An outflow in the Seyfert ESO 362-G18 revealed by Gemini-GMOS/IFU Observations

We present two-dimensional stellar and gaseous kinematics of the inner 0.7 $\times$ 1.2 kpc$^{2}$ of the Seyfert galaxy ESO 362-G18, derived from optical spectra obtained with the GMOS/IFU on the Gemini South telescope at a spatial resolution of $\approx$170 pc and spectral resolution of 36 km s$^{-1}$. ESO 362-G18 is a strongly perturbed galaxy of morphological type Sa or S0/a, with a minor merger approaching along the NE direction. Previous studies have shown that the [OIII] emission shows a fan-shaped extension of $\approx$ 10\arcsec\ to the SE. We detect the [OIII] doublet, [NII] and H${\alpha}$ emission lines throughout our field of view. The stellar kinematics is dominated by circular motions in the galaxy plane, with a kinematic position angle of $\approx$137$^{\circ}$. The gas kinematics is also dominated by rotation, with kinematic position angles ranging from 122$^{\circ}$ to 139$^{\circ}$. A double-Gaussian fit to the [OIII]$\lambda$5007 and H${\alpha}$ lines, which have the highest signal to noise ratios of the emission lines, reveal two kinematic components: (1) a component at lower radial velocities which we interpret as gas rotating in the galactic disk; and (2) a component with line of sight velocities 100-250 km s$^{-1}$ higher than the systemic velocity, interpreted as originating in the outflowing gas within the AGN ionization cone. We estimate a mass outflow rate of 7.4 $\times$ 10$^{-2}$ M$_{\odot}$ yr$^{-1}$ in the SE ionization cone (this rate doubles if we assume a biconical configuration), and a mass accretion rate on the supermassive black hole (SMBH) of 2.2 $\times$ 10$^{-2}$ M$_{\odot}$ yr$^{-1}$. The total ionized gas mass within $\sim$84 pc of the nucleus is 3.3 $\times$ 10$^{5}$ M$_{\odot}$; infall velocities of $\sim$34 km s$^{-1}$ in this gas would be required to feed both the outflow and SMBH accretion.Comment: 18 pages, 14 figure

Association of cardiac and vascular changes with ambient PMin diabetic individuals

Background and Objective Exposure to fine airborne particles (PM2.5) has been shown to be responsible for cardiovascular and hematological effects, especially in older people with cardiovascular disease. Some epidemiological studies suggest that individuals with diabetes may be a particularly susceptible population. This study examined effects of short-term exposures to ambient PM2.5 on markers of systemic inflammation, coagulation, autonomic control of heart rate, and repolarization in 22 adults (mean age: 61 years) with type 2 diabetes. Methods Each individual was studied for four consecutive days with daily assessments of plasma levels of blood markers. Cardiac rhythm and electrocardiographic parameters were examined at rest and with 24-hour ambulatory ECG monitors. PM2.5 and meteorological data were measured daily on the rooftop of the patient exam site. Data were analyzed with models adjusting for season, weekday, meteorology, and a random intercept. To identify susceptible subgroups, effect modification was analyzed by clinical characteristics associated with insulin resistance as well as with oxidative stress and by medication intake. Results Interleukin (IL)-6 and tumor necrosis factor alpha showed a significant increase with a lag of two days (percent change of mean level: 20.2% with 95%-confidence interval [6.4; 34.1] and 13.1% [1.9; 24.4], respectively) in association with an increase of 10 μg/m3 in PM2.5. Obese participants as well as individuals with elevated glycosylated hemoglobin, lower adiponectin, higher ferritin or with glutathione S-transferase M1 null genotype showed higher IL-6 effects. Changes in repolarization were found immediately as well as up to four days after exposure in individuals without treatment with a beta-adrenergic receptor blocker. Conclusions Exposure to elevated levels of PM2.5 alters ventricular repolarization and thus may increase myocardial vulnerability to arrhythmias. Exposure to PM2.5 also increases systemic inflammation. Characteristics associated with insulin resistance or with oxidative stress were shown to enhance the association

Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of L-{alpha}-aminoadipic semialdehyde/L-{Delta}1-piperideine 6-carboxylate. However, whilst this is a highly treatable disorder, there is general uncertainty about when to consider this diagnosis and how to test for it. This study aimed to evaluate the use of measurement of urine L-{alpha}-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary L-{alpha}-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response to antiepileptic drugs; (ii) in infants with multisystem pathology, the response to pyridoxine may not be instant and obvious; and (iii) structural brain abnormalities may co-exist and be considered sufficient cause of epilepsy, whereas the fits may be a consequence of antiquitin deficiency and are then responsive to pyridoxine. These findings support the use of biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine in infants and children with epilepsy across a broad range of clinical scenarios

Association of cardiac and vascular changes with ambient PM2.5 in diabetic individuals

Abstract: Background and Objective: Exposure to fine airborne particles (PM2.5) has been shown to be responsible for cardiovascular and hematological effects, especially in older people with cardiovascular disease. Some epidemiological studies suggest that individuals with diabetes may be a particularly susceptible population. This study examined effects of short-term exposures to ambient PM2.5 on markers of systemic inflammation, coagulation, autonomic control of heart rate, and repolarization in 22 adults (mean age: 61 years) with type 2 diabetes. Methods: Each individual was studied for four consecutive days with daily assessments of plasma levels of blood markers. Cardiac rhythm and electrocardiographic parameters were examined at rest and with 24-hour ambulatory ECG monitors. PM2.5 and meteorological data were measured daily on the rooftop of the patient exam site. Data were analyzed with models adjusting for season, weekday, meteorology, and a random intercept. To identify susceptible subgroups, effect modification was analyzed by clinical characteristics associated with insulin resistance as well as with oxidative stress and by medication intake. Results: Interleukin (IL)-6 and tumor necrosis factor alpha showed a significant increase with a lag of two days (percent change of mean level: 20.2% with 95%-confidence interval [6.4; 34.1] and 13.1% [1.9; 24.4], respectively) in association with an increase of 10 μg/m3 in PM2.5. Obese participants as well as individuals with elevated glycosylated hemoglobin, lower adiponectin, higher ferritin or with glutathione S-transferase M1 null genotype showed higher IL-6 effects. Changes in repolarization were found immediately as well as up to four days after exposure in individuals without treatment with a beta-adrenergic receptor blocker. Conclusions: Exposure to elevated levels of PM2.5 alters ventricular repolarization and thus may increase myocardial vulnerability to arrhythmias. Exposure to PM2.5 also increases systemic inflammation. Characteristics associated with insulin resistance or with oxidative stress were shown to enhance the association

Specific MRI abnormalities reveal severe perrault syndrome due to CLPP defects

In establishing a genetic diagnosis in heterogeneous neurological disease, clinical characterization and whole exome sequencing (WES) go hand-in-hand. Clinical data are essential, not only to guide WES variant selection and define the clinical severity of a genetic defect but also to identify other patients with defects in the same gene. In an infant patient with sensorineural hearing loss, psychomotor retardation, and epilepsy, WES resulted in identification of a novel homozygous CLPP frameshift mutation (c.21delA). Based on the gene defect and clinical symptoms, the diagnosis Perrault syndrome type 3 (PRLTS3) was established. The patient's brain-MRI revealed specific abnormalities of the subcortical and deep cerebral white matter and the middle blade of the corpus callosum, which was used to identify similar patients in the Amsterdam brain-MRI database, containing over 3000 unclassified leukoencephalopathy cases. In three unrelated patients with similar MRI abnormalities the CLPP gene was sequenced, and in two of them novel missense mutations were identified together with a large deletion that covered part of the CLPP gene on the other allele. The severe neurological and MRI abnormalities in these young patients were due to the drastic impact of the CLPP mutations, correlating with the variation in clinical manifestations among previously reported patients. Our data show that similarity in brain-MRI patterns can be used to identify novel PRLTS3 patients, especially during early disease stages, when only part of the disease manifestations are present. This seems especially applicable to the severely affected cases in which CLPP function is drastically affected and MRI abnormalities are pronounced

Thermal Conductivity across the Phase Diagram of Cuprates: Low-Energy Quasiparticles and Doping Dependence of the Superconducting Gap

Heat transport in the cuprate superconductors YBa$_2$Cu$_3$O$_{y}$ and La$_{2-x}$Sr$_x$CuO$_4$ was measured at low temperatures as a function of doping. A residual linear term kappa_{0}/T is observed throughout the superconducting region and it decreases steadily as the Mott insulator is approached from the overdoped regime. The low-energy quasiparticle gap extracted from kappa_{0}/T is seen to scale closely with the pseudogap. The ubiquitous presence of nodes and the tracking of the pseudogap shows that the overall gap remains of the pure d-wave form throughout the phase diagram, which excludes the possibility of a complex component (ix) appearing at a putative quantum phase transition and argues against a non-superconducting origin to the pseudogap. A comparison with superfluid density measurements reveals that the quasiparticle effective charge is weakly dependent on doping and close to unity.Comment: 12 pages, 9 figure

Effects of Increasing Alpha-Linolenic Acid on Growth Performance and Mortality Rate in PRRS-Virus Challenged Nursery Pigs

A total of 91,140 weaned pigs, (DNA 600 × PIC 1050; initially 11.33 ± 0.62 lb) originating from PRRSV-positive sow farms, were used across 8 nursery sites to evaluate growth performance, total removal and mortality rate, and medication usage of nursery pigs fed diets containing 0 or 3% O3 Trial Feed (NBO3 Technologies LLC, Manhattan, KS), a source of omega-3 fatty acids. Each of the 8 sites contained 5 barns with 2 rooms in each barn. Rooms of pigs were blocked by nursery site and allocated by sow source to 1 of 2 dietary treatments. Thus, there were 40 groups (rooms) per treatment with approximately 1,100 pigs per room. The first treatment was a standard nursery diet specific to the production system. The second treatment was the same standard nursery diet with the addition of 3% O3 Trial Feed. At placement, pigs were fed a pre-starter and then fed experimental diets across 3 phases with all diets fed in pelleted form. Overall, there were no significant differences (P \u3e 0.10) observed in growth performance between pigs fed diets containing 0 or 3% O3 Trial Feed. Pigs fed control diets had reduced (P \u3c 0.001) total removals and mortality percentage compared to pigs fed diets containing 3% O3 Trial Feed. When evaluating medication usage, there were no significant differences (P \u3e 0.10) observed in the total number of injections given per 1,000 pig days. However, pigs fed diets containing 3% O3 Trial Feed had a reduced (P \u3c 0.001) number of total injections per pig placed. In summary, the increase in alpha-linolenic acid in the diet, through the inclusion of 3% O3 Trial Feed, did not impact growth performance during the duration of this trial. There was an increase in total removals and mortality in pigs fed diets containing O3 Trial Feed. However, there was a reduction in total injections given per pig placed in pigs fed diets containing O3 Trial Feed. We hypothesize that because of the high prevalence of PRRS at entry, O3 Trial Feed may not have had sufficient time to impact the immune system before the PRRS challenge

Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of l-α-aminoadipic semialdehyde/l-Δ1-piperideine 6-carboxylate. However, whilst this is a highly treatable disorder, there is general uncertainty about when to consider this diagnosis and how to test for it. This study aimed to evaluate the use of measurement of urine l-α-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary l-α-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response to antiepileptic drugs; (ii) in infants with multisystem pathology, the response to pyridoxine may not be instant and obvious; and (iii) structural brain abnormalities may co-exist and be considered sufficient cause of epilepsy, whereas the fits may be a consequence of antiquitin deficiency and are then responsive to pyridoxine. These findings support the use of biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine in infants and children with epilepsy across a broad range of clinical scenario

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

GENCODE: reference annotation for the human and mouse genomes in 2023.

GENCODE produces high quality gene and transcript annotation for the human and mouse genomes. All GENCODE annotation is supported by experimental data and serves as a reference for genome biology and clinical genomics. The GENCODE consortium generates targeted experimental data, develops bioinformatic tools and carries out analyses that, along with externally produced data and methods, support the identification and annotation of transcript structures and the determination of their function. Here, we present an update on the annotation of human and mouse genes, including developments in the tools, data, analyses and major collaborations which underpin this progress. For example, we report the creation of a set of non-canonical ORFs identified in GENCODE transcripts, the LRGASP collaboration to assess the use of long transcriptomic data to build transcript models, the progress in collaborations with RefSeq and UniProt to increase convergence in the annotation of human and mouse protein-coding genes, the propagation of GENCODE across the human pan-genome and the development of new tools to support annotation of regulatory features by GENCODE. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org