High pressure four-way valve Patent

High pressure four-way valve with O ring adapted to pass across inlet por

Nuclear Scissors Mode with Pairing

The coupled dynamics of the scissors mode and the isovector giant quadrupole resonance are studied using a generalized Wigner function moments method taking into account pair correlations. Equations of motion for angular momentum, quadrupole moment and other relevant collective variables are derived on the basis of the time dependent Hartree-Fock-Bogoliubov equations. Analytical expressions for energy centroids and transitions probabilities are found for the harmonic oscillator model with the quadrupole-quadrupole residual interaction and monopole pairing force. Deformation dependences of energies and $B(M1)$ values are correctly reproduced. The inclusion of pair correlations leads to a drastic improvement in the description of qualitative and quantitative characteristics of the scissors mode.Comment: 36 pages, 5 figures, the results of calculation by another method and the section concerning currents are adde

Inhibition of radiation induced migration of human head and neck squamous cell carcinoma cells by blocking of EGF receptor pathways

<p>Abstract</p> <p>Background</p> <p>Recently it has been shown that radiation induces migration of glioma cells and facilitates a further spread of tumor cells locally and systemically. The aim of this study was to evaluate whether radiotherapy induces migration in head and neck squamous cell carcinoma (HNSCC). A further aim was to investigate the effects of blocking the epidermal growth factor receptor (EGFR) and its downstream pathways (Raf/MEK/ERK, PI3K/Akt) on tumor cell migration in vitro.</p> <p>Methods</p> <p>Migration of tumor cells was assessed via a wound healing assay and proliferation by a MTT colorimeritric assay using 3 HNSCC cell lines (BHY, CAL-27, HN). The cells were treated with increasing doses of irradiation (2 Gy, 5 Gy, 8 Gy) in the presence or absence of EGF, EGFR-antagonist (AG1478) or inhibitors of the downstream pathways PI3K (LY294002), mTOR (rapamycin) and MEK1 (PD98059). Biochemical activation of EGFR and the downstream markers Akt and ERK were examined by Western blot analysis.</p> <p>Results</p> <p>In absence of stimulation or inhibition, increasing doses of irradiation induced a dose-dependent enhancement of migrating cells (p < 0.05 for the 3 HNSCC cell lines) and a decrease of cell proliferation (p < 0.05 for the 3 HNSCC cell lines). The inhibition of EGFR or the downstream pathways reduced cell migration significantly (almost all p < 0.05 for the 3 HNSCC cell lines). Stimulation of HNSCC cells with EGF caused a significant increase in migration (p < 0.05 for the 3 HNSCC cell lines). After irradiation alone a pronounced activation of EGFR was observed by Western blot analysis.</p> <p>Conclusion</p> <p>Our results demonstrate that the EGFR is involved in radiation induced migration of HNSCC cells. Therefore EGFR or the downstream pathways might be a target for the treatment of HNSCC to improve the efficacy of radiotherapy.</p

DNA Fragmentation Simulation Method (FSM) and Fragment Size Matching Improve aCGH Performance of FFPE Tissues

Whole-genome copy number analysis platforms, such as array comparative genomic hybridization (aCGH) and single nucleotide polymorphism (SNP) arrays, are transformative research discovery tools. In cancer, the identification of genomic aberrations with these approaches has generated important diagnostic and prognostic markers, and critical therapeutic targets. While robust for basic research studies, reliable whole-genome copy number analysis has been unsuccessful in routine clinical practice due to a number of technical limitations. Most important, aCGH results have been suboptimal because of the poor integrity of DNA derived from formalin-fixed paraffin-embedded (FFPE) tissues. Using self-hybridizations of a single DNA sample we observed that aCGH performance is significantly improved by accurate DNA size determination and the matching of test and reference DNA samples so that both possess similar fragment sizes. Based on this observation, we developed a novel DNA fragmentation simulation method (FSM) that allows customized tailoring of the fragment sizes of test and reference samples, thereby lowering array failure rates. To validate our methods, we combined FSM with Universal Linkage System (ULS) labeling to study a cohort of 200 tumor samples using Agilent 1 M feature arrays. Results from FFPE samples were equivalent to results from fresh samples and those available through the glioblastoma Cancer Genome Atlas (TCGA). This study demonstrates that rigorous control of DNA fragment size improves aCGH performance. This methodological advance will permit the routine analysis of FFPE tumor samples for clinical trials and in daily clinical practice

Control of Oxo-Group Functionalization and Reduction of the Uranyl Ion

yesUranyl complexes of a large, compartmental N8-macrocycle adopt a rigid, “Pacman” geometry that stabilizes the UV oxidation state and promotes chemistry at a single uranyl oxo-group. We present here new and straightforward routes to singly reduced and oxo-silylated uranyl Pacman complexes and propose mechanisms that account for the product formation, and the byproduct distributions that are formed using alternative reagents. Uranyl(VI) Pacman complexes in which one oxo-group is functionalized by a single metal cation are activated toward single-electron reduction. As such, the addition of a second equivalent of a Lewis acidic metal complex such as MgN″2 (N″ = N(SiMe3)2) forms a uranyl(V) complex in which both oxo-groups are Mg functionalized as a result of Mg−N bond homolysis. In contrast, reactions with the less Lewis acidic complex [Zn(N″)Cl] favor the formation of weaker U−O−Zn dative interactions, leading to reductive silylation of the uranyl oxo-group in preference to metalation. Spectroscopic, crystallographic, and computational analysis of these reactions and of oxo-metalated products isolated by other routes have allowed us to propose mechanisms that account for pathways to metalation or silylation of the exo-oxogroup

Probing Flexibility in Porphyrin-Based Molecular Wires Using Double Electron Electron Resonance

A series of butadiyne-linked zinc porphyrin oligomers, with one, two, three, and four porphyrin units and lengths of up to 75 angstrom, have been spin-labeled at both ends with stable nitroxide TEMPO radicals. The pulsed EPR technique of double electron electron resonance (DEER) was used to probe the distribution of intramolecular end-to-end distances, under a range of conditions. DEER measurements were carried out at 50 K in two types of dilute solution glasses: deutero-toluene (with 10% deutero-pyridine) and deutero-o-terphenyl (with 5% 4-benzyl pyridine). The complexes of the porphyrin oligomers with monodentate ligands (pyridine or 4-benzyl pyridine) principally adopt linear conformations. Nonlinear conformations are less populated in the lower glass-transition temperature solvent. When the oligomers bind star-shaped multidentate ligands, they are forced to bend into nonlinear geometries, and the experimental end-to-end distances for these complexes match those from molecular mechanics calculations. Our results show that porphyrin-based molecular wires are shape-persistent, and yet that their shapes can deformed by binding to multivalent ligands. Self-assembled ladder-shaped 2:2 complexes were also investigated to illustrate the scope of DEER measurements for providing structural information on synthetic noncovalent nanostructures

Cell death during sepsis: integration of disintegration in the inflammatory response to overwhelming infection

Sepsis is a major health problem and a leading cause of death worldwide. In recent years, a crescendo of attention has been directed to the mechanisms of cell death that develop during this disease, since these are viewed as important contributors to the proinflammatory and anti-inflammatory responses associated with poor outcome. Here we discuss mechanisms of cell death evident severe bacterial infection and sepsis including necrosis, apoptosis, pyroptosis, and extracellular trap-associated neutrophil death, with a particular emphasis on lymphocyte apoptosis and its contribution to the immunosuppressed phenotype of late sepsis. Individual bacterial pathogens express virulence factors that modulate cell death pathways and influence the sepsis phenotype. A greater knowledge of cell death pathways in sepsis informs the potential for future therapies designed to ameliorate immune dysfunction in this syndrome