Surface Buildup Scenarios and Outpost Architectures for Lunar Exploration

The Constellation Program Architecture Team and the Lunar Surface Systems Project Office have developed an initial set of lunar surface buildup scenarios and associated polar outpost architectures, along with preliminary supporting element and system designs in support of NASA's Exploration Strategy. The surface scenarios are structured in such a way that outpost assembly can be suspended at any time to accommodate delivery contingencies or changes in mission emphasis. The modular nature of the architectures mitigates the impact of the loss of any one element and enhances the ability of international and commercial partners to contribute elements and systems. Additionally, the core lunar surface system technologies and outpost operations concepts are applicable to future Mars exploration. These buildup scenarios provide a point of departure for future trades and assessments of alternative architectures and surface elements

Controlling the self-assembly and material properties of β-sheet peptide hydrogels by modulating intermolecular interactions

Self-assembling peptides are a promising biomaterial with potential applications in medical devices and drug delivery. In the right combination of conditions, self-assembling peptides can form self-supporting hydrogels. Here, we describe how balancing attractive and repulsive intermolecular forces is critical for successful hydrogel formation. Electrostatic repulsion is tuned by altering the peptide’s net charge, and intermolecular attractions are controlled through the degree of hydrogen bonding between specific amino acid residues. We find that an overall net peptide charge of +/−2 is optimal to facilitate the assembly of self-supporting hydrogels. If the net peptide charge is too low then dense aggregates form, while a high molecular charge inhibits the formation of larger structures. At a constant charge, altering the terminal amino acids from glutamine to serine decreases the degree of hydrogen bonding within the assembling network. This tunes the viscoelastic properties of the gel, reducing the elastic modulus by two to three orders of magnitude. Finally, hydrogels could be formed from glutamine-rich, highly charged peptides by mixing the peptides in combinations with a resultant net charge of +/−2. These results illustrate how understanding and controlling self-assembly mechanisms through modulating intermolecular interactions can be exploited to derive a range of structures with tuneable properties

Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription

AbstractBackground: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase, the activity of which is inhibited by a variety of extracellular stimuli including insulin, growth factors, cell specification factors and cell adhesion. Consequently, inhibition of GSK-3 activity has been proposed to play a role in the regulation of numerous signalling pathways that elicit pleiotropic cellular responses. This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3.Results: SB-216763 and SB-415286 are structurally distinct maleimides that inhibit GSK-3α in vitro, with Kis of 9 nM and 31 nM respectively, in an ATP competitive manner. These compounds inhibited GSK-3β with similar potency. However, neither compound significantly inhibited any member of a panel of 24 other protein kinases. Furthermore, treatment of cells with either compound stimulated responses characteristic of extracellular stimuli that are known to inhibit GSK-3 activity. Thus, SB-216763 and SB-415286 stimulated glycogen synthesis in human liver cells and induced expression of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells. In both cases, compound treatment was demonstrated to inhibit cellular GSK-3 activity as assessed by activation of glycogen synthase, which is a direct target of this kinase.Conclusions: SB-216763 and SB-415286 are novel, potent and selective cell permeable inhibitors of GSK-3. Therefore, these compounds represent valuable pharmacological tools with which the role of GSK-3 in cellular signalling can be further elucidated. Furthermore, development of similar compounds may be of use therapeutically in disease states associated with elevated GSK-3 activity such as non-insulin dependent diabetes mellitus and neurodegenerative disease

The mortality after release from incarceration consortium (MARIC): Protocol for a multi-national, individual participant data meta-analysis

Introduction More than 30 million adults are released from incarceration globally each year. Many experience complex physical and mental health problems, and are at markedly increased risk of preventable mortality. Despite this, evidence regarding the global epidemiology of mortality following release from incarceration is insufficient to inform the development of targeted, evidence-based responses. Many previous studies have suffered from inadequate power and poor precision, and even large studies have limited capacity to disaggregate data by specific causes of death, sub-populations or time since release to answer questions of clinical and public health relevance. Objectives To comprehensively document the incidence, timing, causes and risk factors for mortality in adults released from prison. Methods We created the Mortality After Release from Incarceration Consortium (MARIC), a multi-disciplinary collaboration representing 29 cohorts of adults who have experienced incarceration from 11 countries. Findings across cohorts will be analysed using a two-step, individual participant data meta-analysis methodology. Results The combined sample includes 1,337,993 individuals (89% male), with 75,795 deaths recorded over 9,191,393 person-years of follow-up. Conclusions The consortium represents an important advancement in the field, bringing international attention to this problem. It will provide internationally relevant evidence to guide policymakers and clinicians in reducing preventable deaths in this marginalized population

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Advancing peptide hydrogels for intervertebral disc repair

Lower back pain is often caused by degeneration of the intervertebral disc and has a significant socioeconomic cost. Current treatments are limited in terms of their clinical success. Nucleus augmentation is being investigated as a potential treatment for degenerated discs with the aim of restoring the biomechanical function of the disc. A nucleus augmentation material must be delivered minimally invasively, restore the mechanical properties and be biocompatible. Selfassembling peptides have been previously shown to form hydrogels with a range of potential mechanical properties and therefore can be designed to have material properties suitable for nucleus augmentation. The aim of this work was to build upon existing self-assembling peptides with an overall charge of +2 mixed with a glycosaminoglycan (GAG) for nucleus augmentation. By changing the terminal amino acids between glutamine and serine, three peptides were used to investigate the effect of hydrogen bonding on selfassembly. The glutamine amino acids were able to form more and stronger hydrogen bonds that reduced the critical concentration for self-assembly. These differences in self-assembly were shown to affect the hydrogel lifetimes under passive diffusion and during cyclic compression testing. Rheology was used to assess the effect of the terminal amino acids on the mechanical properties of the hydrogels as well as the effect of delivery down minimally invasive needles. The different peptide-GAG hydrogels resulted in a range of mechanical properties suitable for nucleus augmentation. Injection down a needle had little to no effect on the mechanical properties of the hydrogel. Electron microscopy was used to image the fibrous networks of the hydrogels in different states. Cryo-focused ion beam scanning electron microscopy was used to create a 3D image of the fibres. Finally, cytotoxicity assays were used to assess different components of the hydrogels. There was some slight cytotoxicity associated with the soluble components of the peptides, however the hydrogels were not cytotoxic as biomaterials. The slight cytotoxicity was reduced by changing the counterion. Overall, the effect of hydrogen bonding on self-assembly was controlled by using glutamine and serine amino acids and analysed using a variety of multidisciplinary techniques. The peptides met the criteria outlined for nucleus augmentation devices and present a realistic and viable option for a clinically translatable treatment

Disaster Relief

Credits – by Matthew Culbert, actor, editor; Kyoungho Cho, actor,editor; Shawn Newlan, actor; and Stephen Palmer, actor Description - Matthew Culbert is student at UT who has no respectfor the well being of others. He soon realizes his faults after experiencingthe first hand horrors a disaster can bring. Awards: First Place

The landscape of digital resources in radiation oncology

In recent years, the number of educational medical resources accessible to residents and practicing radiation oncologists online has grown exponentially to include discussion boards, wikis, videos, podcasts, journal clubs, online communities, and interactive experiences to augment medical education. In this review, we identify, catalog, and critically evaluate educational websites, smartphone applications, web-based multimedia, and podcasts for radiation oncologists. Literature searches were conducted over a 2-month period (April to May 2022) using OVID-MEDLINE and PubMed with a combination of relevant search terms. Websites of relevant radiation oncology societies were reviewed for e-learning resources. Internet searches including the Google search engine, application stores, and podcast-publisher websites were conducted to identify digital resources for radiation oncology education. To ensure credibility, resources were assessed by two independent reviewers utilizing the criteria of authority, accuracy, objectivity, currency, depth, and appearance per suggested formats for evaluating digital resources in medical literature. Literature searches using OVID-MEDLINE and PubMed yielded 425 citations. Those pertinent to radiation oncology provide examples of resource development, integrations into curriculum, interactive modules, case studies, and learner experiences. The multilevel search identified 47 free digital education resources including online radiation oncology tutorials, podcasts, videos, slide sets, applications, and other interactive resources, some requiring membership or a fee for full access. The myriad online educational tools available to radiation oncology residents represent excellent resources for continuing education. This review represents the first comprehensive summary of available online education resources for radiation oncologists to guide clinicians who are increasingly reliant on digital resources, especially during the COVID-19 pandemic