The Two Faces of the Liquid Ordered Phase

Coexisting liquid ordered (L-o) and liquid disordered (L-d) lipid phases in synthetic and plasma membrane-derived vesicles are commonly used to model the heterogeneity of biological membranes, including their putative ordered rafts. However, raft-associated proteins exclusively partition to the L-d and not the L-o phase in these model systems. We believe that the difference stems from the different microscopic structures of the lipid rafts at physiological temperature and the L-o phase studied at room temperature. To probe this structural diversity across temperatures, we performed atomistic molecular dynamics simulations, differential scanning calorimetry, and fluorescence spectroscopy on L-o phase membranes. Our results suggest that raftassociated proteins are excluded from the L-o phase at room temperature due to the presence of a stiff, hexagonally packed lipid structure. This structure melts upon heating, which could lead to the preferential solvation of proteins by order-preferring lipids. This structural transition is manifested as a subtle crossover in membrane properties; yet, both temperature regimes still fulfill the definition of the L-o phase. We postulate that in the compositionally complex plasma membrane and in vesicles derived therefrom, both molecular structures can be present depending on the local lipid composition. These structural differences must be taken into account when using synthetic or plasma membrane-derived vesicles as a model for cellular membrane heterogeneity below the physiological temperature.Peer reviewe

An empirical investigation of the dimensionality of the physical literacy environment in early childhood classrooms

This study investigated the dimensionality of the physical literacy environment of early childhood education classrooms. Data on the classroom physical literacy environment were collected from 245 classrooms using the Classroom Literacy Observation Profile. A combination of confirmatory and exploratory factor analysis was used to identify five separate dimensions of the physical literacy environment; including (a) variety and use of books, (b) variety and use of writing center materials, (c) variety and use of technology, (d) variety of environmental print and (e) variety and use of other literacy-related materials. Overall, these five dimensions demonstrated reasonable reliability and validity. Implications for investigating the physical literacy environment and future directions for research are discussed

1ES 0229+200: An extreme blazar with a very high minimum Lorentz factor

The blazar 1ES 0229+200 is a high frequency peaked BL Lac object with a hard TeV spectrum extending to 10 TeV. Its unusual spectral characteristics make it a frequently used probe for intergalactic radiation and magnetic fields. With new, simultaneous observations in the optical, ultraviolet (UV) and X-rays, the synchrotron emission is probed in great detail. The X-ray emission varies by a factor of ~2 in 2009, while being rather stable in 2010. The X-ray spectrum is very hard (\Gamma ~ 1.8) and it shows an indication of excess absorption above the Galactic value. The X-ray emission is detected up to ~100 keV without any significant cut-off, thus 1ES 0229+200 belongs to the class of extreme blazars. The simultaneous measured, host galaxy- and extinction-corrected optical and UV fluxes illustrate that the cut-off of the low energy part of the synchrotron emission is located in the UV regime. The minimum energy of the electron distribution has to be rather high to account for this cut-off. This implies that there is a narrow-band energy distribution function of radiating electrons, which is responsible for the unusually hard TeV spectrum. Other extreme blazars have similar synchrotron peak frequencies but much softer TeV spectra, hence 1ES 0229+200 has one of the highest inverse Compton (IC) peak frequency and the narrowest electron distribution among the extreme blazars known to date.Comment: accepted for publication in Astronomy&Astrophysic

Research on stress and smoking: progress and problems

Despite evidence that smoking behaviour increases in the context of stress, there has yet to be a clear-cut demonstration that nicotine intake is similarly enhanced. Although nicotine intake has been shown to reduce reported anxiety in the context of stress, the controlling conditions (type of stressor, intensity, temporal relationships, etc.) need further exploration. Recent findings involving nicotine's effects on the hypophyseal-adrenal axis provide a new perspective on these issues, in that increased nicotine intake during exposure to a stressor may represent, at least in part, behavioral compensation for diminished sensitivity to nicotine brought about by nicotine-stimulated corticosteroid release. Corticosteroids may decrease central nervous system excitability in a way that could account for anxiety reduction; on the other hand, anxiety reduction may be an epiphenomenon with respect to the reinforcement of smoking behaviour. The integration of behavioural, physiological, and biochemical research exemplified by the above approach should lead to a better understanding of stress and smoking.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73317/1/j.1360-0443.1991.tb01815.x.pd

An open-source deep learning algorithm for efficient and fully-automatic analysis of the choroid in optical coherence tomography

Purpose: To develop an open-source, fully-automatic deep learning algorithm, DeepGPET, for choroid region segmentation in optical coherence tomography (OCT) data. Methods: We used a dataset of 715 OCT B-scans (82 subjects, 115 eyes) from 3 clinical studies related to systemic disease. Ground truth segmentations were generated using a clinically validated, semi-automatic choroid segmentation method, Gaussian Process Edge Tracing (GPET). We finetuned a UNet with MobileNetV3 backbone pre-trained on ImageNet. Standard segmentation agreement metrics, as well as derived measures of choroidal thickness and area, were used to evaluate DeepGPET, alongside qualitative evaluation from a clinical ophthalmologist. Results: DeepGPET achieves excellent agreement with GPET on data from 3 clinical studies (AUC=0.9994, Dice=0.9664; Pearson correlation of 0.8908 for choroidal thickness and 0.9082 for choroidal area), while reducing the mean processing time per image on a standard laptop CPU from 34.49s ($\pm$15.09) using GPET to 1.25s ($\pm$0.10) using DeepGPET. Both methods performed similarly according to a clinical ophthalmologist, who qualitatively judged a subset of segmentations by GPET and DeepGPET, based on smoothness and accuracy of segmentations. Conclusions :DeepGPET, a fully-automatic, open-source algorithm for choroidal segmentation, will enable researchers to efficiently extract choroidal measurements, even for large datasets. As no manual interventions are required, DeepGPET is less subjective than semi-automatic methods and could be deployed in clinical practice without necessitating a trained operator. DeepGPET addresses the lack of open-source, fully-automatic and clinically relevant choroid segmentation algorithms, and its subsequent public release will facilitate future choroidal research both in ophthalmology and wider systemic health.Comment: 8 pages, 2 figures, 3 tables. Currently in submission to ARVO TVST (Association for Research in Vision and Ophthalmology, Translational Vision Science & Technology). GitHub link to codebase provided upon publicatio

Treaty Compliance and Violation

International law has enjoyed a recent renaissance as an important subfield of study within international relations. Two trends are evident in the recent literature. First, the obsession with theoretical labels is on the decline. Second, empirical, especially quantitative, work is burgeoning. This article reviews the literature in four issues areas — security, war, and peace; international trade; protection of the environment; and human rights — and concludes we have a much stronger basis for assessing claims about compliance and violation now than was the case only a few years ago. Still, the literature suffers from a few weaknesses, including problems of selection and endogeneity of treaties themselves and an enduring state-centric focus, despite the fact that researchers recognize that nonstate and substate actors influence treaty behavior. Nonetheless, the quality and quantity of new work demonstrates that international law has regained an important place in the study of international politics

Integrating an NTD with One of “The Big Three”: Combined Malaria and Trachoma Survey in Amhara Region of Ethiopia

The “big three” killer diseases are malaria, HIV/AIDS, and tuberculosis; control programs for these diseases are usually well developed and financed. The neglected tropical diseases (NTDs) are a group of ancient afflictions that are frequently sidelined by planners and are under-resourced. Opportunities of integrating the big three with NTDs have been talked about but not widely acted upon. There is potential synergy for an integrated trachoma and malaria control program since control of both diseases is community-based. The first step in accessing these synergies has been an integrated malaria prevalence and indicator and trachoma prevalence and risk factor survey. This has been achieved at the incremental cost of one additional staff member per field team. The results give unprecedented precision for the calculation of intervention targets for the integrated program and demonstrate that it is possible to integrate NTDs with the “big three.

R|S Atlas: Identifying Existing Cohort Study Data Resources to Accelerate Epidemiological Research on the Influence of Religion and Spirituality on Human Health

OBJECTIVE: Many studies have documented significant associations between religion and spirituality (R/S) and health, but relatively few prospective analyses exist that can support causal inferences. To date, there has been no systematic analysis of R/S survey items collected in US cohort studies. We conducted a systematic content analysis of all surveys ever fielded in 20 diverse US cohort studies funded by the National Institutes of Health (NIH) to identify all R/S-related items collected from each cohort\u27s baseline survey through 2014. DESIGN: An R|S Ontology was developed from our systematic content analysis to categorise all R/S survey items identified into key conceptual categories. A systematic literature review was completed for each R/S item to identify any cohort publications involving these items through 2018. RESULTS: Our content analysis identified 319 R/S survey items, reflecting 213 unique R/S constructs and 50 R|S Ontology categories. 193 of the 319 extant R/S survey items had been analysed in at least one published paper. Using these data, we created the R|S Atlas (https://atlas.mgh.harvard.edu/), a publicly available, online relational database that allows investigators to identify R/S survey items that have been collected by US cohorts, and to further refine searches by other key data available in cohorts that may be necessary for a given study (eg, race/ethnicity, availability of DNA or geocoded data). CONCLUSIONS: R|S Atlas not only allows researchers to identify available sources of R/S data in cohort studies but will also assist in identifying novel research questions that have yet to be explored within the context of US cohort studies

Are we over-treating with checkpoint inhibitors?

Anti-PD-1 antibodies offer potentially life-saving treatment for some cancer patients, but their chronic administration generates high and ever-increasing costs. Despite licensing for long-term use, optimal treatment duration is unknown. We challenge the need for long-term treatment duration, using evidence from melanoma research, both published and in process

Unravelling the nature of HD 81032 - a new RS CVn Binary

BVR photometric and quasi-simultaneous optical spectroscopic observations of the star HD 81032 have been carried out during the years 2000 - 2004. A photometric period of $18.802 \pm 0.07$ d has been detected for this star. A large group of spots with a migration period of $7.43 \pm 0.07$ years is inferred from the first three years of the data. H$\alpha$ and Ca II H and K emissions from the star indicate high chromospheric activity. The available photometry in the BVRIJHK bands is consistent with spectral type of K0 IV previously found for this star. We have also examined the spectral energy distribution of HD 81032 for the presence of an infrared colour excess using the 2MASS JHK and IRAS photometry, but found no significant excess in any band abovethe normal values expected for a star with this spectral type. We have also analyzed the X-ray emission properties of this star using data obtained by the ROSAT X-ray observatory during its All-Sky Survey phase. An X-ray flare of about 12 hours duration was detected during the two days of X-ray coverage obtained for this star. Its X-ray spectrum, while only containing 345 counts, is inconsistent with a single-temperature component solar-abundance coronal plasma model, but implies either the presence of two or more plasma components, non-solar abundances, or a combination of both of these properties. All of the above properties of HD 81032 suggest that it is a newly identified, evolved RS CVn binary.Comment: 18 pages, 10 figures, 3 tables, Accepted for the publication in JAp