Single Gate P-N Junctions in Graphene-Ferroelectric Devices

Graphene's linear dispersion relation and the attendant implications for bipolar electronics applications have motivated a range of experimental efforts aimed at producing p-n junctions in graphene. Here we report electrical transport measurements of graphene p-n junctions formed via simple modifications to a PbZr$_{0.2}$Ti$_{0.8}$O$_3$ substrate, combined with a self-assembled layer of ambient environmental dopants. We show that the substrate configuration controls the local doping region, and that the p-n junction behavior can be controlled with a single gate. Finally, we show that the ferroelectric substrate induces a hysteresis in the environmental doping which can be utilized to activate and deactivate the doping, yielding an `on-demand' p-n junction in graphene controlled by a single, universal backgate

The Effects of Age and Lifetime Flight Behavior on Flight Capacity in Drosophila Melanogaster

The Effects of Flight Behavior on Physiology and Senescence May Be Profound in Insects Because of the Extremely High Metabolic Costs of Flight. Flight Capacity in Insects Decreases with Age; in Contrast, Limiting Flight Behavior Extends Lifespan and Slows the Age-Related Loss of Antioxidant Capacity and Accumulation of Oxidative Damage in Flight Muscles. in This Study, We Tested the Effects of Age and Lifetime Flight Behavior on Flight Capacity by Measuring Wingbeat Frequency, the Ability to Fly in a Hypo-Dense Gas Mixture, and Metabolic Rate in Drosophila Melanogaster. Specifically, 5-Day-Old Adult Flies Were Separated into Three Life-Long Treatments: (1) Those Not Allowed to Fly (No Flight), (2) Those Allowed - But Not Forced - to Fly (Voluntary Flight) and (3) Those Mechanically Stimulated to Fly (Induced Flight). Flight Capacity Senesced Earliest in Flies from the No-Flight Treatment, Followed by the Induced-Flight Group and Then the Voluntary Flight Group. Wingbeat Frequency Senesced with Age in All Treatment Groups, But Was Most Apparent in the Voluntary- and Induced-Flight Groups. Metabolic Rate during Agitated Flight Senesced Earliest and Most Rapidly in the Induced Flight Group, and Was Low and Uniform throughout Age in the No-Flight Group. Early Senescence in the Induced-Flight Group Was Likely Due to the Acceleration of Deleterious Aging Phenomena Such as the Rapid Accumulation of Damage at the Cellular Level, While the Early Loss of Flight Capacity and Low Metabolic Rates in the No-Flight Group Demonstrate that Disuse Effects Can Also Significantly Alter Senescence Patterns of Whole-Insect Performance

Assessment of Subjective Experiences of Boys Entering the Community From a Correctional School

The purpose of this study was to explore, classify, and evaluate the personal experiences of juvenile offenders following release from a state training school. During a two month period beginning in the fall of 1967, a group of twenty-three releasees from the MacLaren School for Boys in Woodburn, Oregon were interviewed on a weekly basis in the Portland metropolitan area. The boys, ranging in age from thirteen to seventeen were contacted in their homes, schools, and other settings to learn of positive, negative, and critical experiences encountered in the community. Open ended questions based upon a twenty- seven item schedule were administered to the boys, focusing upon personal experiences in six major areas: school, family, peer group, community, work and authority. Responses were recorded verbatim and classified according to the boys\u27 judgments of positive and negative connotations. Critical experiences were also recorded to determine specific incidents which brought the boys into contact with legal authorities or otherwise seriously affected their parole status. Positive, negative, and critical experiences from this study were analyzed both descriptively and statistically. Null hypotheses were tested to determine the quality, quantity, and intensity of experiences with respect to such major variables as age of the boys, race, length of stay in the community, records of school attendance, and personality inventory characteristics. Experiences were similarly related with respect to other variables found to be present as a result of the interviewing experience. Findings yielded evidence to indicate a predominance of negative experiences in the boys’ contacts with the community following release. The highest proportion of these occurred within the boys’ families, followed by contacts with authority and school, respectively. Peer group relationships for the boys indicated the highest proportion of positive experiences when compared with other major categories

Multi-taxa consequences of management for an avian umbrella species

Whether management for so-called umbrella species actually benefits co-occurring biota has rarely been tested. Here, we studied consequences for multiple invertebrate taxa of two ground-disturbance treatments designed to support an avian umbrella species (Eurasian stone-curlew, Burhinus oedicnemus), and whether analysing ecological requirements across the regional species pool predicted beneficiaries. Responses were assessed for the abundance of five bird species of conservation concern, and the abundance, species richness and composition of carabids, staphylinids, other beetles (non-carabid, non-staphylinid), true bugs and ants, sampling 31258 individuals of 402 species in an extensively-replicated experiment across the UK’s largest grass-heath. Both treatments provided suitable habitat for the umbrella species, in contrast to controls. Treatment influenced the abundance of only one bird species; but carabid, other beetle and ant richness increased with one or both treatments, while staphylinid richness and abundance increased and true bug richness and abundance decreased with both treatments. Richness of ‘priority’ (rare, scarce or threatened) invertebrates a priori considered to share ecological requirements with the umbrella species (predicted beneficiaries) increased with both treatments. Resampling and rarefaction showed landscapes diversified by treatment supported a greater cumulative species richness of other beetles, ants and true bugs, and importantly priority invertebrates, than a landscape comprising only untreated controls. Such experiments provide strong evidence to assess co-benefits of umbrella species management, but are costly and time consuming. The systematic examination of the autoecological requirements of co-occurring taxa (the ‘Biodiversity Audit Approach’) successfully predicted likely beneficiaries. Demonstrating wider biodiversity benefits strengthens the case for avian conservation management

Topology of the Future Chronological Boundary: Universality for Spacelike Boundaries

A method is presented for imputing a topology for any chronological set, i.e., a set with a chronology relation, such as a spacetime or a spacetime with some sort of boundary. This topology is shown to have several good properties, such as replicating the manifold topology for a spacetime and replicating the expected topology for some simple examples of spacetime-with-boundary; it also allows for a complete categorical characterization, in topological categories, of the Future Causal Boundary construction of Geroch, Kronheimer, and Penrose, showing that construction to have a universal property for future-completing chronological sets with spacelike boundaries. Rigidity results are given for any reasonable future completion of a spacetime, in terms of the GKP boundary: In the imputed topology, any such boundary must be homeomorphic to the GKP boundary (if all points have indecomposable pasts) or to a topological quotient of a closely related boundary (if boundaries are spacelike). A large class of warped-product-type spacetimes with spacelike boundaries is examined, calculating the GKP and other possible boundaries, and showing that the imputed topology gives expected results; included among these are the Schwarzschild singularity and those Robertson-Walker singularities which are spacelike.Comment: 56 pages, AMS-TeX; 1 page of figure captions (TeX); 22 figures, EPS format; to be published in Quantum Class. Grav.; principal reason for replacement is to have the figures included (also, introduction is expanded slightly, and one example is simplified

The Cognitive Change Index as a Measure of Self and Informant Perception of Cognitive Decline: Relation to Neuropsychological Tests

BACKGROUND: The perception of cognitive decline by individuals and those who know them well ("informants") has been inconsistently associated with objective cognitive performance, but strongly associated with depressive symptoms. OBJECTIVE: We investigated associations of self-report, informant-report, and discrepancy between self- and informant-report of cognitive decline obtained from the Cognitive Change Index (CCI) with cognitive test performance and self-reported depressive symptoms. METHODS: 267 participants with normal cognition, mild cognitive impairment (MCI), or mild dementia were included from a cohort study and memory clinic. Association of test performance and self-rated depression (Geriatric Depression Scale, GDS) with CCI scores obtained from subjects (CCI-S), their informants (CCI-I), and discrepancy scores between subjects and informants (CCI-D; CCI-S minus CCI-I) were analyzed using correlation and analysis of covariance (ANCOVA) models. RESULTS: CCI-S and CCI-I scores showed high internal consistency (Cronbach alpha 0.96 and 0.98, respectively). Higher scores on CCI-S and CCI-I, and lower scores on the CCI-D, were associated with lower performance on various cognitive tests in both univariate and in ANCOVA models adjusted for age, gender, and education. Adjustment for GDS slightly weakened the relationships between CCI and test performance but most remained significant. CONCLUSION: Self- and informant-report of cognitive decline, as measured by the CCI, show moderately strong relationships with objective test performance independent of age, gender, education, and depressive symptoms. The CCI appears to be a valid cross-sectional measure of self and informant perception of cognitive decline across the continuum of functioning. Studies are needed to address the relationship of CCI scores to longitudinal outcome

The cell fate determinant Llgl1 influences HSC fitness and prognosis in AML

A unique characteristic of hematopoietic stem cells (HSCs) is the ability to self-renew. Several genes and signaling pathways control the fine balance between self-renewal and differentiation in HSCs and potentially also in leukemia stem cells. Recently, studies have shed light on developmental molecules and evolutionarily conserved signals as regulators of stem cells in hematopoiesis and leukemia. In this study, we provide evidence that the cell fate determinant Llgl1 (lethal giant larvae homolog 1) plays an important role in regulation of HSCs. Loss of Llgl1 leads to an increase in HSC numbers that show increased repopulation capacity and competitive advantage after transplantation. This advantage increases upon serial transplantation or when stress is applied to HSCs. Llgl1−/− HSCs show increased cycling but neither exhaust nor induce leukemia in recipient mice. Llgl1 inactivation is associated with transcriptional repression of transcription factors such as KLF4 (Krüppel-like factor 4) and EGR1 (early-growth-response 1) that are known inhibitors of HSC self-renewal. Decreased Llgl1 expression in human acute myeloid leukemia (AML) cells is associated with inferior patient survival. Thus, inactivation of Llgl1 enhances HSC self-renewal and fitness and is associated with unfavorable outcome in human AML

Host suppression and bioinformatics for sequence-based characterization of unknown pathogens.

Bioweapons and emerging infectious diseases pose formidable and growing threats to our national security. Rapid advances in biotechnology and the increasing efficiency of global transportation networks virtually guarantee that the United States will face potentially devastating infectious disease outbreaks caused by novel ('unknown') pathogens either intentionally or accidentally introduced into the population. Unfortunately, our nation's biodefense and public health infrastructure is primarily designed to handle previously characterized ('known') pathogens. While modern DNA assays can identify known pathogens quickly, identifying unknown pathogens currently depends upon slow, classical microbiological methods of isolation and culture that can take weeks to produce actionable information. In many scenarios that delay would be costly, in terms of casualties and economic damage; indeed, it can mean the difference between a manageable public health incident and a full-blown epidemic. To close this gap in our nation's biodefense capability, we will develop, validate, and optimize a system to extract nucleic acids from unknown pathogens present in clinical samples drawn from infected patients. This system will extract nucleic acids from a clinical sample, amplify pathogen and specific host response nucleic acid sequences. These sequences will then be suitable for ultra-high-throughput sequencing (UHTS) carried out by a third party. The data generated from UHTS will then be processed through a new data assimilation and Bioinformatic analysis pipeline that will allow us to characterize an unknown pathogen in hours to days instead of weeks to months. Our methods will require no a priori knowledge of the pathogen, and no isolation or culturing; therefore it will circumvent many of the major roadblocks confronting a clinical microbiologist or virologist when presented with an unknown or engineered pathogen

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status

Global prevalence of carbapenem resistance in neutropenic patients and association with mortality and carbapenem use: systematic review and meta-analysis

Background: Carbapenem-resistant Gram-negative bacteria are recognized as a cause of difficult-to-treat infections associated with high mortality. Objectives: To perform a systematic review of currently available data on distribution, characteristics and outcome associated with carbapenem-resistant bloodstream infections in adult neutropenic patients. Methods: Included studies were identified through Medline, Embase and Cochrane databases between January 1995 and April 2016. Random effect meta-analysis was used to quantify the association between carbapenem resistance and mortality and between carbapenem exposure and resistance. Results: A total of 30 studies from 21 countries were included. Overall carbapenem resistance varied from 2% to 53% (median 9%) among studies. Infections due to carbapenem-resistant Pseudomonas spp. were reported in 18 (60%) studies showing high median resistance rates (44% of all carbapenem-resistant Gram-negatives and 19% of Pseudomonas isolates). Resistance of Enterobacteriaceae was less commonly reported and bloodstream infections due to carbapenem-resistant Klebsiella spp. were mainly documented from endemic areas (Greece, Italy, Israel). Carbapenem resistance in Acinetobacter spp. was reported in 9 (30%) studies (median resistance 58% of Acinetobacter isolates). Mortality rates ranged from 33% to 71% (median 50%) in patients with carbapenem-resistant infections. Carbapenemresistance appeared to correlate with mortality (OR 4.89, 95% CI 3.30-7.26) and previous exposure to carbapenems (OR 4.63, 95% CI 3.08-6.96). Conclusions: Carbapenem resistance represents a threat to neutropenic patients. In this group, resistance is likely promoted by previous carbapenem use and leads to high mortality rates. The knowledge of resistance patterns is crucial and can direct clinicians in the use of alternatives to carbapenem-based regimens