A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration

Toxicolog

Atoms interacting with intense, high-frequency laser pulses: Effect of the magnetic-field component on atomic stabilization

Published versio

Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale

Searches for electroweak neutralino and chargino production in channels with Higgs, Z, and W bosons in pp collisions at 8 TeV

Searches for supersymmetry (SUSY) are presented based on the electroweak pair production of neutralinos and charginos, leading to decay channels with Higgs, Z, and W bosons and undetected lightest SUSY particles (LSPs). The data sample corresponds to an integrated luminosity of about 19.5 fb(-1) of proton-proton collisions at a center-of-mass energy of 8 TeV collected in 2012 with the CMS detector at the LHC. The main emphasis is neutralino pair production in which each neutralino decays either to a Higgs boson (h) and an LSP or to a Z boson and an LSP, leading to hh, hZ, and ZZ states with missing transverse energy (E-T(miss)). A second aspect is chargino-neutralino pair production, leading to hW states with E-T(miss). The decays of a Higgs boson to a bottom-quark pair, to a photon pair, and to final states with leptons are considered in conjunction with hadronic and leptonic decay modes of the Z and W bosons. No evidence is found for supersymmetric particles, and 95% confidence level upper limits are evaluated for the respective pair production cross sections and for neutralino and chargino mass values

Isolated Tumor Cells in Breast

Contains fulltext : 80046.pdf (publisher's version ) (Open Access

SIRT1 stimulation by polyphenols is affected by their stability and metabolism

Silent information regulator two ortholog 1 (SIRT1) is the human ortholog of the yeast sir2 protein; one of the most important regulators of lifespan extension by caloric restriction in several organisms. Dietary polyphenols, abundant in vegetables, fruits, cereals, wine and tea, were reported to stimulate the deacetylase activity of recombinant SIRT1 protein and could therefore be potential regulators of aging associated processes. However, inconsistent data between effects of polyphenols on the recombinant SIRT1 and on in vivo SIRT1, led us to investigate the influence of (1) stability of polyphenols under experimental conditions and (2) metabolism of polyphenols in human HT29 cells, on stimulation of SIRT1. With an improved SIRT1 deacetylation assay we found three new polyphenolic stimulators. Epigallocatechin galate (EGCg, 1.76-fold), epicatechin galate (ECg, 1.85-fold) and myricetin (3.19-fold) stimulated SIRT1 under stabilizing conditions, whereas without stabilization, these polyphenols strongly inhibited SIRT1, probably due to H2O2 formation. Using metabolically active HT29 cells we were able to show that quercetin (a stimulator of recombinant SIRT1) could not stimulate intracellular SIRT1. The major quercetin metabolite in humans, quercetin 3-O-glucuronide, slightly inhibited the recombinant SIRT1 activity which explains the lack of stimulatory action of quercetin in HT29 cells. This study shows that the stimulation of SIRT1 is strongly affected by polyphenol stability and metabolism, therefore extrapolation of in vitro SIRT1 stimulation results to physiological effects should be done with caution

Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis

SummaryBackground & aimsOxidative stress and low antioxidant levels are implicated in the aetiology of sarcoidosis, an inflammatory disease. Quercetin is a potent dietary antioxidant that also displays anti-inflammatory activities. Consequently, the aim is to examine the effect of quercetin supplementation on markers of oxidative stress and inflammation in sarcoidosis.MethodsA double-blind intervention study has been conducted with two groups of non-smoking, un-treated sarcoidosis patients, matched for age and gender. One group was given 4x500 mg quercetin (n = 12) orally within 24 h, the other one placebo (n = 6). Plasma malondialdehyde levels were used as marker of oxidative damage, plasma ratios of TNFα/IL-10 and IL-8/IL-10 as pro-inflammatory markers.ResultsQuercetin supplementation improved the antioxidant defence, indicated by the increased total plasma antioxidant capacity. Moreover, quercetin supplementation also reduced markers of oxidative stress and inflammation in the blood of sarcoidosis patients. The effects of quercetin supplementation appeared to be more pronounced when the levels of the oxidative stress and inflammation markers were higher at baseline.ConclusionsSarcoidosis patients might benefit from the use of antioxidants, such as quercetin, to reduce the occurring oxidative stress as well as inflammation. The effects of long-term use of antioxidant supplementation in sarcoidosis, using e.g. quercetin, on improvement of lung function remain to be investigated. (www.clinicaltrials.gov; NCT-00402623)

Diagnostic challenges of respiratory adverse events during everolimus treatment

Contains fulltext : 137780.pdf (publisher's version ) (Closed access)Everolimus has important clinical activity in various malignancies, but its use can be complicated by respiratory adverse events. Important everolimus-induced respiratory adverse events are interstitial lung disease (ILD) and infections, either typical or opportunistic. Furthermore, non-everolimus-related respiratory events can occur. Due to the non-specific presentation of most of these respiratory disorders, it is often not possible to differentiate between these causes on clinical and radiological grounds only. Considering the potential fatal nature of opportunistic infections, these are especially important to recognize. To be able to distinguish between ILD and (opportunistic) infections as the underlying cause, an aggressive diagnostic workup, including bronchoalveolar lavage, should be performed in patients treated with everolimus who develop respiratory disease. We report three cases of severe opportunistic pulmonary infections during everolimus treatment, concerning two Pneumocystis jirovecii pneumonia infections. These cases illustrate the diagnostic challenges of respiratory adverse events and the importance of a thorough diagnostic workup for correct diagnosis and treatment