Arpeggio: A Web Server for Calculating and Visualising Interatomic Interactions in Protein Structures

Interactions between proteins and their ligands, such as small molecules, other proteins, and DNA, depend on specific interatomic interactions that can be classified on the basis of atom type and distance and angle constraints. Visualisation of these interactions provides insights into the nature of molecular recognition events and has practical uses in guiding drug design and understanding the structural and functional impacts of mutations. We present Arpeggio, a web server for calculating interactions within and between proteins and protein, DNA, or small-molecule ligands, including van der Waals', ionic, carbonyl, metal, hydrophobic, and halogen bond contacts, and hydrogen bonds and specific atom-aromatic ring (cation-π, donor-π, halogen-π, and carbon-π) and aromatic ring-aromatic ring (π-π) interactions, within user-submitted macromolecule structures. PyMOL session files can be downloaded, allowing high-quality publication images of the interactions to be generated. Arpeggio is implemented in Python and available as a user-friendly web interface at http://structure.bioc.cam.ac.uk/arpeggio/ and as a downloadable package at https://bitbucket.org/harryjubb/arpeggio.H.C.J. was supported by the Biotechnology and Biological Sciences Research Council and UCB [BB/J500574/1]. B.O.-M. was supported by the Bill and Melinda Gates Foundation. D.B.A. is the recipient of a C. J. Martin Research Fellowship from the National Health and Medical Research Council of Australia (APP1072476) and is funded by the Jack Brockhoff Foundation (JBF 4186, 2016) and a Wellcome Trust Programme Grant to TLB (093167/Z/10/Z). D.B.A. and T.L.B. are funded by a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (MR/M026302/1). T.L.B. wishes to acknowledge the University of Cambridge and The Wellcome Trust for facilities and support. This work builds on work funded by the Wellcome Trust

The Role of Aldosterone Blockade in Patients with Heart Failure

The mechanisms associated with aldosterone production both systemically and locally as well as the effects of aldosterone blockade on the pathophysiology of heart failure (HF) have been extensively reviewed in this series and elsewhere. This article will review the clinical evidence supporting the use of aldosterone blocking agents (AB)in patients with HF and speculate on some potential future uses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45819/1/10741_2005_Article_2352.pd

Adjuvant concurrent chemoradiation therapy (CCRT) alone versus CCRT followed by adjuvant chemotherapy: Which is better in patients with radically resected extrahepatic biliary tract cancer?: a non-randomized, single center study

<p>Abstract</p> <p>Background</p> <p>There is currently no standard adjuvant therapy for patients with curatively resected extrahepatic biliary tract cancer (EHBTC). The aim of this study was to analyze the clinical features and outcomes between patients undergoing adjuvant concurrent chemoradiation therapy (CCRT) alone and those undergoing CCRT followed by adjuvant chemotherapy after curative resection.</p> <p>Methods</p> <p>We included 120 patients with EHBTC who underwent radical resection and then received adjuvant CCRT with or without further adjuvant chemotherapy between 2000 and 2006 at Seoul National University Hospital.</p> <p>Results</p> <p>Out of 120 patients, 30 received CCRT alone, and 90 received CCRT followed by adjuvant chemotherapy. Baseline characteristics were comparable between the two groups. Three-year disease-free survival (DFS) rates for CCRT alone and CCRT followed by adjuvant chemotherapy were 26.6% and 45.2% (p = 0.04), respectively, and 3-year overall survival (OS) rates were 30.8% and 62.6% (p < 0.01), respectively. CCRT followed by adjuvant chemotherapy showed longer survival than did CCRT alone, especially in R1 resection (microscopically positive margins) or negative lymph node.</p> <p>Conclusion</p> <p>Adjuvant CCRT followed by adjuvant chemotherapy prolonged DFS and OS, compared with CCRT alone in patients with curatively resected EHBTC. Adjuvant chemotherapy deserves to consider after adjuvant CCRT. In the future, a randomized prospective study will be needed, with the objective of investigating the role of adjuvant chemotherapy.</p

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial

This prospective multicentre phase II study characterises the toxicity and activity of first-line capecitabine and oxaliplatin combination therapy (CAPOX) in advanced biliary system adenocarcinomas. Patients received oxaliplatin (130 mg m−2, day 1) plus capecitabine (1000 mg m−2 b.i.d., days 1–14) every 3 weeks. Patients were stratified prospectively into two groups based on location of the primary (gallbladder carcinoma (GBC) or extrahepatic cholangiocarcinoma (ECC) versus intrahepatic mass-forming type cholangiocarcinoma (ICC)). Sixty-five patients were evaluable. The response rate in 47 patients with GBC/ECC was 27% (4% complete responses), and in 23 patients (49%) stable disease (SD) was encountered. In 18 patients with ICC, we observed no objective responses, but 6 patients (33%) had SD. Median survival was 12.8 months (95% CI, 10.0–15.6) for patients with GBC or ECC (GBC: 8.2 months; 95% CI, 4.3–11.7; ECC: 16.8 months; 95% CI, 12.7–20.5), and 5.2 months (95% CI, 0.6–9.8) for ICC patients. In both cohorts, therapy was well tolerated. The most common grade 3–4 toxicity was peripheral sensory neuropathy (11 patients). Our data suggest that the CAPOX regimen is a well-tolerated and active treatment option for advanced ECC and GBC but might produce poorer results for ICC

Need for criteria for the diagnosis and severity assessment of acute cholangitis and cholecystitis: Tokyo Guidelines

The Tokyo Guidelines formulate clinical guidance for healthcare providers regarding the diagnosis, severity assessment, and treatment of acute cholangitis and acute cholecystitis. The Guidelines were developed through a comprehensive literature search and selection of evidence. Recommendations were based on the strength and quality of evidence. Expert consensus opinion was used to enhance or formulate important areas where data were insufficient. A working group, composed of gastroenterologists and surgeons with expertise in biliary tract surgery, supplemented with physicians in critical care medicine, epidemiology, and laboratory medicine, was selected to formulate draft guidelines. Several other groups (including members of the Japanese Society for Abdominal Emergency Medicine, the Japan Biliary Association, and the Japanese Society of Hepato-Biliary-Pancreatic Surgery) have reviewed and revised the draft guidelines. To build a global consensus on the management of acute biliary infection, an international expert panel, representing experts in this area, was established. Between April 1 and 2, 2006, an International Consensus Meeting on acute biliary infections was held in Tokyo. A consensus was determined based on best available scientific evidence and discussion by the panel of experts. This report describes the highlights of the Tokyo International Consensus Meeting in 2006. Some important areas focused on at the meeting include proposals for internationally accepted diagnostic criteria and severity assessment for both clinical and research purposes

SeqAn An efficient, generic C++ library for sequence analysis

<p>Abstract</p> <p>Background</p> <p>The use of novel algorithmic techniques is pivotal to many important problems in life science. For example the sequencing of the human genome <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> would not have been possible without advanced assembly algorithms. However, owing to the high speed of technological progress and the urgent need for bioinformatics tools, there is a widening gap between state-of-the-art algorithmic techniques and the actual algorithmic components of tools that are in widespread use.</p> <p>Results</p> <p>To remedy this trend we propose the use of SeqAn, a library of efficient data types and algorithms for sequence analysis in computational biology. SeqAn comprises implementations of existing, practical state-of-the-art algorithmic components to provide a sound basis for algorithm testing and development. In this paper we describe the design and content of SeqAn and demonstrate its use by giving two examples. In the first example we show an application of SeqAn as an experimental platform by comparing different exact string matching algorithms. The second example is a simple version of the well-known MUMmer tool rewritten in SeqAn. Results indicate that our implementation is very efficient and versatile to use.</p> <p>Conclusion</p> <p>We anticipate that SeqAn greatly simplifies the rapid development of new bioinformatics tools by providing a collection of readily usable, well-designed algorithmic components which are fundamental for the field of sequence analysis. This leverages not only the implementation of new algorithms, but also enables a sound analysis and comparison of existing algorithms.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente