Successful Flash-Cooling of Xenon Derivatized Myoglobin Crystals

This paper demonstrates for the first time a method for preparing cryocooled xenon-derivatized protein crystals. The method is based upon the hypothesis and subsequent observation that the diffusion of a xenon atom from a tight binding site following depressurization occurs on a timescale of minutes. We have observed significant changes in diffraction intensities from myoglobin crystals for up to 5 min following depressurization from 1 MPa of xenon. In accordance with this observation, a xenon-derivatized myoglobin crystal was cryocooled at ~95 K within 20 s of complete depressurization. A crystallographic data set was then collected to 2.0 Å resolution and isomorphous and anomalous difference Patterson maps revealed the presence of a well ordered xenon site with an occupancy of approximately 0.5. Phasing statistics for this site were of good quality and demonstrate the practicality of this method. The ability to cryocool xenon-derivatized crystals will make this heavy-atom substitution method even more useful for single-isomorphous-replacement and multiple-isomorphous-replacement phasing of macromolecules

Enhanced Software for Scheduling Space-Shuttle Processing

The Ground Processing Scheduling System (GPSS) computer program is used to develop streamlined schedules for the inspection, repair, and refurbishment of space shuttles at Kennedy Space Center. A scheduling computer program is needed because space-shuttle processing is complex and it is frequently necessary to modify schedules to accommodate unanticipated events, unavailability of specialized personnel, unexpected delays, and the need to repair newly discovered defects. GPSS implements constraint-based scheduling algorithms and provides an interactive scheduling software environment. In response to inputs, GPSS can respond with schedules that are optimized in the sense that they contain minimal violations of constraints while supporting the most effective and efficient utilization of space-shuttle ground processing resources. The present version of GPSS is a product of re-engineering of a prototype version. While the prototype version proved to be valuable and versatile as a scheduling software tool during the first five years, it was characterized by design and algorithmic deficiencies that affected schedule revisions, query capability, task movement, report capability, and overall interface complexity. In addition, the lack of documentation gave rise to difficulties in maintenance and limited both enhanceability and portability. The goal of the GPSS re-engineering project was to upgrade the prototype into a flexible system that supports multiple- flow, multiple-site scheduling and that retains the strengths of the prototype while incorporating improvements in maintainability, enhanceability, and portability

Adding authenticity to controlled conditions assessment: introduction of an online, open book, essay based exam

© 2018, The Author(s). In the practice of designing examinations, where the emphasis is normally on the assessment of knowledge and understanding of content covered, the authenticity of that assessment model related to skills required for employability, as well as our growing access to instant information, is often missed. Some traditional methods of this form of assessment, particularly the paper based essay exam, have expectations of writing quality and structure as well as of knowledge and understanding, but without providing the tools with which to appropriately meet those expectations. To address this, a computer based, unseen, essay format exam was introduced to a final year module for applied science students, where access was permitted to specific online journal resources. Students wrote their submissions under controlled conditions in Microsoft Word and submitted it through the Virtual Learning Environment (VLE), Blackboard for grading. In addition to an improvement in average mark across the cohort compared to the previous year of paper based essay examinations on the same module, student feedback highlighted an improvement in their ability to organise and arrange their knowledge, and the usefulness of using research material to better evidence their own knowledge. Feedback, being completed online and returned to the students also provided greater understanding of grades achieved and of how to improve for future examinations, a unusual process for exams where graded papers are not normally returned. Though upskilling of staff is likely required for more widespread use, and repeat cohorts will no doubt demonstrate further pros and cons of this form of assessment, the model presented here shows promise for assessment of student communication of depth and breadth of knowledge, and of demonstrating skills more relevant to future employment

Galectin-4 Controls Intestinal Inflammation by Selective Regulation of Peripheral and Mucosal T Cell Apoptosis and Cell Cycle

Galectin-4 is a carbohydrate-binding protein belonging to the galectin family. Here we provide novel evidence that galectin-4 is selectively expressed and secreted by intestinal epithelial cells and binds potently to activated peripheral and mucosal lamina propria T-cells at the CD3 epitope. The carbohydrate-dependent binding of galectin-4 at the CD3 epitope is fully functional and inhibited T cell activation, cycling and expansion. Galectin-4 induced apoptosis of activated peripheral and mucosal lamina propria T cells via calpain-, but not caspase-dependent, pathways. Providing further evidence for its important role in regulating T cell function, galectin-4 blockade by antisense oligonucleotides reduced TNF-alpha inhibitor induced T cell death. Furthermore, in T cells, galectin-4 reduced pro-inflammatory cytokine secretion including IL-17. In a model of experimental colitis, galectin-4 ameliorated mucosal inflammation, induced apoptosis of mucosal T-cells and decreased the secretion of pro-inflammatory cytokines. Our results show that galectin-4 plays a unique role in the intestine and assign a novel role of this protein in controlling intestinal inflammation by a selective induction of T cell apoptosis and cell cycle restriction. Conclusively, after defining its biological role, we propose Galectin-4 is a novel anti-inflammatory agent that could be therapeutically effective in diseases with a disturbed T cell expansion and apoptosis such as inflammatory bowel disease

Coordinating the impact of structural genomics on the human α-helical transmembrane proteome

Given the recent successes in determining membrane-protein structures, we explore the tractability of determining representatives for the entire human membrane proteome. This proteome contains 2,925 unique integral α-helical transmembrane-domain sequences that cluster into 1,201 families sharing more than 25% sequence identity. Structures of 100 optimally selected targets would increase the fraction of modelable human α-helical transmembrane domains from 26% to 58%, providing structure and function information not otherwise available

Examining the effects of social media in co-located classrooms: A case study based on SpeakUp

The broad availability of mobile computing devices has prompted the apparition of social media applications that support teaching and learning. However, so far, there is conflicting evidence as to whether the benefits such applications provide in terms of engagement and interaction, outweigh their potential cost as a source of distraction. To help in clarifying these issues, the present paper presents a case study on the impact of using SpeakUp (an app aimed at promoting student participation through anonymous chatrooms) in an authentic face-to-face learning scenario. Concretely, we focus on the connection between SpeakUp and the student engagement, distraction, social interaction, and the influence of the teachers' style. Our findings highlight that SpeakUp favored students' engagement and social interaction, but they also point towards its limitations in keeping students communicating about content relevant to the course

Dynein-Dynactin Complex Is Essential for Dendritic Restriction of TM1-Containing Drosophila Dscam

BACKGROUND: Many membrane proteins, including Drosophila Dscam, are enriched in dendrites or axons within neurons. However, little is known about how the differential distribution is established and maintained. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the mechanisms underlying the dendritic targeting of Dscam[TM1]. Through forward genetic mosaic screens and by silencing specific genes via targeted RNAi, we found that several genes, encoding various components of the dynein-dynactin complex, are required for restricting Dscam[TM1] to the mushroom body dendrites. In contrast, compromising dynein/dynactin function did not affect dendritic targeting of two other dendritic markers, Nod and Rdl. Tracing newly synthesized Dscam[TM1] further revealed that compromising dynein/dynactin function did not affect the initial dendritic targeting of Dscam[TM1], but disrupted the maintenance of its restriction to dendrites. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest multiple mechanisms of dendritic protein targeting. Notably, dynein-dynactin plays a role in excluding dendritic Dscam, but not Rdl, from axons by retrograde transport

Development of a core set of outcome measures for OAB treatment

© 2017, The Author(s). Introduction and hypothesis: Standardized measures enable the comparison of outcomes across providers and treatments giving valuable information for improving care quality and efficacy. The aim of this project was to define a minimum standard set of outcome measures and case-mix factors for evaluating the care of patients with overactive bladder (OAB). Methods: The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group (WG) of leading clinicians and patients to engage in a structured method for developing a core outcome set. Consensus was determined by a modified Delphi process, and discussions were supported by both literature review and patient input. Results: The standard set measures outcomes of care for adults seeking treatment for OAB, excluding residents of long-term care facilities. The WG focused on treatment outcomes identified as most important key outcome domains to patients: symptom burden and bother, physical functioning, emotional health, impact of symptoms and treatment on quality of life, and success of treatment. Demographic information and case-mix factors that may affect these outcomes were also included. Conclusions: The standardized outcome set for evaluating clinical care is appropriate for use by all health providers caring for patients with OAB, regardless of specialty or geographic location, and provides key data for quality improvement activities and research