The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

The GAPS Experiment to Search for Dark Matter using Low-energy Antimatter

The GAPS experiment is designed to carry out a sensitive dark matter search by measuring low-energy cosmic ray antideuterons and antiprotons. GAPS will provide a new avenue to access a wide range of dark matter models and masses that is complementary to direct detection techniques, collider experiments and other indirect detection techniques. Well-motivated theories beyond the Standard Model contain viable dark matter candidates which could lead to a detectable signal of antideuterons resulting from the annihilation or decay of dark matter particles. The dark matter contribution to the antideuteron flux is believed to be especially large at low energies (E < 1 GeV), where the predicted flux from conventional astrophysical sources (i.e. from secondary interactions of cosmic rays) is very low. The GAPS low-energy antiproton search will provide stringent constraints on less than 10 GeV dark matter, will provide the best limits on primordial black hole evaporation on Galactic length scales, and will explore new discovery space in cosmic ray physics. Unlike other antimatter search experiments such as BESS and AMS that use magnetic spectrometers, GAPS detects antideuterons and antiprotons using an exotic atom technique. This technique, and its unique event topology, will give GAPS a nearly background-free detection capability that is critical in a rare-event search. GAPS is designed to carry out its science program using long-duration balloon flights in Antarctica. A prototype instrument was successfully flown from Taiki, Japan in 2012. GAPS has now been approved by NASA to proceed towards the full science instrument, with the possibility of a first long-duration balloon flight in late 2020. Here we motivate low-energy cosmic ray antimatter searches and discuss the current status of the GAPS experiment and the design of the payload.Comment: 8 pags, 3 figures, Proc. 35th International Cosmic Ray Conference (ICRC 2017), Busan, Kore

Multi-colony tracking reveals segregation in foraging range, space use, and timing in a tropical seabird

Colonial animals experience density-dependent competition for food, which is posited to influence foraging range and lead to inter-colony segregation. However, such patterns are poorly studied in the tropics, where predictable day lengths, oligotrophic conditions, and facultative foraging may alter the relationships between foraging and intra-specific competition. Here, we GPS-tracked 207 breeding red-footed boobies Sula sula rubripes (RFB) from 4 neighbouring Chagos Archipelago colonies (~1100 to 9200 breeding pairs) in the central Indian Ocean, to determine how foraging strategies (i.e. effort, segregation, and timing) vary with colony, while accounting for sex, monsoon season, stage of reproduction, year, and individual. During incubation and chick-rearing, RFBs commute to pelagic foraging grounds (maximum distance mean ± SE: 112.9 ± 3.7 km; total distance: 298.4 ± 6.2 km) over 1 to 5 d (18.5 ± 1.6 h). Foraging effort was highest at the largest colony, and greater among females than males. Departure angles varied among colonies, leading to foraging areas that were largely spatially segregated. Timing of departures and arrivals were strongly constrained by daylight hours, although females and birds at the largest colony left earliest. Our study highlights the importance of inter-colony differences in tropical seabird foraging, which may relate to different levels of intra-specific competition. Moreover, links between foraging times and colony size suggest a previously undescribed outcome of density-dependent competition, highlighting the importance of understanding colonial living across multiple dimensions.</jats:p

Comparison of breast and bowel cancer screening uptake patterns in a common cohort of South Asian women in England

Background: Inequalities in uptake of cancer screening by ethnic minority populations are well documented in a number of international studies. However, most studies to date have explored screening uptake for a single cancer only. This paper compares breast and bowel cancer screening uptake for a cohort of South Asian women invited to undertake both, and similarly investigates these women's breast cancer screening behaviour over a period of fifteen years. Methods: Screening data for rounds 1, 2 and 5 (1989-2004) of the NHS breast cancer screening programme and for round 1 of the NHS bowel screening pilot (2000-2002) were obtained for women aged 50-69 resident in the English bowel screening pilot site, Coventry and Warwickshire, who had been invited to undertake breast and bowel cancer screening in the period 2000-2002. Breast and bowel cancer screening uptake levels were calculated and compared using the chi-squared test. Results: 72,566 women were invited to breast and bowel cancer screening after exclusions. Of these, 3,539 were South Asian and 69,027 non-Asian; 18,730 had been invited to mammography over the previous fifteen years (rounds 1 to 5). South Asian women were significantly less likely to undertake both breast and bowel cancer screening; 29.9% (n = 1,057) compared to 59.4% (n = 40,969) for non-Asians (p < 0.001). Women in both groups who consistently chose to undertake breast cancer screening in rounds 1, 2 and 5 were more likely to complete round 1 bowel cancer screening. However, the likelihood of completion of bowel cancer screening was still significantly lower for South Asians; 49.5% vs. 82.3% for non-Asians, p < 0.001. South Asian women who undertook breast cancer screening in only one round were no more likely to complete bowel cancer screening than those who decided against breast cancer screening in all three rounds. In contrast, similar women in the non-Asian population had an increased likelihood of completing the new bowel cancer screening test. The likelihood of continued uptake of mammography after undertaking screening in round 1 differed between South Asian religio-linguistic groups. Noticeably, women in the Muslim population were less likely to continue to participate in mammography than those in other South Asian groups. Conclusions: Culturally appropriate targeted interventions are required to reduce observed disparities in cancer screening uptakes

Storytelling as 'unorthodox' agency:negotiating the 2012 family immigration rules (United Kingdom)

This article attends to the lived experience of binational families subject to the 2012 family immigration rules (FIR). It seeks to enrich the pre-existing discussions of family migration within the European Union (EU) and the United Kingdom, focusing on the ‘micro-political’ experiences of those whose lives have been adversely affected by their introduction. It draws on the life writings of binational families, suggesting that a micro-political focus reveals an ongoing neuropolitical experience that traditional accounts of moral agency are ill-equipped to negotiate. The article suggests an unorthodox interpretation of agency premised on storytelling, while probing the tensions that emerge when this lived experience is framed in such a manner. It concludes by positing a series of questions relating to the value of a neuropolitical labelling of the subject and suggests a need to further engage with traumatic interpretations of harm at the intersection of citizenship rights and mobility rights

The effects of migrant remittances on population–environment dynamics in migrant origin areas: international migration, fertility, and consumption in highland Guatemala

International migration impacts origin regions in many ways. As examples, remittances from distant migrants may alter consumption patterns within sending communities, while exposure to different cultural norms may alter other behaviors. This paper combines these insights to offer a unique lens on migration’s environmental impact. From an environmental perspective, we ask the following question: is the likely rise in consumption brought about by remittances counterbalanced by a reduction in fertility in migrant households following exposure to lower fertility cultures? Based on ethnographic case studies in two western highland Guatemalan communities, we argue that the near-term rise in consumption due to remittances is not counterbalanced by rapid decline in migrant household fertility. However, over time, the environmental cost of consumption may be mitigated at the community level through diffusion of contraception and family planning norms yielding lower family size

Self-hypnosis for anxiety associated with severe asthma: a case report

BACKGROUND: Management of asthma can be complicated by both medical and psychiatric conditions, such as gastroesophageal reflux, chronic sinusitis, and anxiety. When symptoms of asthma are interpreted without regard to such conditions treatment may yield a suboptimal outcome. For example, anxiety-associated dyspnea, tachypnea, and chest tightness can be mistakenly interpreted as resulting from an exacerbation of asthma. Medical treatment directed only for asthma may thus lead to overuse of asthma medications and increased hospitalizations. CASE PRESENTATION: The described case illustrates how a systemic steroid-dependent patient with asthma benefited from receiving care from a pediatric pulmonologist who also was well versed in the diagnosis and treatment of anxiety. By using self-hypnosis, the patient was able to reduce her dependence on bronchodilators. Following modification of her medical therapy under supervision of the pulmonologist, and regular use of hypnosis, the patient ultimately was weaned off her systemic steroid therapy. CONCLUSIONS: This report emphasizes that anxiety must be considered as a comorbid condition in the treatment of asthma. Self-hypnosis can be a useful skill in the treatment of a patient with anxiety and asthma