Inhibition of apoptosis prevents West Nile virus induced cell death

We found that WNV infection induces cell death in the brain-derived tumour cell line T98G by apoptosis under involvement of constituents of the extrinsic as well as the intrinsic apoptotic pathways. Our results illuminate the molecular mechanism of WNV-induced neural cell death

Effect of operating temperature on degradation of solder joints in crystalline silicon photovoltaic modules for improved reliability in hot climates

Accelerated degradation of solder joint interconnections in crystalline silicon photovoltaic (c-Si PV) modules drives the high failure rate of the system operating in elevated temperatures. The phenomenon challenges the thermo-mechanical reliability of the system for hot climatic operations. This study investigates the degradation of solder interconnections in c-Si PV modules for cell temperature rise from 25 °C STC in steps of 1 °C to 120 °C. The degradation is measured using accumulated creep strain energy density (Wacc). Generated Wacc magnitudes are utilised to predict the fatigue life of the module for ambient temperatures ranging from European to hot climates. The ANSYS mechanical package coupled with the IEC 61,215 standard accelerated thermal cycle (ATC) profile is employed in the simulation. The Garofalo creep model is used to model the degradation response of solder while other module component materials are simulated with appropriate material models. Solder degradation is found to increase with every 1 °C cell temperature rise from the STC. Three distinct degradation rates in Pa/°C are observed. Region 1, 25 to 42 °C, is characterised by degradation rate increasing quadratically from 1.53 to 10.03 Pa/°C. The degradation rate in region 2, 43 to 63 °C, is critical with highest constant magnitude of 12.06 Pa/°C. Region 3, 64 to 120 °C, demonstrates lowest degradation rate of logarithmic nature with magnitude 5.47 at the beginning of the region and 2.25 Pa/°C at the end of the region. The module fatigue life, L (in years) is found to decay according to the power function L=721.48T-1.343. The model predicts module life in London and hot climate to be 18.5 and 9 years, respectively. The findings inform on the degradation of c-Si PV module solder interconnections in different operating ambient temperatures and advise on its operational reliability for improved thermo-mechanical design for hot climatic operations

Activation of Cytotoxic and Regulatory Functions of NK Cells by Sindbis Viral Vectors

Oncolytic viruses (OVs) represent a relatively novel anti-cancer modality. Like other new cancer treatments, effective OV therapy will likely require combination with conventional treatments. In order to design combinatorial treatments that work well together, a greater scrutiny of the mechanisms behind the individual treatments is needed. Sindbis virus (SV) based vectors have previously been shown to target and kill tumors in xenograft, syngeneic, and spontaneous mouse models. However, the effect of SV treatment on the immune system has not yet been studied. Here we used a variety of methods, including FACS analysis, cytotoxicity assays, cell depletion, imaging of tumor growth, cytokine blockade, and survival experiments, to study how SV therapy affects Natural Killer (NK) cell function in SCID mice bearing human ovarian carcinoma tumors. Surprisingly, we found that SV anti-cancer efficacy is largely NK cell-dependent. Furthermore, the enhanced therapeutic effect previously observed from Sin/IL12 vectors, which carry the gene for interleukin 12, is also NK cell dependent, but works through a separate IFNγ-dependent mechanism, which also induces the activation of peritoneal macrophages. These results demonstrate the multimodular nature of SV therapy, and open up new possibilities for potential synergistic or additive combinatorial therapies with other treatments

Interleukin-15 Plays a Central Role in Human Kidney Physiology and Cancer through the γc Signaling Pathway

The ability of Interleukin-15 (IL-15) to activate many immune antitumor mechanisms renders the cytokine a good candidate for the therapy of solid tumors, particularly renal cell carcinoma. Although IL-15 is being currently used in clinical trials, the function of the cytokine on kidney's components has not been extensively studied; we thus investigated the role of IL-15 on normal and tumor renal epithelial cells. Herein, we analyzed the expression and the biological functions of IL-15 in normal renal proximal tubuli (RPTEC) and in their neoplastic counterparts, the renal clear cell carcinomas (RCC). This study shows that RPTEC express a functional heterotrimeric IL-15Rαβγc complex whose stimulation with physiologic concentrations of rhIL-15 is sufficient to inhibit epithelial mesenchymal transition (EMT) commitment preserving E-cadherin expression. Indeed, IL-15 is not only a survival factor for epithelial cells, but it can also preserve the renal epithelial phenotype through the γc-signaling pathway, demonstrating that the cytokine possess a wide range of action in epithelial homeostasis. In contrast, in RCC in vitro and in vivo studies reveal a defect in the expression of γc-receptor and JAK3 associated kinase, which strongly impacts IL-15 signaling. Indeed, in the absence of the γc/JAK3 couple we demonstrate the assembly of an unprecedented functional high affinity IL-15Rαβ heterodimer, that in response to physiologic concentrations of IL-15, triggers an unbalanced signal causing the down-regulation of the tumor suppressor gene E-cadherin, favoring RCC EMT process. Remarkably, the rescue of IL-15/γc-dependent signaling (STAT5), by co-transfecting γc and JAK3 in RCC, inhibits EMT reversion. In conclusion, these data highlight the central role of IL-15 and γc-receptor signaling in renal homeostasis through the control of E-cadherin expression and preservation of epithelial phenotype both in RPTEC (up-regulation) and RCC (down-regulation)

A review of photovoltaic module technologies for increased performance in tropical climate

The global adoption and use of photovoltaic modules (PVMs) as the main source of energy is the key to realising the UN Millennium Development Goals on Green Energy. The technology – projected to contribute about 20% of world energy supply by 2050, over 60% by 2100 and leading to 50% reduction in global CO2 emissions – is threatened by its poor performance in tropical climate. Such performance discourages its regional acceptance. The magnitude of crucial module performance influencing factors (cell temperature, wind speed and relative humidity) reach critical values of 90 °C, 0.2 m/s and 85%, respectively in tropical climates which negatively impact module performance indices which include power output (PO), power conversion efficiency (PCE) and energy payback time (EPBT). This investigation reviews PVM technologies which include cell, contact and interconnection technologies. It identifies critical technology route(s) with potential to increase operational reliability of PVMs in the tropics when adopted. The cell performance is measured by PO, PCE and EPBT while contacts and interconnections performance is measured by the degree of recombination, shading losses and also the rate of thermo-mechanical degradation. It is found that the mono-crystalline cell has the best PCE of 25% while the Cadmium Telluride (CdTe) cell has the lowest EPBT of 8-months. Results show that the poly-crystalline cell has the largest market share amounting to 54%. The CdTe cell exhibits 0% drop in PCE at high-temperatures and low irradiance operations – demonstrating least affected PO by the conditions. Further results establish that back contacts and back-to-back interconnection technologies produce the least recombination losses and demonstrate absence of shading in addition to possessing longest interconnection fatigue life. Based on these findings, the authors propose a PVM comprising CdTe cell, back contacts and back-to-back interconnection technologies as the technology with latent capacity to produce improved performance in tropical climates

Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression

Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease

Acquired resistance to oxaliplatin is not directly associated with increased resistance to DNA damage in SK-N-ASrOXALI4000, a newly established oxaliplatin-resistant sub-line of the neuroblastoma cell line SK-N-AS

The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin. SK-N-ASrOXALI4000 cells exhibited a stable resistance phenotype that was not affected by culturing the cells for 10 weeks in the absence of oxaliplatin. Interestingly, SK-N-ASrOXALI4000 cells showed no cross resistance to gemcitabine and increased sensitivity to doxorubicin and UVC radiation, alternative treatments that like platinum drugs target DNA integrity. Notably, UVC-induced DNA damage is thought to be predominantly repaired by nucleotide excision repair and nucleotide excision repair has been described as the main oxaliplatin-induced DNA damage repair system. SK-N-ASrOXALI4000 cells were also more sensitive to lysis by influenza A virus, a candidate for oncolytic therapy, than SK-N-AS cells. In conclusion, we introduce a novel oxaliplatin resistance model. The oxaliplatin resistance mechanisms in SK-N-ASrOXALI4000 cells appear to be complex and not to directly depend on enhanced DNA repair capacity. Models of oxaliplatin resistance are of particular relevance since research on platinum drugs has so far predominantly focused on cisplatin and carboplatin

Evaluation of the burden of opioid abuse among US veteran patients

Onur Başer (MEF Author)##nofulltext##..

FIA-SYSTEMS FOR THE DETERMINATION OF MALTOSE, LACTATE AND VOLATILE SUBSTANCES IN BEER, WINE AND FERMENTATION BROTHS

FIA-systems with immobilized enzymes for analysis of substrates in biological matrices are described. Direct or coupled reactions lead to the commonproduct NADH, which is determined byfluorimetry. The flow systems imply modulesfor the purification, dilution and pH adjustment of the samples. A system is presented for the determinationof volatile substrates using pervaporation as sample purification. Applications for the quantification of ethanol in beer (measurable range 0.5 - 20 mM) and acetaldehyde in wine (measurable range 0.01 - 0.05 mM) are given. By automated switching of the analyte between parallel assembled dehydrogenase columnsthe control of ethanol (calibration range 0.03 -10 mM) and lactate (calibration range 0.01 - 10 mM)in a fermentation of Clostridium thermohydrosulfuricum is possible. The determinations show goodreproducibility and Satisfactory agreement with results of a common enzymatic test-kit. A more sophisticated experimental setup including ion exchange and dialysis as purification steps is developedfor cyclic/parallel determination of glucose, maltose(linear range 0.3 - 15 mM for both sugars) and ethanol(linear range 6 - 500 mM)in beer. Process stability of the enzymes proved to be Satisfying