Haloquadratum walsbyi represents up to 80 % of cells in NaCl-saturated brines worldwide, but is notoriously difficult to maintain under laboratory conditions. In order to establish the extent of genetic diversity in a natural population of this microbe, we screened a H. walsbyi enriched metagenomic fosmid library and recovered seven novel version of its cell-wall associated genomic island. The fosmid inserts were sequenced and analysed. The novel cell-wall associated islands delineated two major clades within H. walsbyi. The islands predominantly contained genes putatively involved in biosynthesis of surface layer, genes encoding cell surface glycoproteins and genes involved in envelope formation. We further found that these genes are maintained in the population and that the diversity of this region arises through homologous recombination but also through the action of mobile genetic elements, including viruses. The population of H. walsbyi in the studied saltern brine is composed of numerous clonal lineages that differ in surface structures including the cell wall. This type of variation probably reflects a number of mechanisms that minimize the infection rate of predating viruses.

BackgroundHaloquadratum walsbyi represents up to 80 % of cells in NaCl-saturated brines worldwide, but is notoriously difficult to maintain under laboratory conditions. In order to establish the extent of genetic diversity in a natural population of this microbe, we screened a H. walsbyi enriched metagenomic fosmid library and recovered seven novel version of its cell-wall associated genomic island. The fosmid inserts were sequenced and analysed.ResultsThe novel cell-wall associated islands delineated two major clades within H. walsbyi. The islands predominantly contained genes putatively involved in biosynthesis of surface layer, genes encoding cell surface glycoproteins and genes involved in envelope formation. We further found that these genes are maintained in the population and that the diversity of this region arises through homologous recombination but also through the action of mobile genetic elements, including viruses.ConclusionsThe population of H. walsbyi in the studied saltern brine is composed of numerous clonal lineages that differ in surface structures including the cell wall. This type of variation probably reflects a number of mechanisms that minimize the infection rate of predating viruses.

The approach of metric-affine gravity initially distinguishes it from Einstein’s general relativity. Using an independent affine connection produces a theory with 10

During the war in Bosnia and Herzegovina (1992–1995) cultural heritage was explicitly targeted and the state of destruction was extensive to both sacral and secular monuments. Two decades after the end of hostilities the perception of the historic environment is still defined from the angles of national, religious or ethnic belonging. Enabling recognition, reconciliation, tolerance and respect within the community of Stolac, Bosnia & Herzegovina through a better understanding and sharing of cultural heritage was the focus of this project. Stolac is representative of the problems in the region and stands out for its particularly sharp divisions. Until recently there was segregation with local schools and their curriculum was divided with cultural heritage generally not addressed. How can this small community engage with heritage and develop a dialogue that encourages tolerance, respect and as a base for development? How does one understand, then document areas significance to the community? Finally, how can technology assist? The focus of this paper is to relate the experiences and findings of a project that incorporated participatory imaging mapping and the use of technology to bridge between the internal borders of this small community. It will outline a methodology, experiences of the participants and results from their exercises in order to assist other communities facing similar issues.

The fundamental basis for implementation of reengineering is: experimental measurement of forces and torques on the rollers-tools production line for profile sheet metal forming. The paper presents the experiments of measuring forces and torques, modeling and simulation in the aim of redesigning the process of sheet metal forming, selecting of the optimal process of sheet metal forming for each forming module and totally for the production line and increasing productivity on production lines. In the experimental research forces and torques were measured on the rollers of forming modules for profile forming of sheets for different values of the input parameters of the process: material type σm, sheet thickness s and sheet width b. Based on the experimental results mathematical models were defined, which enabled the analysis and implementation of reengineering the production system.

The aims of this study were: 1) To determine the effects of a 12-week recreational soccer training programme and continuous endurance running on body composition of young adult men and 2) to determine which of these two programmes was more effective concerning body composition. Sixty-four participants completed the randomized controlled trial and were randomly assigned to one of three groups: a soccer training group (SOC; n=20), a running group (RUN; n=21) or a control group performing no physical training (CON; n=23). Training programmes for SOC and RUN lasted 12-week with 3 training sessions per week. Soccer sessions consisted of 60 min ordinary five-a-side, six-a-side or seven-a-side matches on a 30-45 m wide and 45-60 m long plastic grass pitch. Running sessions consisted of 60 min of continuous moderate intensity running at the same average heart rate as in SOC (~80% HRmax). All participants, regardless of group assignment, were tested for each of the following dependent variables: body weight, body height, body mass index, percent body fat, body fat mass, fat-free mass and total body water. In the SOC and RUN groups there was a significant decrease (p < 0.05) in body composition parameters from pre- to post-training values for all measures with the exception of fat-free mass and total body water. Body mass index, percent body fat and body fat mass did not differ between groups at baseline, but by week 12 were significantly lower (p < 0.05) in the SOC and RUN groups compared to CON. To conclude, recreational soccer training provides at least the same changes in body composition parameters as continuous running in young adult men when the training intensity is well matched.

Staphylococcus aureus is a major cause of hospital-acquired infections worldwide. Increased frequency of methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized patients and possibility of vancomycin resistance requires rapid and reliable characterization of isolates and control of MRSA spread in hospitals. Typing of isolates helps to understand the route of a hospital pathogen spread. The aim of this study was to investigate and compare genotypic and phenotypic characteristics of MRSA samples on three different geography locations. In addition, our aim was to evaluate three different methods of MRSA typing: spa-typing, agr-typing and GenoType MRSA.  We included 104 samples of MRSA, isolated in 3 different geographical locations in clinical hospitals in Zagreb, Mostar, and Heidelberg, during the period of six months. Genotyping and phenotyping were done by spa-typing, agr-typing and dipstick assay GenoType MRSA. We failed to type all our samples by spa-typing.  The most common spa-type in clinical hospital Zagreb was t041, in Mostar t001, and in Heidelberg t003.We analyzed 102/104 of our samples by agr-typing method. We did not find any agr-type IV in our locations. We analyzed all our samples by the dipstick assay GenoType MRSA. All isolates in our study were MRSA strains. In Zagreb there were no positive strains to PVL gene. In Mostar we have found 5/25 positive strains to PVL gene, in Heidelberg there was 1/49. PVL positive isolates were associated with spa-type t008 and agr-type I, thus, genetically, they were community-associated MRSA (CA-MRSA). Dipstick assay GenoType MRSA has demonstrated sufficient specificity, sensibility, simple performance and low cost, so we could introduce it to work in smaller laboratories. Using this method may expedite MRSA screening, thus preventing its spread in hospitals.

We present a combined analysis of LHC Higgs data (signal strengths) together with LEP-2 WW production measurements. To characterize possible deviations from the standard model (SM) predictions, we employ the framework of an effective field theory (EFT) where the SM is extended by higher-dimensional operators suppressed by the mass scale of new physics Λ. The analysis is performed consistently at the order Λ(-2) in the EFT expansion keeping all the relevant operators. While the two data sets suffer from flat directions, together they impose stringent model-independent constraints on the anomalous triple gauge couplings.

Highlights from ASCO 2015 demonstrate the impasse we face in solid tumour oncology: the compelling novel immune and targeted therapies are often associated with cost–benefit ratios significantly above the thresholds for reimbursement. This is at least in part a consequence of our incomplete understanding of the mechanisms of response and resistance to these agents. For example, ipilimumab is associated with durable clinical benefit in 15%–20% of unselected advanced melanoma patients (∼£75 000 per patient treated), and while the responses to single-agent targeted therapies such as vemurafenib are higher, they are often relatively short-lived (∼£42 000 per median PFS of 6–7 months). New trial design strategies such as basket and umbrella studies have improved upon patient selection, but have not yielded detailed biological understanding of the drug targets, nor polygenic mechanisms of resistance within or between patients. Academically led studies have the opportunity and the responsibility to prioritize biological insights as trial end points, maximising research gain, increasing patient benefit/safety and ultimately, improving cost-effectiveness. Collection of tumour material is fundamental to these aims but the timing, handling and sample analysis are of critical importance (Figure ​(Figure11). Figure 1. A schematic for biological sample collection throughout the course of disease and treatment. TILs, tumour-infiltrating lymphocytes; cfDNA, cell-free tumour DNA; PBMCs, peripheral mononuclear blood cells; PK, pharmacokinetic; PD, pharmacodynamic; PDX, ... Resistance to targeted therapies can be mediated by pre-existing rather than de novo alterations. High resolution tracking of cancer cells in vitro demonstrated that only 10% of resistant clones arise de novo [1], while mathematical models of tumour growth suggest that radiographically detectable lesions harbour at least 10 resistant sub-clones [2]. Thus, comprehensive upfront tumour profiling could anticipate the genetic composition of such clone(s), while taking into account spatial and temporal tumour heterogeneity. Extensive sampling of metastatic sites at autopsy revealed 10 distinct PTEN alterations emerging under the selective pressure of PI(3)Kα inhibition [3], and five independent reversion events in a germline BRCA2 mutant carrier who progressed on olaparib and carboplatin [4]. Distinct mechanisms of BRAF and EGFR inhibitor resistance were detected across multiple metastases within individual patients with melanoma [5] and colorectal cancer [6], respectively. The benefit of combination strategies can be limited by excess toxicity (combined targeting of the PI3K and MAPK pathways [7]), cross-resistance (BRAF and MEK inhibitors in melanoma [8]) and the persistent role of intra-tumour heterogeneity (targeting of the T790M EGFR mutation in lung cancer [9]). Informed by pre-clinical models, such as discontinuous dosing in BRAF-mutant melanoma [10], academically led trials can address more finely tuned ways of managing treatment resistance. In colorectal cancer cell-free tumour DNA (cfDNA) shows pulsatile levels of mutant KRAS in response to intermittent EGFR inhibition [11], providing the molecular rationale for re-challenge with targeted therapy. Similar frameworks are required to prospectively evaluate alternative or sequential scheduling as well as the role of cfDNA in tracking tumour progression. PD-L1 expression, a putative predictive marker for PD1/PDL1 inhibition, is also spatially heterogeneous [12]. Genomic data are a promising alternative biomarker in this area [13]. Mutational data, integrated with HLA typing, and tumour and peripheral T-cell profiling can define individual neo-antigenic repertoires. Academically led studies of immunotherapeutic agents must evaluate the ability of this approach to predict responses, inform immunotherapy/targeted combinations, and ultimately, facilitate adoptive T-cell therapy. Non-genetic causes of treatment resistance have been largely overlooked but studies that incorporate longitudinal biological sample collection and novel imaging techniques are well placed to examine tumour drug exposure (including heterogeneity of drug distribution [14]) and individual variation in drug metabolising enzymes, receptors, and transporters. Patient-derived xenografts can provide a useful platform for investigating personalised therapy in co-clinical trials [15], but only if robustly characterised and used in the full knowledge of their limitations (e.g. immunosuppressed host, mouse stroma and disparities in tumour burden between mouse and patient). There clearly are challenges to implementation of such complex studies but they can be overcome through close interdisciplinary work of academic/clinical consortia as illustrated by the Lung TRACERx programme [16], the use of measures such as one-time consent [17], post-mortem studies and stakeholder engagement (patient and public). In summary, we argue for a change of emphasis in drug development from learning little from many patients towards biologically rich clinical studies focussed on gleaning the maximum amount of biological information that might inform drug response and resistance for every patient entered into academic trial protocols.

Tendo como base o conceito de modernizacao territorial proposto por Milton Santos, a pesquisa em curso analisa os impactos economico, social e ambiental causados pela implantacao de um projeto imobiliario tipo resort denominado Complexo Turistico-Residencial Fazenda de Sao Bento da Lagoa em uma Area de Protecao Ambiental (APA) no municipio de Marica/Rio de Janeiro. Trata-se de espaco de extrema relevância, pois ali ocorre tanto a pesca artesanal da comunidade tradicional de Zacarias quanto uma serie pesquisas cientificas coordenadas por biologos de todo o pais. Resgatando a situacao dos atingidos e a conjuntura que envolve tal implantacao, examinamos tambem os Estudos de Impacto Ambiental (EIA) apresentado pelo grupo imobiliario ao Instituto Estadual do Ambiente (INEA), bem como a posicao do governo do Estado do Rio de Janeiro nas audiencias publicas ocorridas para a aprovacao do resort.