Generalized Fock spaces and the Stirling numbers

The Bargmann-Fock-Segal space plays an important role in mathematical physics, and has been extended into a number of directions. In the present paper we imbed this space into a Gelfand triple. The spaces forming the Fr\'echet part (i.e. the space of test functions) of the triple are characterized both in a geometric way and in terms of the adjoint of multiplication by the complex variable, using the Stirling numbers of the second kind. The dual of the space of test functions has a topological algebra structure, of the kind introduced and studied by the first named author and G. Salomon.Comment: revised versio

A framework for application of metabolic modeling in yeast to predict the effects of nsSNV in human orthologs

Background We have previously suggested a method for proteome wide analysis of variation at functional residues wherein we identified the set of all human genes with nonsynonymous single nucleotide variation (nsSNV) in the active site residue of the corresponding proteins. 34 of these proteins were shown to have a 1:1:1 enzyme:pathway:reaction relationship, making these proteins ideal candidates for laboratory validation through creation and observation of specific yeast active site knock-outs and downstream targeted metabolomics experiments. Here we present the next step in the workflow toward using yeast metabolic modeling to predict human metabolic behavior resulting from nsSNV. Results For the previously identified candidate proteins, we used the reciprocal best BLAST hits method followed by manual alignment and pathway comparison to identify 6 human proteins with yeast orthologs which were suitable for flux balance analysis (FBA). 5 of these proteins are known to be associated with diseases, including ribose 5-phosphate isomerase deficiency, myopathy with lactic acidosis and sideroblastic anaemia, anemia due to disorders of glutathione metabolism, and two porphyrias, and we suspect the sixth enzyme to have disease associations which are not yet classified or understood based on the work described herein. Conclusions Preliminary findings using the Yeast 7.0 FBA model show lack of growth for only one enzyme, but augmentation of the Yeast 7.0 biomass function to better simulate knockout of certain genes suggested physiological relevance of variations in three additional proteins. Thus, we suggest the following four proteins for laboratory validation: delta-aminolevulinic acid dehydratase, ferrochelatase, ribose-5 phosphate isomerase and mitochondrial tyrosyl-tRNA synthetase. This study indicates that the predictive ability of this method will improve as more advanced, comprehensive models are developed. Moreover, these findings will be useful in the development of simple downstream biochemical or mass-spectrometric assays to corroborate these predictions and detect presence of certain known nsSNVs with deleterious outcomes. Results may also be useful in predicting as yet unknown outcomes of active site nsSNVs for enzymes that are not yet well classified or annotated

Simultaneous submission of seven CTSA proposals: UM1, K12, R25, T32-predoctoral, T32-postdoctoral, and RC2: strategies, evaluation, and lessons learned

Translation is the process of turning observations in the research laboratory, clinic, and community into interventions that improve people\u27s health. The Clinical and Translational Science Awards (CTSA) program is a National Center for Advancing Translational Sciences (NCATS) initiative to advance translational science and research. Currently, 64 CTSA hubs exist across the nation. Since 2006, the Houston-based Center for Clinical Translational Sciences (CCTS) has assembled a well-integrated, high-impact hub in Texas that includes six partner institutions within the state, encompassing ∼23,000 sq. miles and over 16 million residents. To achieve the NCATS goal of more treatments for all people more quickly, the CCTS promotes diversity and inclusion by integrating underrepresented populations into clinical studies, workforce training, and career development. In May 2023, we submitted the UM1 application and six companion proposals: K12, R25, T32-Predoctoral, T32-Postdoctoral, and RC2 (two applications). In October 2023, we received priority scores for the UM1 (22), K12 (25), T32-Predoctoral (20), and T32-Postdoctoral (23), which historically fall within the NCATS funding range. This report describes the grant preparation and submission approach, coupled with data from an internal survey designed to assimilate feedback from principal investigators, writers, reviewers, and administrative specialists. Herein, we share the challenges faced, the approaches developed, and the lessons learned

The CTSA University of Texas Health Science Center (UTHSC) Northeast—Tyler and Rio Grande Valley Success Story: How Rural, Underserved Academic Communities Rapidly Built a Robust Engine for Collaborative COVID-19 Clinical Research

In 2018, The University of Texas Health Science Center– Tyler and University of Texas Rio Grande Valley were invited to develop clinical research units for an existing Clinical and Translational Science Award (CTSA) consortium with the objective to equip medically underserved, economically disadvantaged communities and subsequently to deploy COVID-19 clinical trials in response to a public health emergency

A Portable Chemotaxis Platform for Short and Long Term Analysis

Flow-based microfluidic systems have been widely utilized for cell migration studies given their ability to generate versatile and precisely defined chemical gradients and to permit direct visualization of migrating cells. Nonetheless, the general need for bulky peripherals such as mechanical pumps and tubing and the complicated setup procedures significantly limit the widespread use of these microfluidic systems for cell migration studies. Here we present a simple method to power microfluidic devices for chemotaxis assays using the commercially available ALZET® osmotic pumps. Specifically, we developed a standalone chemotaxis platform that has the same footprint as a multiwell plate and can generate well-defined, stable chemical gradients continuously for up to 7 days. Using this platform, we validated the short-term (24 hours) and long-term (72 hours) concentration dependent PDGF-BB chemotaxis response of human bone marrow derived mesenchymal stem cells.Harvard Stem Cell InstituteNational Institutes of Health (U.S.) (grant HL095722)National Institutes of Health (U.S.) (grant HL097172)Massachusetts Institute of Technology (MIT-UROP program)Massachusetts Institute of Technology (John Reed Fund)National Institute of Biomedical Imaging and Bioengineering (U.S.) (BioMEMS Resource Center (P41 EB 002503)

Understanding the pathways from biodiversity to agro-ecological outcomes: A new, interactive approach

The adoption of agro-ecological practices in agricultural systems worldwide can contribute to increased food production without compromising future food security, especially under the current biodiversity loss and climate change scenarios. Despite the increase in publications on agro-ecological research and practices during the last 35 years, a weak link between that knowledge and changed farmer practices has led to few examples of agro-ecological protocols and effective delivery systems to agriculturalists. In an attempt to reduce this gap, we synthesised the main concepts related to biodiversity and its functions by creating a web-based interactive spiral (www.biodiversityfunction.com). This tool explains and describes a pathway for achieving agro-ecological outcomes, starting from the basic principle of biodiversity and its functions to enhanced biodiversity on farms. Within this pathway, 11 key steps are identified and sequentially presented on a web platform through which key players (farmers, farmer networks, policy makers, scientists and other stakeholders) can navigate and learn. Because in many areas of the world the necessary knowledge needed for achieving the adoption of particular agro-ecological techniques is not available, the spiral approach can provide the necessary conceptual steps needed for obtaining and understanding such knowledge by navigating through the interactive pathway. This novel approach aims to improve our understanding of the sequence from the concept of biodiversity to harnessing its power to improve prospects for ‘sustainable intensification’ of agricultural systems worldwide

Multicenter Phase II Trial of the WEE1 Inhibitor Adavosertib in Refractory Solid Tumors Harboring

PURPOSE: Preclinical cancer models harboring PATIENTS AND METHODS: Patients aged ≥ 18 years with measurable disease and refractory solid tumors harboring RESULTS: Thirty patients were enrolled. The median follow-up duration was 9.9 months. Eight patients had partial responses (PRs), and three had stable disease (SD) ≥ 6 months, with an ORR of 27% (95% CI, 12 to 46), a SD ≥ 6 months/PR rate of 37% (95% CI, 20 to 56), a median progression-free survival duration of 4.1 months (95% CI, 1.8 to 6.4), and a median overall survival duration of 9.9 months (95% CI, 4.8 to 15). Fourteen patients with epithelial ovarian cancer showed an ORR of 36% (95% CI, 13 to 65) and SD ≥ 6 months/PR of 57% (95% CI, 29 to 82), a median progression-free survival duration of 6.3 months (95% CI, 2.4 to 10.2), and a median overall survival duration of 14.9 months (95% CI, 8.9 to 20.9). Common treatment-related toxicities were GI, hematologic toxicities, and fatigue. CONCLUSION: Adavosertib monotherapy demonstrates a manageable toxicity profile and promising clinical activity in refractory solid tumors harborin

Topological and geometrical restrictions, free-boundary problems and self-gravitating fluids

Let (P1) be certain elliptic free-boundary problem on a Riemannian manifold (M,g). In this paper we study the restrictions on the topology and geometry of the fibres (the level sets) of the solutions f to (P1). We give a technique based on certain remarkable property of the fibres (the analytic representation property) for going from the initial PDE to a global analytical characterization of the fibres (the equilibrium partition condition). We study this analytical characterization and obtain several topological and geometrical properties that the fibres of the solutions must possess, depending on the topology of M and the metric tensor g. We apply these results to the classical problem in physics of classifying the equilibrium shapes of both Newtonian and relativistic static self-gravitating fluids. We also suggest a relationship with the isometries of a Riemannian manifold.Comment: 36 pages. In this new version the analytic representation hypothesis is proved. Please address all correspondence to D. Peralta-Sala

Evidence synthesis as the basis for decision analysis: a method of selecting the best agricultural practices for multiple ecosystem services

Agricultural management practices have impacts not only on crops and livestock, but also on soil, water, wildlife, and ecosystem services. Agricultural research provides evidence about these impacts, but it is unclear how this evidence should be used to make decisions. Two methods are widely used in decision making: evidence synthesis and decision analysis. However, a system of evidence-based decision making that integrates these two methods has not yet been established. Moreover, the standard methods of evidence synthesis have a narrow focus (e.g., the effects of one management practice), but the standard methods of decision analysis have a wide focus (e.g., the comparative effectiveness of multiple management practices). Thus, there is a mismatch between the outputs from evidence synthesis and the inputs that are needed for decision analysis. We show how evidence for a wide range of agricultural practices can be reviewed and summarized simultaneously (“subject-wide evidence synthesis”), and how this evidence can be assessed by experts and used for decision making (“multiple-criteria decision analysis”). We show how these methods could be used by The Nature Conservancy (TNC) in California to select the best management practices for multiple ecosystem services in Mediterranean-type farmland and rangeland, based on a subject-wide evidence synthesis that was published by Conservation Evidence (www.conservationevidence.com). This method of “evidence-based decision analysis” could be used at different scales, from the local scale (farmers deciding which practices to adopt) to the national or international scale (policy makers deciding which practices to support through agricultural subsidies or other payments for ecosystem services). We discuss the strengths and weaknesses of this method, and we suggest some general principles for improving evidence synthesis as the basis for multi-criteria decision analysis

Atomic Resonance and Scattering

Contains reports on eight research projects.National Science Foundation (Grant PHY77-09155)Joint Services Electronics Program (Contract DAAG29-78-C-0020)U. S. Department of Energy (Grant EG-77-S-02-4370)National Science Foundation (Grant DMR 77-10084)National Aeronautics and Space Administration (Grant NSG-1551)U. S. Air Force - Office of Scientific Research (Grant AFOSR-76-2972)National Science Foundation (Grant CHE76-81750