage is reversible in mice

BACKGROUND: High-dose radiation-induced blood-brain barrier breakdown contributes to acute radiation toxicity syndrome and delayed brain injury, but there are few data on the effects of low dose cranial irradiation. Our goal was to measure blood-brain barrier changes after low (0.1 Gy), moderate (2 Gy) and high (10 Gy) dose irradiation under in vivo and in vitro conditions. METHODOLOGY: Cranial irradiation was performed on 10-day-old and 10-week-old mice. Blood-brain barrier permeability for Evans blue, body weight and number of peripheral mononuclear and circulating endothelial progenitor cells were evaluated 1, 4 and 26 weeks postirradiation. Barrier properties of primary mouse brain endothelial cells co-cultured with glial cells were determined by measurement of resistance and permeability for marker molecules and staining for interendothelial junctions. Endothelial senescence was determined by senescence associated β-galactosidase staining. PRINCIPLE FINDINGS: Extravasation of Evans blue increased in cerebrum and cerebellum in adult mice 1 week and in infant mice 4 weeks postirradiation at all treatment doses. Head irradiation with 10 Gy decreased body weight. The number of circulating endothelial progenitor cells in blood was decreased 1 day after irradiation with 0.1 and 2 Gy. Increase in the permeability of cultured brain endothelial monolayers for fluorescein and albumin was time- and radiation dose dependent and accompanied by changes in junctional immunostaining for claudin-5, ZO-1 and β-catenin. The number of cultured brain endothelial and glial cells decreased from third day of postirradiation and senescence in endothelial cells increased at 2 and 10 Gy. CONCLUSION: Not only high but low and moderate doses of cranial irradiation increase permeability of cerebral vessels in mice, but this effect is reversible by 6 months. In-vitro experiments suggest that irradiation changes junctional morphology, decreases cell number and causes senescence in brain endothelial cells