Acquisition of a Multi-User Thin Film Synthesis and Processing Facility

A state-of-the-art advanced materials synthesis and processing facility focusing on the growth and fabrication of ceramic- based thin film materials will be funded with the assistance of the Academic Research Infrastructure Program. The facility will include a multi-technique thin film materials synthesis chamber equipped with a microwave plasma source, effusion cells, electron beam evaporators, magnetron sputter sources, and a Kauffman ion source. Characterization capabilities will include in-situ reflection high energy electron diffraction (RHEED), mass spectrometry for controlling growth processes, X-ray photoelectron spectroscopy (XPS), and a novel Hall probe for in- situ film characterization. Three major areas of research will be impacted significantly by the facility, namely 1) solid state micro-sensors, 2) nanomechanics of materials, and 3) surfaces and interfaces in hetero-epitaxial oxide systems. In the sensor work, which has connections with local industry, the synthesis and processing of well-defined doped metal-oxide films will be developed with the goal of understanding and controlling the molecular scale mechanisms by which surface microstructure, dopant type, and operating temperature influence sensor performance. A broad based advanced materials synthesis and processing facility for the growth and fabrication of ceramic-based thin films will be operated for the study of solid state microsensors based on metal-oxide ceramic films. The nanomechanics of these ceramic thin films will be studied, as well as the surfaces and interfaces occurring in heteroepitaxial oxide systems

Collision-Induced Decay of Metastable Baby Skyrmions

Many extensions of the standard model predict heavy metastable particles which may be modeled as solitons (skyrmions of the Higgs field), relating their particle number to a winding number. Previous work has shown that the electroweak interactions admit processes in which these solitons decay, violating standard model baryon number. We motivate the hypothesis that baryon-number-violating decay is a generic outcome of collisions between these heavy particles. We do so by exploring a 2+1 dimensional theory which also possesses metastable skyrmions. We use relaxation techniques to determine the size, shape and energy of static solitons in their ground state. These solitons could decay by quantum mechanical tunneling. Classically, they are metastable: only a finite excitation energy is required to induce their decay. We attempt to induce soliton decay in a classical simulation by colliding pairs of solitons. We analyze the collision of solitons with varying inherent stabilities and varying incident velocities and orientations. Our results suggest that winding-number violating decay is a generic outcome of collisions. All that is required is sufficient (not necessarily very large) incident velocity; no fine-tuning of initial conditions is required.Comment: 24 pages, 7 figures, latex. Very small changes onl

Public opinion on energy crops in the landscape: considerations for the expansion of renewable energy from biomass

Public attitudes were assessed towards two dedicated biomass crops – Miscanthus and Short Rotation Coppice (SRC), particularly regarding their visual impacts in the landscape. Results are based on responses to photographic and computer-generated images as the crops are still relatively scarce in the landscape. A questionnaire survey indicated little public concern about potential landscape aesthetics but more concern about attendant built infrastructure. Focus group meetings and interviews indicated support for biomass end uses that bring direct benefits to local communities. Questions arise as to how well the imagery used was able to portray the true nature of these tall, dense, perennial plants but based on the responses obtained and given the caveat that there was limited personal experience of the crops, it appears unlikely that wide-scale planting of biomass crops will give rise to substantial public concern in relation to their visual impact in the landscape

Carbonic anhydrase enzymes regulate mast cell–mediated inflammation

Type 2 cytokine responses are necessary for the development of protective immunity to helminth parasites but also cause the inflammation associated with allergies and asthma. Recent studies have found that peripheral hematopoietic progenitor cells contribute to type 2 cytokine–mediated inflammation through their enhanced ability to develop into mast cells. In this study, we show that carbonic anhydrase (Car) enzymes are up-regulated in type 2–associated progenitor cells and demonstrate that Car enzyme inhibition is sufficient to prevent mouse mast cell responses and inflammation after Trichinella spiralis infection or the induction of food allergy–like disease. Further, we used CRISPR/Cas9 technology and illustrate that genetically editing Car1 is sufficient to selectively reduce mast cell development. Finally, we demonstrate that Car enzymes can be targeted to prevent human mast cell development. Collectively, these experiments identify a previously unrecognized role for Car enzymes in regulating mast cell lineage commitment and suggest that Car enzyme inhibitors may possess therapeutic potential that can be used to treat mast cell–mediated inflammation

Decentralized clinical trials in the trial innovation network: Value, strategies, and lessons learned

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology

Both the Caspase CSP-1 and a Caspase-Independent Pathway Promote Programmed Cell Death in Parallel to the Canonical Pathway for Apoptosis in Caenorhabditis elegans

Caspases are cysteine proteases that can drive apoptosis in metazoans and have critical functions in the elimination of cells during development, the maintenance of tissue homeostasis, and responses to cellular damage. Although a growing body of research suggests that programmed cell death can occur in the absence of caspases, mammalian studies of caspase-independent apoptosis are confounded by the existence of at least seven caspase homologs that can function redundantly to promote cell death. Caspase-independent programmed cell death is also thought to occur in the invertebrate nematode Caenorhabditis elegans. The C. elegans genome contains four caspase genes (ced-3, csp-1, csp-2, and csp-3), of which only ced-3 has been demonstrated to promote apoptosis. Here, we show that CSP-1 is a pro-apoptotic caspase that promotes programmed cell death in a subset of cells fated to die during C. elegans embryogenesis. csp-1 is expressed robustly in late pachytene nuclei of the germline and is required maternally for its role in embryonic programmed cell deaths. Unlike CED-3, CSP-1 is not regulated by the APAF-1 homolog CED-4 or the BCL-2 homolog CED-9, revealing that csp-1 functions independently of the canonical genetic pathway for apoptosis. Previously we demonstrated that embryos lacking all four caspases can eliminate cells through an extrusion mechanism and that these cells are apoptotic. Extruded cells differ from cells that normally undergo programmed cell death not only by being extruded but also by not being engulfed by neighboring cells. In this study, we identify in csp-3; csp-1; csp-2 ced-3 quadruple mutants apoptotic cell corpses that fully resemble wild-type cell corpses: these caspase-deficient cell corpses are morphologically apoptotic, are not extruded, and are internalized by engulfing cells. We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation.Howard Hughes Medical InstituteDamon Runyon Cancer Research FoundationCharles A. King Trus

Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle

α-Dystrobrevin is a component of the dystrophin-glycoprotein complex (DGC) and is thought to have both structural and signaling roles in skeletal muscle. Mice deficient for α-dystrobrevin (adbn−/−) exhibit extensive myofiber degeneration and neuromuscular junction abnormalities. However, the biochemical stability of the DGC and the functional performance of adbn−/− muscle have not been characterized. Here we show that the biochemical association between dystrophin and β-dystroglycan is compromised in adbn−/− skeletal muscle, suggesting that α-dystrobrevin plays a structural role in stabilizing the DGC. However, despite muscle cell death and DGC destabilization, costamere organization and physiological performance is normal in adbn−/− skeletal muscle. Our results demonstrate that myofiber degeneration alone does not cause functional deficits and suggests that more complex pathological factors contribute to the development of muscle weakness in muscular dystrophy