Detection of the nearest Jupiter analog in radial velocity and astrometry data

© 2019 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society.The presence of Jupiter is crucial to the architecture of the Solar System and models underline this to be a generic feature of planetary systems. We find the detection of the difference between the position and motion recorded by the contemporary astrometric satellite Gaia and its precursor Hipparcos can be used to discover Jupiter-like planets. We illustrate how observations of the nearby star $\varepsilon$ Indi A giving astrometric and radial velocity data can be used to independently find the orbit of its suspected companion. The radial velocity and astrometric data provide complementary detections which allow for a much stronger solution than either technique would provide individually. We quantify $\varepsilon$ Indi A b as the closest Jupiter-like exoplanet with a mass of 3 $M_{Jup}$ on a slightly eccentric orbit with an orbital period of 45 yr. While other long-period exoplanets have been discovered, $\varepsilon$ Indi A b provides a well constrained mass and along with the well-studied brown dwarf binary in orbit around $\varepsilon$ Indi A means that the system provides a benchmark case for our understanding of the formation of gas giant planets and brown dwarfs.Peer reviewe

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice

Insulin resistance and impaired glucose homoeostasis are important indicators of Type 2 diabetes and are early risk factors of AD (Alzheimer's disease). An essential feature of AD pathology is the presence of BACE1 (β-site amyloid precursor protein-cleaving enzyme 1), which regulates production of toxic amyloid peptides. However, whether BACE1 also plays a role in glucose homoeostasis is presently unknown. We have used transgenic mice to analyse the effects of loss of BACE1 on body weight, and lipid and glucose homoeostasis. BACE1−/− mice are lean, with decreased adiposity, higher energy expenditure, and improved glucose disposal and peripheral insulin sensitivity than wild-type littermates. BACE1−/− mice are also protected from diet-induced obesity. BACE1-deficient skeletal muscle and liver exhibit improved insulin sensitivity. In a skeletal muscle cell line, BACE1 inhibition increased glucose uptake and enhanced insulin sensitivity. The loss of BACE1 is associated with increased levels of UCP1 (uncoupling protein 1) in BAT (brown adipose tissue) and UCP2 and UCP3 mRNA in skeletal muscle, indicative of increased uncoupled respiration and metabolic inefficiency. Thus BACE1 levels may play a critical role in glucose and lipid homoeostasis in conditions of chronic nutrient excess. Therefore strategies that ameliorate BACE1 activity may be important novel approaches for the treatment of diabetes

Telemonitoring in Chronic Obstructive Pulmonary Disease (CHROMED). A Randomized Clinical Trial

Rationale: Early detection of COPD exacerbations using tele-monitoring of physiological variables might reduce the frequency of hospitalisation. Objectives: To evaluate the efficacy of home monitoring of lung mechanics by the forced oscillation technique (FOT) and cardiac parameters in older COPD patients with co-morbidities. Methods: This multicentre, randomized clinical trial recruited 312 GOLD grade II-IV COPD patients (median age 71 years [IQR:66-76], 49.6% grade II, 50.4% grade III-IV), with a history of exacerbation in the previous year and at least one non-pulmonary co-morbidity. Patients were randomised to usual care (n=158) or tele-monitoring (n=154) and followed for 9 months. All tele-monitoring patients self-assessed lung mechanics daily and in a subgroup with congestive heart failure (n=37) cardiac parameters were also monitored. An algorithm identified deterioration, triggering a telephone contact to determine appropriate interventions. Measurements and Main results: Primary outcomes were time to first hospitalisation (TTFH) and change in EQ-5D utility index score. Secondary outcomes included: rate of antibiotic/corticosteroid prescriptions, hospitalisation, CAT, PHQ-9 and MLHF questionnaire scores, quality-adjusted life years and healthcare costs. Tele-monitoring did not affect TTFH, EQ-5D utility index score, antibiotic prescriptions, hospitalization rate and questionnaire scores. In an exploratory analysis, tele-medicine was associated with fewer repeat hospitalizations (-54%, p=0.017). Conclusions: In older COPD patients with co-morbidities remote monitoring of lung function by FOT and cardiac parameters did not change TTFH and EQ-5D. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01960907

Randomised controlled trial of telemonitoring with addition of daily forced oscillation in older people with COPD and co-morbidity

Evidence of clinical benefit and cost-effectiveness from daily symptom and simple telemonitoring in COPD is unproven. The CHROMED study explored the effect of telemonitoring in older people with COPD and significant co-morbidity who performed daily forced oscillation measurements via RESMON PRO DIARY to identify early physiological change associated with an exacerbation. Six centres in 5 countries randomised 312 people to 9 months telemonitoring (154) or daily symptom questionnaires (158). Each day the monitored group recorded symptoms, pulse, BP, oxygen saturation and airway resistance and reactance. An alert was generated if results exceeded pre-determined parameters and the participant was contacted by their local clinical centre to consider additional treatment. Baseline characteristics were evenly matched: mean age 71 years, FEV1 1.3L (50% predicted) and SGRQ score 49. 61% of subjects had 2+ exacerbations and 42% had been hospitalised in the previous year. Time to first hospitalisation did not differ albeit the monitoring group had fewer hospitalisations (79 vs 103; p=ns) and days in hospital (329 vs. 650; p=ns). However, subjects hospitalized with an AE COPD in the previous year (n=128) had a lower hospitalisation rate (p<0.04). Quality of life (EQ-5D) and health status (CAT) did not differ between groups. Mean cost in the monitored group was marginally lower (€4,615 vs €4,831; p=ns). Telemonitoring including daily forced oscillation impacted neither time to first hospitalisation nor health status. Reduction in hospitalisation rate in subjects with previous hospitalisation suggests these individuals may benefit from telemonitoring and earlier treatment

SwarmDock and the Use of Normal Modes in Protein-Protein Docking

Here is presented an investigation of the use of normal modes in protein-protein docking, both in theory and in practice. Upper limits of the ability of normal modes to capture the unbound to bound conformational change are calculated on a large test set, with particular focus on the binding interface, the subset of residues from which the binding energy is calculated. Further, the SwarmDock algorithm is presented, to demonstrate that the modelling of conformational change as a linear combination of normal modes is an effective method of modelling flexibility in protein-protein docking

Lung function assessed by home forced oscillation and self reported symptoms during COPD exacerbations

CHROMED (clinical trials for elderly people with multiple diseases, www.chromed.eu) is an EU-funded project involving 9 partners from 7 European countries aimed at evaluating the impact of a new home care approach to reduce costs and improve quality of life in elderly patients with COPD and comorbidity. The trial involves 300 patients with a prior history of exacerbations randomly assigned to a monitoring or observational arm. Monitored patients performed daily self-assessment of lung mechanics with a FOT (Forced Oscillation Technique) device (RESMON PRO DIARY, Restech srl, Italy) and completed a symptom diary card on touchscreen device (HOME PATIENT MONITOR, EBM srl, Italy). Any detected worsening in lung mechanics generated an alert triggering a phone interview directed at verifying the patient's status and optimizing treatment. By the end of March 2015, 70 monitored patients had completed the trial resulting in 16198 measurements with an adherence of 90.1%. Based on lung mechanics, 311 worsening events were detected, resulting in 0.65±0.3 alerts/patient/month. At least one major symptom (dyspnea, sputum purulence and volume) was reported in 70% of events and 41% were associated with an exacerbation according to diary cards (Seemungal et al., Am J Respir Crit Care Med 1998). A total of 77 exacerbations were confirmed during the phone interview and treated, but 48% of them were not associated with an exacerbation defined by diary cards only. These results suggest that a significant percentage of exacerbations cannot be identified by diary cards only. Self-assessment of lung mechanics using FOT provides complementary information which can be useful to manage COPD patients at home

Finding the Cell Center by a Balance of Dynein and Myosin Pulling and Microtubule Pushing: A Computational Study

By comparing computer modeling predictions with observations, we conclude that strong dynein and weaker myosin-generated forces pull the microtubules inward competing with microtubule plus-ends pushing the microtubule aster outward and that the balance of these forces positions the centrosome at the cell center

The Role of Actin Turnover in Retrograde Actin Network Flow in Neuronal Growth Cones

The balance of actin filament polymerization and depolymerization maintains a steady state network treadmill in neuronal growth cones essential for motility and guidance. Here we have investigated the connection between depolymerization and treadmilling dynamics. We show that polymerization-competent barbed ends are concentrated at the leading edge and depolymerization is distributed throughout the peripheral domain. We found a high-to-low G-actin gradient between peripheral and central domains. Inhibiting turnover with jasplakinolide collapsed this gradient and lowered leading edge barbed end density. Ultrastructural analysis showed dramatic reduction of leading edge actin filament density and filament accumulation in central regions. Live cell imaging revealed that the leading edge retracted even as retrograde actin flow rate decreased exponentially. Inhibition of myosin II activity before jasplakinolide treatment lowered baseline retrograde flow rates and prevented leading edge retraction. Myosin II activity preferentially affected filopodial bundle disassembly distinct from the global effects of jasplakinolide on network turnover. We propose that growth cone retraction following turnover inhibition resulted from the persistence of myosin II contractility even as leading edge assembly rates decreased. The buildup of actin filaments in central regions combined with monomer depletion and reduced polymerization from barbed ends suggests a mechanism for the observed exponential decay in actin retrograde flow. Our results show that growth cone motility is critically dependent on continuous disassembly of the peripheral actin network

Season of Sampling and Season of Birth Influence Serotonin Metabolite Levels in Human Cerebrospinal Fluid

BACKGROUND: Animal studies have revealed seasonal patterns in cerebrospinal fluid (CSF) monoamine (MA) turnover. In humans, no study had systematically assessed seasonal patterns in CSF MA turnover in a large set of healthy adults. METHODOLOGY/PRINCIPAL FINDINGS: Standardized amounts of CSF were prospectively collected from 223 healthy individuals undergoing spinal anesthesia for minor surgical procedures. The metabolites of serotonin (5-hydroxyindoleacetic acid, 5-HIAA), dopamine (homovanillic acid, HVA) and norepinephrine (3-methoxy-4-hydroxyphenylglycol, MPHG) were measured using high performance liquid chromatography (HPLC). Concentration measurements by sampling and birth dates were modeled using a non-linear quantile cosine function and locally weighted scatterplot smoothing (LOESS, span = 0.75). The cosine model showed a unimodal season of sampling 5-HIAA zenith in April and a nadir in October (p-value of the amplitude of the cosine = 0.00050), with predicted maximum (PC(max)) and minimum (PC(min)) concentrations of 173 and 108 nmol/L, respectively, implying a 60% increase from trough to peak. Season of birth showed a unimodal 5-HIAA zenith in May and a nadir in November (p = 0.00339; PC(max) = 172 and PC(min) = 126). The non-parametric LOESS showed a similar pattern to the cosine in both season of sampling and season of birth models, validating the cosine model. A final model including both sampling and birth months demonstrated that both sampling and birth seasons were independent predictors of 5-HIAA concentrations. CONCLUSION: In subjects without mental illness, 5-HT turnover shows circannual variation by season of sampling as well as season of birth, with peaks in spring and troughs in fall