Relating the Cosmological Constant and Supersymmetry Breaking in Warped Compactifications of IIB String Theory

It has been suggested that the observed value of the cosmological constant is related to the supersymmetry breaking scale M_{susy} through the formula Lambda \sim M_p^4 (M_{susy}/M_p)^8. We point out that a similar relation naturally arises in the codimension two solutions of warped space-time varying compactifications of string theory in which non-isotropic stringy moduli induce a small but positive cosmological constant.Comment: 7 pages, LaTeX, references added and minor changes made, (v3) map between deSitter and global cosmic brane solutions clarified, supersymmetry breaking discussion improved and references adde

Mixed-mode oscillations and interspike interval statistics in the stochastic FitzHugh-Nagumo model

We study the stochastic FitzHugh-Nagumo equations, modelling the dynamics of neuronal action potentials, in parameter regimes characterised by mixed-mode oscillations. The interspike time interval is related to the random number of small-amplitude oscillations separating consecutive spikes. We prove that this number has an asymptotically geometric distribution, whose parameter is related to the principal eigenvalue of a substochastic Markov chain. We provide rigorous bounds on this eigenvalue in the small-noise regime, and derive an approximation of its dependence on the system's parameters for a large range of noise intensities. This yields a precise description of the probability distribution of observed mixed-mode patterns and interspike intervals.Comment: 36 page

Health-related quality of life in homo- and bisexual men attending a sexually transmitted disease clinic in Sweden

Men who have sex with men (MSM) have an increased risk of contracting sexually transmitted diseases (STDs) and HIV. Studies of their health-related quality of life (HRQL) are uncommon, though such studies may provide additional knowledge that is of interest in counselling and care. The HRQL in MSM attending a clinic for STD- and HIV testing in Stockholm, Sweden, was investigated in 1996 and 2004, measured by means of the Swedish Health-Related Quality of Life questionnaire. The results were compared with those for men from a general Swedish population sample and with HIV-infected men. The HIV-negative MSM had significantly worse emotional wellbeing, satisfaction with family life, relation to their partner and general health perception, and better physical HRQL compared with the general Swedish population. There were no differences in the emotional and family dimensions between HIV-infected and HIV-negative MSM, but the HIV-negative group scored at a higher level in respect of their physical and general health than the HIV-infected group. No apparent differences over time were seen in the HIV-negative group. This study shows that psychosocial HRQL is lower for MSM than for a general male population sample, which calls for increased attention in the care of MSM patients

A repulsive trap for two electrons in a magnetic field

We study numerically and analytically the dynamics of two classical electrons with Coulomb interaction in a two dimensional antidot superlattice potential in the presence of crossed electric and magnetic fields. It is found that near one antidot the electron pair can be trapped for a long time and the escape rate from such a trap is proportional to the square of a weak electric field. This is qualitatively different from the case of noninteracting electrons which are trapped forever by the antidot. For the pair propagation in the antidot superlattice we found a broad parameter regime for which the pair is stable and where two repulsive electrons propagate together on an enormously large distance.Comment: revtex, 5 pages, 6 figure

Conservation of context-dependent splicing activity in distant Muscleblind homologs

The Muscleblind (MBL) protein family is a deeply conserved family of RNA binding proteins that regulate alternative splicing, alternative polyadenylation, RNA stability and RNA localization. Their inactivation due to sequestration by expanded CUG repeats causes symptoms in the neuromuscular disease myotonic dystrophy. MBL zinc fingers are the most highly conserved portion of these proteins, and directly interact with RNA. We identified putative MBL homologs in Ciona intestinalis and Trichoplax adhaerens, and investigated their ability, as well as that of MBL homologs from human/mouse, fly and worm, to regulate alternative splicing. We found that all homologs can regulate alternative splicing in mouse cells, with some regulating over 100 events. The cis-elements through which each homolog exerts its splicing activities are likely to be highly similar to mammalian Muscleblind-like proteins (MBNLs), as suggested by motif analyses and the ability of expanded CUG repeats to inactivate homolog-mediated splicing. While regulation of specific target exons by MBL/MBNL has not been broadly conserved across these species, genes enriched for MBL/MBNL binding sites in their introns may play roles in cell adhesion, ion transport and axon guidance, among other biological pathways, suggesting a specific, conserved role for these proteins across a broad range of metazoan species.National Institutes of Health (U.S.) (DP5 OD017865

Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval

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Mutations in cancer cause gain of cysteine, histidine, and tryptophan at the expense of a net loss of arginine on the proteome level

Accumulation of somatic mutations is critical for the transition of a normal cell to become cancerous. Mutations cause amino acid substitutions that change properties of proteins. However, it has not been studied as to what extent the composition and accordingly chemical properties of the cell proteome is altered as a result of the increased mutation load in cancer. Here, we analyzed data on amino acid substitutions caused by mutations in about 2000 protein coding genes from the Cancer Cell Line Encyclopedia that contains information on nucleotide and amino acid alterations in 782 cancer cell lines, and validated the analysis with information on amino acid substitutions for the same set of proteins in the Catalogue of Somatic Mutations in Cancer (COSMIC; v78) in circa 18,000 tumor samples. We found that nonsynonymous single nucleotide substitutions in the analyzed proteome subset ultimately result in a net gain of cysteine, histidine, and tryptophan at the expense of a net loss of arginine. The extraordinary loss of arginine may be attributed to some extent to composition of its codons as well as to the importance of arginine in the functioning of prominent tumor suppressor proteins like p53

A mathematical framework for critical transitions: normal forms, variance and applications

Critical transitions occur in a wide variety of applications including mathematical biology, climate change, human physiology and economics. Therefore it is highly desirable to find early-warning signs. We show that it is possible to classify critical transitions by using bifurcation theory and normal forms in the singular limit. Based on this elementary classification, we analyze stochastic fluctuations and calculate scaling laws of the variance of stochastic sample paths near critical transitions for fast subsystem bifurcations up to codimension two. The theory is applied to several models: the Stommel-Cessi box model for the thermohaline circulation from geoscience, an epidemic-spreading model on an adaptive network, an activator-inhibitor switch from systems biology, a predator-prey system from ecology and to the Euler buckling problem from classical mechanics. For the Stommel-Cessi model we compare different detrending techniques to calculate early-warning signs. In the epidemics model we show that link densities could be better variables for prediction than population densities. The activator-inhibitor switch demonstrates effects in three time-scale systems and points out that excitable cells and molecular units have information for subthreshold prediction. In the predator-prey model explosive population growth near a codimension two bifurcation is investigated and we show that early-warnings from normal forms can be misleading in this context. In the biomechanical model we demonstrate that early-warning signs for buckling depend crucially on the control strategy near the instability which illustrates the effect of multiplicative noise.Comment: minor corrections to previous versio

Mirror Symmetry, Mirror Map and Applications to Calabi-Yau Hypersurfaces

Mirror Symmetry, Picard-Fuchs equations and instanton corrected Yukawa couplings are discussed within the framework of toric geometry. It allows to establish mirror symmetry of Calabi-Yau spaces for which the mirror manifold had been unavailable in previous constructions. Mirror maps and Yukawa couplings are explicitly given for several examples with two and three moduli.Comment: 59 pages. Some changes in the references, a few minor points have been clarifie

In silico druggability assessment of the NUDIX hydrolase protein family as a workflow for target prioritization

Computational chemistry has now been widely accepted as a useful tool for shortening lead times in early drug discovery. When selecting new potential drug targets, it is important to assess the likelihood of finding suitable starting points for lead generation before pursuing costly high-throughput screening campaigns. By exploiting available high-resolution crystal structures, an in silico druggability assessment can facilitate the decision of whether, and in cases where several protein family members exist, which of these to pursue experimentally. Many of the algorithms and software suites commonly applied for in silico druggability assessment are complex, technically challenging and not always user-friendly. Here we applied the intuitive open access servers of DoGSite, FTMap and CryptoSite to comprehensively predict ligand binding pockets, druggability scores and conformationally active regions of the NUDIX protein family. In parallel we analyzed potential ligand binding sites, their druggability and pocket parameter using Schrödinger's SiteMap. Then an in silico docking cascade of a subset of the ZINC FragNow library using the Glide docking program was performed to assess identified pockets for large-scale small-molecule binding. Subsequently, this initial dual ranking of druggable sites within the NUDIX protein family was benchmarked against experimental hit rates obtained both in-house and by others from traditional biochemical and fragment screening campaigns. The observed correlation suggests that the presented user-friendly workflow of a dual parallel in silico druggability assessment is applicable as a standalone method for decision on target prioritization and exclusion in future screening campaigns