Cluster Computing - The MapReduce (MR) scheduling is a prominent area of research to minimize energy consumption in the Hadoop framework in the era of green computing. Very few scheduling... 相似文献
Chronic obstructive pulmonary disease (COPD) patients with higher eosinophil counts are associated with increased clinical response to phosphodiesterase-4-inhibitors (PDE4i). However, the underlying inflammatory mechanisms associated with this increased response is not yet elucidated. This post hoc analysis focused on sputum gene expression in patients with chronic bronchitis who underwent 32-day treatment with two doses of the inhaled PDE4i CHF6001 (tanimilast) or placebo on top of triple therapy. Biological characterization and treatment effects were assessed between patients with different sputum eosinophil levels (eosinophilhigh ≥ 3%; eosinophillow < 3%) at baseline (primary samples) or at the end of the treatment of the placebo arm (validation samples). Forty-one genes were differentially expressed in primary samples (p-adjusted for false discovery rate < 0.05); all up-regulated in eosinophilhigh patients and functionally enriched for type-2 and PDE4 inflammatory processes. Eleven out of nineteen genes having immune system biological processes annotations including IL5RA, ALOX15, IL1RL1, CLC, GATA1 and PDE4D were replicated using validation samples. The expression of a number of these inflammatory mediators was reduced by tanimilast treatment, with greater effects observed in eosinophilhigh patients. These findings suggest that type-2 and PDE4 overexpression in COPD patients with higher sputum eosinophil counts contribute to the differential clinical response to PDE4i observed in previous clinical trials. 相似文献
Superoxide dismutase is one of the key antioxidant enzymes accountable for the eradication of free radicals generated during various metabolic processes. This is first study reporting a thermostable MnSOD obtained from a xerophytic plant, Nerium oleander. The full-length gene identified using Rapid amplification of cDNA ends revealed an open reading frame of 699 bp flanked by 5′UTR and 3′UTR of 134 bp and 198 bp respectively. The corresponding NeMnSOD protein was cloned and expressed in Escherichia coli. The purified protein yields a band of 25.4 kDa, which established a specific activity of 2617 units mg?1 of protein and under native condition yield bands of 52 kDa and 110 kDa, confirming the dimeric and tetrameric state of the protein. The Km and Vmax of 0.078?±?0.008 mM and 1052.3?±?33.59 units mg?1 of protein, respectively. The purified enzyme demonstrated thermostability by retaining more than 20% activity at a temperature 70 ℃. The enzyme functioned at pH range of 4–9.0 with maximum activity at pH 7.4. Sodium azide, effectively inhibited the activity of enzyme confirming it to be MnSOD. The enzyme activity was least affected on treatment with strong denaturants (Urea, guanidine HCl and SDS) and harsh chemicals (DTT, CHAPS and β-mercapto-ethanol) These experimental data validated with Insilco analysis revealed that NeMnSOD possessed thermo as well as kinetically stable moiety which can be further exploited with its applications in the field of pharmaceutical, food and cosmetic industry, which urge for such thermostable enzyme.
Background: Parkinson's disease (PD) is a common progressive neurodegenerative and the prevailing treatments are ineffective in the early stages of the disease. Therefore, other strategies must be devised to halt the steady decrease of dopaminergic neurons in the brain. In Parkinson's disease, a dysregulated ACE/Ang II/AT1R axis in the brain causes free radical damage, apoptosis, and neuronal destruction. Current PD treatments only alleviate symptoms and do not reverse the degradation mechanism of dopaminergic neurons. As a result, it is critical to discover alternate, dependable medicines for the treatment of Parkinson's disease. Method : In the present study, homology modelling of MAS receptor, in silico docking and molecular dynamic studies (MDS) were employed to determine the efficacy of flavonoids as MASR activators. Result : The flavonoids Pterosupin and Amentoflavone exhibited best binding and therefore, the stability of these complexes were evaluated with MDS studies. The Pterosupin-MASR complex demonstrated better stability, stronger interactions and minimal fluctuation than the Amentoflavone-MASR complex. Conclusion : The data from the present study indicated that the flavonoid Pterosupin possesses better binding, favourable pharmacokinetic properties and stability. However, subsequent in vitro and in vivo assessments are necessary to validate its efficacy. 相似文献
Six monogenic mutants of K. marxianus, affected in their ability to tolerate ethanol, were assigned to 6 loci etr1 through etr6, probably the hot spots for ethyl methane sulfonate as these loci were found mutated in each of the non-monogenic mutants as well. Differential ethanol tolerance of allelic hexagenic mutants suggests that even more than 6 genes may be involved in controlling ethanol tolerance in K. marxianus. 相似文献