An ALMA Constraint on the GSC 6214-210 B Circum-Substellar Accretion Disk Mass

We present Atacama Large Millimeter/submillimeter Array (ALMA) observations of GSC 6214-210 A and B, a solar-mass member of the 5-10 Myr Upper Scorpius association with a 15 $\pm$ 2 Mjup companion orbiting at $\approx$330 AU (2.2"). Previous photometry and spectroscopy spanning 0.3-5 $\mu$m revealed optical and thermal excess as well as strong H$\alpha$ and Pa~$\beta$ emission originating from a circum-substellar accretion disk around GSC 6214-210 B, making it the lowest mass companion with unambiguous evidence of a subdisk. Despite ALMA's unprecedented sensitivity and angular resolution, neither component was detected in our 880 $\mu$m (341 GHz) continuum observations down to a 3-$\sigma$ limit of 0.22 mJy/beam. The corresponding constraints on the dust mass and total mass are <0.15 Mearth and <0.05 Mjup, respectively, or <0.003% and <0.3% of the mass of GSC 6214-210 B itself assuming a 100:1 gas-to-dust ratio and characteristic dust temperature of 10-20 K. If the host star possesses a putative circum-stellar disk then at most it is a meager 0.0015% of the primary mass, implying that giant planet formation has certainly ceased in this system. Considering these limits and its current accretion rate, GSC 6214-210 B appears to be at the end stages of assembly and is not expected to gain any appreciable mass over the next few Myr.Comment: Accepted to ApJ

Phosphorothioate Anti-sense Oligonucleotides: The Kinetics and Mechanism of the Generation of the Sulfurising Agent from Phenylacetyl Disulfide (PADS)

The synthesis of phosphorothioate oligonucleotides is often accomplished in the pharmaceutical industry by the sulfurisation of the nucleotide-phosphite using phenylacetyl disulfide (PADS) which has an optimal combination of properties. This is best achieved by an initial ‘ageing’ of PADS for 48 hrs in acetonitrile with 3-picoline to generate polysulfides. The initial base-catalysed degradation of PADS occurs by an E1cB-type elimination to generate a ketene and acyldisulfide anion. Proton abstraction to reversibly generate a carbanion is demonstrated by H/D exchange, the rate of which is greatly increased by electron-withdrawing substituents in the aromatic ring of PADS. The ketene can be trapped intramolecularly by an o-allyl group. The disulfide anion generated subsequently attacks unreacted PADS on sulfur to give polysulfides, the active sulfurising agent. The rate of degradation of PADS is decreased by less basic substituted pyridines and is only first order in PADS indicating that the rate-limiting step is formation of the disulfide anion from the carbanion

Protoplanetary Disk Masses in the Young NGC 2024 Cluster

We present the results from a Submillimeter Array survey of the 887 micron continuum emission from the protoplanetary disks around 95 young stars in the young cluster NGC 2024. Emission was detected from 22 infrared sources, with flux densities from ~5 to 330 mJy; upper limits (at 3sigma) for the other 73 sources range from 3 to 24 mJy. For standard assumptions, the corresponding disk masses range from ~0.003 to 0.2Msolar, with upper limits at 0.002--0.01Msolar. The NGC 2024 sample has a slightly more populated tail at the high end of its disk mass distribution compared to other clusters, but without more information on the nature of the sample hosts it remains unclear if this difference is statistically significant or a superficial selection effect. Unlike in the Orion Trapezium, there is no evidence for a disk mass dependence on the (projected) separation from the massive star IRS2b in the NGC 2024 cluster. We suggest that this is due to either the cluster youth or a comparatively weaker photoionizing radiation field.Comment: ApJ, in pres

Health Care Professionals’ Views on Using Remote Measurement Technology in Managing Central Nervous System Disorders: Qualitative Interview Study

Background: Remote measurement technologies (RMT) can be used to collect data on a variety of bio-behavioral variables, which may improve the care of patients with central nervous system disorders. Although various studies have explored their potential, prior work has highlighted a knowledge gap in health care professionals’ (HCPs) perceptions of the value of RMT in clinical practice.Objective: This study aims to understand HCPs’ perspectives on using RMT in health care practice for the care of patients with depression, epilepsy, or multiple sclerosis (MS).Methods: Semistructured interviews were conducted with 26 multidisciplinary primary and secondary care HCPs who care for patients with epilepsy, depression, or MS. Interviews were transcribed verbatim and analyzed using thematic analysis.Results: A total of 8 main themes emerged from the analysis: (1) potential clinical value of RMT data; (2) when to use RMT in care pathways; (3) roles of health care staff who may use RMT data; (4) presentation and accessibility of data; (5) obstacles to successful use of RMT; (6) limits to the role of RMT; (7) empowering patients; and (8) considerations around alert-based systems.Conclusions: RMT could add value to the system of care for patients with central nervous system disorders by providing clinicians with graphic summaries of data in the patient record. Barriers of both technical and human nature should be considered when using these technologies, as should the limits to the benefits they can offer

Phosphonodifluoropyruvate is a mechanism-based inhibitor of phosphonopyruvate decarboxylase from Bacteroides fragilis

Bacteroides fragilis, a human pathogen, helps in the formation of intra-abdominal abscesses and is involved in 90% of anaerobic peritoneal infections. Phosphonopyruvate decarboxylase (PnPDC), a thiamin diphosphate (ThDP)-dependent enzyme, plays a key role in the formation of 2-aminoethylphosphonate, a component of the cell wall of B. fragilis. As such PnPDC is a possible target for therapeutic intervention in this, and other phosphonate producing organisms. However, the enzyme is of more general interest as it appears to be an evolutionary forerunner to the decarboxylase family of ThDP-dependent enzymes. To date, PnPDC has proved difficult to crystallize and no X-ray structures are available. In the past we have shown that ThDP-dependent enzymes will often crystallize if the cofactor has been irreversibly inactivated. To explore this possibility, and the utility of inhibitors of phosphonate biosynthesis as potential antibiotics, we synthesized phosphonodifluoropyruvate (PnDFP) as a prospective mechanism-based inhibitor of PnPDC. Here we provide evidence that PnDFP indeed inactivates the enzyme, that the inactivation is irreversible, and is accompanied by release of fluoride ion, i.e., PnDFP bears all the hallmarks of a mechanism-based inhibitor. Unfortunately, the enzyme remains refractive to crystallization

Mechanisms Underlying the Morning Increase in Platelet Aggregation: A Flow Cytometry Study

ObjectivesMechanisms underlying the morning increase in platelet aggregation produced by arising and assuming the upright posture were studied by examining 1) the expression on the platelet surface of activation-dependent markers; 2) platelet aggregation in whole blood; and 3) hematologic factors likely to influence aggregation.BackgroundThe morning increase in thrombotic cardiovascular events has been attributed, in part, to the morning surge in platelet aggregability, but its mechanisms are poorly understood.MethodsExpression of seven platelet surface antigens (including P-selectin, activated GPIIb-IIIa and GPIb-IX), whole-blood platelet aggregation, platelet count and hematocrit were measured before and after arising in 17 normal volunteers. The fibrinolytic variables, tissue-type plasminogen activator, plasminogen activator inhibitor 1 and catecholamine levels were also measured.ResultsOn arising and standing, platelet aggregation increased by 71% (p ≤ 0.01) and 27% (p ≤ 0.03) in response to collagen and adenosine diphosphate, respectively. However, there was no change in any of the activation-dependent platelet surface markers. Whole-blood platelet count and hematocrit increased by 15% and 7% (both p < 0.0001), respectively. Norepinephrine and epinephrine levels increased by 189% (p < 0.0001) and 130% (p < 0.01), respectively. Tissue-type plasminogen activator antigen increased (31%, p < 0.01), but there was no significant increase in plasminogen activator inhibitor 1, suggesting an overall increase in fibrinolysis on standing. Prothrombin fragment 1.2 increased by 28% (p < 0.02), indicating a small increase in thrombin generation. The increases in hematocrit and platelet count that occurred on standing were carefully mimicked in vitro and resulted in a 115% (p < 0.05) increase in platelet aggregation in response to adenosine diphosphate.ConclusionsThese data demonstrate that the morning increase in platelet aggregation is not accompanied by expression of activation-dependent platelet surface receptors and suggest that the increase in whole-blood aggregation may be primarily due to the increases in catecholamine levels, platelet count and hemocon-centration

Observation of ultrafast internal conversion in fullerene anions in solution

The ultrafast decay rates of photoexcited View the MathML source ions have been measured in the condensed phase. The mechanism for decay is internal conversion, and the decay rate is a strong function of the charge on the ion. A bottleneck in the ground state recovery has also been detected, and its interpretation is discussed

Submillimeter Array Observations of the RX J1633.9-2442 Transition Disk: Evidence for Multiple Planets in the Making

We present continuum high resolution Submillimeter Array (SMA) observations of the transition disk object RX J1633.9-2442, which is located in the Ophiuchus molecular cloud and has recently been identified as a likely site of ongoing giant planet formation. The observations were taken at 340 GHz (880 micron) with the SMA in its most extended configuration, resulting in an angular resolution of 0.3" (35 AU at the distance of the target). We find that the disk is highly inclined (i ~50 deg) and has an inner cavity ~25 AU in radius, which is clearly resolved by our observations. We simultaneously model the entire optical to millimeter wavelength spectral energy distribution (SED) and SMA visibilities of RX J1633.9-2442 in order to constrain the structure of its disk. We find that an empty cavity ~25 AU in radius is inconsistent with the excess emission observed at 12, 22, and 24 micron. Instead, the mid-IR excess can be modeled by either a narrow, optically thick ring at ~10 AU or an optically thin region extending from ~7 AU to ~25 AU. The inner disk (r < 5 AU) is mostly depleted of small dust grains as attested by the lack of detectable near-IR excess. We also present deep Keck aperture masking observations in the near-IR, which rule out the presence of a companion up to 500 times fainter than the primary star (in K-band) for projected separations in the 5-20 AU range. We argue that the complex structure of the RX J1633.9-2442 disk is best explained by multiple planets embedded within the disk. We also suggest that the properties and incidence of objects such as RX J1633.9-2442, T Cha, and LkCa 15 (and those of the companions recently identified to these two latter objects) are most consistent with the runaway gas accretion phase of the core accretion model, when giant planets gain their envelopes and suddenly become massive enough to open wide gaps in the disk.Comment: Accepted for publication in Ap

An ALMA Disk Mass for the Candidate Protoplanetary Companion to FW Tau

We present ALMA observations of the FW Tau system, a close binary pair of M5 stars with a wide-orbit (300 AU projected separation) substellar companion. The companion is extremely faint and red in the optical and near-infrared, but boasts a weak far-infrared excess and optical/near-infrared emission lines indicative of a primordial accretion disk of gas and dust. The component-resolved 1.3 mm continuum emission is found to be associated only with the companion, with a flux (1.78 +/- 0.03 mJy) that indicates a dust mass of 1-2 M_Earth. While this mass reservoir is insufficient to form a giant planet, it is more than sufficient to produce an analog of the Kepler-42 exoplanetary system or the Galilean satellites. The mass and geometry of the disk-bearing FW Tau companion remains unclear. Near-infrared spectroscopy shows deep water bands that indicate a spectral type later than M5, but substantial veiling prevents a more accurate determination of the effective temperature (and hence mass). Both a disk-bearing "planetary-mass" companion seen in direct light or a brown dwarf tertiary viewed in light scattered by an edge-on disk or envelope remain possibilities.Comment: 5 pages, 2 figures; accepted to ApJ

“It just makes me feel a little less alone” a qualitative exploration of the podcast “menopause unmuted” on women's perceptions of menopause

Objective: Menopause can negatively impact women's quality of life, with many women reporting inadequate information and support. Podcasts have grown in popularity in recent years and have been found to be accessible methods for increasing knowledge and challenging perceptions of stigmatized topics. The current research aimed to understand the impact of the podcast “menopause: unmuted” on women's menopause-related knowledge, understanding, and communication practices. Methods: A diverse sample of 30 women aged 40 to 60 years listened to the podcast series, which focused on menopause stories, before taking part in semistructured interviews to discuss the impact of the podcast on how they understood and communicated about menopause. The interviews were analyzed thematically. Results: Two overarching themes were identified in the data. A “journey of knowledge gain” explores participants’ understanding of menopause before listening to the podcast and describes how this is deepened by hearing and connecting with women's stories. “Reframing menopause” describes the impact of the podcast, where women reflect on the value of communication amongst women, challenge and re-evaluate the stigmatization of menopause, and discuss ways to make positive behavioral changes in their lives. Conclusions: The podcast “menopause: unmuted” helped women to learn about the menopause experience, have a greater sense of belonging to a community of women, and feel empowered to make changes in their own lives. Sharing stories via podcasts has potential as an accessible and impactful medium to educate women and reduce the widespread stigma associated with menopause