Dynamic Vortex Phases and Pinning in Superconductors with Twin Boundaries

We investigate the pinning and driven dynamics of vortices interacting with twin boundaries using large scale molecular dynamics simulations on samples with near one million pinning sites. For low applied driving forces, the vortex lattice orients itself parallel to the twin boundary and we observe the creation of a flux gradient and vortex free region near the edges of the twin boundary. For increasing drive, we find evidence for several distinct dynamical flow phases which we characterize by the density of defects in the vortex lattice, the microscopic vortex flow patterns, and orientation of the vortex lattice. We show that these different dynamical phases can be directly related to microscopically measurable voltage - current V(I) curves and voltage noise. By conducting a series of simulations for various twin boundary parameters we derive several vortex dynamic phase diagrams.Comment: 5 figures, to appear in Phys. Rev.

An Orally Active Galectin-3 Antagonist Inhibits Lung Adenocarcinoma Growth and Augments Response to PD-L1 Blockade

A combination therapy approach is required to improve tumor immune infiltration and patient response to immune checkpoint inhibitors that target negative regulatory receptors. Galectin-3 is a β-galactoside-binding lectin that is highly expressed within the tumor microenvironment of aggressive cancers and whose expression correlates with poor survival particularly in patients with non-small cell lung cancer (NSCLC). To examine the role of galectin-3 inhibition in NSCLC, we tested the effects of galectin-3 depletion using genetic and pharmacologic approaches on syngeneic mouse lung adenocarcinoma and human lung adenocarcinoma xenografts. Galectin-3-/- mice developed significantly smaller and fewer tumors and metastases than syngeneic C57/ Bl6 wild-type mice. Macrophage ablation retarded tumor growth, whereas reconstitution with galectin-3-positive bone marrow restored tumor growth in galectin-3-/- mice, indicating that macrophages were a major driver of the antitumor response. Oral administration of a novel small molecule galectin-3 inhibitor GB1107 reduced human and mouse lung adenocarcinoma growth and blocked metastasis in the syngeneic model. Treatment with GB1107 increased tumor M1 macrophage polarization and CD8 + T-cell infiltration. Moreover, GB1107 potentiated the effects of a PD-L1 immune checkpoint inhibitor to increase expression of cytotoxic (IFNγ, granzyme B, perforin-1, Fas ligand) and apoptotic (cleaved caspase-3) effector molecules. In summary, galectin-3 is an important regulator of lung adenocarcinoma progression. The novel galectin-3 inhibitor presented could provide an effective, nontoxic monotherapy or be used in combination with immune checkpoint inhibitors to boost immune infiltration and responses in lung adenocarcinoma and potentially other aggressive cancers. Significance: A novel and orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and metastasis and augments response to PD-L1 blockade

Osteogenesis imperfecta type 3 in South Africa : causative mutations in FKBP10

BACKGROUND : A relatively high frequency of autosomal recessively inherited osteogenesis imperfecta (OI) type 3 (OI-3) is present in the indigenous black southern African population. Affected persons may be severely handicapped as a result of frequent fractures, progressive deformity of the tubular bones and spinal malalignment. OBJECTIVE : To delineate the molecular basis for the condition. METHODS : Molecular investigations were performed on 91 affected persons from seven diverse ethnolinguistic groups in this population. RESULTS : Following polymerase chain reaction amplification and direct cycle sequencing, FKBP10 mutations were identified in 45.1% (41/91) OI-3-affected persons. The homozygous FKBP10 c.831dupC frameshift mutation was confirmed in 35 affected individuals in the study cohort. Haplotype analysis suggests that this mutation is identical among these OI-3-affected persons by descent, thereby confirming that they had a common ancestor. Compound heterozygosity of this founder mutation was observed, in combination with three different deleterious FKBP10 mutations, in six additional persons in the cohort. Four of these individuals had the c.831delC mutation. CONCLUSION : The burden of the disorder, both in frequency and severity, warrants the establishment of a dedicated service for molecular diagnostic confirmation and genetic management of persons and families with OI in southern Africa.The South African Medical Research Council and the National Research Foundation.http://www.samj.org.zaam2017Genetic

Association of Visual Impairment with Risk of Incident Dementia in a Women's Health Initiative Population

Importance: Dementia affects a large and growing population of older adults. Although past studies suggest an association between vision and cognitive impairment, there are limited data regarding longitudinal associations of vision with dementia. Objective: To evaluate associations between visual impairment and risk of cognitive impairment. Design, Setting, and Participants: A secondary analysis of a prospective longitudinal cohort study compared the likelihood of incident dementia or mild cognitive impairment (MCI) among women with and without baseline visual impairment using multivariable Cox proportional hazards regression models adjusting for characteristics of participants enrolled in Women's Health Initiative (WHI) ancillary studies. The participants comprised community-dwelling older women (age, 66-84 years) concurrently enrolled in WHI Sight Examination (enrollment 2000-2002) and WHI Memory Study (enrollment 1996-1998, ongoing). The study was conducted from 2000 to the present. Exposures: Objectively measured visual impairment at 3 thresholds (visual acuity worse than 20/40, 20/80, or 20/100) and self-reported visual impairment (determined using composite survey responses). Main Outcomes and Measures: Hazard ratios (HRs) and 95% CIs for incident cognitive impairment after baseline eye examination were determined. Cognitive impairment (probable dementia or MCI) was based on cognitive testing, clinical assessment, and centralized review and adjudication. Models for (1) probable dementia, (2) MCI, and (3) probable dementia or MCI were evaluated. Results: A total of 1061 women (mean [SD] age, 73.8 [3.7] years) were identified; 206 of these women (19.4%) had self-reported visual impairment and 183 women (17.2%) had objective visual impairment. Forty-two women (4.0%) were ultimately classified with probable dementia and 28 women (2.6%) with MCI that did not progress to dementia. Mean post-eye examination follow-up was 3.8 (1.8) years (range, 0-7 years). Women with vs without baseline objective visual impairment were more likely to develop dementia. Greatest risk for dementia was among women with visual acuity of 20/100 or worse at baseline (HR, 5.66; 95% CI, 1.75-18.37), followed by 20/80 or worse (HR, 5.20; 95% CI, 1.94-13.95), and 20/40 or worse (HR, 2.14; 95% CI, 1.08-4.21). Findings were similar for risk of MCI, with the greatest risk among women with baseline visual acuity of 20/100 or worse (HR, 6.43; 95% CI, 1.66-24.85). Conclusions and Relevance: In secondary analysis of a prospective longitudinal cohort study of older women with formal vision and cognitive function testing, objective visual impairment appears to be associated with an increased risk of incident dementia. However, incident cases of dementia and the proportion of those with visual impairment were low. Research is needed to evaluate the effect of specific ophthalmic interventions on dementia.

From Interstellar Ice Grains to Evolved Planetary Systems: The Role of Laboratory Studies

Interstellar matter and star formatio

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

Influence of nucleon Fermi motion on incomplete fusion

Velocity spectra were measured for evaporation residues produced in fusion reactions induced by 5-35 MeV/A14N. The results, together with published data for 16O and 20Ne induced fusion, are shown to reveal a projectile dependence of incomplete fusion processes. The data can be qualitatively described in terms of a picture which takes into account the vector addition of the center-of-mass velocities of the interacting nuclei with the intrinsic Fermi velocities of the nucleons

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters