Potential application of mesh-free SPH method in turbulent river flows

A comprehensive review has been completed on the simulation of turbulent flow over rough beds using mesh-free particle models. Based on the outcomes of this review, an improved Smoothed Particle Hydrodynamics (SPH) method has been developed for open channel flows over a rough bed, in which a mixing length model is used for modeling the 2D turbulence and a drag force equation is proposed for treating the boundary shear. The proposed model was applied to simulate a depth-limited open channel flow over a rough bed surface. The results of the velocity profile and shear stress distribution show a good agreement with the experimental data and existing analytical solutions. This work reveals that in order to correctly model turbulent open channel flow over a rough bed, the treatment of both flow turbulence and bed roughness effect is equally important

Thymoquinone inhibits tumor growth and induces apoptosis in a breast cancer xenograft mouse model: The role of p38 MAPK and ROS

Due to narrow therapeutic window of cancer therapeutic agents and the development of resistance against these agents, there is a need to discover novel agents to treat breast cancer. The antitumor activities of thymoquinone (TQ), a compound isolated from Nigella sativa oil, were investigated in breast carcinoma in vitro and in vivo. Cell responses after TQ treatment were assessed by using different assays including MTT assay, annexin V-propidium iodide staining, Mitosox staining and Western blot. The antitumor effect was studied by breast tumor xenograft mouse model, and the tumor tissues were examined by histology and immunohistochemistry. The level of antioxidant enzymes/molecules in mouse liver tissues was measured by commercial kits. Here, we show that TQ induced p38 phosphorylation and ROS production in breast cancer cells. These inductions were found to be responsible for TQ’s anti-proliferative and pro-apoptotic effects. Moreover, TQ-induced ROS production regulated p38 phosphorylation but not vice versa. TQ treatment was found to suppress the tumor growth and this effect was further enhanced by combination with doxorubicin. TQ also inhibited the protein expression of anti-apoptotic genes, such as XIAP, survivin, Bcl-xL and Bcl-2, in breast cancer cells and breast tumor xenograft. Reduced Ki67 and increased TUNEL staining were observed in TQ-treated tumors. TQ was also found to increase the level of catalase, superoxide dismutase and glutathione in mouse liver tissues. Overall, our results demonstrated that the antiproliferative and pro-apoptotic effects of TQ in breast cancer are mediated through p38 phosphorylation via ROS generation

The Potential and Challenges of Nanopore Sequencing

A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore. The nanopore provides a highly confined space within which single nucleic acid polymers can be analyzed at high throughput by one of a variety of means, and the perfect processivity that can be enforced in a narrow pore ensures that the native order of the nucleobases in a polynucleotide is reflected in the sequence of signals that is detected. Kilobase length polymers (single-stranded genomic DNA or RNA) or small molecules (e.g., nucleosides) can be identified and characterized without amplification or labeling, a unique analytical capability that makes inexpensive, rapid DNA sequencing a possibility. Further research and development to overcome current challenges to nanopore identification of each successive nucleotide in a DNA strand offers the prospect of ‘third generation’ instruments that will sequence a diploid mammalian genome for ~$1,000 in ~24 h.Molecular and Cellular BiologyPhysic

Human Mesenchymal Stem Cells Prolong Survival and Ameliorate Motor Deficit through Trophic Support in Huntington's Disease Mouse Models

We investigated the therapeutic potential of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in Huntington's disease (HD) mouse models. Ten weeks after intrastriatal injection of quinolinic acid (QA), mice that received hBM-MSC transplantation showed a significant reduction in motor function impairment and increased survival rate. Transplanted hBM-MSCs were capable of survival, and inducing neural proliferation and differentiation in the QA-lesioned striatum. In addition, the transplanted hBM-MSCs induced microglia, neuroblasts and bone marrow-derived cells to migrate into the QA-lesioned region. Similar results were obtained in R6/2-J2, a genetically-modified animal model of HD, except for the improvement of motor function. After hBM-MSC transplantation, the transplanted hBM-MSCs may integrate with the host cells and increase the levels of laminin, Von Willebrand Factor (VWF), stromal cell-derived factor-1 (SDF-1), and the SDF-1 receptor Cxcr4. The p-Erk1/2 expression was increased while Bax and caspase-3 levels were decreased after hBM-MSC transplantation suggesting that the reduced level of apoptosis after hBM-MSC transplantation was of benefit to the QA-lesioned mice. Our data suggest that hBM-MSCs have neural differentiation improvement potential, neurotrophic support capability and an anti-apoptotic effect, and may be a feasible candidate for HD therapy

Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke.

OBJECTIVE: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. METHODS: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. RESULTS: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10(-6)) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p = 2.2 × 10(-8); rs941898 [EVL], p = 4.0 × 10(-8); rs962888 [C1QL1], p = 1.1 × 10(-8); rs9515201 [COL4A2], p = 6.9 × 10(-9)). CONCLUSIONS: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.Funding for collection, genotyping, and analysis of stroke samples was provided by Wellcome Trust Case Control Consortium-2, a functional genomics grant from the Wellcome Trust (DNA-Lacunar), the Stroke Association (DNA-lacunar), the Intramural Research Program of National Institute of Ageing (Massachusetts General Hospital [MGH] and Ischemic Stroke Genetics Study [ISGS]), National Institute of Neurological Disorders and Stroke (Siblings With Ischemic Stroke Study, ISGS, and MGH), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (MGH), Deane Institute for Integrative Study of Atrial Fibrillation and Stroke (MGH), National Health and Medical Research Council (Australian Stroke Genetics Collaborative), and Italian Ministry of Health (Milan). Additional support for sample collection came from the Medical Research Council, National Institute of Health Research Biomedical Research Centre and Acute Vascular Imaging Centre (Oxford), Wellcome Trust and Binks Trust (Edinburgh), and Vascular Dementia Research Foundation (Munich). MT is supported by a project grant from the Stroke Association (TSA 2013/01). HSM is supported by an NIHR Senior Investigator award. HSM and SB are supported by the NIHR Cambridge University Hospitals Comprehensive Biomedical Research Centre. VT and RL are supported by grants from FWO Flanders. PR holds NIHR and Wellcome Trust Senior Investigator Awards. PAS is supported by an MRC Fellowship. CML’s research is supported by the National Institute for Health Research Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London, and the BRC for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London. This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.1212/WNL.000000000000226

Ultrasound for Distal Forearm Fracture:A Systematic Review and Diagnostic Meta-Analysis

STUDY OBJECTIVE:To determine the diagnostic accuracy of ultrasound for detecting distal forearm fractures. METHODS:A systematic review and diagnostic meta-analysis was performed according to the PRISMA statement. We searched MEDLINE, Web of Science and the Cochrane Library from inception to September 2015. All prospective studies of the diagnostic accuracy of ultrasound versus radiography as the reference standard were included. We excluded studies with a retrospective design and those with evidence of verification bias. We assessed the methodological quality of the included studies with the QUADAS-2 tool. We performed a meta-analysis of studies evaluating ultrasound to calculate the pooled sensitivity and specificity with 95% confidence intervals (CI95%) using a bivariate model with random effects. Subgroup and sensitivity analysis were used to examine the effect of methodological differences and other study characteristics. RESULTS:Out of 867 publications we included 16 studies with 1,204 patients and 641 fractures. The pooled test characteristics for ultrasound were: sensitivity 97% (CI95% 93-99%), specificity 95% (CI95% 89-98%), positive likelihood ratio (LR) 20.0 (8.5-47.2) and negative LR 0.03 (0.01-0.08). The corresponding pooled diagnostic odds ratio (DOR) was 667 (142-3,133). Apparent differences were shown for method of viewing, with the 6-view method showing higher specificity, positive LR, and DOR, compared to the 4-view method. CONCLUSION:The present meta-analysis showed that ultrasound has a high accuracy for the diagnosis of distal forearm fractures in children when used by proper viewing method. Based on this, ultrasound should be considered a reliable alternative, which has the advantages of being radiation free