Searching for an Intermediate Mass Black Hole in the Blue Compact Dwarf galaxy MRK 996

The possibility is explored that accretion on an intermediate mass black hole contributes to the ionisation of the interstellar medium of the Compact Blue Dwarf galaxy MRK996. Chandra observations set tight upper limits (99.7 per cent confidence level) in both the X-ray luminosity of the posited AGN, Lx(2-10keV)<3e40erg/s, and the black hole mass, <1e4/\lambda Msolar, where \lambda, is the Eddington ratio. The X-ray luminosity upper limit is insufficient to explain the high ionisation line [OIV]25.89\mu m, which is observed in the mid-infrared spectrum of the MRK996 and is proposed as evidence for AGN activity. This indicates that shocks associated with supernovae explosions and winds of young stars must be responsible for this line. It is also found that the properties of the diffuse X-ray emission of MRK996 are consistent with this scenario, thereby providing direct evidence for shocks that heat the galaxy's interstellar medium and contribute to its ionisation.Comment: Submitted to MNRA

The M81 Group Dwarf Irregular Galaxy DDO 165. II. Connecting Recent Star Formation with ISM Structures and Kinematics

We compare the stellar populations and complex neutral gas dynamics of the M81 group dIrr galaxy DDO 165 using data from the HST and the VLA. Paper I identified two kinematically distinct HI components, multiple localized high velocity gas features, and eight HI holes and shells (the largest of which spans ~2.2x1.1 kpc). Using the spatial and temporal information from the stellar populations in DDO 165, we compare the patterns of star formation over the past 500 Myr with the HI dynamics. We extract localized star formation histories within 6 of the 8 HI holes identified in Paper I, as well as 23 other regions that sample a range of stellar densities and neutral gas properties. From population synthesis modeling, we derive the energy outputs (from stellar winds and supernovae) of the stellar populations within these regions over the last 100 Myr, and compare with refined estimates of the energies required to create the HI holes. In all cases, we find that "feedback" is energetically capable of creating the observed structures in the ISM. Numerous regions with significant energy inputs from feedback lack coherent HI structures but show prominent localized high velocity gas features; this feedback signature is a natural product of temporally and spatially distributed star formation. In DDO 165, the extended period of heightened star formation activity (lasting more than 1 Gyr) is energetically capable of creating the observed holes and high velocity gas features in the neutral ISM.Comment: The Astrophysical Journal, in press. Full-resolution version available on request from the first autho

The M81 Group Dwarf Irregular Galaxy DDO 165. I. High Velocity Neutral Gas in a Post-Starburst System

We present new multi-configuration VLA HI spectral line observations of the M81 group dIrr post-starburst galaxy DDO 165. The HI morphology is complex, with multiple column density peaks surrounding a large region of very low HI surface density that is offset from the center of the stellar distribution. The bulk of the neutral gas is associated with the southern section of the galaxy; a secondary peak in the north contains ~15% of the total HI mass. These components appear to be kinematically distinct, suggesting that either tidal processes or large-scale blowout have recently shaped the ISM of DDO 165. Using spatially-resolved position-velocity maps, we find multiple localized high-velocity gas features. Cross-correlating with radius-velocity analyses, we identify eight shell/hole structures in the ISM with a range of sizes (~400-900 pc) and expansion velocities (~7-11 km/s). These structures are compared with narrow- and broad-band imaging from KPNO and HST. Using the latter data, recent works have shown that DDO 165's previous "burst" phase was extended temporally (>1 Gyr). We thus interpret the high-velocity gas features, HI holes, and kinematically distinct components of the galaxy in the context of the immediate effects of "feedback" from recent star formation. In addition to creating HI holes and shells, extended star formation events are capable of creating localized high velocity motion of the surrounding interstellar material. A companion paper connects the energetics from the HI and HST data.Comment: The Astrophysical Journal, in press. Full-resolution version available on request from the first autho

Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial

BACKGROUND: The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. METHODS: HELIOS-A was a phase 3, global, open-label study comparing the efficacy and safety of vutrisiran with an external placebo group (APOLLO study). Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg every 3 weeks (Q3W) for 18 months. RESULTS: HELIOS-A enrolled 164 patients (vutrisiran, n = 122; patisiran reference group, n = 42); external placebo, n = 77. Vutrisiran met the primary endpoint of change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months (p = 3.54 × 10−12), and all secondary efficacy endpoints; significant improvements versus external placebo were observed in Norfolk Quality of Life-Diabetic Neuropathy, 10-meter walk test (both at 9 and 18 months), mNIS+7, modified body-mass index, and Rasch-built Overall Disability Scale (all at 18 months). TTR reduction with vutrisiran Q3M was non-inferior to within-study patisiran Q3W. Most adverse events were mild or moderate in severity, and consistent with ATTRv amyloidosis natural history. There were no drug-related discontinuations or deaths. CONCLUSIONS: Vutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile

Simplified RNA secondary structure mapping by automation of SHAPE data analysis

SHAPE (Selective 2′-hydroxyl acylation analysed by primer extension) technology has emerged as one of the leading methods of determining RNA secondary structure at the nucleotide level. A significant bottleneck in using SHAPE is the complex and time-consuming data processing that is required. We present here a modified data collection method and a series of algorithms, embodied in a program entitled Fast Analysis of SHAPE traces (FAST), which significantly reduces processing time. We have used this method to resolve the secondary structure of the first ∼900 nt of the hepatitis C virus (HCV) genome, including the entire core gene. We have also demonstrated the ability of SHAPE/FAST to detect the binding of a small molecule inhibitor to the HCV internal ribosomal entry site (IRES). In conclusion, FAST allows for high-throughput data processing to match the current high-throughput generation of data possible with SHAPE, reducing the barrier to determining the structure of RNAs of interest

Neurovisceral phenotypes in the expression of psychiatric symptoms

This review explores the proposal that vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily state, exemplified by a set of conditions that include Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope. Research is revealing how brainbody mechanisms underlie individual differences in psychophysiological reactivity that can be important for predicting, stratifying and treating individuals with anxiety disorders and related conditions. One common constitutional difference is Joint Hypermobility, in which there is an increased range of joint movement as a result of a variant of collagen. Joint hypermobility is over-represented in people with anxiety, mood and neurodevelopmental disorders. It is also linked to stress-sensitive medical conditions such as irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia. Structural differences in 'emotional' brain regions are reported in hypermobile individuals, and many people with joint hypermobility manifest autonomic abnormalities, typically Postural Tachycardia Syndrome. Enhanced heart rate reactivity during postural change and as recently recognised factors causing vasodilatation (as noted post prandially, post exertion and with heat) is characteristic of Postural Tachycardia Syndrome, and there is a phenomenological overlap with anxiety disorders, which may be partially accounted for by exaggerated neural reactivity within ventromedial prefrontal cortex. People who experience Vasovagal Syncope, a heritable tendency to fainting induced by emotional challenges (and needle/blood phobia), are also more vulnerable to anxiety disorders. Neuroimaging implicates brainstem differences in vulnerability to faints, yet the structural integrity of the caudate nucleus appears important for the control of fainting frequency in relation to parasympathetic tone and anxiety. Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety

Exploring How We Teach: Lived Experiences, Lessons, and Research about Graduate Instructors by Graduate Instructors

This book combines the knowledge of 30 graduate student instructors sharing about how they teach and how they’ve learned how to teach

The SPRY domain–containing SOCS box protein SPSB2 targets iNOS for proteasomal degradation

Macrophages lacking SPSB2 have increased NO production and enhanced pathogen-killing capabilities due to decreased ubiquitin-mediated destruction of iNOS

Where Is East Asia in STS?

The international spread of STS has reshaped the discipline in many ways, pushing it from its original core focus on technoscience in Euro-America to embrace new and wider agendas in other locations. For the practitioners of STS in East Asia, the complex relations between geographical region and forms of knowledge in technoscience are firmly on the agenda, and they have conceptualized these in a range of different and sometimes contradictory ways. The multiplicity of East Asian STS is also reflexively refracted in different assumptions about the character and location of the discipline in relation to other regional versions of STS. In what follows we simplify the complexities of a large and sophisticated body of writing by exploring a double question. On the one hand, we ask how scholars conceptualize the location of East Asian technoscience in the world. And on the other, a related question, we consider how they imagine the location of East Asian STS in relation to other forms of STS. We suggest that it is possible to identify at least six distinct spatially related strategies for understanding knowledge and technoscience in the East Asian literatures. In this article, we characterize these as diffusion, distortion, circulation, localizing, translation, and mistranslation and argue that East Asian STS may be understood as distinctive in the way it collaborates with other forms of STS not only because it identifies and characterizes other and different East Asian empirical contexts, but also because it makes possible the exploration of alternative and situated methodological approaches

Physiological Correlates of Volunteering

We review research on physiological correlates of volunteering, a neglected but promising research field. Some of these correlates seem to be causal factors influencing volunteering. Volunteers tend to have better physical health, both self-reported and expert-assessed, better mental health, and perform better on cognitive tasks. Research thus far has rarely examined neurological, neurochemical, hormonal, and genetic correlates of volunteering to any significant extent, especially controlling for other factors as potential confounds. Evolutionary theory and behavioral genetic research suggest the importance of such physiological factors in humans. Basically, many aspects of social relationships and social activities have effects on health (e.g., Newman and Roberts 2013; Uchino 2004), as the widely used biopsychosocial (BPS) model suggests (Institute of Medicine 2001). Studies of formal volunteering (FV), charitable giving, and altruistic behavior suggest that physiological characteristics are related to volunteering, including specific genes (such as oxytocin receptor [OXTR] genes, Arginine vasopressin receptor [AVPR] genes, dopamine D4 receptor [DRD4] genes, and 5-HTTLPR). We recommend that future research on physiological factors be extended to non-Western populations, focusing specifically on volunteering, and differentiating between different forms and types of volunteering and civic participation