6,063 research outputs found
Second-class Citizenship: The Tension between the Supremacy of the People and Minority Rights, 43 J. Marshall L. Rev. 963 (2010)
Genotoxicity of cytokines at chemotherapy-induced 'storm' concentrations in a model of the human bone marrow
Donor cell leukaemia (DCL) is a complication of haematopoietic stem cell transplantation where donated cells become malignant within the patient's bone marrow. As DCL predominates as acute myeloid leukaemia, we hypothesised that the cytokine storm following chemotherapy played a role in promoting and supporting leukaemogenesis. Cytokines have also been implicated in genotoxicity, thus we explored a cell line model of the human BM to secrete myeloid cytokines following drug treatment, and their potential to induce micronuclei. HS-5 human stromal cells were exposed to mitoxantrone (MTX) and chlorambucil (CHL) and for the first time, were profiled for 80 cytokines using an array. Fifty-four cytokines were detected in untreated cells, of which 24 were upregulated, and 10 were downregulated by both drugs. FGF-7 was the lowest cytokine to be detected in both untreated and treated cells. Eleven cytokines not detected at baseline were detected following drug exposure. TNFι, IL6, GM-CSF, G-CSF and TGFβ1 were selected for micronuclei induction. TK6 cells were exposed to these cytokines in isolation and in paired combinations. Only TNFι and TGFβ1 induced micronuclei at healthy concentrations, but all five cytokines induced micronuclei at storm levels, which was further increased when combined in pairs. Of particular concern was that some combinations induced micronuclei at levels above the mitomycin C positive control, however most combinations were less than the sum of micronuclei induced following exposure to each cytokine in isolation. These data infer a possible role for cytokines through chemotherapy-induced cytokine storm, in the instigation and support of leukaemogenesis in the BM, and implicate the need to evaluate individuals for variability in cytokine secretion as a potential risk factor for complications such as DCL. [Abstract copyright: Š The Author(s) 2023. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.
Quantitative Microscopy of Hepatic Changes Induced by Phenethyl Isothiocyanate in Fischer-344 Rats Fed Either a Cereal-Based Diet or a Purified Diet
Hepatic changes induced by phenethyl isothiocyanate (PEITC) in the liver of rats were determined by quantitative microscopy. Groups of male Fischer-344 rats were fed either a standard, cereal-based diet (Wayne rodent meal) or a purified diet (AIN-76A) containing PEITC at concentrations of 0.75 and 6.0 mmol/kg for 13 wk. Severe hepatic lipidosis was observed in control rats fed the purified diet. Addition of PEITC to the purified diet significantly reduced lipid content in hepatocytes. In contrast, lipid content in the liver of the rats fed the cereal-based diet containing PEITC was greater than in control rats maintained on the same diet. In addition, dose-related reductions in hepatocyte, lipid droplet, peroxisome, and mitochondrial volumes were observed in PEITC-treated rats fed the cereal-based diet. These results indicate that PEITC exerts differential effects on the liver of rats fed either the cereal-based or purified diet.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68493/2/10.1177_019262339502300602.pd
The Diboson Excess: Experimental Situation and Classification of Explanations; A Les Houches Pre-Proceeding
We examine the `diboson' excess at TeV seen by the LHC experiments
in various channels. We provide a comparison of the excess significances as a
function of the mass of the tentative resonance and give the signal cross
sections needed to explain the excesses. We also present a survey of available
theoretical explanations of the resonance, classified in three main approaches.
Beyond that, we discuss methods to verify the anomaly, determining the major
properties of the various surpluses and exploring how different models can be
discriminated. Finally, we give a tabular summary of the numerous explanations,
presenting their main phenomenological features.Comment: 37 pages, 9 Figures, 1 Tabl
Instability in clinical risk stratification models using deep learning
While it has been well known in the ML community that deep learning models
suffer from instability, the consequences for healthcare deployments are under
characterised. We study the stability of different model architectures trained
on electronic health records, using a set of outpatient prediction tasks as a
case study. We show that repeated training runs of the same deep learning model
on the same training data can result in significantly different outcomes at a
patient level even though global performance metrics remain stable. We propose
two stability metrics for measuring the effect of randomness of model training,
as well as mitigation strategies for improving model stability.Comment: Accepted for publication in Machine Learning for Health (ML4H) 202
TTN genotype is associated with fascicle length and marathon running performance
Titin provides a molecular blueprint for muscle sarcomere assembly, and sarcomere length can vary according to titin isoform expression. If variations in sarcomere length influence muscle fascicle length, this may provide an advantage for running performance. Thus, the aim of this study was to investigate whether the titin (TTN) rs10497520 polymorphism was associated with muscle fascicle length in recreationally active men (RA; n=137) and marathon personal best time in male marathon runners (MR; n=141). Fascicle length of the vastus lateralis was assessed in vivo using B-mode ultrasonography at 50% of muscle length in RA. All participants provided either a whole blood, saliva or buccal cell sample, from which DNA was isolated and genotyped using real-time polymerase chain reaction. Vastus lateralis fascicle length was 10.4% longer in CC homozygotes, those carrying two copies of the C-allele, than CT heterozygotes (P=.003) in RA. In the absence of any TT homozygotes, reflective of the low T-allele frequency within Caucasian populations, it is unclear whether fascicle length for this group would have been smaller still. No differences in genotype frequency between the RA and MR groups were observed (P=.500), although within the MR group, the T-allele carriers demonstrated marathon personal best times 2Â minutes 25Â seconds faster than CC homozygotes (P=.020). These results suggest that the T-allele at rs10497520 in the TTN gene is associated with shorter skeletal muscle fascicle length and conveys an advantage for marathon running performance in habitually trained men
Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV
A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay
channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7
TeV is presented. The data were collected at the LHC, with the CMS detector,
and correspond to an integrated luminosity of 4.6 inverse femtobarns. No
significant excess is observed above the background expectation, and upper
limits are set on the Higgs boson production cross section. The presence of the
standard model Higgs boson with a mass in the 270-440 GeV range is excluded at
95% confidence level.Comment: Submitted to JHE
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A Search for Dark Higgs Bosons
Recent astrophysical and terrestrial experiments have motivated the proposal
of a dark sector with GeV-scale gauge boson force carriers and new Higgs
bosons. We present a search for a dark Higgs boson using 516 fb-1 of data
collected with the BABAR detector. We do not observe a significant signal and
we set 90% confidence level upper limits on the product of the Standard
Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots
for b/w printin
Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV
A search for new physics is presented based on an event signature of at least
three jets accompanied by large missing transverse momentum, using a data
sample corresponding to an integrated luminosity of 36 inverse picobarns
collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector
at the LHC. No excess of events is observed above the expected standard model
backgrounds, which are all estimated from the data. Exclusion limits are
presented for the constrained minimal supersymmetric extension of the standard
model. Cross section limits are also presented using simplified models with new
particles decaying to an undetected particle and one or two jets
Combined search for the quarks of a sequential fourth generation
Results are presented from a search for a fourth generation of quarks
produced singly or in pairs in a data set corresponding to an integrated
luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in
2011. A novel strategy has been developed for a combined search for quarks of
the up and down type in decay channels with at least one isolated muon or
electron. Limits on the mass of the fourth-generation quarks and the relevant
Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a
simple extension of the standard model with a sequential fourth generation of
fermions. The existence of mass-degenerate fourth-generation quarks with masses
below 685 GeV is excluded at 95% confidence level for minimal off-diagonal
mixing between the third- and the fourth-generation quarks. With a mass
difference of 25 GeV between the quark masses, the obtained limit on the masses
of the fourth-generation quarks shifts by about +/- 20 GeV. These results
significantly reduce the allowed parameter space for a fourth generation of
fermions.Comment: Replaced with published version. Added journal reference and DO
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