167 research outputs found
A Novel Method of Linguistic Topsis for DMSS Technique
This paper extends the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) for solving multi-attribute group decision making (MAGDM) problems under trapezoidal fuzzy linguistic variables. In situations where the information or the data is of the form of trapezoidal fuzzy linguistic numbers (TFLNs), some arithmetic aggregation operators have to be defined, namely the Trapezoid Fuzzy Linguistic Weighted Harmonic Averaging (TFLWHA)operator, Trapezoid Fuzzy Linguistic Ordered Weighted Harmonic Averaging (TFLOWHA) operator and Trapezoid Fuzzy Linguistic Hybrid Harmonic Averaging(TFLHHA) operator. A new method for determining decision maker?s weights is also proposed in the paper, which is used to determine the best alternative. An extended TOPSIS model is developed to solve the MAGDM problems using a new algorithm and an illustration is given
Efficient likelihood evaluation of state-space representations
We develop a numerical procedure that facilitates efficient likelihood evaluation in applications involving non-linear and non-Gaussian state-space models. The procedure approximates necessary integrals using continuous approximations of target densities. Construction is achieved via efficient importance sampling, and approximating densities are adapted to fully incorporate current information. We illustrate our procedure in applications to dynamic stochastic general equilibrium models. --particle filter,adaption,efficient importance sampling,kernel density approximation,dynamic stochastic general equilibrium model
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HP1 reshapes nucleosome core to promote phase separation of heterochromatin
Heterochromatin affects genome function at many levels. It enables heritable gene repression, maintains chromosome integrity and provides mechanical rigidity to the nucleus1,2. These diverse functions are proposed to arise in part from compaction of the underlying chromatin2. A major type of heterochromatin contains at its core the complex formed between HP1 proteins and chromatin that is methylated on histone H3, lysine 9 (H3K9me). HP1 is proposed to use oligomerization to compact chromatin into phase-separated condensates3-6. Yet, how HP1-mediated phase separation relates to chromatin compaction remains unclear. Here we show that chromatin compaction by the Schizosaccharomyces pombe HP1 protein Swi6 results in phase-separated liquid condensates. Unexpectedly, we find that Swi6 substantially increases the accessibility and dynamics of buried histone residues within a nucleosome. Restraining these dynamics impairs compaction of chromatin into liquid droplets by Swi6. Our results indicate that Swi6 couples its oligomerization to the phase separation of chromatin by a counterintuitive mechanism, namely the dynamic exposure of buried nucleosomal regions. We propose that such reshaping of the octamer core by Swi6 increases opportunities for multivalent interactions between nucleosomes, thereby promoting phase separation. This mechanism may more generally drive chromatin organization beyond heterochromatin
Impact of perioperative period on disease-free survival among carcinoma ovary patients treated with the interval cyto-reductive surgery at a tertiary cancer centre in Kerala, India: a retrospective study
Background: Global incidence of ovarian malignancies is 300,000 as per GLOBOCAN 2018. The treatment protocol for advanced ovarian malignancies (stage IIIc and stage IV) includes neo-adjuvant chemotherapy and surgery followed by adjuvant chemotherapy. Aims of the study was to determine the effect of duration of chemo interruption on disease free survival of ovarian malignancies treated by interval cytoreduction followed by surgery.Methods: A total 48 patients were studied for events such as recurrence, death, patient’s status on last follow up, peri-operative period between 3rd cycle of chemo therapy and 4th cycle of chemo therapy. Based on the median duration of peri operative period patients was classified as early or delayed receivers of adjuvant chemo therapy. Difference in duration of over-all survival and disease-free survival was analysed through Kaplan Meier survival analysis using log-rank test. Hazard ratio adjusted for background characteristics such as staging, performance status, grade of tumour were analysed using cox proportional hazard model.Results: The two peri operative period categories based on mean value (85 days) didn’t show any significant association to disease free interval (minimum-21days, maximum-146 days, Hr = 1.3, p-value = 0.52). Other established factors like stage, extent of resection, response to chemotherapy, also didn’t show any significant association. Serum marker level showed a significant negative correlation with disease free survival (minimum-9 days, maximum-30659, p-value =.04, Hr = 3.19).Conclusions: The study could not establish any correlation between peri operative period and median disease-free survival. The small sample size is a limiting factor, well controlled randomized trials may needed for further clarification
Critical Review of Methods for Sampling, Analysis, and Monitoring of Vapor-Phase Toluene Diisocyanate
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91959/1/TLVpaper2002.pd
Bhoochetana: Building Resilience and Livelihoods through Integrated Watershed Management. Resilient Dryland Systems Report No. 62.
Rainfed areas are hotspots of poverty and malnutrition, and are prone to
severe land degradation of natural resources. Globally, 80% of agriculture is
rainfed providing 62% of the world’s staple food. With increasing population
over the years, per capita availability and quality of land and water resources
have declined substantially resulting to water scarcity. Agriculture is the major
consumer of water, accounting for 70-80% of water withdrawal. With the
impacts of climate change, existing water and land scarcity will be aggravated
further. Producing food for the ever growing population to achieve food and
nutrition security, and improving rural livelihoods are challenges to be met today
as well as in the near future.
Agriculture is the major contributor in the growth of the state of Karnataka,
India and is still the mainstay for a large number of population in the state
economy. However, trends are showing that the agriculture and allied sectors’
contribution to Karnataka’s GDP was around 43% in 1980-1981 that came
down to 26% in 2001-2002, which further came down to 16.8% in 2007-2008,
remaining stagnant in 2009-2010. This declining contribution of agriculture in
the state GDP was a big concern for the state government
Hospital Variability in Use of Anticoagulant Strategies During Acute Myocardial Infarction Treated With an Early Invasive Strategy
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139118/1/jah31000.pd
Phosphoenolpyruvate carboxylase dentified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism
Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in thePlasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10Δpepc), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10Δpepc had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using 13C-U-D-glucose and 13C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10Δpepc and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of 13C,15N-U-glutamine was similar in both parasite lines, although the flux was lower in D10Δpepc; it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery
Wnt antagonist secreted frizzled-related protein 4 upregulates adipogenic differentiation in human adipose tissue-derived mesenchymal stem cells
With more than 1.4 billion overweight or obese adults worldwide, obesity and progression of the metabolic syndrome are major health and economic challenges. To address mechanisms of obesity, adipose tissue-derived mesenchymal stem cells (ADSCs) are being studied to detail the molecular mechanisms involved in adipogenic differentiation. Activation of the Wnt signalling pathway has inhibited adipogenesis from precursor cells. In our study, we examined this anti-adipogenic effect in further detail stimulating Wnt with lithium chloride (LiCl) and 6-bromo indirubin 3'oxime (BIO). We also examined the effect of Wnt inhibition using secreted frizzled-related protein 4 (sFRP4), which we have previously shown to be pro-apoptotic, anti-angiogenic, and anti-tumorigenic. Wnt stimulation in LiCl and BIOtreated ADSCs resulted in a significant reduction (2.7-fold and 12-fold respectively) in lipid accumulation as measured by Oil red O staining while Wnt inhibition with sFRP4 induced a 1.5-fold increase in lipid accumulation. Furthermore, there was significant 1.2-fold increase in peroxisome proliferator-activated receptor gamma (PPAR ?) and CCAAT/enhancer binding protein alpha (C/EBPa), and 1.3-fold increase in acetyl CoA carboxylase protein levels. In contrast, the expression of adipogenic proteins (PPAR?, C/EBPa, and acetyl CoA carboxylase) were decreased significantly with LiCl (by 1.6, 2.6, and 1.9-fold respectively) and BIO (by 7, 17, and 5.6-fold respectively) treatments. These investigations demonstrate interplay between Wnt antagonism and Wnt activation during adipogenesis and indicate pathways for therapeutic intervention to control this process
The effects of phenoxodiol on the cell cycle of prostate cancer cell lines
Background: Prostate cancer is associated with a poor survival rate. The ability of cancer cells to evade apoptosis and exhibit limitless replication potential allows for progression of cancer from a benign to a metastatic phenotype. The aim of this study was to investigate in vitro the effect of the isoflavone phenoxodiol on the expression of cell cycle genes. Methods: Three prostate cancer cell lines-LNCaP, DU145, and PC3 were cultured in vitro, and then treated with phenoxodiol (10 μM and 30 μM) for 24 and 48 h. The expression of cell cycle genes p21WAF1, c-Myc, Cyclin-D1, and Ki-67 was investigated by Real Time PCR. Results: Here we report that phenoxodiol induces cell cycle arrest in the G1/S phase of the cell cycle, with the resultant arrest due to the upregulation of p21WAF1 in all the cell lines in response to treatment, indicating that activation of p21WAF1 and subsequent cell arrest was occurring via a p53 independent manner, with induction of cytotoxicity independent of caspase activation. We found that c-Myc and Cyclin-D1 expression was not consistently altered across all cell lines but Ki-67 signalling expression was decreased in line with the cell cycle arrest. Conclusions: Phenoxodiol demonstrates an ability in prostate cancer cells to induce significant cytotoxicity in cells by interacting with p21WAF1 and inducing cell cycle arrest irrespective of p53 status or caspase pathway interactions. These data indicate that phenoxodiol would be effective as a potential future treatment modality for both hormone sensitive and hormone refractory prostate cancer
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