Analysis of human vergence dynamics

Disparity vergence is commonly viewed as being controlled by at least two mechanisms, an open-loop vergence-specific burst mechanism analogous to the ballistic drive of saccades, and a closed-loop feedback mechanism controlled by the disparity error. We show that human vergence dynamics for disparity jumps of a large textured field have a typical time course consistent with predominant control by the open-loop vergence-specific burst mechanism, although various subgroups of the population show radically different vergence behaviors. Some individuals show markedly slow divergence responses, others slow convergence responses, others slow responses in both vergence directions, implying that the two vergence directions have separate control mechanisms. The faster time courses usually had time-symmetric velocity waveforms implying open-loop burst control, while the slow response usually had time-asymmetric velocity waveforms implying closed-loop feedback control. A further type of behavior in a distinct subpopulation is a compound anomalous divergence response consisting of an initial convergence movement followed by a large corrective divergence movement with time courses implying closed-loop feedback control. The closed-loop response for slow responses to disparity steps exhibited pronounced oscillations in the velocity trace, implying the involvement of a sampled-data system with a rate of about 3 samples/s. This analysis of the variety of human vergence responses thus contributes substantially to the understanding of the oculomotor control mechanisms underlying the generation of vergence movements

Synthesis of a protected keto-lysidine analogue via improved preparation of arabino-isocytosine nucleosides

Anhydrouridines react with aliphatic amines to give N-alkyl isocytosines, but reported procedures often demand very long reaction times and can be low yielding, with narrow scope. A modified procedure for such reactions has been developed, using microwave irradiation, significantly reducing reaction time and allowing facile access to a diverse range of novel nucleosides on the gram scale. The method has been used to prepare a precursor to a novel analogue of lysidine, a naturally occurring iminonucleoside found in (t)RNA

Clinical and molecular characterization of HER2 amplified-pancreatic cancer

<p>Background: Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.</p> <p>Methods: HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).</p> <p>Results: An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2- amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is >22,000 per annum.</p> <p>Conclusions: HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.</p&gt

Increased BDNF levels and NTRK2 gene association suggest a disruption of BDNF/TrkB signaling in autism

The brain-derived neurotrophic factor (BDNF), a neurotrophin fundamental for brain development and function, has previously been implicated in autism. In this study, the levels of BDNF in platelet-rich plasma were compared between autistic and control children, and the role of two genetic factors that might regulate this neurotrophin and contribute to autism etiology, BDNF and NTRK2, was examined. We found that BDNF levels in autistic children (n = 146) were significantly higher (t = 6.82; P < 0.0001) than in control children (n = 50) and were positively correlated with platelet serotonin distribution (r = 0.22; P = 0.004). Heritability of BDNF was estimated at 30% and therefore candidate genes BDNF and NTRK2 were tested for association with BDNF level distribution in this sample, and with autism in 469 trio families. Genetic association analysis provided no evidence for BDNF or NTRK2 as major determinants of the abnormally increased BDNF levels in autistic children. A significant association with autism was uncovered for six single nucleotide polymorphisms (SNPs) [0.004 (Z((1df)) = 2.85) < P < 0.039 (Z((1df)) = 2.06)] and multiple haplotypes [5 × 10(-4) (χ((3df)) = 17.77) < P < 0.042 (χ((9df)) = 17.450)] in the NTRK2 gene. These results do not withstand correction for multiple comparisons, however, reflect a trend toward association that supports a role of NTRK2 as a susceptibility factor for the disorder. Genetic variation in the BDNF gene had no impact on autism risk. By substantiating the previously observed increase in BDNF levels in autistic children in a larger patient set, and suggesting a genetic association between NTRK2 and autism, this study integrates evidence from multiple levels supporting the hypothesis that alterations in BDNF/tyrosine kinase B (TrkB) signaling contribute to an increased vulnerability to autism

Determinants of flammability in savanna grass species

1. Tropical grasses fuel the majority of fires on Earth. In fire-prone landscapes, enhanced flammabil-ity may be adaptive for grasses via the maintenance of an open canopy and an increase in spa-tiotemporal opportunities for recruitment and regeneration. In addit ion, by burning intensely butbriefly, high flammability may protect resprouting buds from lethal temperatures. Despite thesepotential benefits of high flammability to fire-prone grasses, variation in flammability among grassspecies, and how trait differences underpin this variation, remains unknown.2. By burning leaves and plant parts, we experimentally determined how five plant traits (biomassquantity, biomass density, biomass moisture content, leaf surface-area-to-volume ratio and leaf effec-tive heat of combustion) combined to determine the three components of flammability (ignitability,sustainability and combustibility) at the leaf and plant scales in 25 grass species of fire-pr one SouthAfrican grasslands at a time of peak fire occurrence. The influence of evolutionary history onflammability was assessed based on a phylogeny built here for the study species.3. Grass speci es differed significantly in all components of flammability. Accounting for evolution-ary history helped to explain patterns in leaf-scale combustibility and sustainability. The five mea-sured plant traits predicted components of flammability, particularly leaf ignitability and plantcombustibility in which 70% and 58% of variation, respectively, could be explained by a combina-tion of the traits. Total above-ground biomass was a key drive r o f combustibility and sustainabi litywith high biomass species burning more intensely and for longer, and producing the highest pre-dicted fire spread rates. Moisture content was the main influence on ignitability, where speci es withhigher moisture conten ts took longer to ignite and once alight burnt at a slower rate. Bioma ss den-sity, leaf surface-area-to-volume ratio and leaf effective heat of combustion were weaker predictorsof flammability components.4. Synthesis. We demonstrate that grass flammability is predicted from easily measurable plant func-tional traits and is influenced by evolutionary history with some components showing phylogeneticsignal. Grasses are not homogenous fuels to fire. Rather, species differ in functional traits that inturn demonstrably influence flammability. This diver sity is consistent with the idea that flammabilitymay be an adaptive trait for grasses of fire-prone ecosystems

Racism, anti-racist practice and social work: articulating the teaching and learning experiences of Black social workers

In the mid 1990s a Black practice teacher programme was established in Manchester and Merseyside with the primary aim to increase the number of Black practice teachers in social work organisations, and in turn provide a supportive and encouraging learning environment for Black student social workers whilst on placement. In the north‐west of England research has been undertaken, to establish the quality of the practice teaching and student learning taking place with Black practice teachers and students. This paper is an exploration of the ideas generated within the placement process that particularly focused on the discourse of racism and ant‐racist practice. Black students and practice teachers explain their understanding of racism and anti‐racist practice within social work. From the research, the paper will critique some of the ideas concerning anti‐racism. In particular, it will question whether anti‐racist social work practice needs to be re‐evaluated in the light of a context with new migrants, asylum seekers and refugees. It will concluded, by arguing that whilst the terms anti‐racism, Black and Minority Ethnic have resonance as a form of political strategic essentialism, it is important to develop more positive representations in the future

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

Promised Land? Immigration, Religiosity, and Space in Southern California

This article looks at how immigrants and their supporters appropriate and use religious space and other public spaces for religious and socio-political purposes in Southern California. While the everyday living conditions of many immigrants, particularly the unauthorized Latino immigrants, force unto them an embodied disciplinarity that maintains spatialities of restricted citizenship, the public appropriations of space for and through religious practices allow for them -even if only momentarily -to express an embodied transgression. This practice in public space helps realize spaces of freedom and hope, however ephemerally. Potentially, these rehearsing exercises can help revert internalized disempowering subjectivities and create social empowerment. Negative stereotypes about immigrants held by the larger public can also be challenged through these spatial practices, as the public demonstrations make visible the invisible. We focus on “Posadas Without Borders” and “the New Sanctuary Movement,” considering both the role of progressive civic and religious institutions in supporting immigrants and the agency of the immigrants themselves. The theoretical analysis builds on concepts drawn from a conversation between geography and religious and theological studies. We use a triangulated methodological approach that includes observation and participant observation, content-analysis of multimedia, interviews, and intellectual advocacy for the immigrant movement. The cases discussed here show that progressive religious groups and coalitions can be important allies to progressive planners, geographers, and policy makers in advancing social and environmental justice for the disenfranchised. They also show that the theological underpinnings of such groups share a lot in common with planning epistemologies for the just city

Discovery of potent and selective MRCK inhibitors with therapeutic effect on skin cancer

The myotonic dystrophy-related Cdc42-binding kinases MRCKα and MRCKβ contribute to the regulation of actin-myosin cytoskeleton organization and dynamics, acting in concert with the Rho-associated coiled-coil kinases ROCK1 and ROCK2. The absence of highly potent and selective MRCK inhibitors has resulted in relatively little knowledge of the potential roles of these kinases in cancer. Here we report the discovery of the azaindole compounds BDP8900 and BDP9066 as potent and selective MRCK inhibitors that reduce substrate phosphorylation, leading to morphological changes in cancer cells along with inhibition of their motility and invasive character. In over 750 human cancer cell lines tested, BDP8900 and BDP9066 displayed consistent anti-proliferative effects with greatest activity in hematological cancer cells. Mass spectrometry identified MRCKα S1003 as an autophosphorylation site, enabling development of a phosphorylation-sensitive antibody tool to report on MRCKα status in tumor specimens. In a two-stage chemical carcinogenesis model of murine squamous cell carcinoma, topical treatments reduced MRCKα S1003 autophosphorylation and skin papilloma outgrowth. In parallel work, we validated a phospho-selective antibody with the capability to monitor drug pharmacodynamics. Taken together, our findings establish an important oncogenic role for MRCK in cancer, and they offer an initial preclinical proof of concept for MRCK inhibition as a valid therapeutic strategy

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