PhyloCSF: a comparative genomics method to distinguish protein-coding and non-coding regions

As high-throughput transcriptome sequencing provides evidence for novel transcripts in many species, there is a renewed need for accurate methods to classify small genomic regions as protein-coding or non-coding. We present PhyloCSF, a novel comparative genomics method that analyzes a multi-species nucleotide sequence alignment to determine whether it is likely to represent a conserved protein-coding region, based on a formal statistical comparison of phylogenetic codon models. We show that PhyloCSF's classification performance in 12-species _Drosophila_ genome alignments exceeds all other methods we compared in a previous study, and we provide a software implementation for use by the community. We anticipate that this method will be widely applicable as the transcriptomes of many additional species, tissues, and subcellular compartments are sequenced, particularly in the context of ENCODE and modENCODE

Security Theorems via Model Theory

A model-theoretic approach can establish security theorems for cryptographic protocols. Formulas expressing authentication and non-disclosure properties of protocols have a special form. They are quantified implications for all xs . (phi implies for some ys . psi). Models (interpretations) for these formulas are *skeletons*, partially ordered structures consisting of a number of local protocol behaviors. Realized skeletons contain enough local sessions to explain all the behavior, when combined with some possible adversary behaviors. We show two results. (1) If phi is the antecedent of a security goal, then there is a skeleton A_phi such that, for every skeleton B, phi is satisfied in B iff there is a homomorphism from A_phi to B. (2) A protocol enforces for all xs . (phi implies for some ys . psi) iff every realized homomorphic image of A_phi satisfies psi. Hence, to verify a security goal, one can use the Cryptographic Protocol Shapes Analyzer CPSA (TACAS, 2007) to identify minimal realized skeletons, or "shapes," that are homomorphic images of A_phi. If psi holds in each of these shapes, then the goal holds

A comparative study for the pair-creation contact process using series expansions

A comparative study between two distinct perturbative series expansions for the pair-creation contact process is presented. In contrast to the ordinary contact process, whose supercritical series expansions provide accurate estimates for its critical behavior, the supercritical approach does not work properly when applied to the pair-creation process. To circumvent this problem a procedure is introduced in which one-site creation is added to the pair-creation. An alternative method is the generation of subcritical series expansions which works even for the case of the pure pair-creation process. Differently from the supercritical case, the subcritical series yields estimates that are compatible with numerical simulations

A grid-based infrastructure for distributed retrieval

In large-scale distributed retrieval, challenges of latency, heterogeneity, and dynamicity emphasise the importance of infrastructural support in reducing the development costs of state-of-the-art solutions. We present a service-based infrastructure for distributed retrieval which blends middleware facilities and a design framework to ‘lift’ the resource sharing approach and the computational services of a European Grid platform into the domain of e-Science applications. In this paper, we give an overview of the DILIGENT Search Framework and illustrate its exploitation in the field of Earth Science

Comorbidities of atopic dermatitis—what does the evidence say?

Atopic dermatitis (AD) is a common disease that is associated with atopic and nonatopic comorbidities. There has been a growing interest in this area of AD, because presence or risk of comorbidities can in many ways impact the management of patients with AD. Thus, some treatments for AD may improve its comorbidities as well, whereas others may increase their risk. In this review article, we discuss various comorbidities of AD mostly on the basis of the results of recent multiple systematic reviews and meta-analyses to update readers about this rapidly developing area of dermatology. We emphasize the important information provided by studies presenting both relative risk and absolute risk, and show that AD is associated with, among others, atopic comorbidities such as asthma, rhinitis, and food allergy, nonatopic comorbidities such as ocular, psychiatric, infectious, endocrine, autoimmune, and cardiovascular diseases, and certain cancers. Clinicians need to be aware of these and be cognizant about positive and negative effects of existing and new treatments for AD

IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis.

Dupilumab is a fully human antibody to interleukin-4 receptor α that improves the signs and symptoms of moderate to severe atopic dermatitis (AD). To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate to severe AD randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S ribosomal RNA, and absolute S. aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S. aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S. aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S. aureus abundance during dupilumab treatment correlated with clinical improvement of AD and biomarkers of type 2 immunity. We conclude that clinical improvement of AD that is mediated by interleukin-4 receptor α inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus