The detection of gravitational waves remains one of the most challenging prospects faced by experimental physicists. One of the most significant limits to the sensitivity of current, and future, ...long-baseline interferometric gravitational wave detectors is thermal displacement noise of the test masses and their suspensions. Suspension thermal noise will be an important noise source at operating frequencies between approximately 10 and 30 Hz, and it results from a combination of thermoelastic damping, surface loss and bulk loss associated with the suspension fibres, and weld loss from their attachment. Its effects can be reduced by minimizing thermoelastic loss and optimizing pendulum dilution factor via the appropriate choice of geometry of the suspension fibre and attachment geometry. This paper will discuss the design and fabrication of a prototype of the fused silica suspension stage for use in the advanced LIGO (aLIGO) detector network, analysing in detail the design of the fused silica attachment pieces (ears), together with the suspension assembly techniques. We also present a full thermal noise analysis of the prototype suspension, taking into account for the first time the precise shape of the actual fibres used, and weld loss. We shall demonstrate the suitability of this suspension for installation into aLIGO.
Abstract
The Differential Speckle Survey Instrument (DSSI) was relocated to the Astrophysical Research Consortium 3.5 m telescope at Apache Point Observatory (APO) in early 2022. Here we present ...results from the first year of observations along with an updated instrument description for DSSI at APO, including a detailed description of a new internal slit mask assembly used to measure the instrument plate scale from first principles. Astrometric precision for DSSI at APO during this time was measured to be 2.06 ± 0.11 mas, with a photometric precision of 0.14 ± 0.04 mag. Results of 40 resolved binary systems are reported, including two that were previously unknown to be binaries: HIP 7535 and HIP 9603. We also present updated orbital fits for two systems: HIP 93903 and HIP 100714. Finally, we report updated or confirmed dispositions for five Kepler Objects of Interest (KOIs) that were previously explored in Colton et al., using speckle imaging to discern common proper motions pairs from line of sight companions: KOI-270, KOI-959, KOI-1613, KOI-1962, and KOI-3214AB.
We previously developed a computer-assisted image analysis algorithm to detect and quantify the microscopic features of rodent progressive cardiomyopathy (PCM) in rat heart histologic sections and ...validated the results with a panel of five veterinary toxicologic pathologists using a multinomial logistic model. In this study, we assessed both the inter-rater and intra-rater agreement of the pathologists and compared pathologists’ ratings to the artificial intelligence (AI)-predicted scores. Pathologists and the AI algorithm were presented with 500 slides of rodent heart. They quantified the amount of cardiomyopathy in each slide. A total of 200 of these slides were novel to this study, whereas 100 slides were intentionally selected for repetition from the previous study. After a washout period of more than six months, the repeated slides were examined to assess intra-rater agreement among pathologists. We found the intra-rater agreement to be substantial, with weighted Cohen’s kappa values ranging from k = 0.64 to 0.80. Intra-rater variability is not a concern for the deterministic AI. The inter-rater agreement across pathologists was moderate (Cohen’s kappa k = 0.56). These results demonstrate the utility of AI algorithms as a tool for pathologists to increase sensitivity and specificity for the histopathologic assessment of the heart in toxicology studies.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial ...morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intravenous gadolinium diethylene triamine penta-acetic acid (Gadopentetate dimeglumine, Gd-DTPA) is visualized as a radiographic contrast agent in the renal tract on computed tomography (CT). In ...this study the CT appearance of this contrast agent within the renal collecting systems of 12 patients is described following a Gd-DTPA enhanced magnetic resonance imaging (MRI) study. The CT appearances are variable and not predictable on the basis of time from injection, age, sex or indices of renal function.
Trypanosoma brucei N-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis (HAT). From previous studies, we identified pyrazole ...sulfonamide, DDD85646 (1), a potent inhibitor of TbNMT. Although this compound represents an excellent lead, poor central nervous system (CNS) exposure restricts its use to the hemolymphatic form (stage 1) of the disease. With a clear clinical need for new drug treatments for HAT that address both the hemolymphatic and CNS stages of the disease, a chemistry campaign was initiated to address the shortfalls of this series. This paper describes modifications to the pyrazole sulfonamides which markedly improved blood–brain barrier permeability, achieved by reducing polar surface area and capping the sulfonamide. Moreover, replacing the core aromatic with a flexible linker significantly improved selectivity. This led to the discovery of DDD100097 (40) which demonstrated partial efficacy in a stage 2 (CNS) mouse model of HAT.
The GEOTRACES program has greatly increased basin‐scale concentration measurements for a large number of elements in the ocean, both constraining external sources and internal sinks and exposing ...complex internal cycles of trace elements. Our conceptual frameworks for marine trace element cycling, however, often remain simplified as the production and remineralization of phytoplankton biomass. Despite their complexity, or perhaps because of it, trace element cycles are often predominantly considered as an extension of traditional Redfield macronutrient ratios to C or P. Here we utilize extensive data sets of particulate trace element concentrations from GEOTRACES section cruises in the South Pacific and North Atlantic Oceans to look for evidence of the internal cycles of multiple trace elements without requiring normalization to phytoplankton biomass. Using both traditional and expanded power law regression analyses and multi‐element factor analysis, we expose the internal distributions of six authigenic, biogenic, and lithogenic particulate phases and their multi‐element associations. Critically, no particulate trace element is observed to behave identically to P. Observations include a scavenged Fe phase with a slight surface maximum, which increases linearly with depth below ~ 300 m and which appears to co‐scavenge Cu, V, and La. Particulate Co is found to be associated with phytoplankton, Mn‐biooxides just below the mixed layer, and with a putative heterotrophic phase observed in the surface and at depth. We present an expanded conceptual framework for particulate trace element cycling that has explicit roles for these multiple particulate phases.
Key Points
Particulate trace element data sets contain evidence of multiple biomass, scavenged, and lithogenic phases that can be statistically revealed
Scavenged Fe and Mn phases have unique internal distributions and co‐scavenge several bioactive elements
Phytoplankton and putative heterotrophic biomass phases have unique elemental associations and internal distributions
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Brownian thermal noise in dielectric multilayer coatings limits the sensitivity of current and future interferometric gravitational wave detectors. In this work we explore the possibility of ...improving the mechanical losses of tantala, often used as the high refractive index material, by depositing it on a substrate held at elevated temperature. Promising results have been previously obtained with this technique when applied to amorphous silicon. We show that depositing tantala on a hot substrate reduced the mechanical losses of the as-deposited coating, but subsequent thermal treatments had a larger impact, as they reduced the losses to levels previously reported in the literature. We also show that the reduction in mechanical loss correlates with increased medium range order in the atomic structure of the coatings using x-ray diffraction and Raman spectroscopy. Finally, a discussion is included on our results, which shows that the elevated temperature deposition of pure tantala coatings does not appear to reduce mechanical loss in a similar way to that reported in the literature for amorphous silicon; and we suggest possible future research directions.
N-Myristoyltransferase (NMT) represents a promising drug target within the parasitic protozoa Trypanosoma brucei (T. brucei), the causative agent for human African trypanosomiasis (HAT) or sleeping ...sickness. We have previously validated T. brucei NMT as a promising druggable target for the treatment of HAT in both stages 1 and 2 of the disease. We report on the use of the previously reported DDD85646 (1) as a starting point for the design of a class of potent, brain penetrant inhibitors of T. brucei NMT.
Family caregivers of patients with acute cardiorespiratory failure are at high risk for distress, which is typically defined as the presence of psychological symptoms such as anxiety, depression, or ...posttraumatic stress. Interventions to reduce caregiver distress and increase wellness have been largely ineffective to date. An incomplete understanding of caregiver wellness and distress may hinder efforts at developing effective support interventions.
To allow family caregivers to define their experiences of wellness and distress 6 months after patient intensive care unit (ICU) admission and to identify moderators that influence wellness and distress.
Primary family caregivers of adult patients admitted to the medical ICU with acute cardiorespiratory failure were invited to participate in a semistructured interview 6 months after ICU admission as part of a larger prospective cohort study. Interview guides were used to assess caregiver perceptions of their own well-being, record caregiver descriptions of their experiences of family caregiving, and identify key stress events and moderators that influenced well-being during and after the ICU admission. This study was guided by the Chronic Traumatic Stress Framework conceptual model, and data were analyzed using the five-step framework approach.
Among 21 interviewees, the mean age was 58 years, 67% were female, and 76% were White. Nearly half of patients (47%) had died before the caregiver interview. At the time of the interview, 9 caregivers endorsed an overall sense of distress, 10 endorsed a sense of wellness, and 2 endorsed a mix of both. Caregivers defined their experiences of wellness and distress as multidimensional and composed of four main elements:
) positive versus negative physical and psychological outcomes,
) high versus low capacity for self-care,
) thriving versus struggling in the caregiving role, and
) a sense of normalcy versus ongoing life disruption. Postdischarge support from family, friends, and the community at large played a key role in moderating caregiver outcomes.
Caregiver wellness and distress are multidimensional and extend beyond the absence or presence of psychological outcomes. Future intervention research should incorporate novel outcome measures that include elements of self-efficacy, preparedness, and adaptation and optimize postdischarge support for family caregivers.
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