1,214 research outputs found

    Checking T and CPT violation with sterile neutrino

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    Post LSND results, sterile neutrinos have drawn attention and motivated the high energy physics, astronomy and cosmology to probe physics beyond the standard model considering minimal 3+1 (3 active and 1 sterile) to 3+N neutrino schemes. The analytical equations for neutrino conversion probabilities are developed in this work for 3+1 neutrino scheme. Here, we have tried to explore the possible signals of T and CPT violations with four flavor neutrino scheme at neutrino factory. Values of sterile parameters considered in this analysis are taken from two different types of neutrino experiments viz. long baseline experiments and reactor+atmospheric experiments. In this work golden and discovery channels are selected for the investigation of T violation. While observing T violation we stipulate that neutrino factory working at 50 GeV energy have the potential to observe the T violation signatures for the considered range of baselines(3000 km-7500 km). The ability of neutrino factory for constraining CPT violation is enhanced with increase in energy for normal neutrino mass hierarchy(NH). Neutrino factory with the exposure time of 500 kt-yr will be able to capture CPT violation with δc31≥3.6×10−23 \delta c_{31}\geq 3.6\times10^{-23} GeV at 3σ \sigma level for NH and for IH with δc31≥4×10−23 \delta c_{31}\geq 4\times10^{-23} GeV at 3σ \sigma level

    Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy

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    Although important strides have been made in targeted therapy for certain leukemias and subtypes of breast cancer, the standard of care for most carcinomas still involves chemotherapy, radiotherapy, surgery, or a combination of these. Two processes serve as obstacles to the successful treatment of carcinomas. First, a majority of deaths from these types of cancers occurs as a result of distant metastases and not the primary tumors themselves. Second, subsets of cells that are able to survive conventional therapy drive the aggressive relapse of the tumors, often in forms that are resistant to treatment. A frequently observed feature of malignant carcinomas is the loss of epithelial traits and the gain of certain mesenchymal ones that are programmed by the cell-biological program termed the epithelial-to-mesenchymal transition (EMT). The EMT program can confer (i) an ability to disseminate, (ii) an ability to become stem-like tumor-initiating cells, (iii) an ability to found new tumor colonies at distant anatomical sites, and (iv) an elevated resistance to therapy. These multiple powers of the EMT program explain why it has become an attractive target for therapeutic intervention. Recent work has revealed the variable nature of the EMT, with multiple versions of the program being observed depending on the tissue context and the stage of tumor progression. In this review, we attempt to crystallize emerging concepts in the research on EMTand stemness and discuss the benefits of using a differentiation-based therapeutic strategy for the eradication of stem-like populations that have adopted various versions of the EMT program.National Institutes of Health (U.S.) (grant R01 CA078461)National Institutes of Health (U.S.) (grant (P01 CA080111)Samuel Waxman Cancer Research FoundationMassachusetts Institute of Technology. Ludwig Center for Cancer Researc

    Tackling the cancer stem cells — what challenges do they pose?

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    Since their identification in 1994, cancer stem cells (CSCs) have been objects of intensive study. Their properties and mechanisms of formation have become a major focus of current cancer research, in part because of their enhanced ability to initiate and drive tumour growth and their intrinsic resistance to conventional therapeutics. The discovery that activation of the epithelial-to-mesenchymal transition (EMT) programme in carcinoma cells can give rise to cells with stem-like properties has provided one possible mechanism explaining how CSCs arise and presents a possible avenue for their therapeutic manipulation. Here we address recent developments in CSC research, focusing on carcinomas that are able to undergo EMT. We discuss the signalling pathways that create these cells, cell-intrinsic mechanisms that could be exploited for selective elimination or induction of their differentiation, and the role of the tumour microenvironment in sustaining them. Finally, we propose ways to use our current knowledge of the complex biology of CSCs to design novel therapies to eliminate them.National Institutes of Health (U.S.) (Grant U54-CA163109)United States. Army Research Office (Grant 1210095

    Emerging Biological Principles of Metastasis

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    Metastases account for the great majority of cancer-associated deaths, yet this complex process remains the least understood aspect of cancer biology. As the body of research concerning metastasis continues to grow at a rapid rate, the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning to come into view. In this review we summarize the cellular and molecular mechanisms involved in metastasis, with a focus on carcinomas where the most is known, and we highlight the general principles of metastasis that have begun to emerge

    SYNTHESIS AND IN-VITRO STUDY OF NOVEL (Z)-1-BENZHYDRYL-4-CINNAMYLPIPERAZINE DERIVATIVES AS POTENTIAL ANTICANCER AGENTS

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    Objective: The objective of this study was to synthesize Z- 1-benzhydryl-4-cinnamylpiperazines by novel stereo selective synthetic method and evaluation of their anticancer properties.Methods: A series of novel (Z)-1-benzhydryl-4-cinnamylpiperazine derivatives (9a-j) were synthesized, starting from benzophenones in six steps. Wittig condensation of appropriate benzyltriphenyl phosphonium halides with various 1-benzhydryl- 4-(2-ethanal) piperazines (3a-j), and column purification over silica gel afforded pure Z- 1-benzhydryl-4-cinnamylpiperazines.Results: The structures of newly synthesized compounds 9a-j were established by 1H & 13C NMR and mass spectral analysis. The anticancer potential (MTT assay) of synthesized compounds was tested against human cervical cancer (HeLa) and murine microglial (BV-2) cell lines. Results indicated that the most of the Z-derivatives exhibited moderate to good anticancer activity on both the cell lines over their E- antipodes.Conclusion: Compound 9i (cis- flunarizine) exhibited exceptionally superior activity against both HeLa and BV-2 cell lines with IC50 value of 13.23±3.51 µM and 23.1±4.12 µM respectively. Hence, this compound may be considered to be a potential lead molecule for further developmentÂ

    Hazard Assessment for Manufacture of Combustible Cartridge Cases using Picrite

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    A systematic study of the effect of impact, friction, flame and electric spark sensitivity was carried out on the samples combustible cartridge case (CCC) withdrawn at different stages of manufacture. These are Stage I dried felted CCC; stage II-CCC from stage III Coated with nitrocellulose coating. based on the results obtained from various experiments, the CCC can be classified for handling storage and transportation as Group 3, for safety distance category as UN 1.3 and for fire fighting as class 2. further it is concluded from hazard analysis study that the CCCs are safe to handle but these should be protected from naked flame

    Thioltransferase (glutaredoxin) mediates recovery of motor neurons from excitotoxic mitochondrial injury

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    Mitochondrial dysfunction involving electron transport components is implicated in the pathogenesis of several neurodegenerative disorders and is a critical event in excitotoxicity. Excitatory amino acid L-β-N-oxalylamino-L-alanine (L-BOAA), causes progressive corticospinal neurodegeneration in humans. In mice, L-BOAA triggers glutathione loss and protein thiol oxidation that disrupts mitochondrial complex I selectively in motor cortex and lumbosacral cord, the regions affected in humans. We examined the factors regulating postinjury recovery of complex I in CNS regions after a single dose of L-BOAA. The expression of thioltransferase (glutaredoxin), a protein disulfide oxidoreductase regulated through AP1 transcription factor was upregulated within 30 min of L-BOAA administration, providing the first evidence for functional regulation of thioltransferase during restoration of mitochondrial function. Regeneration of complex I activity in motor cortex was concurrent with increase in thioltransferase protein and activity, 1 hr after the excitotoxic insult. Pretreatment with α-lipoic acid, a thiol delivery agent that protects motor neurons from L-BOAA-mediated toxicity prevented the upregulation of thioltransferase and AP1 activation, presumably by maintaining thiol homeostasis. Downregulation of thioltransferase using antisense oligonucleotides prevented the recovery of complex I in motor cortex and exacerbated the mitochondrial dysfunction in lumbosacral cord, providing support for the critical role for thioltransferase in maintenance of mitochondrial function in the CNS

    Double-pulse Nd:YAG-CO2 LIBS Excitation for Bulk and Trace Analytes

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    Laser-induced breakdown spectroscopy [LIBS] is a commonly used technique for multi-element analyses for various applications such as space exploration, nuclear forensics, environmental analysis, process monitoring. The advantages of the LIBS technique include robustness, ease of use, field portability, and real-time, non-invasive multi-element analyses. However, in comparison to other lab based analytical techniques, it suffers from low precision and low sensitivity. In order to overcome these drawbacks, various approaches have been used, including double-pulse LIBS [DPLIBS]. Typically, various wavelength combinations of two Nd: yttrium aluminum garnet [YAG] lasers have been used for DPLIBS. However, the use of long wavelength (CO2) laser in combination with Nd:YAG laser has not been sufficiently studied. In this study, signal enhancement mechanisms in Nd:YAG:CO2 DPLIBS are investigated. Nd:YAG laser pulse at 1064 nm was used as pre-ablation laser while CO2 laser at 10.6 μm was used as reheating laser pulse. The results exhibit significant improvement in sensitivity of both bulk and trace analytes in the sample using DPLIBS as compared to conventional single-pulse LIBS [SPLIBS]. The bulk and trace analytes used for comparing figures of merit in the brass sample were Cu and Fe emission lines, respectively. Pre-pulse energies ranging from 20 to 120 mJ from a 1064 nm Nd: YAG laser reheated by a 10.6 μm TEA CO2 laser at constant energy of 400 mJ aligned in near collinear geometry. The observed signal intensity and signal-to-background ratio of bulk analyte as well as trace analyte increased significantly. In order to understand signal enhancement mechanisms, various experimental parameters apart from pre-pulse energy were also studied, including inter-pulse delay and ICCD gate delay. Time resolved studies showed that persistence of neutral lines increases by ~10 times for DPLIBS as compared to SPLIBS. Plasma was characterized by estimation of excitation temperature and electron density using the Boltzmann method and Stark broadening method, respectively. Plasma temperature was found to be higher for DPLIBS, which shows that reheating mechanism is dominant mechanism for signal enhancement and increased persistence in YAG:CO2 DPLIBS. The mechanisms involved in signal enhancement and persistence of neutral and ionic species from bulk and trace analyte are presented and their implications to improving figures of merit are discussed

    Disease Control and Plant Growth Promotion of \u3cem\u3e Miscanthus \u3c/em\u3e × \u3cem\u3e giganteus \u3c/em\u3e with \u3cem\u3e Trichoderma \u3c/em\u3e Bio-Inoculants

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    The second-generation bioenergy crop Miscanthus (Miscanthus × giganteus) is being assessed in New Zealand for its potential to provide shelter on irrigated dairy farms. Miscanthus is a perennial sterile hybrid vegetatively propagated rhizomatous C4 grass and the young rhizomes and roots are prone to infection by soil-borne fungal pathogens (Glynn et al., 2015) which can cause deleterious effects on plant establishment and growth. In Europe, several species of Fusarium such as F. avenaceum, F. culmorum, F. moniliforme and F. oxysporum have been implicated as causal agents of root and rhizome rot (Thinggaard, 1997; Covarelli et al., 2012) leading to poor field establishment of in-vitro propagated Miscanthus plants. When tested for their ability to cause disease of Miscanthus, Rhizoctonia solani (Kuhn) was reported as the most aggressive species among nineteen fungal pathogens of cereal crops (Glynn et al. 2015). In New Zealand, R. solani reduces seedling emergence and plant establishment of several herbage species and the problem may be alleviated through biocontrol using Trichoderma fungi (Kandula et al., 2015). In a glass-house study, the effect of four T. atroviride isolates on growth of tissue culture propagated Miscanthus plants in a soil naturally infested with R. solani was investigated
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