462 research outputs found

    ANFIS Based Temporally Ordered Routing Algorithm to Enhance the Performance in Mobile Ad-hoc Networks

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    A Mobile Ad hoc network (MANET) consists of mobile nodes, a router with multiple hosts and wireless communication devices. Mobile Adhoc Networks can operate without any fixed infrastructure and can survive rapid changes in the network topology. Link failure and route failure takes place. Provisioning of QoS is a problem in MANETs. TORA is the only protocol which supports either Proactive or Reactive modes in routing. In this paper, we incorporated the ANFIS to the existing TORA to enhance the performance. Evaluating the performance of ANFIS-TORA is the simulation by using OPNET MODELLER. Evaluating the relative performance with respect to performance metrics are Throughput, End-to-End delay, and Network Load. We generate various simulation scenarios with varying network size such as small, medium and large. In this paper, ANFIS based TORA for MANETs are considered and their performance was analyzed for different network size. From the simulation results, we conclude that ANFIS based TORA outperforms for small medium and large network. Throughput was increased by 48.27% in small network, 61.29% in medium network and 8.29% in the large network in Reactive mode. In Proactive, the throughput is increased by 103.46% in small network, 4.58% in medium network and 5.05% in large network

    Multi component one pot synthesis and characterization of derivatives of 2-amino-7,7- dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile and study of anti-microbial activity

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    An efficient and convenient procedure has been described for one-pot multi-component synthesisof tetrahydrobenzo[b]pyrans known as 2-amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile which can be obtained from the reaction of substituted aromatic aldehydes, dimedone, malonitrile, in the presence of base such as potassium tertiary butoxide and THF in methanol as solvent at RT condition. All the compounds were examined by advanced spectroscopic data (1H NMR, 13C NMR and LCMS) and the structural determination was evaluated by elemental analysis. In addition to this, all the newly synthesized compounds were examined for their antibacterial activities and antifungal activity by disc diffusion method against the organism of Aspergillus niger and Candida ablicans L.               KEY WORDS: Aromatic aldehydes, Dimedone, Malonitrile, Potasium tertiary butoxide, 2-Amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile, Anti-microbial activity Bull. Chem. Soc. Ethiop. 2018, 32(1), 133-138DOI: https://dx.doi.org/10.4314/bcse.v32i1.1

    The Radiation Transfer at a Layer of Magnetized Plasma With Random Irregularities

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    The problem of radio wave reflection from an optically thick plane monotonous layer of magnetized plasma is considered at present work. The plasma electron density irregularities are described by spatial spectrum of an arbitrary form. The small-angle scattering approximation in the invariant ray coordinates is suggested for analytical investigation of the radiation transfer equation. The approximated solution describing spatial-and-angular distribution of radiation reflected from a plasma layer has been obtained. The obtained solution has been investigated numerically for the case of the ionospheric radio wave propagation. Two effects are the consequence of multiple scattering: change of the reflected signal intensity and anomalous refraction.Comment: 22 pages, 4 figure

    An open-label multi-center phase 1 safety study of BXQ-350 in children and young adults with relapsed solid tumors, including recurrent malignant brain tumors

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    BACKGROUND: BXQ-350 is a novel anti-neoplastic agent composed of saposin C (SapC) and phospholipid dioleoylphosphatidyl-serine sodium (DOPS) that selectively binds tumor cell phosphatidylserine (PS), inducing apoptosis. BXQ-350 has demonstrated preclinical antitumor effects in high-grade gliomas (HGG) and clinical activity in adult patients with recurrent HGG. METHODS: A phase 1 study was conducted in pediatric patients with relapsed/refractory solid tumors, including recurrent brain tumors. Primary objectives were to characterize safety and determine maximum tolerated dose (MTD) and preliminary antitumor activity. Sequential dose cohorts were assessed up to 3.2 mg/kg using an accelerated titration design. Each cycle was 28 days; dosing occurred on days 1-5, 8, 10, 12, 15, and 22 of cycle 1, and day 1 of subsequent cycles, until disease progression or toxicity. RESULTS: Nine patients, median age 10 years (range: 4-23), were enrolled. Seven patients (78%) had central nervous system (CNS) and two (22%) had non-CNS tumors. Eight patients completed cycle 1. No dose limiting toxicity (DLT) or BXQ-350-related serious adverse events (SAEs) were observed. Six patients experienced at least one adverse event (AE) considered possibly BXQ-350-related, most were grade ≤2. One patient with diffuse intrinsic pontine glioma experienced stable disease for 5 cycles. The study was terminated after part 1 to focus development on the frontline setting. CONCLUSION: No DLTs or BXQ-350-related SAEs were reported, and the maximal planned dose of 3.2 mg/kg IV was tolerable. Limited safety and efficacy data support continued BXQ-350 development in pediatric HGG; however, early discontinuations for progression suggest novel therapies be assessed at earlier disease stages

    Quantum sticking, scattering and transmission of 4He atoms from superfluid 4He surfaces

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    We develop a microscopic theory of the scattering, transmission, and sticking of 4He atoms impinging on a superfluid 4He slab at near normal incidence, and inelastic neutron scattering from the slab. The theory includes coupling between different modes and allows for inelastic processes. We find a number of essential aspects that must be observed in a physically meaningful and reliable theory of atom transmission and scattering; all are connected with multiparticle scattering, particularly the possibility of energy loss. These processes are (a) the coupling to low-lying (surface) excitations (ripplons/third sound) which is manifested in a finite imaginary part of the self energy, and (b) the reduction of the strength of the excitation in the maxon/roton region

    Rab4A organizes endosomal domains for sorting cargo to lysosome-related organelles

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    Sorting endosomes (SEs) are the regulatory hubs for sorting cargo to multiple organelles, including lysosome-related organelles such as melanosomes in melanocytes. In parallel, melanosome biogenesis is initiated from SEs with the processing and sequential transport of melanocyte-specific proteins toward maturing melanosomes. However, the mechanism of cargo segregation on SEs is largely unknown. RNAi screening in melanocytes revealed that knockdown of Rab4A results in defective melanosome maturation. Rab4A-depletion increases vacuolar endosomes and disturbs the cargo sorting, which in turn lead to the mislocalization of melanosomal proteins to lysosomes, cell surface and exosomes. Rab4A localizes to the SEs and forms endosomal complex with AP-3 adaptor, Rabenosyn-5 effector and KIF3 motor, which possibly coordinates cargo segregation on SEs. Consistently, inactivation of Rabenosyn-5 or KIF3A/B phenocopied the defects observed in Rab4A-knockdown melanocytes. Further, Rabenosyn-5 associates with Rabaptin-5 or Rabip4/4' and differentially regulate cargo sorting from SEs. Thus, Rab4A acts a key regulator of cargo segregation on SEs

    Reconstructing Gene Regulatory Networks That Control Hematopoietic Commitment.

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    Hematopoietic stem cells (HSCs) reside at the apex of the hematopoietic hierarchy, possessing the ability to self-renew and differentiate toward all mature blood lineages. Along with more specialized progenitor cells, HSCs have an essential role in maintaining a healthy blood system. Incorrect regulation of cell fate decisions in stem/progenitor cells can lead to an imbalance of mature blood cell populations-a situation seen in diseases such as leukemia. Transcription factors, acting as part of complex regulatory networks, are known to play an important role in regulating hematopoietic cell fate decisions. Yet, discovering the interactions present in these networks remains a big challenge. Here, we discuss a computational method that uses single-cell gene expression data to reconstruct Boolean gene regulatory network models and show how this technique can be applied to enhance our understanding of transcriptional regulation in hematopoiesis.Work in the author’s laboratory is supported by grants from the Wellcome, Bloodwise, Cancer Research UK, NIH-NIDDK and core support grants by the Wellcome to the Cambridge Institute for Medical Research and Wellcome & MRC Cambridge Stem Cell Institute. F.K.H. is a recipient of a Medical Research Council PhD Studentship

    Accurate HLA type inference using a weighted similarity graph

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    Abstract Background The human leukocyte antigen system (HLA) contains many highly variable genes. HLA genes play an important role in the human immune system, and HLA gene matching is crucial for the success of human organ transplantations. Numerous studies have demonstrated that variation in HLA genes is associated with many autoimmune, inflammatory and infectious diseases. However, typing HLA genes by serology or PCR is time consuming and expensive, which limits large-scale studies involving HLA genes. Since it is much easier and cheaper to obtain single nucleotide polymorphism (SNP) genotype data, accurate computational algorithms to infer HLA gene types from SNP genotype data are in need. To infer HLA types from SNP genotypes, the first step is to infer SNP haplotypes from genotypes. However, for the same SNP genotype data set, the haplotype configurations inferred by different methods are usually inconsistent, and it is often difficult to decide which one is true. Results In this paper, we design an accurate HLA gene type inference algorithm by utilizing SNP genotype data from pedigrees, known HLA gene types of some individuals and the relationship between inferred SNP haplotypes and HLA gene types. Given a set of haplotypes inferred from the genotypes of a population consisting of many pedigrees, the algorithm first constructs a weighted similarity graph based on a new haplotype similarity measure and derives constraint edges from known HLA gene types. Based on the principle that different HLA gene alleles should have different background haplotypes, the algorithm searches for an optimal labeling of all the haplotypes with unknown HLA gene types such that the total weight among the same HLA gene types is maximized. To deal with ambiguous haplotype solutions, we use a genetic algorithm to select haplotype configurations that tend to maximize the same optimization criterion. Our experiments on a previously typed subset of the HapMap data show that the algorithm is highly accurate, achieving an accuracy of 96% for gene HLA-A, 95% for HLA-B, 97% for HLA-C, 84% for HLA-DRB1, 98% for HLA-DQA1 and 97% for HLA-DQB1 in a leave-one-out test. Conclusions Our algorithm can infer HLA gene types from neighboring SNP genotype data accurately. Compared with a recent approach on the same input data, our algorithm achieved a higher accuracy. The code of our algorithm is available to the public for free upon request to the corresponding authors

    The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

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    <p>Abstract</p> <p>Background</p> <p>Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated.</p> <p>Methods</p> <p>Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) <it>in vitro</it>. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA.</p> <p>Results</p> <p>The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased.</p> <p>Conclusion</p> <p>The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The NF-kappa B signaling pathway plays an important role in this process. Therefore, combining GA and celastrol may be a promising modality for treating oral squamous cell carcinoma.</p
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