CRANKITE: a fast polypeptide backbone conformation sampler

Background: CRANKITE is a suite of programs for simulating backbone conformations of polypeptides and proteins. The core of the suite is an efficient Metropolis Monte Carlo sampler of backbone conformations in continuous three-dimensional space in atomic details. Methods: In contrast to other programs relying on local Metropolis moves in the space of dihedral angles, our sampler utilizes local crankshaft rotations of rigid peptide bonds in Cartesian space. Results: The sampler allows fast simulation and analysis of secondary structure formation and conformational changes for proteins of average length

Large-area epitaxial growth of curvature-stabilized ABC trilayer graphene.

The properties of van der Waals (vdW) materials often vary dramatically with the atomic stacking order between layers, but this order can be difficult to control. Trilayer graphene (TLG) stacks in either a semimetallic ABA or a semiconducting ABC configuration with a gate-tunable band gap, but the latter has only been produced by exfoliation. Here we present a chemical vapor deposition approach to TLG growth that yields greatly enhanced fraction and size of ABC domains. The key insight is that substrate curvature can stabilize ABC domains. Controllable ABC yields ~59% were achieved by tailoring substrate curvature levels. ABC fractions remained high after transfer to device substrates, as confirmed by transport measurements revealing the expected tunable ABC band gap. Substrate topography engineering provides a path to large-scale synthesis of epitaxial ABC-TLG and other vdW materials

Challenging SO(10) SUSY GUTs with family symmetries through FCNC processes

We perform a detailed analysis of the SO(10) SUSY GUT model with D3 family symmetry of Dermisek and Raby (DR). The model is specified in terms of 24 parameters and predicts, as a function of them, the whole MSSM set of parameters at low energy scales. Concerning the SM subset of such parameters, the model is able to give a satisfactory description of the quark and lepton masses, of the PMNS matrix and of the CKM matrix. We perform a global fit to the model, including flavour changing neutral current (FCNC) processes Bs --> mu+ mu-, B --> Xs gamma, B --> Xs l+ l- and the B(d,s) - bar B(d,s) mass differences Delta M(d,s) as well as the flavour changing (FC) process B+ --> tau+ nu. These observables provide at present the most sensitive probe of the SUSY mass spectrum and couplings predicted by the model. Our analysis demonstrates that the simultaneous description of the FC observables in question represents a serious challenge for the DR model, unless the masses of the scalars are moved to regions which are problematic from the point of view of naturalness and probably beyond the reach of the LHC. We emphasize that this problem could be a general feature of SUSY GUT models with third generation Yukawa unification and weak-scale minimal flavour violation.Comment: 1 + 37 pages, 5 figures, 11 tables. v3: minor typos fixed. Matches JHEP published versio

Changes in and predictors of length of stay in hospital after surgery for breast cancer between 1997/98 and 2004/05 in two regions of England: a population-based

BACKGROUND Decreases in length of stay (LOS) in hospital after breast cancer surgery can be partly attributed to the change to less radical surgery, but many other factors are operating at the patient, surgeon and hospital levels. This study aimed to describe the changes in and predictors of length of stay (LOS) in hospital after surgery for breast cancer between 1997/98 and 2004/05 in two regions of England. METHODS Cases of female invasive breast cancer diagnosed in two English cancer registry regions were linked to Hospital Episode Statistics data for the period 1st April 1997 to 31st March 2005. A subset of records where women underwent mastectomy or breast conserving surgery (BCS) was extracted (n = 44,877). Variations in LOS over the study period were investigated. A multilevel model with patients clustered within surgical teams and NHS Trusts was used to examine associations between LOS and a range of factors. RESULTS Over the study period the proportion of women having a mastectomy reduced from 58% to 52%. The proportion varied from 14% to 80% according to NHS Trust. LOS decreased by 21% from 1997/98 to 2004/05 (LOSratio = 0.79, 95%CI 0.77-0.80). BCS was associated with 33% shorter hospital stays compared to mastectomy (LOSratio = 0.67, 95%CI 0.66-0.68). Older age, advanced disease, presence of comorbidities, lymph node excision and reconstructive surgery were associated with increased LOS. Significant variation remained amongst Trusts and surgical teams. CONCLUSION The number of days spent in hospital after breast cancer surgery has continued to decline for several decades. The change from mastectomy to BCS accounts for only 9% of the overall decrease in LOS. Other explanations include the adoption of new techniques and practices, such as sentinel lymph node biopsy and early discharge. This study has identified wide variation in practice with substantial cost implications for the NHS. Further work is required to explain this variation

Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

Background: Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity. Methods/Design: Sixty patients with stable angina will be recruited and randomised 1: 1 to exercise training or conventional care. Patients randomised to exercise training will attend an exercise physiology laboratory up to three times weekly for supervised aerobic interval training sessions of one hour in total duration. Patients will undergo assessments of angina, anxiety, depression, and peripheral blood gene expression at baseline, after six and twelve weeks of training, and twelve weeks after formal exercise training ceases. Discussion: This study will provide comprehensive data on the effect of exercise training on peripheral blood gene expression in patients with angina. By correlating this with improvement in angina status we will identify candidate peripheral blood transcriptional markers predictive of improvements in angina level in response to exercise training

The role of bacterial and algal exopolymeric substances in iron chemistry

© 2015 Elsevier B.V. It is widely accepted that the complexation of iron (Fe) with organic compounds is the primary factor that regulates Fe reactivity and its bioavailability to phytoplankton in the open ocean. Despite considerable efforts to unravel the provenance of the many organic ligands present in the 'ligand soup' and their contribution to Fe chemistry, much of this pool remains largely unresolved. Bacteria and phytoplankton are known to release exopolymeric substances (EPS) for a variety of functions and it is known that this material has metal binding properties. However, the contribution that bacterial and algal EPS makes to Fe biogeochemistry is not well documented. This study revealed that both bacterial and algal EPS contain functional components known to bind Fe (uronic acid, saccharides) and details the molecular weight distribution of the EPS. It is also demonstrated that components of the EPS have a high affinity for Fe-binding, in some cases similar to that of bacterial siderophores (~KFe'L 1012) and that this material greatly enhances Fe solubility (and, possibly, Fe oxyhydroxide reactivity via prevention of aggregation) in seawater. However, EPS may also accelerate Fe(II) oxidation and thus Fe(II) removal from the system. Our findings indicate that, in remote ocean regions, bacterial and algal EPS could play a significant role in the biogeochemical cycling of Fe and their contribution should be considered to further our understanding of the dynamics of Fe-limited oceans

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder

Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive–compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder

Development and Validation of a Tool for Assessing Glucose Impairment in Adolescents

INTRODUCTION: Childhood obesity is associated with an increased risk for type 2 diabetes. Early identification of adolescents at risk for impaired fasting blood glucose may lead to earlier and more comprehensive evaluation and intervention. Because widespread blood glucose testing of adolescents is not recommended, community-based tools are needed to identify those who could benefit from further testing. One such tool, developed for adults, was the Tool for Assessing Glucose ImpairmenT (TAG-IT). Our objective was to validate whether a similar tool could be useful for community-based screening of glucose impairment risk among adolescents. METHODS: Our study sample consisted of 3,050 adolescents aged 12 to18 years who had participated in the 1999-2008 National Health and Nutrition Examination Survey (NHANES). Half of participants were female and 40% were nonwhite. NHANES measured fasting blood glucose and height, weight, and resting heart rate. We used Pearson correlations and regression analysis to determine key variables for predicting glucose impairment. From these measurements, we created a composite TAG-IT score for adolescents called TAG-IT-A. We then applied the TAG-IT-A model to 1988-1994 NHANES data, using linear regression analysis and receiver operating characteristic analysis to determine how well the TAG-IT-A score predicted a fasting blood glucose at or above 100 mg/dL. RESULTS: We determined that age, sex, body mass index, and resting heart rate were predictors of impaired fasting blood glucose and that TAG-IT-A was a better predictor of impaired fasting blood glucose than body mass index alone (area under the curve, 0.61, P < .001 vs 0.55, P = .10, respectively). A TAG-IT-A score of 3 or higher correctly identified 50% of adolescents with impaired fasting blood glucose, while a score of 5 or higher correctly identified 76% . CONCLUSION: The TAG-IT-A score is a simple screening tool that clinicians and public health professionals could use to easily identify adolescents who may have impaired fasting blood glucose and need a more comprehensive evaluation