Episodic mass ejections from common-envelope objects

After the initial fast spiral-in phase experienced by a common-envelope binary, the system may enter a slow, self-regulated phase, possibly lasting 100s of years, in which all the energy released by orbital decay can be efficiently transported to the surface, where it is radiated away. If the remaining envelope is to be removed during this phase, this removal must occur through some as-yet-undetermined mechanism. We carried out 1-d hydrodynamic simulations of a low-mass red giant undergoing a synthetic common-envelope event in such a slow spiral-in phase, using the stellar evolutionary code MESA. We simulated the heating of the envelope due to frictional dissipation from a binary companion's orbit in multiple configurations and investigated the response of the giant's envelope. We find that our model envelopes become dynamically unstable and develop large-amplitude pulsations, with periods in the range 3-20 years and very short growth time-scales of similar order. The shocks and associated rebounds that emerge as these pulsations grow are in some cases strong enough to dynamically eject shells of matter of up to 0.1 $\mathrm{M}_{\odot}$, $\sim 10$ % of the mass of the envelope, from the stellar surface at above escape velocity. These ejections are seen to repeat within a few decades, leading to a time-averaged mass-loss rate of order $10^{-3}$ $\mathrm{M}_{\odot} \: \mathrm{yr}^{-1}$ which is sufficiently high to represent a candidate mechanism for removing the entire envelope over the duration of the slow spiral-in phase.Comment: 24 pages, 15 figures. This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society, published by Oxford University Pres

Daughters do not affect political beliefs in a new democracy

A consistent finding in industrialized democracies is that having a daughter shapes parents' attitudes and behaviors in gender-egalitarian ways. We test whether this finding travels to a young middle-income democracy where women's rights are more tenuous: South Africa. Using a dataset of over 7,500 respondents with information on family structure, we find no discernible effect on attitudes about women's rights or on partisan identification. We speculate that our null findings relate to opportunity: daughter effects are more likely when parents perceive economic, social, and political opportunities for women. When women's customary status and de facto opportunities are low, as in South Africa, having a daughter may have no effect on parents' political behavior. Our results demonstrate the virtues of diversifying case selection in political behavior beyond economically wealthy democracies

How Does the Canadian General Public Rate Moderate Alzheimer's Disease?

Objectives. The objectives of this study were to elicit health utility scores for moderate Alzheimer's disease (AD) using members of the general public. Methods. Five-hundred Canadians were chosen randomly to participate in a telephone interview. The EQ-5D was administered to estimate the health utility score for respondents' current health status (i.e., no AD) and for a hypothetical moderate AD health state. Regression analyses were conducted to explain the perceived utility decrement associated with AD. Results. The mean age of the respondents was 51 years, 60% were female, and 42% knew someone with AD. Respondents' mean EQ-5D scores for their current health status and a hypothetical moderate AD were 0.873 (SD: 0.138) and 0.638 (SD: 0.194), respectively (P < 0.001). Age, gender, and education were significant factors explaining this decrement in utility. Conclusion. Members of the general public may serve as an alternative to patients and caregivers in the elicitation of health-related quality of life in AD

Inhibition of Ral GTPases Using a Stapled Peptide Approach

Aberrant Ras signalling drives numerous cancers and drugs to inhibit this are urgently required. This compelling clinical need, combined with recent innovations in drug discovery including the advent of biologic therapeutic agents, has propelled Ras back to the forefront of targeting efforts. Activated Ras has proved extremely difficult to target directly and the focus has moved to the main downstream Ras-signalling pathways. In particular, the Ras-Raf and Ras-PI3K pathways have provided conspicuous enzyme therapeutic targets, which were more accessible to conventional drug-discovery strategies. The Ras-RalGEF-Ral pathway is a more difficult challenge for traditional medicinal development and there have therefore been few inhibitors reported that disrupt this axis. We have used our structure of a Ral-effector complex as a basis for the design and characterization of α-helical stapled peptides that bind selectively to active, GTP-bound Ral proteins and that compete with downstream effector proteins. The peptides have been thoroughly characterized biophysically. Crucially, the lead peptide enters cells and is biologically active, inhibiting isoform-specific RalB-driven cellular processes. This therefore provides a starting point for therapeutic inhibition of the Ras-RalGEF-Ral pathway.This work was supported by a Cambridge Cancer Centre Pump Priming award to CA, DO and HRM, a BBSRC Studentship to NSC, and a National Institutes for Health grant (CA71443) and the Welch Foundation (grant number I-1414) to MAW.This is the final version of the article. It first appeared from the American Society for Biochemistry and Molecular Biology via https://doi.org/10.1074/jbc.M116.72024

Inhibition of Ral GTPases Using a Stapled Peptide Approach.

Aberrant Ras signaling drives numerous cancers, and drugs to inhibit this are urgently required. This compelling clinical need combined with recent innovations in drug discovery including the advent of biologic therapeutic agents, has propelled Ras back to the forefront of targeting efforts. Activated Ras has proved extremely difficult to target directly, and the focus has moved to the main downstream Ras-signaling pathways. In particular, the Ras-Raf and Ras-PI3K pathways have provided conspicuous enzyme therapeutic targets that were more accessible to conventional drug-discovery strategies. The Ras-RalGEF-Ral pathway is a more difficult challenge for traditional medicinal development, and there have, therefore, been few inhibitors reported that disrupt this axis. We have used our structure of a Ral-effector complex as a basis for the design and characterization of α-helical-stapled peptides that bind selectively to active, GTP-bound Ral proteins and that compete with downstream effector proteins. The peptides have been thoroughly characterized biophysically. Crucially, the lead peptide enters cells and is biologically active, inhibiting isoform-specific RalB-driven cellular processes. This, therefore, provides a starting point for therapeutic inhibition of the Ras-RalGEF-Ral pathway.This work was supported by a Cambridge Cancer Centre Pump Priming award to CA, DO and HRM, a BBSRC Studentship to NSC, and a National Institutes for Health grant (CA71443) and the Welch Foundation (grant number I-1414) to MAW.This is the final version of the article. It first appeared from the American Society for Biochemistry and Molecular Biology via https://doi.org/10.1074/jbc.M116.72024

Data and Digital Solutions to Support Surveillance Strategies in the Context of the COVID-19 Pandemic

Background: In order to prevent spread and improve control of infectious diseases, public health experts need to closely monitor human and animal populations. Infectious disease surveillance is an established, routine data collection process essential for early warning, rapid response, and disease control. The quantity of data potentially useful for early warning and surveillance has increased exponentially due to social media and other big data streams. Digital epidemiology is a novel discipline that includes harvesting, analysing, and interpreting data that were not initially collected for healthcare needs to enhance traditional surveillance. During the current COVID-19 pandemic, the importance of digital epidemiology complementing traditional public health approaches has been highlighted. Objective: The aim of this paper is to provide a comprehensive overview for the application of data and digital solutions to support surveillance strategies and draw implications for surveillance in the context of the COVID-19 pandemic and beyond. Methods: A search was conducted in PubMed databases. Articles published between January 2005 and May 2020 on the use of digital solutions to support surveillance strategies in pandemic settings and health emergencies were evaluated. Results: In this paper, we provide a comprehensive overview of digital epidemiology, available data sources, and components of 21st-century digital surveillance, early warning and response, outbreak management and control, and digital interventions. Conclusions: Our main purpose was to highlight the plausible use of new surveillance strategies, with implications for the COVID-19 pandemic strategies and then to identify opportunities and challenges for the successful development and implementation of digital solutions during non-emergency times of routine surveillance, with readiness for early-warning and response for future pandemics. The enhancement of traditional surveillance systems with novel digital surveillance methods opens a direction for the most effective framework for preparedness and response to future pandemics

Sexual Risk Behaviors of African American Adolescent Females: The Role of Cognitive and Religious Factors

Introduction: African American (AA) high school-age girls are more likely to have had sex before age 13 years and have higher rates of all sexually transmitted infections. Cognition and religion/spirituality are associated with adolescent sexuality, therefore, the purpose of this study was to identify cognitive and religious substrates of AA girls’ risky sexual behaviors. Method: A descriptive study was conducted with 65 AA girls aged 15 to 20 years using computerized questionnaires and cognitive function tasks. Results: Average age was 17.8 ± 1.9 years and average sexual initiation age was 15.5 ± 2.6 years. Overall, 57.6% reported a history of vaginal sex. Girls who reported low/moderate religious importance were significantly younger at vaginal sex initiation than girls for whom religion was very/extremely important. Girls who attended church infrequently reported significantly more sexual partners. Implications: Health care providers can use these findings to deliver culturally congruent health care by assessing and addressing these psychosocial factors in this population

The Natural History of Uterine Leiomyomas: Morphometric Concordance with Concepts of Interstitial Ischemia and Inanosis

Based upon our morphologic observations, we hypothesize and also provide morphometric evidence for the occurrence of progressive developmental changes in many uterine fibroids, which can be arbitrarily divided into 4 phases. These developmental phases are related to the ongoing production of extracellular collagenous matrix, which eventually exceeds the degree of angiogenesis, resulting in the progressive separation of myocytes from their blood supply and a condition of interstitial ischemia. The consequence of this process of slow ischemia with nutritional and oxygen deprivation is a progressive myocyte atrophy (or inanition), culminating in cell death, a process that we refer to as inanosis. The studies presented here provide quantitative and semiquantitative evidence to support the concept of the declining proliferative activity as the collagenous matrix increases and the microvascular density decreases

Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.

The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78 Å resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity