Towards use of Dijkstra Algorithm for Optimal Navigation of an Unmanned Surface Vehicle in a Real-Time Marine Environment with Results from Artificial Potential Field

The growing need of ocean surveying and exploration for scientific and industrial application has led to the requirement of routing strategies for ocean vehicles which are optimal in nature. Most of the optimal path planning for marine vehicles had been conducted offline in a self‐made environment. This paper takes into account a practical marine environment, i.e. Portsmouth Harbour, for finding an optimal path in terms of computational time between source and end points on a real time map for an USV. The current study makes use of a grid map generated from original and uses a Dijkstra algorithm to find the shortest path for a single USV. In order to benchmark the study, a path planning study using a well‐known local path planning method artificial path planning (APF) has been conducted in a real time marine environment and effectiveness is measured in terms of path length and computational time

Australian Sphingidae – DNA Barcodes Challenge Current Species Boundaries and Distributions

© 2014 Rougerie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Stalking influenza by vaccination with pre-fusion headless HA mini-stem.

Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity

An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are heterogeneous with respect to biological behaviour and prognosis. As angiogenesis is a renowned pathogenic hallmark as well as a therapeutic target, we aimed to investigate the prognostic and clinico-pathological role of tissue markers of hypoxia and angiogenesis in GEP-NETs. METHODS: Tissue microarray (TMA) blocks were constructed with 86 tumours diagnosed from 1988 to 2010. Tissue microarray sections were immunostained for hypoxia inducible factor 1α (Hif-1α), vascular endothelial growth factor-A (VEGF-A), carbonic anhydrase IX (Ca-IX) and somatostatin receptors (SSTR) 1–5, Ki-67 and CD31. Biomarker expression was correlated with clinico-pathological variables and tested for survival prediction using Kaplan–Meier and Cox regression methods. RESULTS: Eighty-six consecutive cases were included: 51% male, median age 51 (range 16–82), 68% presenting with a pancreatic primary, 95% well differentiated, 51% metastatic. Higher grading (P=0.03), advanced stage (P<0.001), high Hif-1α and low SSTR-2 expression (P=0.03) predicted for shorter overall survival (OS) on univariate analyses. Stage, SSTR-2 and Hif-1α expression were confirmed as multivariate predictors of OS. Median OS for patients with SSTR-2+/Hif-1α-tumours was not reached after median follow up of 8.8 years, whereas SSTR-2-/Hif-1α+ GEP-NETs had a median survival of only 4.2 years (P=0.006). CONCLUSION: We have identified a coherent expression signature by immunohistochemistry that can be used for patient stratification and to optimise treatment decisions in GEP-NETs independently from stage and grading. Tumours with preserved SSTR-2 and low Hif-1α expression have an indolent phenotype and may be offered less aggressive management and less stringent follow up

Gene expression and splicing alterations analyzed by high throughput RNA sequencing of chronic lymphocytic leukemia specimens.

BackgroundTo determine differentially expressed and spliced RNA transcripts in chronic lymphocytic leukemia specimens a high throughput RNA-sequencing (HTS RNA-seq) analysis was performed.MethodsTen CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system.ResultsAn average of 48.5 million reads for B cells, and 50.6 million reads for CLL specimens were obtained with 10396 and 10448 assembled transcripts for normal B cells and primary CLL specimens respectively. With the Cuffdiff analysis, 2091 differentially expressed genes (DEG) between B cells and CLL specimens based on FPKM (fragments per kilobase of transcript per million reads and false discovery rate, FDR q &lt; 0.05, fold change &gt;2) were identified. Expression of selected DEGs (n = 32) with up regulated and down regulated expression in CLL from RNA-seq data were also analyzed by qRT-PCR in a test cohort of CLL specimens. Even though there was a variation in fold expression of DEG genes between RNA-seq and qRT-PCR; more than 90 % of analyzed genes were validated by qRT-PCR analysis. Analysis of RNA-seq data for splicing alterations in CLL and B cells was performed by Multivariate Analysis of Transcript Splicing (MATS analysis). Skipped exon was the most frequent splicing alteration in CLL specimens with 128 significant events (P-value &lt;0.05, minimum inclusion level difference &gt;0.1).ConclusionThe RNA-seq analysis of CLL specimens identifies novel DEG and alternatively spliced genes that are potential prognostic markers and therapeutic targets. High level of validation by qRT-PCR for a number of DEG genes supports the accuracy of this analysis. Global comparison of transcriptomes of B cells, IGVH non-mutated CLL (U-CLL) and mutated CLL specimens (M-CLL) with multidimensional scaling analysis was able to segregate CLL and B cell transcriptomes but the M-CLL and U-CLL transcriptomes were indistinguishable. The analysis of HTS RNA-seq data to identify alternative splicing events and other genetic abnormalities specific to CLL is an added advantage of RNA-seq that is not feasible with other genome wide analysis

Zingiber officinale Roscoe aqueous extract modulates Matrixmetalloproteinases and tissue inhibitors of Metalloproteinases expressions in Dengue virus-infected cells: implications for prevention of vascular permeability

Purpose: To investigate the effect of the aqueous extract of Zingiber officinale Roscoe. (ZOA) rhizome on the activity and expression of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 using an in vitro model of Dengue virus (DV) infection.Methods: Z. officinale rhizomes were extracted with water by continuous shaking for 5 days. The total phenolic content in extract was measured by Folin-Ciocalteu method. High performance liquid chromatography (HPLC) was employed to define qualitative and quantitative content of [6]-gingerol in ZOA. The median inhibitory concentration (IC50) value of ZOA for Vero cells was determined by 3-(4,5 dimethylthiazol-2- yl)-2,5- diphenyltetrazolium bromide (MTT) assay. To induce MMPs production, Vero cells were infected with DV3. The modulatory effect of ZOA on the activity and expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed using gelatin zymography and quantitative Real-time polymerase chain reaction (RTPCR), respectively.Results: The yield of the ZOA was 7.98%. Total phenolics in ZOA was 68.17 ± 0.28 mg GAE/g of extract and it contained 29.32 ± 1.97 mg 6-gingerol/g of extract.The half-maximal inhibition concentration (IC50) of ZOA was 348.8 μg/mL for Vero cells. DV infection of Vero cells significantly elevated the production of soluble gelatinolytic MMP-2 and to a lesser extent, MMP-9, and their activities were significantly inhibited by ZOA in a dose-dependent manner. A significant down-regulation of MMP-2, MMP-9 mRNA expression and up-regulation of TIMP-1, TIMP-2 mRNA expression were observed in DV-infected Vero cells following treatment with ZOA, and it occurred in a  dose-dependent manner.Conclusion: The findings of this study suggest that ZOA may ameliorate plasma leakage in dengue virus infection and decrease the chances of severe dengue complications, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) by inhibiting the activities and expression of MMP-2 and MMP-9 while upregulating the expression of TIMP-1 and TIMP-2

An integrated silicon sensor with microfluidic chip for monitoring potassium and pH

We present ion-sensitive field effect transistor-based sensors, integrated with a microfluidic chip, for monitoring pH and potassium cations. The sensor is strategically located at the base of a well so that the response time of the device depends both on the mean flow through the device and the diffusion coefficient of the analyte being monitored. This would enable monitoring of ions in the presence of larger molecules. The dependence of the device response time on diffusive transport of analytes was examined through a numerical study of the flow field and the passive diffusion of a chemical species. The predicted device response time was compared with the experimental measurements and reasonable agreement found. The general dependence of device response time on geometry, flow rate, and analyte diffusion coefficient was derived. These devices can be used with biological fluids where monitoring of pH and cations provide vital information about the well-being of patients. © 2010 Springer-Verlag

Process evaluation of complex interventions tested in randomised controlled trials in musculoskeletal disorders: A systematic review protocol

Introduction The effectiveness of complex interventions for the management of musculoskeletal disorders has been estimated in many randomised clinical trials (RCTs). These trials inform which interventions are the most effective, however they do not always inform how an intervention achieved its clinical outcomes, nor how and what elements of an intervention were delivered to patients. Such information is useful for translating findings into clinical practice. A few process evaluation studies have been conducted alongside RCTs and a variety of methods have been used. To gain a better understanding of current practices of process evaluation in RCTs in musculoskeletal disorders, this systematic review is designed to answer the following research question: How are process evaluation of complex interventions tested in RCTs in musculoskeletal disorders being conducted? Methods and analysis We will systematically search seven electronic databases (MEDLINE, SCOPUS, CINAHL, PsycINFO, EMBASE, Web of Science and Cochrane database) from the date of inception to August 2018 for studies on process evaluation of RCTs on non-surgical and non-pharmacological management of musculoskeletal disorders. We will include qualitative and quantitative studies conducted alongside RCTs, reported with the RCTs or separate studies that assessed interventions for musculoskeletal disorders. Two reviewers will screen abstracts and apply prespecified inclusion criteria to identify relevant studies, extract the data and assess the risk of bias within included studies. We will follow recommendations from the Cochrane Qualitative and Implementation Methods Group Guidance Series' when assessing methodological strengths and limitations of included studies. We will use a narrative synthesis to describe findings. Ethics and dissemination Ethical approval is not required as this review will not collect original data. Findings from this systematic review will be presented at a scientific conference and published in a peer reviewed journal. PROSPERO registration number CRD4201810960

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease

Background Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes. Methods We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants. Results Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among patients with the aggressive phenotype, with BRCA2, ATM and NBN the most frequently mutated genes. Differential burden of rare variants was identified between metastatic and non-aggressive cases for several genes implicated in angiogenesis, conferring both deleterious and protective effects. Conclusions Inherited PTVs in several DNA repair genes distinguish aggressive from non-aggressive PrCa cases. Furthermore, inherited variants in genes with roles in angiogenesis may be potential predictors for risk of metastases. If validated in a larger dataset, these findings have potential for future clinical application