Dark-adapted red flash ERGs in healthy adults

Purpose: The x-wave of the dark-adapted (DA) ERG to a red flash reflects DA cone function. This exploratory study of healthy adults aimed to investigate changes in the DA red ERG with flash strength and during dark adaptation to optimise visualisation and therefore quantification of the x-wave. Methods: The effect of altering red flash strength was investigated in four subjects by recording ERGs after 20 minutes dark adaptation to red flashes (0.2–2.0 cd s m-2) using skin electrodes and natural pupils. The effect of dark adaptation duration was investigated in 16 subjects during 20 minutes in the dark, by recording DA 1.5 red ERGs at 1, 2, 3, 4, 5, 10, 15 and 20 minutes. Results: For a dark adaption period of 20 minutes, the x-wave was more clearly visualised to weaker (< 0.6 cd s m-2) red flash strengths: to stronger flashes it became obscured by the b-wave. For red flashes of 1.5 cd s m-2, the x-wave was most prominent in ERGs recorded after 1–5 minutes of dark adaptation: with longer dark-adaptation, it was subsumed into the b-wave’s rising edge. Conclusions: This small study suggests that x-wave visibility in healthy subjects after 20 minutes dark adaptation is improved by using flashes weaker than around 0.6 cd s m-2; for flash strengths of 1.5 cd s m-2, x-wave visibility is enhanced by recording after only around 5 minutes of dark adaptation. No evidence was found that interim red flash ERGs affecting the dark-adapted state of the normal retina

Geometry of Schroedinger Space-Times II: Particle and Field Probes of the Causal Structure

We continue our study of the global properties of the z=2 Schroedinger space-time. In particular, we provide a codimension 2 isometric embedding which naturally gives rise to the previously introduced global coordinates. Furthermore, we study the causal structure by probing the space-time with point particles as well as with scalar fields. We show that, even though there is no global time function in the technical sense (Schroedinger space-time being non-distinguishing), the time coordinate of the global Schroedinger coordinate system is, in a precise way, the closest one can get to having such a time function. In spite of this and the corresponding strongly Galilean and almost pathological causal structure of this space-time, it is nevertheless possible to define a Hilbert space of normalisable scalar modes with a well-defined time-evolution. We also discuss how the Galilean causal structure is reflected and encoded in the scalar Wightman functions and the bulk-to-bulk propagator.Comment: 32 page

Thermoluminescence of zircon: a kinetic model

The mineral zircon, ZrSiO4, belongs to a class of promising materials for geochronometry by means of thermoluminescence (TL) dating. The development of a reliable and reproducible method for TL dating with zircon requires detailed knowledge of the processes taking place during exposure to ionizing radiation, long-term storage, annealing at moderate temperatures and heating at a constant rate (TL measurements). To understand these processes one needs a kinetic model of TL. This paper is devoted to the construction of such amodel. The goal is to study the qualitative behaviour of the system and to determine the parameters and processes controlling TL phenomena of zircon. The model considers the following processes: (i) Filling of electron and hole traps at the excitation stage as a function of the dose rate and the dose for both (low dose rate) natural and (high dose rate) laboratory irradiation. (ii) Time dependence of TL fading in samples irradiated under laboratory conditions. (iii) Short time annealing at a given temperature. (iv) Heating of the irradiated sample to simulate TL experiments both after laboratory and natural irradiation. The input parameters of the model, such as the types and concentrations of the TL centres and the energy distributions of the hole and electron traps, were obtained by analysing the experimental data on fading of the TL-emission spectra of samples from different geological locations. Electron paramagnetic resonance (EPR) data were used to establish the nature of the TL centres. Glow curves and 3D TL emission spectra are simulated and compared with the experimental data on time-dependent TL fading. The saturation and annealing behaviour of filled trap concentrations has been considered in the framework of the proposed kinetic model and comparedwith the EPR data associated with the rare-earth ions Tb3+ and Dy3+, which play a crucial role as hole traps and recombination centres. Inaddition, the behaviour of some of the SiOmn− centres has been compared with simulation results.

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Sexual (Dis)satisfaction and Its Contributors Among People Living with HIV Infection in Sweden

Earlier research reports lower sexual satisfaction among people living with HIV (PLHIV) compared to HIV-negative persons. A number of psychosocial factors directly associated with sexual dissatisfaction have been identified. Little is known about sexual satisfaction and their contributors among PLHIV in Sweden. The aim of this study was to examine direct and indirect effects of variables within sociodemographic, clinical HIV-related, psychological, and sexual domains on sexual(dis)satisfaction among PLHIV in Sweden. Data for this study was derived from a national representative, anonymous survey among PLHIV conducted in 2014 (n=1096). Statistical analysis included four steps: descriptive analyses, identification of variables associated with sexual (dis)satisfaction, identification of variables associated with those contributors of sexual (dis)satisfaction, and a path model integrating all these analyses. A total of 49% of participants reported being sexually dissatisfied and no significant differences were observed when non-heterosexual men, heterosexual men and women were compared. Among women, a negative change in sex life after HIV diagnosis and distress with orgasmic difficulties were directly associated with sexual dissatisfaction. For men, hopelessness, high HIV stigma, sexual inactivity in the last 6 months, and a negative change in sex life after HIV diagnosis were directly associated with sexual dissatisfaction. Path analyses showed in both men and women significant indirect association between not being involved in an intimate relationship, lower self-reported CD4 cell counts, and perceiving obligation to disclose HIV status to sexual partners as a barrier to look for a long-term partner and sexual dissatisfaction. Our results show that despite good treatment outcomes, the HIV diagnosis has a negative bearing on sexual satisfaction. The need for gender-tailored interventions and clinical implications of these findings are discussed

Chronic Hypoxia Impairs Muscle Function in the Drosophila Model of Duchenne's Muscular Dystrophy (DMD)

Duchenne's muscular dystrophy (DMD) is a severe progressive myopathy caused by mutations in the DMD gene leading to a deficiency of the dystrophin protein. Due to ongoing muscle necrosis in respiratory muscles late-stage DMD is associated with respiratory insufficiency and chronic hypoxia (CH). To understand the effects of CH on dystrophin-deficient muscle in vivo, we exposed the Drosophila model for DMD (dmDys) to CH during a 16-day ascent to the summit of Mount Denali/McKinley (6194 meters above sea level). Additionally, dmDys and wild type (WT) flies were also exposed to CH in laboratory simulations of high altitude hypoxia. Expression profiling was performed using Affymetrix GeneChips® and validated using qPCR. Hypoxic dmDys differentially expressed 1281 genes, whereas the hypoxic WT flies differentially expressed 56 genes. Interestingly, a number of genes (e.g. heat shock proteins) were discordantly regulated in response to CH between dmDys and WT. We tested the possibility that the disparate molecular responses of dystrophin-deficient tissues to CH could adversely affect muscle by performing functional assays in vivo. Normoxic and CH WT and dmDys flies were challenged with acute hypoxia and time-to-recover determined as well as subjected to climbing tests. Impaired performance was noted for CH-dmDys compared to normoxic dmDys or WT flies (rank order: Normoxic-WT ≈ CH-WT> Normoxic-dmDys> CH-dmDys). These data suggest that dystrophin-deficiency is associated with a disparate, pathological hypoxic stress response(s) and is more sensitive to hypoxia induced muscle dysfunction in vivo. We hypothesize that targeting/correcting the disparate molecular response(s) to hypoxia may offer a novel therapeutic strategy in DMD

Photo-tautomerization of acetaldehyde as a photochemical source of formic acid in the troposphere

Organic acids play a key role in the troposphere, contributing to atmospheric aqueous-phase chemistry, aerosol formation, and precipitation acidity. Atmospheric models currently account for less than half the observed, globally averaged formic acid loading. Here we report that acetaldehyde photo-tautomerizes to vinyl alcohol under atmospherically relevant pressures of nitrogen, in the actinic wavelength range, λ = 300–330 nm, with measured quantum yields of 2–25%. Recent theoretical kinetics studies show hydroxyl-initiated oxidation of vinyl alcohol produces formic acid. Adding these pathways to an atmospheric chemistry box model (Master Chemical Mechanism) demonstrates increased formic acid concentrations by a factor of ~1.7 in the polluted troposphere and a factor of ~3 under pristine conditions. Incorporating this mechanism into the GEOS-Chem 3D global chemical transport model reveals an estimated 7% contribution to worldwide formic acid production, with up to 60% of the total modeled formic acid production over oceans arising from photo-tautomerization