1,147 research outputs found

    A REVIEW ON REDUCING JITTER AND POWER IN PHASE LOCKED LOOP

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    Jitter is extremely important in PLL based systems. The effects of jitter range from not having any effect on system operation to rendering the system completely non -functional. Reducing Jitter and power supply is one way to help to improve the system performance. This review will concentrate on jitter and power supply in PLL building blocks

    Tumor-Targeted Delivery of siRNA Using Fatty Acyl-CGKRK Peptide Conjugates

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    Tumor-targeted carriers provide efficient delivery of chemotherapeutic agents to tumor tissue. CGKRK is one of the well-known tumor targeting peptides with significant specificity for angiogenic blood vessels and tumor cells. Here, we designed fatty acyl conjugated CGKRK peptides, based on the hypothesis that hydrophobically-modified CGKRK peptide could enhance cellular permeation and delivery of siRNA targeted to tumor cells for effective silencing of selected proteins. We synthesized six fatty acyl-peptide conjugates, using a diverse chain of saturated and unsaturated fatty acids to study the efficiency of this approach. At peptide:siRNA weight/weight ratio of 10:1 (N/P ≈ 13.6), almost all the peptides showed complete binding with siRNA, and at a w/w ratio of 20:1 (N/P ≈ 27.3), complete protection of siRNA from early enzymatic degradation was observed. Conjugated peptides and peptide/ siRNA complexes did not show significant cytotoxicity in selected cell lines. The oleic acid-conjugated peptide showed the highest efficiency in siRNA uptake and silencing of kinesin spindle protein at peptide:siRNA w/w ratio of 80:1 (N/P ≈ 109). The siRNA internalization into non-tumorigenic kidney cells was negligible with all fatty acyl-peptide conjugates. These results indicate that conjugation of fatty acids to CGKRK could create an efficient delivery system for siRNA silencing specifically in tumor cells

    Potential Role of Cancer Stem Cells in Glioblastoma: A Therapeutic Aspect

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    High-grade glioma (HGG) such as glioblastoma multiforme (GBM) is an aggressive brain tumor that is still associated with poor prognosis. With the discovery and advancement in understanding of cancer stem cells (CSC) in glioma, these cells have emerged as seed cells for tumor growth and recurrence and appear as a potential target for therapeutics. Glioma stem cells (GSCs) demonstrate capacity of self-renewal, proliferation, and differentiation into multiple cell types and can contribute to tumor heterogeneity. Their role is established in tumorigenesis, metastasis, chemo- and radio-resistance and appears as a major cause for tumor recurrence. Thus, targeting GSCs by various therapeutics may improve effectiveness of the drugs in use alone or in combination to significantly improve patient survival outcome in GBM cases. In this chapter, we have discussed various mechanisms that drive GSC including signaling pathways and tumor microenvironment. We have also discussed the mechanism behind resistance of GSCs toward therapeutics and the pathways that can be targeted to improve the outcome of the patients

    Synthesis, Characterization, and In Vitro Cytotoxicity of Fatty Acyl-CGKRK-chitosan Oligosaccharides Conjugates for siRNA Delivery

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    In this studies, three fatty acyl derivatives of CGKRK homing peptides were coupled successfully to chitosan oligosaccharides (COS) using sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate sodium salt (sulfo-SMCC). The COS-SMCC was prepared by direct coupling between COS and sulfo-SMCC in PBS (pH 7.5) at RT for 48 h. The structure of COS-SMCC and the three fatty acyl-CGKRK-SMCC-COS conjugates were characterized by FT-IR, 13C NMR, and SEM. The ability of three conjugates to condense siRNA into nanosized polyplexes and their efficacy in protecting siRNA from serum nucleases degradation were investigated. Among the investigated derivatives, S-CGKRK-COS showed higher siRNA binding affinity as compared to the P-CGKRK-COS and O-CGKRK-COS respectively. At a ratio of 10:1, complete protection for siRNA from early enzymatic degradation was achieved. The polymers and the polymer/siRNA polyplexes showed negligible cytotoxicity on human breast cancer cell line MDA-MB-231 at all investigated ratios. However, the polyplexes prepared with palmitoyl and oleoyl derivatives at polymer concentration 10 μg/mL reduced the cell viability by 21.5% and 35% respectively. The results of this study revealed the impact of using fatty acyl-CGKRK-COS as a siRNA carrier and confirmed the importance of incorporating a hydrophobic moiety into chitosan to improve its capacity in complexing with siRNA and protection from degradation

    Complete genome sequence of Mesorhizobium ciceri bv. biserrulae type strain (WSM1271T)

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    Mesorhizobium ciceri bv. biserrulae strain WSM1271(T) was isolated from root nodules of the pasture legume Biserrula pelecinus growing in the Mediterranean basin. Previous studies have shown this aerobic, motile, Gram negative, non-spore-forming rod preferably nodulates B. pelecinus - a legume with many beneficial agronomic attributes for sustainable agriculture in Australia. We describe the genome of Mesorhizobium ciceri bv. biserrulae strain WSM1271(T) consisting of a 6,264,489 bp chromosome and a 425,539 bp plasmid that together encode 6,470 protein-coding genes and 61 RNA-only encoding genes

    Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

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    Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

    Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

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    An embedding technique to determine ττ backgrounds in proton-proton collision data

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    An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe
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