Letter from Moses Gomez who wishes to change his seat in synagogue

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Notice to change constitution of K. K. S. I.

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The emerging role of microRNAs in resistance to lung cancer treatments

One of the major challenges in the treatment of lung cancer is the development of drug resistance. This represents a major obstacle in the treatment of patients, limiting the efficacy of both conventional chemotherapy and biological therapies. Deciphering the mechanisms of resistance is critical to further understanding the multifactorial pathways involved, and in developing more specific targeted treatments. To date, numerous studies have reported the potential role of microRNAs (miRNAs) in resistance to various cancer treatments. MicroRNAs are a family of small non-coding RNAs that regulate gene expression by sequence-specific targeting of mRNAs causing translational repression or mRNA degradation. More than 1200 validated human miRNAs have been identified to date. While as little as one miRNA can regulate hundreds of targets, a single target can also be affected by multiple miRNAs. Evidence suggests that dysregulation of specific miRNAs may be involved in the acquisition of resistance to a number of cancer treatments, thereby modulating the sensitivity of cancer cells to such therapies. Therefore, targeting miRNAs may be an attractive strategy for developing novel and more effective individualized therapies, improving drug efficiency, and for predicting patient response to different treatments. In this review, we provide an overview on the role of miRNAs in resistance to current lung cancer therapies and novel biological agents.

Open Access to Scientific Publications – An Analysis of the Barriers to Change?

One of the effects of the Internet is that the dissemination of scientific publications in a few years has migrated to electronic formats. The basic business practices between libraries and publishers for selling and buying the content, however, have not changed much. In protest against the high subscription prices of mainstream publishers, scientists have started Open Access (OA) journals and e-print repositories, which distribute scientific information freely. Despite widespread agreement among academics that OA would be the optimal distribution mode for publicly financed research results, such channels still constitute only a marginal phenomenon in the global scholarly communication system. This paper discusses, in view of the experiences of the last ten years, the many barriers hindering a rapid proliferation of Open Access. The discussion is structured according to the main OA channels; peer-reviewed journals for primary publishing, subject- specific and institutional repositories for secondary parallel publishing. It also discusses the types of barriers, which can be classified as consisting of the legal framework, the information technology infrastructure, business models, indexing services and standards, the academic reward system, marketing, and critical mass.

DNA duplex with the potential to change handedness after every half a turn

Polymorphic forms of the DNA duplex with long stretches of structural monotony are known. Several alternating purine-pyrimidine sequences have been shown to adopt left-handed Z-conformation. We report a DNA sequence d(CGCGCGATCGAT)n exhibiting alternating right-handed B and left-handed Z helical conformation after every half a turn. Further, this unusual conformation with change in handedness after every six base pairs was induced at physiological superhelical density.

The ability of prolactin to change the sensitivity of the pituitary of the lactating rat to luteinising hormone releasing hormonein vitro

The ability of prolactin to influence the responsiveness of the lactating rat pituitary to luteinising hormone releasing hormone has been examinedin vitro. The pituitary responsivenessin vivo to luteinising hormone releasing hormone decreased as a function of increase in the lactational stimulus. Prolactin inhibited the spontaneousin vitro release of luteinising hormone and follicle stimulating hormone to a small extent, from the pituitary of lactating rats with the suckling stimulus. However, it significantly inhibited the release of these two hormones from luteinising hormone releasing hormone-stimulated pituitaries. The responsiveness of pituitaries of rats deprived of their litter 24 h earlier, to luteinising hormone releasing hormone was also inhibited by prolactin, although minimal. It was concluded that prolactin could be influencing the functioning of the pituitary of the lactating rat by (a) partially suppressing the spontaneous release of gonadotropin and (b) inhibiting the responsiveness of the pituitary to luteinising hormone releasing hormone.

The Multifunctional PE_PGRS11 Protein from Mycobacterium tuberculosis Plays a Role in Regulating Resistance to Oxidative Stress

Mycobacterium tuberculosis utilizes unique strategies to survive amid the hostile environment of infected host cells. Infection-specific expression of a unique mycobacterial cell surface antigen that could modulate key signaling cascades can act as a key survival strategy in curtailing host effector responses like oxidative stress. We demonstrate here that hypothetical PE_PGRS11 ORF encodes a functional phosphoglycerate mutase. The transcriptional analysis revealed that PE_PGRS11 is a hypoxia-responsive gene, and enforced expression of PE_PGRS11 by recombinant adenovirus or Mycobacterium smegmatis imparted resistance to alveolar epithelial cells against oxidative stress. PE_PGRS11-induced resistance to oxidative stress necessitated the modulation of genetic signatures like induced expression of Bcl2 or COX-2. This modulation of specific antiapoptotic molecular signatures involved recognition of PE_PGRS11 by TLR2 and subsequent activation of the PI3K-ERK1/ 2-NF-kappa B signaling axis. Furthermore, PE_PGRS11 markedly diminished H2O2-induced p38 MAPK activation. Interestingly, PE_PGRS11 protein was exposed at the mycobacterial cell surface and was involved in survival of mycobacteria under oxidative stress. Furthermore, PE_PGRS11 displayed differential B cell responses during tuberculosis infection. Taken together, our investigation identified PE_PGRS11 as an in vivo expressed immunodominant antigen that plays a crucial role in modulating cellular life span restrictions imposed during oxidative stress by triggering TLR2-dependent expression of COX-2 and Bcl2. These observations clearly provide a mechanistic basis for the rescue of pathogenic Mycobacterium-infected lung epithelial cells from oxidative stress.

Involvement of Cytochrome P450 in Conferring Chloroquine Resistance to the Malarial Parasite, Plasmodium falciparum

The higher levels of cytochrone P-450 dependent enzyme activities reported earlier are traced to higher levels of cytochrome P-450 (CYPIIB1/B2 like) messenger RNA in the chloroquine resistant than the sensitive strains. The messenger RNA is also induced by phenobarbitone in the sensitive strain. Pretreatment with phenobarbitone affords partial protection to chloroquine toxicity in the sensitive strain and this is not due to a differential accumulation of the drug.

Exceptional resistance to grain growth in nanocrystalline CoCrFeNi high entropy alloy at high homologous temperatures

Nanocrystalline CoCrFeNi high entropy alloy, synthesized by mechanical alloying followed by spark plasma sintering, demonstrated extremely sluggish grain growth even at very high homologous temperature of 0.68 T-m (900 degrees C) for annealing duration of 600 h. Mechanically alloyed powder had carbon and oxygen as impurities, which in turn led to the formation of two-phase mixture of FCC and Cr-rich carbide with fine distribution of Cr-rich oxide during spark plasma sintering. Sluggish grain growth is attributed to the Zener pinning effect from the fine dispersion of oxide, mutual retardation of grain boundaries in the presence of two phases, and sluggish diffusivity because of cooperative diffusion of multi-principle elements. (C) 2015 Elsevier B.V. All rights reserved.

Characterisation of cell adhesion to substrate materials and the resistance to enzymatic and mechanical cell-removal

Cell-implant adhesive strength is important for prostheses. In this paper, an investigation is described into the adhesion of bovine chondrocytes to Ti6Al4V-based substrates with different surface roughnesses and compositions. Cells were cultured for 2 or 5 days, to promote adhesion. The ease of cell removal was characterised, using both biochemical (trypsin) and mechanical (accelerated buoyancy and liquid flow) methods. Computational fluid dynamics (CFD) modelling has been used to estimate the shear forces applied to the cells by the liquid flow. A comparison is presented between the ease of cell detachment indicated using these methods, for the three surfaces investigated. © 2008 Materials Research Society.

Bassenthwaite Lake: a general assessment of environmental and biological features and their susceptibility to change

Bassenthwaite (Lake) is one of the larger Cumbrian lakes, certainly one of the most distinctive, and of considerable conservation and amenity value. Although its shores lack sizeable settlements, its main inflow receives sewage effluent from a major tourist centre (Keswick) and is subject to episodic floods. These influences, the growing development of leisure activities at the lake (e.g. sailing, time-share units), and recent road-construction, have led to past appraisals of ecological impacts and lake management. The lake has not been the subject of intense and long-term ecological study, but much scattered information exists that is relevant to future management decisions. In the present Report, commissioned by North West Water, such information - published and unpublished - is surveyed. Especial attention is given to evidence bearing on susceptibility to change, affecting the lake environment and its biota or species of conservation interest. Extensive use has been made of the results of a recent (1986-7) seasonal survey by the FBA.

A general assessment of environmental and biological features of Windermere and their susceptibility to change

Bassenthwaite (Lake) is one of the larger Cumbrian lakes, certainly one of the most distinctive, and of considerable conservation and amenity value. Although its shores lack sizeable settlements, its main inflow receives sewage effluent from a major tourist centre (Keswick) and is subject to episodic floods. These influences, the growing development of leisure activities at the lake (e.g. sailing, time-share units), and recent road-construction, have led to past appraisals of ecological impacts and lake management. The lake has not been the subject of intense and long-term ecological study, but much scattered information exists that is relevant to future management decisions. In the present Report, commissioned by North West Water, such information - published and unpublished - is surveyed. Especial attention is given to evidence bearing on susceptibility to change, affecting the lake environment and its biota or species of conservation interest. Extensive use has been made of the results of a recent (1986-7) seasonal survey by the FBA.