3,382 research outputs found

    Multi-domain Software Defined Networking: Research status and challenges

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    A key focus of the transition to next generation computer networking is to improve management of network services thereby enhancing traffic control and flows while simplifying higher-level functionality. Software-defined networking (SDN) is an approach that is being developed to facilitate next generation computer networking by decoupling the traffic control system from the underlying traffic transmission system. SDN offers programmability in network services by separating the control plane from the data plane within network devices and providing programmability for network services. Enhanced connectivity services across the global digital network require a multi-domain capability. This paper presents a review of the current research status in SDN and multi-domain SDN, focusing on OpenFlow protocol, and its future related challenges

    Identifying the motives for and against drinking during pregnancy and motherhood, and factors associated with increased maternal alcohol use

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    Aim: Maternal drinking (alcohol use during pregnancy/motherhood) is a hidden public health concern which can have significant negative effects on the woman and child. This pilot survey explored several domains that might influence maternal drinking. Subject and methods: Two cross-sectional, online surveys recruited (1) women who were pregnant and (2) mothers who were not pregnant. Surveys captured data on alcohol use and harmful drinking, attitudes on and motives for drinking/not drinking, and perceived barriers to drinking less. Content analysis of free text responses complemented quantitative data. Results: In this convenience sample of 836 pregnant women and 589 mothers, 91% of pregnant women and 28% of mothers reported abstinence. Of those reporting alcohol use, median consumption was 2.3 units/week in pregnant women, and 6.9 units/week in non-pregnant mothers. Of mothers currently drinking, 25.1% reported hazardous or harmful levels. Heavier drinking was associated with numerous motives, including using alcohol as a coping strategy. Child welfare was a key motivating factor for not drinking, as were practical issues of motherhood. The stresses of motherhood were a perceived barrier to reducing drinking, and mothers reported more barriers than pregnant women. Conclusion: Stress reduction motives may be a risk factor for heavier maternal drinking, while motives for not drinking seem to be focused on child welfare and maternal well-being. Stress and a lack of knowledge about how to reduce drinking appear to be barriers for mothers to change their drinking behaviour. These findings can inform the development of effective public health interventions to reduce maternal drinking

    Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours

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    BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of Ξ³-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1Β h treatment. Peak ICL was achieved within 1Β h and no removal was observed over 48Β h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of Ξ³-H2AX foci was slow, becoming evident after 4Β h and reaching a peak at 24Β h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3Β mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2Β h and persisted at 24Β h. ICL increased following the second and third doses in a repeated dose schedule. At 24Β h, dose dependent Ξ³-H2AX foci were more numerous than at 2Β h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and Ξ³-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users

    Effect of Zinc Supplementation on Growth of Low Birth Weight Infants Aged 1–6 Mo in Ardabil, Iran

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    Objective To assess the effect of zinc supplementation on growth of low birth weight (LBW) infants aged 1–6 mo. Methods LBW infants were enrolled at birth and randomly assigned to receive 5 mg elemental Zn per day (n=45) or placebo (n=45) until 6 mo of age. They were followed monthly for information on compliance; anthropometric measurements were performed monthly. Results After randomization, 5 infants from zinc group and 9 from placebo group were excluded. At 6 mo of age, significantly greater weight gains were observed in the zinc than in the placebo group (4995Β±741g in zinc group vs. 3896Β±865 g in placebo group, p = 0.036). Length gain during the study period improved in zinc group (16.9Β±8.2 cm vs. 15.1Β±4.1 cm, p = 0.039); after zinc supplementation head circumference were increased (8.7Β±1.4 cm vs.7.4Β± 1.5 cm p<0.001). In male infants, total weight gain and height and head circumference gain were higher in the zinc than in the placebo group. However, only head circumference change was statistically significant. A similar trend was observed among female infants, but these differences were not statistically significant. There was no significant relation between breast-feeding status and the main outcome variables. Conclusions Infants in the present study showed improveΒ¬ments in growth rate, but more studies are required in this field to confirm this fact

    Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth

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    The overexpression of the protein tyrosine kinase, Focal adhesion kinase (FAK), in endothelial cells has implicated its requirement in angiogenesis and tumour growth, but how pericyte FAK regulates tumour angiogenesis is unknown. We show that pericyte FAK regulates tumour growth and angiogenesis in multiple mouse models of melanoma, lung carcinoma and pancreatic B-cell insulinoma and provide evidence that loss of pericyte FAK enhances Gas6-stimulated phosphorylation of the receptor tyrosine kinase, Axl with an upregulation of Cyr61, driving enhanced tumour growth. We further show that pericyte derived Cyr61 instructs tumour cells to elevate expression of the proangiogenic/protumourigenic transmembrane receptor Tissue Factor. Finally, in human melanoma we show that when 50% or more tumour blood vessels are pericyte-FAK negative, melanoma patients are stratified into those with increased tumour size, enhanced blood vessel density and metastasis. Overall our data uncover a previously unknown mechanism of tumour growth by pericytes that is controlled by pericyte FAK

    Clinicopathological Profile and Surgical Treatment of Abdominal Tuberculosis: A Single Centre Experience in Northwestern Tanzania.

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    Abdominal tuberculosis continues to be a major public health problem worldwide and poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. This study was conducted to describe the clinicopathological profile and outcome of surgical treatment of abdominal tuberculosis in our setting and compare with what is described in literature. A prospective descriptive study of patients who presented with abdominal tuberculosis was conducted at Bugando Medical Centre (BMC) in northwestern Tanzania from January 2006 to February 2012. Ethical approval to conduct the study was obtained from relevant authorities. Statistical data analysis was performed using SPSS version 17.0. Out of 256 patients enrolled in the study, males outnumbered females. The median age was 28 years (range = 16-68 years). The majority of patients (77.3%) had primary abdominal tuberculosis. A total of 127 (49.6%) patients presented with intestinal obstruction, 106 (41.4%) with peritonitis, 17 (6.6%) with abdominal masses and 6 (2.3%) patients with multiple fistulae in ano. Forty-eight (18.8%) patients were HIV positive. A total of 212 (82.8%) patients underwent surgical treatment for abdominal tuberculosis. Bands /adhesions (58.5%) were the most common operative findings. Ileo-caecal region was the most common bowel involved in 122 (57.5%) patients. Release of adhesions and bands was the most frequent surgical procedure performed in 58.5% of cases. Complication and mortality rates were 29.7% and 18.8% respectively. The overall median length of hospital stay was 32 days and was significantly longer in patients with complications (p < 0.001). Advanced age (age β‰₯ 65 years), co-morbid illness, late presentation, HIV positivity and CD4+ count < 200 cells/ΞΌl were statistically significantly associated with mortality (p < 0.0001). The follow up of patients were generally poor as only 37.5% of patients were available for follow up at twelve months after discharge. Abdominal tuberculosis constitutes a major public health problem in our environment and presents a diagnostic challenge requiring a high index of clinical suspicion. Early diagnosis, early anti-tuberculous therapy and surgical treatment of the associated complications are essential for survival

    Accurate reconstruction of insertion-deletion histories by statistical phylogenetics

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    The Multiple Sequence Alignment (MSA) is a computational abstraction that represents a partial summary either of indel history, or of structural similarity. Taking the former view (indel history), it is possible to use formal automata theory to generalize the phylogenetic likelihood framework for finite substitution models (Dayhoff's probability matrices and Felsenstein's pruning algorithm) to arbitrary-length sequences. In this paper, we report results of a simulation-based benchmark of several methods for reconstruction of indel history. The methods tested include a relatively new algorithm for statistical marginalization of MSAs that sums over a stochastically-sampled ensemble of the most probable evolutionary histories. For mammalian evolutionary parameters on several different trees, the single most likely history sampled by our algorithm appears less biased than histories reconstructed by other MSA methods. The algorithm can also be used for alignment-free inference, where the MSA is explicitly summed out of the analysis. As an illustration of our method, we discuss reconstruction of the evolutionary histories of human protein-coding genes.Comment: 28 pages, 15 figures. arXiv admin note: text overlap with arXiv:1103.434

    Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

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    The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis. Β© 2013 Cray et al

    Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice

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    We combined in silico, in vivo, and in vitro studies to gain insights into age-dependent changes in acute inflammation in response to bacterial endotoxin (LPS). Time-course cytokine, chemokine, and NO2-/NO3- data from "middle-aged" (6-8 months old) C57BL/6 mice were used to re-parameterize a mechanistic mathematical model of acute inflammation originally calibrated for "young" (2-3 months old) mice. These studies suggested that macrophages from middle-aged mice are more susceptible to cell death, as well as producing higher levels of pro-inflammatory cytokines, vs. macrophages from young mice. In support of the in silico-derived hypotheses, resident peritoneal cells from endotoxemic middle-aged mice exhibited reduced viability and produced elevated levels of TNF-Ξ±, IL-6, IL-10, and KC/CXCL1 as compared to cells from young mice. Our studies demonstrate the utility of a combined in silico, in vivo, and in vitro approach to the study of acute inflammation in shock states, and suggest hypotheses with regard to the changes in the cytokine milieu that accompany aging. Β© 2013 Namas et al
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