The Evolving Role of Maintenance Therapy Using Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) in the Management of Advanced Non-Small-Cell Lung Cancer

A video abstract by the authors of this paper is available. video-abstract5127.mo

Evaluation of the potential killing performance of novel percussive and cervical dislocation tools in chicken cadavers

1. Four mechanical poultry killing devices; modified Armadillo (MARM), modified Rabbit Zinger (MZIN), modified pliers (MPLI) and a novel mechanical cervical dislocation gloved device (NMCD), were assessed for their killing potential in the cadavers of euthanised birds of 4 type/age combinations: layer/adult, layer/pullet, broiler/slaughter-age and broiler/chick. 2. A 4x4x4 factorial design (batch x device x bird type + age) was employed. Ten bird cadavers per bird type and age were tested with each of the 4 devices (N = 160 birds). All cadavers were examined post-mortem to establish the anatomical damage caused by each device. 3. Three of the mechanical methods: NMCD, MARM and MZIN demonstrated killing potential, as well as consistency in their anatomical effects, with device success rates of over 50% indicating that the devices performed optimally more than half of the time. NMCD had the highest killing potential, with 100% of birds sustaining the required physical trauma to have caused rapid death. 4. The MPLI was inconsistent, and only performed optimally for 27.5% of birds, despite good killing potential when performing well. Severe crushing injury was seen in >50% of MPLI birds, suggesting that birds would die of asphyxia rather than cerebral ischaemia, a major welfare concern. As a result, the modified pliers are not recommended as a humane on-farm killing device for chickens. 5. This experiment provides important data on the killing potential of untried novel percussive and mechanical cervical dislocation methods, informing future studies

Twisted exchange interaction between localized spins embedded in a one- or two-dimensional electron gas with Rashba spin-orbit coupling

We study theoretically the Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction in one- and two-dimensions in presence of a Rashba spin-orbit (SO) coupling. We show that rotation of the spin of conduction electrons due to SO coupling causes a twisted RKKY interaction between localized spins which consists of three different terms: Heisenberg, Dzyaloshinsky-Moriya, and Ising interactions. We also show that the effective spin Hamiltonian reduces to the usual RKKY interaction Hamiltonian in the twisted spin space where the spin quantization axis of one localized spin is rotated.Comment: 4pages, no figur

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more. Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval [CI], 0.91 to 1.45; P=0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatment-related adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy. Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533 .)

Computer-aided design of nano-filter construction using DNA self-assembly

Computer-aided design plays a fundamental role in both top-down and bottom-up nano-system fabrication. This paper presents a bottom-up nano-filter patterning process based on DNA self-assembly. In this study we designed a new method to construct fully designed nano-filters with the pores between 5 nm and 9 nm in diameter. Our calculations illustrated that by constructing such a nano-filter we would be able to separate many molecules

The Attributed Pi Calculus with Priorities

International audienceWe present the attributed $\pi$-calculus for modeling concurrent systems with interaction constraints depending on the values of attributes of processes. The $\pi$-calculus serves as a constraint language underlying the $\pi$-calculus. Interaction constraints subsume priorities, by which to express global aspects of populations. We present a nondeterministic and a stochastic semantics for the attributed $\pi$-calculus. We show how to encode the $\pi$-calculus with priorities and polyadic synchronization $\pi$@ and thus dynamic compartments, as well as the stochastic $\pi$-calculus with concurrent objects spico. We illustrate the usefulness of the attributed $\pi$-calculus for modeling biological systems at two particular examples: Euglena’s spatial movement in phototaxis, and cooperative protein binding in gene regulation of bacteriophage lambda. Furthermore, population-based model is supported beside individual-based modeling. A stochastic simulation algorithm for the attributed $\pi$-calculus is derived from its stochastic semantics. We have implemented a simulator and present experimental results, that confirm the practical relevance of our approach

The Drosophila melanogaster Genetic Reference Panel

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics