Isotopic Dependence of the Nuclear Caloric Curve

The A/Z dependence of projectile fragmentation at relativistic energies has been studied with the ALADIN forward spectrometer at SIS. A stable beam of 124Sn and radioactive beams of 124La and 107Sn at 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. Chemical freeze-out temperatures are found to be nearly invariant with respect to the A/Z of the produced spectator sources, consistent with predictions for expanded systems. Small Coulomb effects (\Delta T \approx 0.6 MeV) appear for residue production near the onset of multifragmentation.Comment: 11 pages, 3 figures, accepted for publ. in Phys. Rev. Let

Genome-scale metabolic representation of Amycolatopsis balhimycina

Infection caused by methicillin-resistant Staphylococcus aureus (MRSA) is an increasing societal problem. Typically, glycopeptide antibiotics are used in the treatment of these infections. The most comprehensively studied glycopeptide antibiotic biosynthetic pathway is that of balhimycin biosynthesis in Amycolatopsis balhimycina. The balhimycin yield obtained by A. balhimycina is, however, low and there is therefore a need to improve balhimycin production. In this study, we performed genome sequencing, assembly and annotation analysis of A. balhimycina and further used these annotated data to reconstruct a genome-scale metabolic model for the organism. Here we generated an almost complete A. balhimycina genome sequence comprising 10,562,587 base pairs assembled into 2,153 contigs. The high GC-genome (similar to 69%) includes 8,585 open reading frames (ORFs). We used our integrative toolbox called SEQTOR for functional annotation and then integrated annotated data with biochemical and physiological information available for this organism to reconstruct a genome-scale metabolic model of A. balhimycina. The resulting metabolic model contains 583 ORFs as protein encoding genes (7% of the predicted 8,585 ORFs), 407 EC numbers, 647 metabolites and 1,363 metabolic reactions. During the analysis of the metabolic model, linear, quadratic and evolutionary programming algorithms using flux balance analysis (FBA), minimization of metabolic adjustment (MOMA), and OptGene, respectively were applied as well as phenotypic behavior and improved balhimycin production were simulated. The A. balhimycina model shows a good agreement between in silico data and experimental data and also identifies key reactions associated with increased balhimycin production. The reconstruction of the genome-scale metabolic model of A. balhimycina serves as a basis for physiological characterization. The model allows a rational design of engineering strategies for increasing balhimycin production in A. balhimycina and glycopeptide production in general

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy

Characterization of animal models for primary sclerosing cholangitis (PSC)

SummaryPrimary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by biliary fibrosis, development of cholestasis and end stage liver disease, high risk of malignancy, and frequent need for liver transplantation. The poor understanding of its pathogenesis is also reflected in the lack of effective medical treatment. Well-characterized animal models are utterly needed to develop novel pathogenetic concepts and study new treatment strategies. Currently there is no consensus on how to evaluate and characterize potential PSC models, which makes direct comparison of experimental results and effective exchange of study material between research groups difficult. The International Primary Sclerosing Cholangitis Study Group (IPSCSG) has therefore summarized these key issues in a position paper proposing standard requirements for the study of animal models of PSC

Anger problems and posttraumatic stress disorder in male and female National Guard and Reserve Service members

Anger is a common problem among veterans and has been associated with posttraumatic stress disorder (PTSD). This study aimed to improve understanding of how anger and PTSD co-occur by examining gender differences and differences by whether the triggering traumatic event is deployment-related vs. civilian-related in current service members. A representative cohort of Reserve and National Guard service personnel (n = 1293) were interviewed to assess for deployment- or civilian-related traumas, PTSD, and anger. The prevalence of self-reported anger problems was estimated among male (n = 1036) and female (n = 257) service members. Log Poisson regression models with robust standard errors were used to estimate the associations of problems with anger with PTSD and PTSD symptom severity for men and women. Self-reported anger problems were common among male (53.0%) and female (51.3%) service members. Adjusted prevalence ratios (PR) showed associations between anger and PTSD connected to both civilian- and deployment-related traumas (PR were 1.77 (95% CI 1.52–2.05) and 1.85 (95% CI 1.62–2.12), respectively). PTSD symptom severity was also associated with anger. This study was cross-sectional and so a causal relationship between PTSD and anger cannot be established. Problems with anger are common among male and female current Guard and Reserve members. These findings suggest that anger treatment should be made available to current service members and that clinicians should assess anger problems irrespective of gender. Future research should examine the effectiveness of anger treatment protocols by gender

Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis

Background: Tourette syndrome (TS) is a neurodevelopmental condition characterised by chronic motor and vocal tics affecting up to 1% of school-age children and young people and is associated with significant distress and psychosocial impairment. Objective: To conduct a systematic review of the benefits and risks of pharmacological, behavioural and physical interventions for tics in children and young people with TS (part 1) and to explore the experience of treatment and services from the perspective of young people with TS and their parents (part 2). Data Sources: For the systematic reviews (parts 1 and 2), mainstream bibliographic databases, The Cochrane Library, education, social care and grey literature databases were searched using subject headings and text words for tic* and Tourette* from database inception to January 2013. Review/research methods: For part 1, randomised controlled trials and controlled before-and-after studies of pharmacological, behavioural or physical interventions in children or young people (aged < 18 years) with TS or chronic tic disorder were included. Mixed studies and studies in adults were considered as supporting evidence. Risk of bias associated with each study was evaluated using the Cochrane tool. When there was sufficient data, random-effects meta-analysis was used to synthesize the evidence and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. For part 2, qualitative studies and survey literature conducted in populations of children/young people with TS or their carers or in health professionals with experience of treating TS were included in the qualitative review. Results were synthesized narratively. In addition, a national parent/carer survey was conducted via the Tourettes Action website. Participants included parents of children and young people with TS aged under 18 years. Participants (young people with TS aged 10–17 years) for the in-depth interviews were recruited via a national survey and specialist Tourettes clinics in the UK. Results: For part 1, 70 studies were included in the quantitative systematic review. The evidence suggested that for treating tics in children and young people with TS, antipsychotic drugs [standardised mean difference (SMD) –0.74, 95% confidence interval (CI) –1.08 to –0.41; n = 75] and noradrenergic agents [clonidine (Dixarit®, Boehringer Ingelheim) and guanfacine: SMD –0.72, 95% CI –1.03 to –0.40; n = 164] are effective in the short term. There was little difference among antipsychotics in terms of benefits, but adverse effect profiles do differ. Habit reversal training (HRT)/comprehensive behavioural intervention for tics (CBIT) was also shown to be effective (SMD –0.64, 95% CI –0.99 to –0.29; n = 133). For part 2, 295 parents/carers of children and young people with TS contributed useable survey data. Forty young people with TS participated in in-depth interviews. Four studies were in the qualitative review. Key themes were difficulties in accessing specialist care and behavioural interventions, delay in diagnosis, importance of anxiety and emotional symptoms, lack of provision of information to schools and inadequate information regarding medication and adverse effects. Limitations: The number and quality of clinical trials is low and this downgrades the strength of the evidence and conclusions. Conclusions: Antipsychotics, noradrenergic agents and HRT/CBIT are effective in reducing tics in children and young people with TS. The balance of benefits and harms favours the most commonly used medications: risperidone (Risperdal®, Janssen), clonidine and aripiprazole (Abilify®, Otsuka). Larger and better-conducted trials addressing important clinical uncertainties are required. Further research is needed into widening access to behavioural interventions through use of technology including mobile applications (‘apps’) and video consultation. Study registration: This study is registered as PROSPERO CRD42012002059

Cognitive Dysfunction in Huntington's Disease: Mechanisms and Therapeutic Strategies Beyond BDNF

One of the main focuses in Huntington's disease (HD) research, as well as in most of the neurodegenerative diseases, is the development of new therapeutic strategies, as currently there is no treatment to delay or prevent the progression of the disease. Neuronal dysfunction and neuronal death in HD are caused by a combination of interrelated pathogenic processes that lead to motor, cognitive and psychiatric symptoms. Understanding how mutant huntingtin impacts on a plethora of cellular functions could help to identify new molecular targets. Although HD has been classically classified as a neurodegenerative disease affecting voluntary movement, lately cognitive dysfunction is receiving increased attention as it is very invalidating for patients. Thus, an ambitious goal in HD research is to find altered molecular mechanisms that contribute to cognitive decline. In this review we have focused on those findings related to corticostriatal and hippocampal cognitive dysfunction in HD, as well as on the underlying molecular mechanisms, which constitute potential therapeutic targets. These include alterations in synaptic plasticity, transcriptional machinery, and neurotrophic and neurotransmitter signaling. This article is protected by copyright. All rights reserved

Climate Change, Coral Reef Ecosystems, and Management Options for Marine Protected Areas

Marine protected areas (MPAs) provide place-based management of marine ecosystems through various degrees and types of protective actions. Habitats such as coral reefs are especially susceptible to degradation resulting from climate change, as evidenced by mass bleaching events over the past two decades. Marine ecosystems are being altered by direct effects of climate change including ocean warming, ocean acidification, rising sea level, changing circulation patterns, increasing severity of storms, and changing freshwater influxes. As impacts of climate change strengthen they may exacerbate effects of existing stressors and require new or modified management approaches; MPA networks are generally accepted as an improvement over individual MPAs to address multiple threats to the marine environment. While MPA networks are considered a potentially effective management approach for conserving marine biodiversity, they should be established in conjunction with other management strategies, such as fisheries regulations and reductions of nutrients and other forms of land-based pollution. Information about interactions between climate change and more “traditional” stressors is limited. MPA managers are faced with high levels of uncertainty about likely outcomes of management actions because climate change impacts have strong interactions with existing stressors, such as land-based sources of pollution, overfishing and destructive fishing practices, invasive species, and diseases. Management options include ameliorating existing stressors, protecting potentially resilient areas, developing networks of MPAs, and integrating climate change into MPA planning, management, and evaluation