Non cell autonomous upregulation of CDKN2 transcription linked to progression of chronic hepatitis C disease

Chronic hepatitis C virus infection (C-HC) is associated with higher mortality arising from hepatic and extrahepatic disease. This may be due to accelerated biological aging; however, studies in C-HC have thus far been based solely on telomere length as a biomarker of aging (BoA). In this study, we have evaluated CDKN2 locus transcripts as alternative BoAs in C-HC. Our results suggest that C-HC induces non-cell-autonomous senescence and accelerates biological aging. The CDKN2 locus may provide a link between C-HC and increased susceptibility to age-associated diseases and provides novel biomarkers for assessing its impact on aging processes in man

Laser Peening to Improve Fatigue Strength and Lifetime of Critical Components1

AbstractFatigue failure is typically driven by component geometric requirements that result in local areas of high tensile loading stress. Within this paper we discuss the deep protective stress generated by laser peening and show examples of using a newly developed finite element predictive strain and stress tool that accurately models laser peening. The analysis tool and robust process enable the accurate engineering of local compressive stress into critical areas of diverse/all(?) ferrous and non-ferrous materials in a well-defined manner that significantly improves fatigue life and strength. This capability opens the potential for advanced designs with increased performance, enhanced reliability and reduced system weight

Long-Period Giant Companions to Three Compact, Multiplanet Systems

Understanding the relationship between long-period giant planets and multiple smaller short-period planets is critical for formulating a complete picture of planet formation. This work characterizes three such systems. We present Kepler-65, a system with an eccentric (e = 0.28 ± 0.07) giant planet companion discovered via radial velocities (RVs) exterior to a compact, multiply transiting system of sub-Neptune planets. We also use precision RVs to improve mass and radius constraints on two other systems with similar architectures, Kepler-25 and Kepler-68. In Kepler-68 we propose a second exterior giant planet candidate. Finally, we consider the implications of these systems for planet formation models, particularly that the moderate eccentricity in Kepler-65\u27s exterior giant planet did not disrupt its inner system

A Comprehensive Radio and Optical Study of Abell 2256: Activity from an Infalling Group

Abell 2256 is a nearby (z~0.06), rich cluster of galaxies with fascinating observed properties across a range of wavelengths. Long believed to represent a cluster merger, recent X-ray and optical results have suggested that in addition to the primary cluster and subcluster there is evidence for a third, poorer system. We present wide-field, high sensitivity 1.4 GHz VLA radio observations of Abell 2256 in conjunction with optical imaging and additional spectroscopy. Over 40 cluster radio galaxies are identified, with optical spectroscopy indicating the emission source (star formation or AGN) for most of them. While the overall fraction of galaxies exhibiting radio emission is consistent with a large sample of other nearby clusters, we find an increase in the activity level of galaxies belonging to the third system (hereafter, the ``Group''). Specifically, the Group has relatively more star formation than both the primary cluster and main subcluster. The position of the Group is also coincident with the observed cluster radio relic. We suggest that the Group recently (~0.3 Gyr) merged with the primary cluster and that this merger, not the ongoing merger of the primary and the main subcluster, might be responsible for many of the unusual radio properties of Abell 2256. Furthermore, the greater star formation activity of the Group suggests that the infall of groups is an important driver of galaxy evolution in clusters.Comment: 21 pages plus 13 JPEG figures; to appear in the Astronomical Journa

Tracking TCRß sequence clonotype expansions during antiviral therapy using high-throughput sequencing of the hypervariable region

To maintain a persistent infection viruses such as hepatitis C virus (HCV) employ a range of mechanisms that subvert protective T cell responses. The suppression of antigen-specific T cell responses by HCV hinders efforts to profile T cell responses during chronic infection and antiviral therapy. Conventional methods of detecting antigen-specific T cells utilize either antigen stimulation (e.g., ELISpot, proliferation assays, cytokine production) or antigen-loaded tetramer staining. This limits the ability to profile T cell responses during chronic infection due to suppressed effector function and the requirement for prior knowledge of antigenic viral peptide sequences. Recently, high-throughput sequencing (HTS) technologies have been developed for the analysis of T cell repertoires. In the present study, we have assessed the feasibility of HTS of the TCRβ complementarity determining region (CDR)3 to track T cell expansions in an antigen-independent manner. Using sequential blood samples from HCV-infected individuals undergoing antiviral therapy, we were able to measure the population frequencies of >35,000 TCRβ sequence clonotypes in each individual over the course of 12 weeks. TRBV/TRBJ gene segment usage varied markedly between individuals but remained relatively constant within individuals across the course of therapy. Despite this stable TRBV/TRBJ gene segment usage, a number of TCRβ sequence clonotypes showed dramatic changes in read frequency. These changes could not be linked to therapy outcomes in the present study; however, the TCRβ CDR3 sequences with the largest fold changes did include sequences with identical TRBV/TRBJ gene segment usage and high junction region homology to previously published CDR3 sequences from HCV-specific T cells targeting the HLA-B*0801-restricted 1395HSKKKCDEL1403 and HLA-A*0101-restricted 1435ATDALMTGY1443 epitopes. The pipeline developed in this proof of concept study provides a platform for the design of future experiments to accurately address the question of whether T cell responses contribute to SVR upon antiviral therapy. This pipeline represents a novel technique to analyze T cell dynamics in situations where conventional antigen-dependent methods are limited due to suppression of T cell functions and highly diverse antigenic sequences

Geographies for play in austere times

This concluding essay to a collection of 10 papers examining, Best of times to worst of times? Appraising the changing landscape of play in the UK, reviews six key themes that emerge – re-fuelling longstanding tensions within playwork; organisational legacy of the investment years; broad acceptance of the wider value of play in society; the need to develop a critical play intelligence within the sector; the reconfiguration of play geographies and the impact of play provision on local play cultures; and the need for a much more central focus on play cultures in our enquiry. Without question, Austerity has undermined the public investment in play and play services that characterised the UK in early years of the Millennium. Nevertheless, for every ‘threat’ that this poses, others are able and willing to conceptualise this as an opportunity to reprioritise play priorities. It is argued that play is resilient, and adept an adapting to the changing realities of the financial landscape

Substitution Reactions of (C5Ph5)Cr(CO)3: Structural, Electrochemical, and Spectroscopic Characterization of (C5Ph5)Cr(CO)2L, L = PMe3, PMe2Ph, P(OMe)3

The radical complex (C5Ph5)Cr(CO)3 reacts with small, neutral, monodentate Lewis bases (PMe3, PMe2Ph, P(OMe)3) in THF at −78 °C (PMe2Ph reacts at ambient temperature) to yield the monomeric substitution products (C5Ph5)Cr(CO)2L·THF as thermally stable solids. Electrochemical and spectroscopic data are provided. An X-ray crystal structure of the hemisolvate (C5Ph5)Cr(CO)2PMe3·0.5THF was obtained. Frozen-solution ESR spectra of (C5Ph5)Cr(CO)2L in toluene are comparable to those of other low-spin d5 “piano-stool” complexes. Rotation of the Cr(CO)2L moiety relative to the C5Ph5 ring is rapid on the ESR time scale in low-temperature liquid solutions and leads to axial powderlike spectra. Analysis of this effect leads to significant insights into the electronic structure

Braggoriton--Excitation in Photonic Crystal Infiltrated with Polarizable Medium

Light propagation in a photonic crystal infiltrated with polarizable molecules is considered. We demonstrate that the interplay between the spatial dispersion caused by Bragg diffraction and polaritonic frequency dispersion gives rise to novel propagating excitations, or braggoritons, with intragap frequencies. We derive the braggoriton dispersion relation and show that it is governed by two parameters, namely, the strength of light-matter interaction and detuning between the Bragg frequency and that of the infiltrated molecules. We also study defect-induced states when the photonic band gap is divided into two subgaps by the braggoritonic branches and find that each defect creates two intragap localized states inside each subgap.Comment: LaTeX, 8 pages, 5 figure

Workload and Performance in FOPA: A Strategic Planning Interface for Air Traffic Control

The Flight Organizer Planning Aid (FOPA) interface was designed to aid strategic planning in air traffic control. In particular, FOPA was designed to address difficulties in solving en route sequencing problems (combining multiple streams of traffic into a single stream heading for a destination). We compared the planning performance of 12 full performance level air traffic controllers using either the FOPA interface or normal flight progress strips. Planning performance was significantly better when using FOPA; subjective workload was also reduced. The results indicate that a key advantage of FOPA lies in its dynamic linkage between the flight organizer screen where aircraft tokens can be categorized into color-coded blocks and their matching spatial representation on the radar.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline