IDENTIFICATION AND CHARACTERIZATION OF GATase1-LIKE AraC-FAMILY TRANSCRIPTIONAL REGULATORS IN BURKHOLDERIA THAILANDENSIS.

The ability of bacteria to detect their surroundings and enact an appropriate response is critical for survival. Translation of external signals into a coherent response requires specific control over the transcription of DNA into RNA. Much of the regulation at this step is accomplished by transcriptional regulators, proteins that bind to DNA and alter gene expression. A wide-spread variety of regulators in bacteria is the AraC-family. These regulators are divided into two conserved domains and respond to a variety of compounds owing to different N-terminal domains. A subfamily of these regulators, GATase1-like AraC-family transcriptional regulators (GATRs), is described. These proteins contain an N-terminal domain with structural characteristics similar to enzymes that synthesize amine-containing compounds. Members of this subfamily of transcriptional regulators are found in a wide range of bacteria, however, few are characterized. A relatively high number of GATRs are encoded in the Burkholderia thailandensis genome. Therefore, we utilized this bacterium as a model to explore the function and diversity of these regulators. GATRs in B. thailandensis divided into two groups based on bioinformatics analysis. The first group includes three members which we identified that contribute to the positive regulation of glycine betaine (GB) catabolism. GB can be utilized as a nutrient source or as a potent osmoprotectant. The regulation of this pathway in B. thailandensis differs from previously established models due to the interplay of these regulators. Homologs of two other GATRs in this group were identified that regulate carnitine and arginine catabolism. The second group of GATRs contains uncharacterized members with no known functions. A genetic strategy for engineering constitutive GATRs was developed and employed to investigate the transcriptional regulons of these GATRs. This approach yielded the identification of a novel GATR that represses expression of an operon producing a formaldehyde detoxification system, and is the first example of a GATR that functions as a repressor

Production of heralded pure single photons from imperfect sources using cross phase modulation

Realistic single-photon sources do not generate single photons with certainty. Instead they produce statistical mixtures of photons in Fock states $\ket{1}$ and vacuum (noise). We describe how to eliminate the noise in the output of the sources by means of another noisy source or a coherent state and cross phase modulation (XPM). We present a scheme which announces the production of pure single photons and thus eliminates the vacuum contribution. This is done by verifying a XPM related phase shift with a Mach-Zehnder interferometer.Comment: 8 pages, 8 EPS figures, RevTeX4. Following changes have been made in v.3: Title and abstract slightly changed; numerous minor revisions and clarifications within the text; an appendix with three new figures has been added. In version v4 we have included a supplementary analysis of our scheme that takes into account absorption losses. Our analysis is heuristic and based on a phenomenological model, which is independent of the physical realization of the proposed scheme. We have estimated upper bounds up to which absorption losses can be tolerated, so as our scheme to improve the efficiency of single photon sources still works. Accepted for publication in Phys. Rev.

Heralded single-photon generation using imperfect single-photon sources and a two-photon-absorbing medium

We propose a setup for a heralded, i.e. announced generation of a pure single-photon state given two imperfect sources whose outputs are represented by mixtures of the single-photon Fock state $\ket{1}$ with the vacuum $\ket{0}$. Our purification scheme uses beam splitters, photodetection and a two-photon-absorbing medium. The admixture of the vacuum is fully eliminated. We discuss two potential realizations of the scheme.Comment: 22 pages, 8 figures (LaTeX). In version v2 we have slightly modified our setup so as to increase the success probability of single-photon generation by a factor of two. In addition, in an appendix we discuss alternative realizations of single-photon generation without a Mach-Zehnder interferometer. Three new figures have been added. Version v3 is a revised version published in Phys. Rev. A. It contains numerous minor corrections and clarifications. A new figure has been added in order to clarify our convention regarding labelling the field modes. The action of the beam splitters in the Schroedinger picture is introduced. A new reference has been include

Single-Item Measurement of Suicidal Behaviors: Validity and Consequences of Misclassification

Suicide is a leading cause of death worldwide. Although research has made strides in better defining suicidal behaviors, there has been less focus on accurate measurement. Currently, the widespread use of self-report, single-item questions to assess suicide ideation, plans and attempts may contribute to measurement problems and misclassification. We examined the validity of single-item measurement and the potential for statistical errors. Over 1,500 participants completed an online survey containing single-item questions regarding a history of suicidal behaviors, followed by questions with more precise language, multiple response options and narrative responses to examine the validity of single-item questions. We also conducted simulations to test whether common statistical tests are robust against the degree of misclassification produced by the use of single-items. We found that 11.3% of participants that endorsed a single-item suicide attempt measure engaged in behavior that would not meet the standard definition of a suicide attempt. Similarly, 8.8% of those who endorsed a single-item measure of suicide ideation endorsed thoughts that would not meet standard definitions of suicide ideation. Statistical simulations revealed that this level of misclassification substantially decreases statistical power and increases the likelihood of false conclusions from statistical tests. Providing a wider range of response options for each item reduced the misclassification rate by approximately half. Overall, the use of single-item, self-report questions to assess the presence of suicidal behaviors leads to misclassification, increasing the likelihood of statistical decision errors. Improving the measurement of suicidal behaviors is critical to increase understanding and prevention of suicide

Pathways for cross-boundary effects of biodiversity on ecosystem functioning

The biodiversity-ecosystem functioning concept asserts that processes in ecosystems are markedly influenced by species richness and other facets of biodiversity. However, biodiversity-ecosystem functioning studies have been largely restricted to single ecosystems, ignoring the importance of functional links - such as the exchange of matter, energy, and organisms - between coupled ecosystems. Here we present a basic concept and outline three pathways of cross boundary biodiversity effects on ecosystem processes and propose an agenda to assess such effects, focusing on terrestrial-aquatic linkages to illustrate the case. This cross-boundary perspective of biodiversity-ecosystem functioning relationships presents a promising frontier for biodiversity and ecosystem science with repercussions for the conservation, restoration, and management of biodiversity and ecosystems from local to landscape scales.Peer reviewe

Clinical reappraisal of the Composite International Diagnostic Interview Screening Scales (CIDI‐SC) in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)

A clinical reappraisal study was carried out in conjunction with the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) All‐Army Study (AAS) to evaluate concordance of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV) diagnoses based on the Composite International Diagnostic Interview Screening Scales (CIDI‐SC) and post‐traumatic stress disorder (PTSD) checklist (PCL) with diagnoses based on independent clinical reappraisal interviews (Structured Clinical Interview for DSM‐IV [SCID]). Diagnoses included: lifetime mania/hypomania, panic disorder, and intermittent explosive disorder; six‐month adult attention‐deficit/hyperactivity disorder; and 30‐day major depressive episode, generalized anxiety disorder, PTSD, and substance (alcohol or drug) use disorder (abuse or dependence). The sample ( n  = 460) was weighted for over‐sampling CIDI‐SC/PCL screened positives. Diagnostic thresholds were set to equalize false positives and false negatives. Good individual‐level concordance was found between CIDI‐SC/PCL and SCID diagnoses at these thresholds (area under curve [AUC] = 0.69–0.79). AUC was considerably higher for continuous than dichotomous screening scale scores (AUC = 0.80–0.90), arguing for substantive analyses using not only dichotomous case designations but also continuous measures of predicted probabilities of clinical diagnoses. Copyright © 2013 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102145/1/mpr1398.pd

Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib

The Bruton’s tyrosine kinase (Btk) inhibitor ibrutinib induces platelet dysfunction and causes increased risk of bleeding. Off-target inhibition of Tec is believed to contribute to platelet dysfunction and other side-effects of ibrutinib. The second generation Btk inhibitor acalabrutinib was developed with improved specificity for Btk over Tec. We investigated platelet function in patients with Non-Hodgkin Lymphoma (NHL) receiving ibrutinib or acalabrutinib by aggregometry and by measuring thrombus formation on collagen under arterial shear. Both patient groups had similarly dysfunctional aggregation responses to collagen and collagen-related peptide (CRP-XL) and comparison with mechanistic experiments in which platelets from healthy donors were treated with the Btk inhibitors suggested that both drugs inhibit platelet Btk and Tec at physiological concentrations. Only ibrutinib caused dysfunctional thrombus formation, while size and morphology of thrombi following acalabrutinib treatment were of normal size and morphology. We found that ibrutinib but not acalabrutinib inhibited SFKs and that SFKs have a critical role in platelet adhesion to collagen that is likely to underpin unstable thrombus formation observed in ibrutinib patients. We found that platelet function was enhanced by increasing levels of vWF and FVIII ex vivo by addition of intermediate purity FVIII (haemate P) to blood from patients, resulting in consistently larger thrombi. We conclude that acalabrutinib avoids major platelet dysfunction associated with ibrutinib therapy, and platelet function may be enhanced in patients with B-cell NHL by increasing plasma vWF and FVIII

Design of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)

The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a multi‐component epidemiological and neurobiological study designed to generate actionable evidence‐based recommendations to reduce US Army suicides and increase basic knowledge about the determinants of suicidality. This report presents an overview of the designs of the six components of the Army STARRS. These include: an integrated analysis of the Historical Administrative Data Study (HADS) designed to provide data on significant administrative predictors of suicides among the more than 1.6 million soldiers on active duty in 2004–2009; retrospective case‐control studies of suicide attempts and fatalities; separate large‐scale cross‐sectional studies of new soldiers (i.e. those just beginning Basic Combat Training [BCT], who completed self‐administered questionnaires [SAQs] and neurocognitive tests and provided blood samples) and soldiers exclusive of those in BCT (who completed SAQs); a pre‐post deployment study of soldiers in three Brigade Combat Teams about to deploy to Afghanistan (who completed SAQs and provided blood samples) followed multiple times after returning from deployment; and a platform for following up Army STARRS participants who have returned to civilian life. Department of Defense/Army administrative data records are linked with SAQ data to examine prospective associations between self‐reports and subsequent suicidality. The presentation closes with a discussion of the methodological advantages of cross‐component coordination. Copyright © 2013 John Wiley & Sons, Ltd .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102177/1/mpr1401.pd

Prognostic Indicators of Persistent Post-Concussive Symptoms after Deployment-Related Mild Traumatic Brain Injury: A Prospective Longitudinal Study in U.S. Army Soldiers

Mild traumatic brain injury (mTBI), or concussion, is prevalent in the military. The course of recovery can be highly variable. This study investigates whether deployment-acquired mTBI is associated with subsequent presence and severity of post-concussive symptoms (PCS) and identifies predictors of persistent PCS among US Army personnel who sustained mTBI while deployed to Afghanistan. We used data from a prospective longitudinal survey of soldiers assessed 1?2 months before a 10-month deployment to Afghanistan (T0), on redeployment to the United States (T1), approximately 3 months later (T2), and approximately 9 months later (T3). Outcomes of interest were PCS at T2 and T3. Predictors considered were: sociodemographic factors, number of previous deployments, pre-deployment mental health and TBI history, and mTBI and other military-related stress during the index deployment. The study sample comprised 4518 soldiers, 822 (18.2%) of whom experienced mTBI during the index deployment. After adjusting for demographic, clinical, and deployment-related factors, deployment-acquired mTBI was associated with nearly triple the risk of reporting any PCS and with increased severity of PCS when symptoms were present. Among those who sustained mTBI, severity of PCS at follow-up was associated with history of pre-deployment TBI(s), pre-deployment psychological distress, more severe deployment stress, and loss of consciousness or lapse of memory (versus being ?dazed? only) as a result of deployment-acquired mTBI. In summary, we found that sustaining mTBI increases risk for persistent PCS. Previous TBI(s), pre-deployment psychological distress, severe deployment stress, and loss of consciousness or lapse of memory resulting from mTBI(s) are prognostic indicators of persistent PCS after an index mTBI. These observations may have actionable implications for prevention of chronic sequelae of mTBI in the military and other settings.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140173/1/neu.2015.4320.pd