Geometric K-Homology of Flat D-Branes

We use the Baum-Douglas construction of K-homology to explicitly describe various aspects of D-branes in Type II superstring theory in the absence of background supergravity form fields. We rigorously derive various stability criteria for states of D-branes and show how standard bound state constructions are naturally realized directly in terms of topological K-cycles. We formulate the mechanism of flux stabilization in terms of the K-homology of non-trivial fibre bundles. Along the way we derive a number of new mathematical results in topological K-homology of independent interest.Comment: 45 pages; v2: References added; v3: Some substantial revision and corrections, main results unchanged but presentation improved, references added; to be published in Communications in Mathematical Physic

Mitochondrial Mutations in Subjects with Psychiatric Disorders

A considerable body of evidence supports the role of mitochondrial dysfunction in psychiatric disorders and mitochondrial DNA (mtDNA) mutations are known to alter brain energy metabolism, neurotransmission, and cause neurodegenerative disorders. Genetic studies focusing on common nuclear genome variants associated with these disorders have produced genome wide significant results but those studies have not directly studied mtDNA variants. The purpose of this study is to investigate, using next generation sequencing, the involvement of mtDNA variation in bipolar disorder, schizophrenia, major depressive disorder, and methamphetamine use. MtDNA extracted from multiple brain regions and blood were sequenced (121 mtDNA samples with an average of 8,800x coverage) and compared to an electronic database containing 26,850 mtDNA genomes. We confirmed novel and rare variants, and confirmed next generation sequencing error hotspots by traditional sequencing and genotyping methods. We observed a significant increase of non-synonymous mutations found in individuals with schizophrenia. Novel and rare non-synonymous mutations were found in psychiatric cases in mtDNA genes: ND6, ATP6, CYTB, and ND2. We also observed mtDNA heteroplasmy in brain at a locus previously associated with schizophrenia (T16519C). Large differences in heteroplasmy levels across brain regions within subjects suggest that somatic mutations accumulate differentially in brain regions. Finally, multiplasmy, a heteroplasmic measure of repeat length, was observed in brain from selective cases at a higher frequency than controls. These results offer support for increased rates of mtDNA substitutions in schizophrenia shown in our prior results. The variable levels of heteroplasmic/multiplasmic somatic mutations that occur in brain may be indicators of genetic instability in mtDNA

The Chandra Deep Wide-field Survey: A New Chandra Legacy Survey in the Boötes Field. I. X-Ray Point Source Catalog, Number Counts, and Multiwavelength Counterparts

We present a new, ambitious survey performed with the Chandra X-ray Observatory of the 9.3 deg2 Boötes field of the NOAO Deep Wide-Field Survey. The wide field probes a statistically representative volume of the universe at high redshift. The Chandra Deep Wide-field Survey exploits the excellent sensitivity and angular resolution of Chandra over a wide area, combining 281 observations spanning 15 yr, for a total exposure time of 3.4 Ms, and detects 6891 X-ray point sources down to limiting fluxes of 4.7 × 10−16, 1.5 × 10−16, and 9 ×10−16 erg cm−2 s−1 in the 0.5–7, 0.5–2, and 2–7 keV bands, respectively. The robustness and reliability of the detection strategy are validated through extensive, state-of-the-art simulations of the whole field. Accurate number counts, in good agreement with previous X-ray surveys, are derived thanks to the uniquely large number of point sources detected, which resolve 65.0% ± 12.8% of the cosmic X-ray background between 0.5 and 2 keV and 81.0% ± 11.5% between 2 and 7 keV. Exploiting the wealth of multiwavelength data available on the field, we assign redshifts to ~94% of the X-ray sources, estimate their obscuration, and derive absorption-corrected luminosities. We provide an electronic catalog containing all of the relevant quantities needed for future investigations

Building on Progress Towards Fair Access : annual report 2019

Supplementary Table 3: Anti-epileptic drug use in patients with SYNGAP1 mutations or deletion

Lung adenocarcinoma promotion by air pollutants

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1β. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden

The criminal profiling illusion:what's behind the smoke and mirrors?

There is a belief that criminal profilers can predict a criminal's characteristics from crime scene evidence. In this article, the authors argue that this belief may be an illusion and explain how people may have been misled into believing that criminal profiling (CP) works despite no sound theoretical grounding and no strong empirical support for this possibility. Potentially responsible for this illusory belief is the information that people acquire about CP, which is heavily influenced by anecdotes, repetition of the message that profiling works, the expert profiler label, and a disproportionate emphasis on correct predictions. Also potentially responsible are aspects of information processing such as reasoning errors, creating meaning out of ambiguous information, imitating good ideas, and inferring fact from fiction. The authors conclude that CP should not be used as an investigative tool because it lacks scientific support

Data from: SYNGAP1 encephalopathy: a distinctive generalized developmental and epileptic encephalopathy

Objective. To delineate the epileptology, a key part of the SYNGAP1 phenotypic spectrum, in a large patient cohort. Methods. Patients were recruited via investigators’ practices or social media. We included patients with (likely) pathogenic SYNGAP1 variants or chromosome 6p21.32 microdeletions incorporating SYNGAP1. We analysed patients’ phenotypes using a standardized epilepsy questionnaire, medical records, EEG, MRI and seizure videos. Results. We included 57 patients (53% male, median age 8 years) with SYNGAP1 mutations (n=53) or microdeletions (n=4). 56/57 patients had epilepsy: generalized in 55, with focal seizures in seven and infantile spasms in one. Median seizure onset age was 2 years. A novel type of drop attack was identified comprising eyelid myoclonia evolving to a myoclonic-atonic (n=5) or atonic (n=8) seizure. Seizure types included eyelid myoclonia with absences (65%), myoclonic seizures (34%), atypical (20%) and typical (18%) absences and atonic seizures (14%), triggered by eating in 25%. Developmental delay preceded seizure onset in 54/56 (96%) patients of whom early developmental history was available. Developmental plateauing or regression occurred with seizures in 56 in the context of developmental and epileptic encephalopathies (DEEs). 55/57 patients had intellectual disability, which was moderate to severe in 50. Other common features included behavioural problems (73%), high pain threshold (72%), eating problems including oral aversion (68%), hypotonia (67%), sleeping problems (62%), autism spectrum disorder (54%) and ataxia or gait abnormalities (51%). Conclusions. SYNGAP1 mutations cause a generalized DEE with a distinctive syndrome combining epilepsy with eyelid myoclonia and myoclonic-atonic seizures, and predilection to seizures triggered by eating

Data from: SYNGAP1 encephalopathy: a distinctive generalized developmental and epileptic encephalopathy

Objective. To delineate the epileptology, a key part of the SYNGAP1 phenotypic spectrum, in a large patient cohort. Methods. Patients were recruited via investigators’ practices or social media. We included patients with (likely) pathogenic SYNGAP1 variants or chromosome 6p21.32 microdeletions incorporating SYNGAP1. We analysed patients’ phenotypes using a standardized epilepsy questionnaire, medical records, EEG, MRI and seizure videos. Results. We included 57 patients (53% male, median age 8 years) with SYNGAP1 mutations (n=53) or microdeletions (n=4). 56/57 patients had epilepsy: generalized in 55, with focal seizures in seven and infantile spasms in one. Median seizure onset age was 2 years. A novel type of drop attack was identified comprising eyelid myoclonia evolving to a myoclonic-atonic (n=5) or atonic (n=8) seizure. Seizure types included eyelid myoclonia with absences (65%), myoclonic seizures (34%), atypical (20%) and typical (18%) absences and atonic seizures (14%), triggered by eating in 25%. Developmental delay preceded seizure onset in 54/56 (96%) patients of whom early developmental history was available. Developmental plateauing or regression occurred with seizures in 56 in the context of developmental and epileptic encephalopathies (DEEs). 55/57 patients had intellectual disability, which was moderate to severe in 50. Other common features included behavioural problems (73%), high pain threshold (72%), eating problems including oral aversion (68%), hypotonia (67%), sleeping problems (62%), autism spectrum disorder (54%) and ataxia or gait abnormalities (51%). Conclusions. SYNGAP1 mutations cause a generalized DEE with a distinctive syndrome combining epilepsy with eyelid myoclonia and myoclonic-atonic seizures, and predilection to seizures triggered by eating

Drivers of political parties’ climate policy preferences: lessons from Denmark and Ireland

Political parties are important actors in domestic climate politics. What drives variation in parties’ climate policy preferences? To contribute to a growing literature on the party politics of climate change, we focus on the roles of public opinion, party competition, and parties’ traditional policy preferences in shaping parties’ climate policy preferences in Denmark and Ireland. In case studies that draw on in-depth interviews with policy practitioners, we show how parties respond to public opinion, accommodate issue-owners, and are powerfully constrained and enabled by their existing preferences. These mechanisms also help to explain different responses on climate policy across the left-right spectrum. Competition between mainstream parties is particularly powerful, but can constrain as much as it enables ‘greener’ climate policy preferences. While climate change may be a distinctive problem, the party politics of climate change features similar incentives and constraints as other domains