Impact of zumor mutation burden on nivolumab efficacy in second-line urothelial carcinoma patients: Exploratory analysis of the phase ii checkmate 275 study

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Defects induced ferromagnetism in Mn doped ZnO

Single phase Mn doped (2 at %) ZnO samples have been synthesized by solid-state reaction technique. Before the final sintering at 500 C, the mixed powders have been milled for different milling periods (6, 24, 48 and 96 hours). The grain sizes of the samples are very close to each other (~ 32 \pm 4 nm). However, the defective state of the samples is different from each other as manifested from the variation of magnetic properties and electrical resistivity with milling time. All the samples have been found to be ferromagnetic with clear hysteresis loops at room temperature. The maximum value for saturation magnetization (0.11 {\mu}_B / Mn atom) was achieved for 96 hours milled sample. Electrical resistivity has been found to increase with increasing milling time. The most resistive sample bears the largest saturation magnetization. Variation of average positron lifetime with milling time bears a close similarity with that of the saturation magnetization. This indicates the key role played by open volume vacancy defects, presumably zinc vacancies near grain surfaces, in inducing ferromagnetic order in Mn doped ZnO. To attain optimum defect configuration favorable for ferromagnetism in this kind of samples proper choice of milling period and annealing conditions is required.Comment: Accepted in Journal of Magnetism and Magnetic Material

Low-dimensional representations of exact coherent states of the Navier-Stokes equations from the resolvent model of wall turbulence

We report that many exact invariant solutions of the Navier-Stokes equations for both pipe and channel flows are well represented by just few modes of the model of McKeon & Sharma J. Fl. Mech. 658, 356 (2010). This model provides modes that act as a basis to decompose the velocity field, ordered by their amplitude of response to forcing arising from the interaction between scales. The model was originally derived from the Navier-Stokes equations to represent turbulent flows and has been used to explain coherent structure and to predict turbulent statistics. This establishes a surprising new link between the two distinct approaches to understanding turbulence

Seed coat mediated resistance against Aspergillus flavus infection in peanut

Toxic metabolites known as aflatoxins are produced via certain species of the Aspergillus genus, specifically A. flavus, A. parasiticus, A. nomius, and A. tamarie. Although various pre- and post-harvest strategies have been employed, aflatoxin contamination remains a major problem within peanut crop, especially in subtropical environments. Aflatoxins are the most well-known and researched mycotoxins produced within the Aspergillus genus (namely Aspergillus flavus) and are classified as group 1 carcinogens. Their effects and etiology have been extensively researched and aflatoxins are commonly linked to growth defects and liver diseases in humans and livestock. Despite the known importance of seed coats in plant defense against pathogens, peanut seed coat mediated defenses against Aspergillus flavus resistance, have not received considerable attention. The peanut seed coat (testa) is primarily composed of a complex cell wall matrix consisting of cellulose, lignin, hemicellulose, phenolic compounds, and structural proteins. Due to cell wall desiccation during seed coat maturation, postharvest A. flavus infection occurs without the pathogen encountering any active genetic resistance from the live cell(s) and the testa acts as a physical and biochemical barrier only against infection. The structure of peanut seed coat cell walls and the presence of polyphenolic compounds have been reported to inhibit the growth of A. flavus and aflatoxin contamination; however, there is no comprehensive information available on peanut seed coat mediated resistance. We have recently reviewed various plant breeding, genomic, and molecular mechanisms, and management practices for reducing A. flavus infection and aflatoxin contamination. Further, we have also proved that seed coat acts as a physical and biochemical barrier against A. flavus infection. The current review focuses specifically on the peanut seed coat cell wall-mediated disease resistance, which will enable researchers to understand the mechanism and design efficient strategies for seed coat cell wall-mediated resistance against A. flavus infection and aflatoxin contamination

The STAR Photon Multiplicity Detector

Details concerning the design, fabrication and performance of STAR Photon Multiplicity Detector (PMD) are presented. The PMD will cover the forward region, within the pseudorapidity range 2.3--3.5, behind the forward time projection chamber. It will measure the spatial distribution of photons in order to study collective flow, fluctuation and chiral symmetry restoration.Comment: 15 pages, including 11 figures; to appear in a special NIM volume dedicated to the accelerator and detectors at RHI

Two-dimensional differential in-gel electrophoresis-based proteomics of male gametes in relation to oxidative stress

Objective: To identify the relative abundance of proteins in pooled reactive oxygen species (ROS)-positive (ROSþ) and ROS-negative (ROSÀ) semen samples with the use of two-dimensional differential in-gel electrophoresis (2D-DIGE). Design: Spermatozoa suspensions from ROSþ and ROSÀ groups by 2D-DIGE analysis. Setting: Tertiary hospital. Patient(s): 20 donors and 32 infertile men. Intervention(s): Seminal ejaculates evaluated for semen and proteomic analysis. Main Outcome Measure(s): Semen samples from 20 donors and 32 infertile men were pooled, divided into ROSþ and ROSÀ groups based on the cutoff value of <20 relative light units/s/10 6 sperm and frozen. From each pooled group, spermatozoa were labeled with Cy3/Cy5 fluorescent dye. Duplicate 2D-DIGE gels were run. Image analysis was performed with the use of Decider software. Protein spots exhibiting R1.5-fold difference in intensity were excised from the preparatory gel and identified by liquid chromatographymass spectrometry. Data were analyzed with the use of Sequest and Blast programs. Result(s): A total of 1,343 protein spots in gel 1 (ROSÀ) and 1,265 spots in gel 2 (ROSþ) were detected. The majority of protein spots had similar expression, with 31 spots were differentially expressed. Six spots were significantly decreased and 25 increased in the ROSÀ sample compared with the ROSþ sample. Conclusion(s): Significantly different expression of protective proteins against oxidative stress was found in ROSÀcompared with ROSþ samples. These differences may explain the role of oxidation species in the pathology of male infertility. (Fertil Steril Ò 2013;99:1216-26. Ó2013 by American Society for Reproductive Medicine.

Effect of Peritoneal Fluid from Endometriosis Patients on Sperm Motion Characteristics and Acrosome Reaction

ABSTRACT: Objective-To determine whether peritoneal fluid from women with endometriosis contributes to infertility by impairing sperm motion and functional characteristics. Methods-Women with endometriosis (n = 20) underwent laparoscopy for infertility or pelvic pain. Patients undergoing tubal ligation served as controls (n = 14). Peritoneal fluid was aspirated from women with endometriosis, or from women undergoing laparoscopic tubal ligation. Sperm motility, motion characteristics and acrosome reaction were assessed following incubation with peritoneal fluid. Results-Sperm motility, motion characteristics, and acrosome reaction did not differ significantly between the two groups after 3, 5, or 24 hours of incubation with peritoneal fluid. Conclusions-Sperm motion or functional characteristics showed no significant impairment when sperm from normal donors were incubated with peritoneal fluid from patients with endometriosis. It is unlikely that peritoneal fluid in these patients contributes to infertility. Int J Fertil 44 (1)

Rapalogs can promote cancer cell stemness in vitro in a Galectin-1 and H-ras-dependent manner

Currently several combination treatments of mTor- and Ras-pathway inhibitors are being tested in cancer therapy. While multiple feedback loops render these central signaling pathways robust, they complicate drug targeting.Here, we describe a novel H-ras specific feedback, which leads to an inadvertent rapalog induced activation of tumorigenicity in Ras transformed cells. We find that rapalogs specifically increase nanoscale clustering (nanoclustering) of oncogenic H-ras but not K-ras on the plasma membrane. This increases H-ras signaling output, promotes mammosphere numbers in a H-ras-dependent manner and tumor growth in ovo. Surprisingly, also other FKBP12 binders, but not mTor- inhibitors, robustly decrease FKBP12 levels after prolonged (> 2 days) exposure. This leads to an upregulation of the nanocluster scaffold galectin-1 (Gal-1), which is responsible for the rapamycin-induced increase in H-ras nanoclustering and signaling output. We provide evidence that Gal-1 promotes stemness features in tumorigenic cells. Therefore, it may be necessary to block inadvertent induction of stemness traits in H-ras transformed cells by specific Gal-1 inhibitors that abrogate its effect on H-ras nanocluster. On a more general level, our findings may add an important mechanistic explanation to the pleiotropic physiological effects that are observed with rapalogs