A discrete methodology for controlling the sign of curvature and torsion for NURBS

This paper develops a discrete methodology for approximating the so-called convex domain of a NURBS curve, namely the domain in the ambient space, where a user-specified control point is free to move so that the curvature and torsion retains its sign along the NURBS parametric domain of definition. The methodology provides a monotonic sequence of convex polyhedra, converging from the interior to the convex domain. If the latter is non-empty, a simple algorithm is proposed, that yields a sequence of polytopes converging uniformly to the restriction of the convex domain to any user-specified bounding box. The algorithm is illustrated for a pair of planar and a spatial Bézier configuration

Interplay between pleiotropy and secondary selection determines rise and fall of mutators in stress response

Dramatic rise of mutators has been found to accompany adaptation of bacteria in response to many kinds of stress. Two views on the evolutionary origin of this phenomenon emerged: the pleiotropic hypothesis positing that it is a byproduct of environmental stress or other specific stress response mechanisms and the second order selection which states that mutators hitchhike to fixation with unrelated beneficial alleles. Conventional population genetics models could not fully resolve this controversy because they are based on certain assumptions about fitness landscape. Here we address this problem using a microscopic multiscale model, which couples physically realistic molecular descriptions of proteins and their interactions with population genetics of carrier organisms without assuming any a priori fitness landscape. We found that both pleiotropy and second order selection play a crucial role at different stages of adaptation: the supply of mutators is provided through destabilization of error correction complexes or fluctuations of production levels of prototypic mismatch repair proteins (pleiotropic effects), while rise and fixation of mutators occur when there is a sufficient supply of beneficial mutations in replication-controlling genes. This general mechanism assures a robust and reliable adaptation of organisms to unforeseen challenges. This study highlights physical principles underlying physical biological mechanisms of stress response and adaptation

Rigidity of SU(2,2|2)-symmetric solutions in Type IIB

We investigate the existence of half-BPS solutions in Type IIB supergravity which are invariant under the superalgebra SU(2,2|2) realized on either AdS_5 x S^2 x S^1 or AdS_5 x S^3 warped over a Riemann surface \Sigma with boundary. We prove that, in both cases, the only solution is AdS_5 x S^5 itself. We argue that this result provides evidence for the non-existence of fully back-reacted intersecting D3/D7 branes with either AdS_5 x S^2 x S^1 x \Sigma or AdS_5 x S^3 x \Sigma near-horizon limits.Comment: 55 page

Correlation function of null polygonal Wilson loops with local operators

We consider the correlator of a light-like polygonal Wilson loop with n cusps with a local operator (like the dilaton or the chiral primary scalar) in planar N =4 super Yang-Mills theory. As a consequence of conformal symmetry, the main part of such correlator is a function F of 3n-11 conformal ratios. The first non-trivial case is n=4 when F depends on just one conformal ratio \zeta. This makes the corresponding correlator one of the simplest non-trivial observables that one would like to compute for generic values of the `t Hooft coupling \lambda. We compute F(\zeta,\lambda) at leading order in both the strong coupling regime (using semiclassical AdS5 x S5 string theory) and the weak coupling regime (using perturbative gauge theory). Some results are also obtained for polygonal Wilson loops with more than four edges. Furthermore, we also discuss a connection to the relation between a correlator of local operators at null-separated positions and cusped Wilson loop suggested in arXiv:1007.3243.Comment: 36 pages, 2 figure

Correlation functions of three heavy operators - the AdS contribution

We consider operators in N=4 SYM theory which are dual, at strong coupling, to classical strings rotating in S^5. Three point correlation functions of such operators factorize into a universal contribution coming from the AdS part of the string sigma model and a state-dependent S^5 contribution. Consequently a similar factorization arises for the OPE coefficients. In this paper we evaluate the AdS universal factor of the OPE coefficients which is explicitly expressed just in terms of the anomalous dimensions of the three operators.Comment: 49 pages, 3 figures; v.2 references corrected; v3: corrected discussion in section 5, results unchange

Das RECORD-Statement zum Berichten von Beobachtungsstudien, die routinemäßig gesammelte Gesundheitsdaten verwenden [The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement]

Routinely collected health data, obtained for administrative and clinical purposes without specific a priori research goals, are increasingly used for research. The rapid evolution and availability of these data have revealed issues not addressed by existing reporting guidelines, such as Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement was created to fill these gaps. RECORD was created as an extension to the STROBE statement to address reporting items specific to observational studies using routinely collected health data. RECORD consists of a checklist of 13 items related to the title, abstract, introduction, methods, results, and discussion section of articles, and other information required for inclusion in such research reports. This document contains the checklist as well as explanatory and elaboration information to enhance the use of the checklist. Examples of good reporting for each RECORD checklist item are also included. This document, as well as the accompanying website and message board (http://www.record-statement.org), will improve the implementation and understanding of RECORD. By implementing RECORD, authors, journals editors, and peer reviewers can enhance transparency of research reporting

Uncovering the overlapping community structure of complex networks in nature and society

Many complex systems in nature and society can be described in terms of networks capturing the intricate web of connections among the units they are made of. A key question is how to interpret the global organization of such networks as the coexistence of their structural subunits (communities) associated with more highly interconnected parts. Identifying these a priori unknown building blocks (such as functionally related proteins, industrial sectors and groups of people) is crucial to the understanding of the structural and functional properties of networks. The existing deterministic methods used for large networks find separated communities, whereas most of the actual networks are made of highly overlapping cohesive groups of nodes. Here we introduce an approach to analysing the main statistical features of the interwoven sets of overlapping communities that makes a step towards uncovering the modular structure of complex systems. After defining a set of new characteristic quantities for the statistics of communities, we apply an efficient technique for exploring overlapping communities on a large scale. We find that overlaps are significant, and the distributions we introduce reveal universal features of networks. Our studies of collaboration, word-association and protein interaction graphs show that the web of communities has non-trivial correlations and specific scaling properties.Comment: The free academic research software, CFinder, used for the publication is available at the website of the publication: http://angel.elte.hu/clusterin

Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes