The influence of gene expression time delays on Gierer-Meinhardt pattern formation systems

There are numerous examples of morphogen gradients controlling long range signalling in developmental and cellular systems. The prospect of two such interacting morphogens instigating long range self-organisation in biological systems via a Turing bifurcation has been explored, postulated, or implicated in the context of numerous developmental processes. However, modelling investigations of cellular systems typically neglect the influence of gene expression on such dynamics, even though transcription and translation are observed to be important in morphogenetic systems. In particular, the influence of gene expression on a large class of Turing bifurcation models, namely those with pure kinetics such as the Gierer–Meinhardt system, is unexplored. Our investigations demonstrate that the behaviour of the Gierer–Meinhardt model profoundly changes on the inclusion of gene expression dynamics and is sensitive to the sub-cellular details of gene expression. Features such as concentration blow up, morphogen oscillations and radical sensitivities to the duration of gene expression are observed and, at best, severely restrict the possible parameter spaces for feasible biological behaviour. These results also indicate that the behaviour of Turing pattern formation systems on the inclusion of gene expression time delays may provide a means of distinguishing between possible forms of interaction kinetics. Finally, this study also emphasises that sub-cellular and gene expression dynamics should not be simply neglected in models of long range biological pattern formation via morphogens

Fibroblast Growth Factor 7 Releasing Particles Enhance Islet Engraftment and Improve Metabolic Control Following Islet Transplantation in Mice with Diabetes

open access articleTransplantation of islets in Type 1 diabetes is limited by poor islet engraftment into the liver, with 2-3 donor pancreases required per recipient. We aimed to condition the liver to enhance islet engraftment to improve long-term graft function. Diabetic mice received a non-curative islet transplant (n=400 islets) via the hepatic portal vein (HPV) with Fibroblast Growth Factor 7 loaded galactoslyated poly(DL-lactide-co-glycolic acid) (FGF7-GAL-PLGA) particles; 26μm diameter particles specifically targeted the liver, promoting hepatocyte proliferation in short-term experiments: in mice receiving 0.1mg FGF7-GAL-PLGA particles (60ng FGF7) versus vehicle, cell proliferation was induced specifically in the liver with greater efficacy and specificity than subcutaneous FGF7 (1.25mg/kg ×2 doses; ~75μg FGF7). Numbers of engrafted islets and vascularisation were greater in liver sections of mice receiving islets and FGF7-GAL-PLGA particles versus mice receiving islets alone, 72 hours post-transplant. More mice (6 out of 8) that received islets and FGF7-GAL-PLGA particles normalised blood glucose concentrations by 30- days post-transplantation, versus 0 of 8 mice receiving islets alone with no evidence of increased proliferation of cells within the liver at this stage and normal liver function tests. This work shows liver targeted FGF7-GAL-PLGA particles achieve selective FGF7 delivery to the liver promoting islet engraftment to help normalise blood glucose levels with a good safety profile

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Measurement of the top pair production cross section in 8 TeV proton-proton collisions using kinematic information in the lepton plus jets final state with ATLAS

A measurement is presented of the $t\bar{t}$ inclusive production cross-section in $pp$ collisions at a center-of-mass energy of $\sqrt{s}=8$ TeV using data collected by the ATLAS detector at the CERN Large Hadron Collider. The measurement was performed in the lepton+jets final state using a data set corresponding to an integrated luminosity of 20.3 fb$^{-1}$. The cross-section was obtained using a likelihood discriminant fit and $b$-jet identification was used to improve the signal-to-background ratio. The inclusive $t\bar{t}$ production cross-section was measured to be $260\pm 1{\textrm{(stat.)}} ^{+22}_{-23} {\textrm{(syst.)}}\pm 8{\textrm{(lumi.)}}\pm 4{\mathrm{(beam)}}$ pb assuming a top-quark mass of 172.5 GeV, in good agreement with the theoretical prediction of $253^{+13}_{-15}$ pb. The $t\bar{t}\to (e,\mu)+{\mathrm{jets}}$ production cross-section in the fiducial region determined by the detector acceptance is also reported.Comment: Published version, 19 pages plus author list (35 pages total), 3 figures, 2 tables, all figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/TOPQ-2013-06

Technical summary

Human interference with the climate system is occurring. Climate change poses risks for human and natural systems. The assessment of impacts, adaptation, and vulnerability in the Working Group II contribution to the IPCC's Fifth Assessment Report (WGII AR5) evaluates how patterns of risks and potential benefits are shifting due to climate change and how risks can be reduced through mitigation and adaptation. It recognizes that risks of climate change will vary across regions and populations, through space and time, dependent on myriad factors including the extent of mitigation and adaptation

Adhesion and biofilm formation by Staphylococcus aureus from food processing plants as affected by growth medium, surface type and incubation temperature

This study assessed the effect of different growth media [BHI broth, BHI broth plus glucose (10 g/100 mL) and BHI broth plus NaCl (5 g/100 mL)] and incubation temperatures (28 or 37 ºC) on the adherence, detachment and biofilm formation on polypropylene and stainless steel surfaces (2 x 2 cm coupons) for a prolonged period (24-72 h) by some strains of Staphylococcus aureus (S3, S28 and S54) from food processing plants. The efficacy of the sanitizers sodium hypochlorite (250 mg/mL) and peracetic acid (30 mg/mL) in reducing the number of viable bacterial cells in a preformed biofilm was also evaluated. S. aureus strains adhered in highest numbers in BHI broth, regardless of the type of surface or incubation temperature. Cell detachment from surfaces revealed high persistence over the incubation period. The number of cells needed for biofilm formation was noted in all experimental systems after 3 days. Peracetic acid and sodium hypochlorite were not efficient in completely removing the cells of S. aureus adhered onto polypropylene and stainless steel surfaces. From these results, the assayed strains revealed high capacities to adhere and form biofilms on polypropylene and stainless steel surfaces under the different growth conditions, and the cells in biofilm matrixes were resistant to total removal when exposed to the sanitizers sodium hypochlorite and peracetic acid.Este estudo teve como objetivo avaliar o efeito de diferentes meios de crescimento [caldo BHI, caldo BHI adicionado de glucose (10 g/100 mL) e caldo BHI adicionado de NaCl (5 g/100 mL)] e temperaturas de incubação (28 e 37 ºC) sobre a adesão, separação e formação de biofilme sobre superfícies (2 x 2 cm) de polipropileno e aço inoxidável durante longo tempo de incubação (24-72 h) por parte de cepas de Staphylococcus aureus (S3, S58 e S54) isoladas de plantas de processamento de alimentos. Também foi avaliada a eficácia dos sanitizantes hipoclorito de sódio (250 mg/mL) e ácido peracético (30 mg/mL) na redução do número de células bacterianas viáveis presentes em um biofilme pré-formado. As cepas de S. aureus aderiram em número mais elevado quando incubadas em caldo BHI em ambos os tipos de superfícies e temperaturas de incubação testadas. A separação das células das superfícies revelou alta persistência ao longo do período de incubação. Número de células necessário para a formação do biofilme foi detectado depois de três dias de incubação em todos os sistemas experimentais. O ácido peracético e o hipoclorito de sódio não foram eficientes em remover completamente a células de S. aureus aderidas sobre as superfícies de polipropileno e aço inoxidável. Os resultados obtidos revelaram alta capacidade das cepas ensaiadas em aderir e formar biofilme sobre superfícies de polipropileno e aço inoxidável sobre diferentes condições de crescimento e que as células na matriz do biofilme apresentaram-se resistentes à total remoção quando expostas aos sanitizantes hipoclorito de sódio e ácido peracético

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Search for strong gravity in multijet final states produced in pp collisions at √s=13 TeV using the ATLAS detector at the LHC

A search is conducted for new physics in multijet final states using 3.6 inverse femtobarns of data from proton-proton collisions at √s = 13TeV taken at the CERN Large Hadron Collider with the ATLAS detector. Events are selected containing at least three jets with scalar sum of jet transverse momenta (HT) greater than 1TeV. No excess is seen at large HT and limits are presented on new physics: models which produce final states containing at least three jets and having cross sections larger than 1.6 fb with HT > 5.8 TeV are excluded. Limits are also given in terms of new physics models of strong gravity that hypothesize additional space-time dimensions

Dijet production in √s = 7 TeV pp collisions with large rapidity gaps at the ATLAS experiment

A 6.8 nb−¹ sample of pp collision data collected under low-luminosity conditions at √s = 7 TeV by the ATLAS detector at the Large Hadron Collider is used to study diffractive dijet production. Events containing at least two jets with pT > 20 GeV are selected and analysed in terms of variables which discriminate between diffractive and non-diffractive processes. Cross sections are measured differentially in ΔηF, the size of the observable forward region of pseudorapidity which is devoid of hadronic activity, and in an estimator, ξ˜, of the fractional momentum loss of the proton assuming single diffractive dissociation (pp → p X). Model comparisons indicate a dominant non-diffractive contribution up to moderately large ηF and small ξ˜, with a diffractive contribution which is significant at the highest ΔηF and the lowest ξ˜. The rapidity-gap survival probability is estimated from comparisons of the data in this latter region with predictions based on diffractive parton distribution functions

Measurement of jet charge in dijet events from √s = 8 TeV pp collisions with the ATLAS detector

The momentum-weighted sum of the charges of tracks associated to a jet is sensitive to the charge of the initiating quark or gluon. This paper presents a measurement of the distribution of momentum-weighted sums, called jet charge, in dijet events using 20.3 fb−¹ of data recorded with the ATLAS detector at √s = 8 TeV in pp collisions at the LHC. The jet charge distribution is unfolded to remove distortions from detector effects and the resulting particle-level distribution is compared with several models. The pT dependence of the jet charge distribution average and standard deviation are compared to predictions obtained with several leading-order and next-to-leading-order parton distribution functions. The data are also compared to different Monte Carlo simulations of QCD dijet production using various settings of the free parameters within these models. The chosen value of the strong coupling constant used to calculate gluon radiation is found to have a significant impact on the predicted jet charge. There is evidence for a pT dependence of the jet charge distribution for a given jet flavor. In agreement with perturbative QCD predictions, the data show that the average jet charge of quark-initiated jets decreases in magnitude as the energy of the jet increases