54 research outputs found
Opposite effects of two zinc(II) dithiocarbamates on NF-kB pathway
Inhibiting nuclear factor-kappaB (NF-kB) activation in anticancer and antiinflammatory therapy is of topical interest. Current research in molecular biology has dramatically advanced in the understanding of the cellular events involved in NF-kB induction. Dithiocarbamates, in particular diethyldithiocarbamate and pyrrolidinedithiocarbamate, have been known and widely used as strong inhibitors of NF-kB signaling pathway for more than ten years. Their activity is frequently thought to be due to chelating of zinc or copper present in serum supplemented in the culture medium. Zinc(II) diethyldithiocarbamate (Et2Zn) and zinc(II) dibenzyldithiocarbamate (Bz2Zn) were prepared by direct synthesis in aqueous millieu. They were structurally characterized by X-ray analysis (solid phase) and mass spectrometry (aqueous conditions). Et2Zn and Bz2Zn both in 20 micromolar concentration were applied to HeLa cells. The status of NF-kB signaling was assessed as nuclear translocation of p65 subunit. Surprisingly, Et2Zn activated NF-kB pathway, while TNF-dependent activation of NF-kB was inhibited by Bz2Zn. Our results are preliminary
Joint measurement of complementary observables in moment tomography
Wigner and Husimi quasi-distributions, owing to their functional regularity,
give the two archetypal and equivalent representations of all
observable-parameters in continuous-variable quantum information. Balanced
homodyning and heterodyning that correspond to their associated sampling
procedures, on the other hand, fare very differently concerning their state or
parameter reconstruction accuracies. We present a general theory of a now-known
fact that heterodyning can be tomographically more powerful than balanced
homodyning to many interesting classes of single-mode quantum states, and
discuss the treatment for two-mode sources.Comment: 15 pages, 4 figures, conference proceedings for Quantum 2017 in
Torin
A new algorithm for detecting failure to clear mode of circuit breakers using fundamental frequency component of voltage signals
This paper introduces a new algorithm for the early detection of abnormal arcing conditions of circuit breakers (CBs). Any interruption with a higher arcing time compared to maximum permissible arcing time (MPAT) of CB is defined as a CB failure to clear mode. Measuring CB arcing time is not easy because there is no control on the mechanical opening and closing instants of CB contacts. Nevertheless, there is a correlation between the spectral energy densities of CB arcing voltages and arcing times of CB. This correlation is used by calculating the spectral energy densities of the instantaneous system voltage and the instantaneous CB voltage across its terminals utilizing discrete Fourier transform (DFT) for two periods of the system frequency. The difference between the spectral energy densities at the fundamental frequency is defined as a criterion for identifying a failure to clear mode. Whenever this criterion exceeds a predefined trip level, it indicates the occurrence of a failure to clear mode. In this situation, a trip signal is initiated for adjacent CBs to isolate the faulted CB and the fault. The results obtained from computer simulations and measurements show that the algorithm discriminates between normal and abnormal arcing conditions of CB
An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers
Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe
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