A Mechanistic Study on the Non-genotoxic Carcinogenicity of the Food Contaminant Semicarbazide

Semicarbazide was brought to the forefront of scientific discussions by the scientific community in the early 2000’s as the substance was discovered in several food products from both synthetic and natural sources. Although semicarbazide was processed through several toxicological assays and classified as a non-genotoxic carcinogen, underwhelming amounts of toxicological data exists for the compound. The present study is one of the first in-vitro studies to examine the relationship between sub-pathophysiological concentrations of reactive oxygen species and the anomalous non-genotoxic carcinogenicity induced by semicarbazide through the upregulation of intracellular signalling pathways. A novel finding of the present study was where NRK cells were exposed to micromolar concentrations of semicarbazide, an inverse relationship between protein kinase C activity, and free radical concentration proportionally increases \u3e 2-fold. It is the hypothesis of the present study that the \u3e2-fold increase in free radical concentration and upregulation of protein kinase C from the 0.01mM treatment of semicarbazide has the capacity to alter physiological signalling mechanisms into a sub- pathophysiological state. These changes in the cellular environment could be the initiation mechanism that facilitates the manifestation of cancer in a cell population. The induced upregulation of protein kinase C activity within NRK cells by semicarbazide can be extrapolated to downstream mediators of the Ca2+ dependent signalling pathway and the mitogen activated protein kinase signalling pathway. The hypothesis of the present study concludes by highlighting the importance of these pathways in the manifestation of semicarbazide induced non-genotoxic carcinogenicity. In conclusion, this study classifies semicarbazide as an intracellular signalling mitogen based on its capacity to modulate protein kinase C activity and the concentrations of intracellular reactive oxygen species

Eclipsing Binaries as Astrophysical Laboratories: Internal Structure, Convective Core Overshooting and Evolution of the B-star Components of V380 Cygni

New photometric solutions have been carried out on the important eccentric eclipsing system V380 Cygni (B1.5II-III + B2V) from UBV differential photoelectric photometry obtained by us. The photometric elements obtained from the analysis of the light curves have been combined with the spectroscopic solution recently published by Popper & Guinan and have led to the physical properties of the system components. The effective temperature of the stars has been determined by fitting IUE UV spectrophotometry to Kurucz model atmospheres and compared with other determinations from broad-band and intermediate-band standard photometry. The values of mass, absolute radius, and effective temperature, for the primary and secondary stars are: 11.1+/-0.5 Mo, 14.7+/-0.2 Ro, 21350+/-400 K, and 6.95+/-0.25 Mo, 3.74+/-0.07 Ro, 20500+/-500 K, respectively. In addition, a re-determination of the system's apsidal motion rate has been done from the analysis of 12 eclipse timings obtained from 1923 to 1995. Using stellar structure and evolutionary models with modern input physics, tests on the extent of convection in the core of the more massive star of the system have been carried out. Both the analysis of the log g-log Teff diagram and the apsidal motion study indicate a star with a larger convective core, and thus more centrally condensed, than currently assumed. This has been quantified in form of an overshooting parameter with a value of 0.6+/-0.1. Finally, the tidal evolution of the system (synchronization and circularization times) has also been studied.Comment: 23 pages, 5 figures, version accepted for publication in Ap

An Observed Correlation Between Thermal and Non-Thermal Emission in Gamma-Ray Bursts

Recent observations by the $Fermi$ Gamma-ray Space Telescope have confirmed the existence of thermal and non-thermal components in the prompt photon spectra of some Gamma-ray bursts (GRBs). Through an analysis of six bright Fermi GRBs, we have discovered a correlation between the observed photospheric and non-thermal $\gamma$-ray emission components of several GRBs using a physical model that has previously been shown to be a good fit to the Fermi data. From the spectral parameters of these fits we find that the characteristic energies, $E_{\rm p}$ and $kT$, of these two components are correlated via the relation $E_{\rm p} \propto T^{\alpha}$ which varies from GRB to GRB. We present an interpretation in which the value of index $\alpha$ indicates whether the jet is dominated by kinetic or magnetic energy. To date, this jet composition parameter has been assumed in the modeling of GRB outflows rather than derived from the data

Faint NUV/FUV Standards from Swift/UVOT, GALEX and SDSS Photometry

At present, the precision of deep ultraviolet photometry is somewhat limited by the dearth of faint ultraviolet standard stars. In an effort to improve this situation, we present a uniform catalog of eleven new faint (u sim17) ultraviolet standard stars. High-precision photometry of these stars has been taken from the Sloan Digital Sky Survey and Galaxy Evolution Explorer and combined with new data from the Swift Ultraviolet Optical Telescope to provide precise photometric measures extending from the Near Infrared to the Far Ultraviolet. These stars were chosen because they are known to be hot (20,000 < T_eff < 50,000 K) DA white dwarfs with published Sloan spectra that should be photometrically stable. This careful selection allows us to compare the combined photometry and Sloan spectroscopy to models of pure hydrogen atmospheres to both constrain the underlying properties of the white dwarfs and test the ability of white dwarf models to predict the photometric measures. We find that the photometry provides good constraint on white dwarf temperatures, which demonstrates the ability of Swift/UVOT to investigate the properties of hot luminous stars. We further find that the models reproduce the photometric measures in all eleven passbands to within their systematic uncertainties. Within the limits of our photometry, we find the standard stars to be photometrically stable. This success indicates that the models can be used to calibrate additional filters to our standard system, permitting easier comparison of photometry from heterogeneous sources. The largest source of uncertainty in the model fitting is the uncertainty in the foreground reddening curve, a problem that is especially acute in the UV.Comment: Accepted for publication in Astrophysical Journal. 31 pages, 13 figures, electronic tables available from ApJ or on reques

Studies of Diffuse Interstellar Bands. V. Pairwise Correlations of Eight Strong DIBs and Neutral Hydrogen, Molecular Hydrogen, and Color Excess

We establish correlations between equivalent widths of eight diffuse interstellar bands (DIBs), and examine their correlations with atomic hydrogen, molecular hydrogen, and EB-V . The DIBs are centered at \lambda\lambda 5780.5, 6204.5, 6283.8, 6196.0, 6613.6, 5705.1, 5797.1, and 5487.7, in decreasing order of Pearson\^as correlation coefficient with N(H) (here defined as the column density of neutral hydrogen), ranging from 0.96 to 0.82. We find the equivalent width of \lambda 5780.5 is better correlated with column densities of H than with E(B-V) or H2, confirming earlier results based on smaller datasets. We show the same is true for six of the seven other DIBs presented here. Despite this similarity, the eight strong DIBs chosen are not well enough correlated with each other to suggest they come from the same carrier. We further conclude that these eight DIBs are more likely to be associated with H than with H2, and hence are not preferentially located in the densest, most UV shielded parts of interstellar clouds. We suggest they arise from different molecules found in diffuse H regions with very little H (molecular fraction f<0.01). Of the 133 stars with available data in our study, there are three with significantly weaker \lambda 5780.5 than our mean H-5780.5 relationship, all of which are in regions of high radiation fields, as previously noted by Herbig. The correlations will be useful in deriving interstellar parameters when direct methods are not available. For instance, with care, the value of N(H) can be derived from W{\lambda}(5780.5).Comment: Accepted for publication in The Astrophysical Journal; 37 pages, 11 figures, 6 table

Association of leukocyte telomere length with mortality among adult participants in 3 longitudinal studies

Importance: Leukocyte telomere length (LTL) is a trait associated with risk of cardiovascular disease and cancer, the 2 major disease categories that largely define longevity in the United States. However, it remains unclear whether LTL is associated with the human life span. Objective: To examine whether LTL is associated with the life span of contemporary humans. Design, Setting, and Participants: This cohort study included 3259 adults of European ancestry from the Cardiovascular Health Study (CHS), Framingham Heart Study (FHS), and Women's Health Initiative (WHI). Leukocyte telomere length was measured in 1992 and 1997 in the CHS, from 1995 to 1998 in the FHS, and from 1993 to 1998 in the WHI. Data analysis was conducted from February 2017 to December 2019. Main Outcomes and Measures: Death and LTL, measured by Southern blots of the terminal restriction fragments, were the main outcomes. Cause of death was adjudicated by end point committees. Results: The analyzed sample included 3259 participants (2342 [71.9%] women), with a median (range) age of 69.0 (50.0-98.0) years at blood collection. The median (range) follow-up until death was 10.9 (0.2-23.0) years in CHS, 19.7 (3.4-23.0) years in FHS, and 16.6 (0.5-20.0) years in WHI. During follow-up, there were 1525 deaths (482 [31.6%] of cardiovascular disease; 373 [24.5%] of cancer, and 670 [43.9%] of other or unknown causes). Short LTL, expressed in residual LTL, was associated with increased mortality risk. Overall, the hazard ratio for all-cause mortality for a 1-kilobase decrease in LTL was 1.34 (95% CI, 1.21-1.47). This association was stronger for noncancer causes of death (cardiovascular death: hazard ratio, 1.28; 95% CI, 1.08-1.52; cancer: hazard ratio, 1.13; 95% CI, 0.93-1.36; and other causes: hazard ratio, 1.53; 95% CI, 1.32-1.77). Conclusions and Relevance: The results of this study indicate that LTL is associated with a natural life span limit in contemporary humans

Intermittent control models of human standing: similarities and differences

Two architectures of intermittent control are compared and contrasted in the context of the single inverted pendulum model often used for describing standing in humans. The architectures are similar insofar as they use periods of open-loop control punctuated by switching events when crossing a switching surface to keep the system state trajectories close to trajectories leading to equilibrium. The architectures differ in two significant ways. Firstly, in one case, the open-loop control trajectory is generated by a system-matched hold, and in the other case, the open-loop control signal is zero. Secondly, prediction is used in one case but not the other. The former difference is examined in this paper. The zero control alternative leads to periodic oscillations associated with limit cycles; whereas the system-matched control alternative gives trajectories (including homoclinic orbits) which contain the equilibrium point and do not have oscillatory behaviour. Despite this difference in behaviour, it is further shown that behaviour can appear similar when either the system is perturbed by additive noise or the system-matched trajectory generation is perturbed. The purpose of the research is to come to a common approach for understanding the theoretical properties of the two alternatives with the twin aims of choosing which provides the best explanation of current experimental data (which may not, by itself, distinguish beween the two alternatives) and suggesting future experiments to distinguish between the two alternatives

Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

Simplified Models for LHC New Physics Searches

This document proposes a collection of simplified models relevant to the design of new-physics searches at the LHC and the characterization of their results. Both ATLAS and CMS have already presented some results in terms of simplified models, and we encourage them to continue and expand this effort, which supplements both signature-based results and benchmark model interpretations. A simplified model is defined by an effective Lagrangian describing the interactions of a small number of new particles. Simplified models can equally well be described by a small number of masses and cross-sections. These parameters are directly related to collider physics observables, making simplified models a particularly effective framework for evaluating searches and a useful starting point for characterizing positive signals of new physics. This document serves as an official summary of the results from the "Topologies for Early LHC Searches" workshop, held at SLAC in September of 2010, the purpose of which was to develop a set of representative models that can be used to cover all relevant phase space in experimental searches. Particular emphasis is placed on searches relevant for the first ~50-500 pb-1 of data and those motivated by supersymmetric models. This note largely summarizes material posted at http://lhcnewphysics.org/, which includes simplified model definitions, Monte Carlo material, and supporting contacts within the theory community. We also comment on future developments that may be useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results from "Topologies for Early LHC Searches" workshop (SLAC, September 2010). Supplementary material can be found at http://lhcnewphysics.or

The UK medical education database (UKMED) what is it?:Why and how might you use it?

The development of UKMED has not been directly funded by but has received support from the General Medical Council and Medical Schools Council as well as staff time from all participating organisations.Peer reviewedPublisher PD