Distorted HI Gas in the Widely Separated LIRG Arp 256

We present new interferometric HI and CO (1-0) observations of the luminous infrared source, Arp 256. Arp 256 consists of two spiral galaxies in an early stage of merging, with a projected nuclear separation of 29 kpc (54") and an infrared luminosity of 2.0E11 L_sun. Despite the large separation of the galaxies' nuclei and mildly disrupted stellar components, the HI disks are found to be strongly disrupted, and the southern galaxy in Arp 256 shows an elevated star formation efficiency, which is consistent with a nuclear starburst. Both of these results run contrary to expectations, posing interesting questions on the physical mechanisms involved in stimulating star formation during an interaction.Comment: 19 pages, 7 figures. Accepted for publication in AJ. Author added. Full resolution figures available at http://astro.uchicago.edu/home/web/jchen/arp25

Statistics of Magnification Perturbations by Substructure in the Cold Dark Matter Cosmological Model

We study the statistical properties of magnification perturbations by substructures in strong lensed systems using linear perturbation theory and an analytical substructure model including tidal truncation and a continuous substructure mass spectrum. We demonstrate that magnification perturbations are dominated by perturbers found within a tidal radius of an image, and that sizable magnification perturbations may arise from small, coherent contributions from several substructures within the lens halo. We find that the root-mean-square (rms) fluctuation of the magnification perturbation is 10% to 20% and both the average and rms perturbations are sensitive to the mass spectrum and density profile of the perturbers. Interestingly, we find that relative to a smooth model of the same mass, the average magnification in clumpy models is lower (higher) than that in smooth models for positive (negative) parity images. This is opposite from what is observed if one assumes that the image magnification predicted by the best-fit smooth model of a lens is a good proxy for what the observed magnification would have been if substructures were absent. While it is possible for this discrepancy to be resolved via nonlinear perturbers, we argue that a more likely explanation is that the assumption that the best-fit lens model is a good proxy for the magnification in the absence of substructure is not correct. We conclude that a better theoretical understanding of the predicted statistical properties of magnification perturbations by CDM substructure is needed in order to affirm that CDM substructures have been unambiguously detected.Comment: ApJ accepted, minor change

Gravitational Nanolensing from Subsolar Mass Dark Matter Halos

We investigate the feasibility of extracting the gravitational nanolensing signal due to the presence of subsolar mass halos within galaxy-sized dark matter halos. We show that subsolar mass halos in a lensing galaxy can cause strong nanolensing events with shorter durations and smaller amplitudes than microlensing events caused by stars. We develop techniques that can be used in future surveys such as Pan-STARRS, LSST and OMEGA to search for the nanolensing signal from subsolar mass halos.Comment: 12 pages, 10 figures. Replaced with version accepted for publication in ApJ. Very minor changes from version

Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor neurons

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disorder characterised by selective loss of motor neurons leading to fatal paralysis. Current therapeutic approaches are limited in their effectiveness. Substantial advances in understanding ALS disease mechanisms has come from the identification of pathogenic mutations in dominantly inherited familial ALS (FALS). We previously reported a coding mutation in D-amino acid oxidase (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co-agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR). Using primary motor neuron cultures or motor neuron cell lines we demonstrated that expression of DAOR199W, promoted the formation of ubiquitinated protein aggregates, activated autophagy and increased apoptosis. The aim of this study was to characterise the effects of DAOR199W in vivo, using transgenic mice overexpressing DAOR199W. Marked abnormal motor features, e.g. kyphosis, were evident in mice expressing DAOR199W, which were associated with a significant loss (19%) of lumbar spinal cord motor neurons, analysed at 14 months. When separated by gender, this effect was greater in females (26%; p< 0.0132). In addition, we crossed the DAOR199W transgenic mouse line with the SOD1G93A mouse model of ALS to determine whether the effects of SOD1G93A were potentiated in the double transgenic line (DAOR199W/SOD1G93A). Although overall survival was not affected, onset of neurological signs was significantly earlier in female double transgenic animals than their female SOD1G93A littermates (125 days vs 131 days, P = 0.0239). In summary, some significant in vivo effects of DAOR199W on motor neuron function (i.e. kyphosis and loss of motor neurons) were detected which were most marked in females and could contribute to the earlier onset of neurological signs in double transgenic females compared to SOD1G93A littermates, highlighting the importance of recognizing gender effects present in animal models of ALS

Dichroic Filter for Separating W-Band and Ka-Band

The proposed Aerosol/Cloud/Ecosystems (ACEs) mission development would advance cloud profiling radar from that used in CloudSat by adding a 35-GHz (Ka-band) channel to the 94-GHz (W-band) channel used in CloudSat. In order to illuminate a single antenna, and use CloudSat-like quasi-optical transmission lines, a spatial diplexer is needed to add the Ka-band channel. A dichroic filter separates Ka-band from W-band by employing advances in electrical discharge machining (EDM) and mode-matching analysis techniques developed and validated for designing dichroics for the Deep Space Network (DSN), to develop a preliminary design that both met the requirements of frequency separation and mechanical strength. First, a mechanical prototype was built using an approximately 102-micron-diameter EDM process, and tolerances of the hole dimensions, wall thickness, radius, and dichroic filter thickness measured. The prototype validated the manufacturing needed to design a dichroic filter for a higher-frequency usage than previously used in the DSN. The initial design was based on a Ka-band design, but thicker walls are required for mechanical rigidity than one obtains by simply scaling the Ka-band dichroic filter. The resulting trade of hole dimensions for mechanical rigidity (wall thickness) required electrical redesign of the hole dimensions. Updates to existing codes in the linear solver decreased the analysis time using mode-matching, enabling the electrical design to be realized quickly. This work is applicable to missions and instruments that seek to extend W-band cloud profiling measurements to other frequencies. By demonstrating a dichroic filter that passes W-band, but reflects a lower frequency, this opens up the development of instruments that both compare to and enhance CloudSat

Global Analysis of Predicted G Protein-Coupled Receptor Genes in the Filamentous Fungus, Neurospora crassa.

G protein-coupled receptors (GPCRs) regulate facets of growth, development, and environmental sensing in eukaryotes, including filamentous fungi. The largest predicted GPCR class in these organisms is the Pth11-related, with members similar to a protein required for disease in the plant pathogen Magnaporthe oryzae. However, the Pth11-related class has not been functionally studied in any filamentous fungal species. Here, we analyze phenotypes in available mutants for 36 GPCR genes, including 20 Pth11-related, in the model filamentous fungus Neurospora crassa. We also investigate patterns of gene expression for all 43 predicted GPCR genes in available datasets. A total of 17 mutants (47%) possessed at least one growth or developmental phenotype. We identified 18 mutants (56%) with chemical sensitivity or nutritional phenotypes (11 uniquely), bringing the total number of mutants with at least one defect to 28 (78%), including 15 mutants (75%) in the Pth11-related class. Gene expression trends for GPCR genes correlated with the phenotypes observed for many mutants and also suggested overlapping functions for several groups of co-transcribed genes. Several members of the Pth11-related class have phenotypes and/or are differentially expressed on cellulose, suggesting a possible role for this gene family in plant cell wall sensing or utilization

Short Chain Fatty Acids Taken at Time of Thrombectomy in Acute Ischemic Stroke Patients Are Independent of Stroke Severity But Associated with Inflammatory Markers and Worse Symptoms at Discharge

Introduction: Short chain fatty acids (SCFA) are gut microbiota-derived metabolites that contribute to the gut-brain axis and may impact stroke outcomes following gut dysbiosis. We evaluated plasma SCFA concentrations against stroke severity parameters and identified SCFA-associated protein networks. Methods: The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC), a continuously enrolling tissue bank, was used to obtain stroke samples. Arterial blood distal and proximal to the thrombus was obtained from Acute Ischemic Stroke (AIS) Patients (n=53) during thrombectomy. Patient demographics, stroke presentation and outcome parameters were reported. The SCFAs were isolated from proximal plasma via chemical derivatization UHPLC coupled tandem mass spectrometry using electrospray ionization and multiple reaction monitoring. Proteomic levels for 184 cardioembolic and inflammatory proteins was quantified from systemic and intracranial plasma by Olink. Arterial blood from cerebrovascular patients undergoing elective neurointerventional procedures was used as controls. Results: Acetate positively correlated with time from last known normal (LKN) and was significantly lower in stroke patients compared to control. Isobutyrate, Butyrate and 2-Methylbutyrate negatively correlated with %ΔNIHSS. Isobutyrate and 2-Methylbutyrate positively correlated with NIHSS discharge. SCFA concentrations were not associated with NIHSS admission, infarct volume, or edema volume. Multiple SCFAs positively associated with systemic and pro-inflammatory cytokines, most notably IL-6, TNF-α, VCAM1, IL-17, and MCP-1. Conclusions: Plasma SCFA concentrations taken at time of stroke are not associated with stroke severity at presentation. However, higher levels of SCFAs at the time of stroke are associated with increased markers of inflammation, less recovery from admission to discharge, and worse symptom burden at discharge

Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.

BACKGROUND: Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis. METHODS: We investigated in vitro and in vivo effects of metformin in humans. RESULTS: Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity. Metformin administered to healthy human volunteers led to significant downregulation of genes involved in oxidative phosphorylation, mammalian target of rapamycin signaling, and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and upregulation of genes involved in phagocytosis and reactive oxygen species production was increased. These in vivo effects were accompanied by a metformin-induced shift in myeloid cells from classical to nonclassical monocytes. At a functional level, metformin lowered ex vivo production of tumor necrosis factor α, interferon γ, and interleukin 1β but increased phagocytosis activity and reactive oxygen species production. CONCLUSION: Metformin has a range of potentially beneficial effects on cellular metabolism, immune function, and gene transcription involved in innate host responses to M. tuberculosis

Challenges to Implementation of the Co-Curriculum in Accredited Pharmacy Programs

Objective. To determine areas of concern, and challenges to implementing and assessing the co-curriculum in accredited Doctor of Pharmacy programs, along with how confident programs are in their ability to meet the co-curriculum requirement as mandated by the Accreditation Council for Pharmacy Education (ACPE). Methods. A survey was administered to all ACPE-accredited pharmacy programs to collect information regarding areas of concern, challenges, and confidence in their ability to meet the co-curriculum requirement. The frequency of responses to items are presented along with comparisons based on characteristics, including institution type, cohort size, most recent ACPE accreditation review, and supporting offices. Results. The most common concerns centered on the documentation and assessment process. The most commonly reported challenges were lack of enthusiasm or buy-in from faculty, staff, and students; lack of a clear definition of co-curriculum; and faculty time and insufficient staff. Overall, programs had a high level of confidence in their ability to meet the requirements for co-curriculum. The only differences found were related to supporting offices and cohort size. Conclusion. The results suggest that having supporting offices may reduce the co-curriculum burden. Similarly, student cohort size may have an impact on the challenges for some programs, particularly those with moderate-sized cohorts reporting challenges related to faculty and staff. Further research is needed to determine how programs address these critical issues, and to explore whether programs report differently on these areas after completing an accreditation review. The study results may be useful to members of the Academy when evaluating co-curriculum