Solar-pumped laser Final report

Solar pumped modulated laser to generate coherent radiation at optical wavelengths for long range, real time television data transmissio

Semiparametric sieve-type generalized least squares inference

This article considers the problem of statistical inference in linear regression models with dependent errors. A sieve-type generalized least squares (GLS) procedure is proposed based on an autoregressive approximation to the generating mechanism of the errors. The asymptotic properties of the sieve-type GLS estimator are established under general conditions, including mixingale-type conditions as well as conditions which allow for long-range dependence in the stochastic regressors and/or the errors. A Monte Carlo study examines the finite-sample properties of the method for testing regression hypotheses

Distinguishing the contribution of type 1 pili from that of other QseB-misregulated factors when QseC is absent during urinary tract infection

Urinary tract infections (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), are one of the leading bacterial infections due to their high frequency and rate of recurrence. Both type 1 pilus adhesive organelles (fim) and the QseC sensor kinase have been implicated in UPEC virulence during UTI and have been individually reported to be promising drug targets. Deletion of qseC leads to pleiotropic effects due to unregulated activation of the cognate response regulator QseB, influencing conserved metabolic processes and diminishing expression of virulence genes, including type 1 pili. Here, we discern the type 1 pilus-dependent and -independent effects that contribute to the virulence attenuation of a UPEC qseC deletion mutant in a murine model of experimental UTI. We show that although a ΔqseC mutant restored for type 1 pilus expression regains the ability to colonize the host and initiate acute infection up to 16 h postinfection, it is rapidly outcompeted during acute infection when coinoculated with a wild-type strain. As a result, this strain has a diminished capacity to establish chronic infection. A prophylactic oral dose of a FimH small-molecular-weight antagonist (ZFH-02056) further reduced the ability of the qseC mutant to establish chronic infection. Thus, loss of QseC significantly enhances the efficacy of ZFH-02056. Collectively, our work indicates that type 1 pili and QseC become critical in different infection stages, and that dual targeting of these factors has an additive effect on ablating UPEC virulence

Evolutionary fine-tuning of conformational ensembles in FimH during host-pathogen interactions

Positive selection in the two-domain type 1 pilus adhesin FimH enhances Escherichia coli fitness in urinary tract infection (UTI). We report a comprehensive atomic-level view of FimH in two-state conformational ensembles in solution, composed of one low-affinity tense (T) and multiple high-affinity relaxed (R) conformations. Positively selected residues allosterically modulate the equilibrium between these two conformational states, each of which engages mannose through distinct binding orientations. A FimH variant that only adopts the R state is severely attenuated early in a mouse model of uncomplicated UTI but is proficient at colonizing catheterized bladders in vivo or bladder transitional-like epithelial cells in vitro. Thus, the bladder habitat has barrier(s) to R state–mediated colonization possibly conferred by the terminally differentiated bladder epithelium and/or decoy receptors in urine. Together, our studies reveal the conformational landscape in solution, binding mechanisms, and adhesive strength of an allosteric two-domain adhesin that evolved “moderate” affinity to optimize persistence in the bladder during UTI

Familial correlates of adolescent girls' physical activity, television use, dietary intake, weight, and body composition

<p>Abstract</p> <p>Background</p> <p>The family environment offers several opportunities through which to improve adolescents' weight and weight-related behaviors. This study aims to examine the cross-sectional relationships between multiple factors in the family environment and physical activity (PA), television use (TV), soft drink intake, fruit and vegetable (FV) intake, body mass index (BMI), and body composition among a sample of sociodemographically-diverse adolescent girls.</p> <p>Methods</p> <p>Subjects included girls (mean age = 15.7), 71% of whom identified as a racial/ethnic minority, and one of their parents (dyad n = 253). Parents completed surveys assessing factors in the family environment including familial support for adolescents' PA, healthful dietary intake, and limiting TV use; parental modeling of behavior; and resources in the home such as availability of healthful food. Girls' PA and TV use were measured by 3-Day Physical Activity Recall (3DPAR) and dietary intake by survey measures. BMI was measured by study staff, and body fat by dual-energy X-ray absorptiometry (DXA). Hierarchical linear regression models tested individual and mutually-adjusted relationships between family environment factors and girls' outcomes.</p> <p>Results</p> <p>In the individual models, positive associations were observed between family support for PA and girls' total PA (p = .011) and moderate-to-vigorous PA (p=.016), home food availability and girls' soft drink (p < .001) and FV (p < .001) intake, and family meal frequency and girls' FV intake (p = .023). Across the individual and mutually-adjusted models, parental modeling of PA, TV, and soft drink and FV intake was consistently associated with girls' behavior.</p> <p>Conclusions</p> <p>Helping parents improve their physical activity and dietary intake, as well as reduce time watching television, may be an effective way to promote healthful behaviors and weight among adolescent girls.</p

Single-molecule super-resolution imaging of chromosomes and in situ haplotype visualization using Oligopaint FISH probes

Fluorescence in situ hybridization (FISH) is a powerful single-cell technique for studying nuclear structure and organization. Here we report two advances in FISH-based imaging. We first describe the in situ visualization of single-copy regions of the genome using two single-molecule super-resolution methodologies. We then introduce a robust and reliable system that harnesses single-nucleotide polymorphisms (SNPs) to visually distinguish the maternal and paternal homologous chromosomes in mammalian and insect systems. Both of these new technologies are enabled by renewable, bioinformatically designed, oligonucleotide-based Oligopaint probes, which we augment with a strategy that uses secondary oligonucleotides (oligos) to produce and enhance fluorescent signals. These advances should substantially expand the capability to query parent-of-origin-specific chromosome positioning and gene expression on a cell-by-cell basis

Competing with stationary prediction strategies

In this paper we introduce the class of stationary prediction strategies and construct a prediction algorithm that asymptotically performs as well as the best continuous stationary strategy. We make mild compactness assumptions but no stochastic assumptions about the environment. In particular, no assumption of stationarity is made about the environment, and the stationarity of the considered strategies only means that they do not depend explicitly on time; we argue that it is natural to consider only stationary strategies even for highly non-stationary environments.Comment: 20 page

A novel approach to latent class modelling: identifying the various types of body mass index individuals

Given the increasing prevalence of adult obesity, furthering understanding of the determinants of measures such as Body Mass Index (BMI) remains high on the policy agenda. We contribute to existing literature on modelling BMI by proposing an extension to latent class modelling, which serves to unveil a more detailed picture of the determinants of BMI. Interest here lies in latent class analysis with: a regression model and predictor variables explaining class membership; a regression model and predictor variables explaining the outcome variable within BMI classes; and instances where the BMI classes are naturally ordered and labelled by expected values within class. A simple and generic way of parameterising both the class probabilities and the statistical representation of behaviours within each class is proposed, that simultaneously preserves the ranking according to class-specific expected values and yields a parsimonious representation of the class probabilities. Based on a wide range of metrics, the newly proposed approach is found to dominate the prevailing one; and moreover, results are often quite different across the two

Don't stand so close to me: Competitive pressures, proximity and inter-organizational collaboration

This paper investigates how geographical proximity moderates the nonmonotonic relation between niche overlap and the propensity of organizations to collaborate. The main prediction is that the strength of this relation is different for organizations with low versus high levels of geographical proximity. Proposed hypotheses are tested by using data collected within a community of hospital organizations serving more than five million residents in one of the largest Italian geographical regions. After controlling for internal resource complementarities and differences in organizational forms, behavioural orientations and institutional constraints among hospitals, this paper finds strong empirical support to the research hypotheses