Grants

NSF

Software plays an increasingly important role in scientific discovery and innovation. Nuclear fusion, quantum science, space exploration, cancer research, and biotechnology are just a few of the many scientific disciplines benefitting from software. However, like all software, programs used in science may contain defects ("bugs") --- errors in the code or mistaken assumptions ---that can render the output erroneous. Consequently, developers of scientific software expend significant effort debugging their code, reducing their productivity. Worse, some defects evade even the most extensive debugging efforts. This project is developing tools to help developers easily find subtle defects in their code and even verify (under reasonable assumptions) that the code is defect-free. The project's novelties are: a new modular approach to the specification of program components based on simple mathematical abstractions that are familiar to scientists; simple-to-use, automated methods to verify a program component adheres to its specification (or report a defect when it does not); and the application of these techniques to two state-of-the-art scientific software packages. The project's impacts are, first, the advancement of software verification technology generally, which can reduce development costs and increase software quality throughout industry, government laboratories, and academia. Second, improving public confidence in the soundness of conclusions based on scientific software. Third, the training of students and scientists in the use of advanced verification techniques, contributing to a cultural change in the way scientific software is constructed. These advances are based on new symbolic execution techniques implemented in the CIVL model checker. Libraries are being developed to support abstract mathematical concepts such as "vector" and "matrix". Symbolic "representation functions" are used to tie these abstractions to the significantly more complex data structures in a scientific program. Such a function consumes a data structure (which may be distributed across multiple processes) in the program and returns the abstract construct represented by that structure. This allows the user to specify correctness properties on the abstract level while the model checker verifies that the program structures implement the abstract operations correctly. Model checking techniques are used to verify concurrent algorithms, such as those expressed using Message Passing Interface (MPI), OpenMP, or Compute Unified Device Architecture (CUDA). These techniques are being applied to select components of PETSc, a widely used numerical linear algebra library and core component of numerous software projects, and to Flash-X, a state-of-the-art multiphysics simulation system used in astrophysics and other scientific disciplines. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

Density Functional Theory (DFT) is a phenomenally successful approach to finding approximate solutions to the Schrodinger equation, the fundamental equation that describes the quantum behavior of atoms and molecules. The fundamental results of Kohn, Hohenberg, and Sham showed that the ground-state energy from the Schrodinger equation is a unique functional of the electron density and subsequently reduced solving a complicated many-body problem to finding a consistent solution to a set of single-particle equations. However, the exact density functional is not known and scientists have developed hundreds of density functional approximations (DFAs). Choosing a DFA is perhaps the most important decision when performing a DFT calculation. The project's novelties are in using formal methods to ensure that the implementation of a DFA is provably correct. DFT calculations are widely used in a number of scientific and engineering fields, including solid state physics, computational chemistry, and materials science. Consequently, the project's impacts are in improving the correctness of scientific software in these application domains. The key insight of the project is that each DFA is a mathematical function with a known, albeit complicated, analytical form, and, hence, can be analyzed using formal-methods techniques such as Satisfiability Modulo Theory (SMT) solvers. The project will automatically verify whether a DFA implementation satisfies DFT exact conditions (known analytical properties of the exact functional). The project will automatically verify numerical properties of a DFA implementation (generation of Not a Number (NaN) and infinities, and numerical instabilities slowing down convergence). The project will develop techniques to generate provably correct minimal edits to a DFA implementation that are guaranteed to be numerically stable and continue to satisfy the same exact conditions. By analyzing existing DFAs and developing new DFAs, the project will have tremendous impact in a number of scientific and engineering fields. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

The goal of CS4NorthCal is to scale up an effective, evidence-based model for preparation, PD, and ongoing support of high school CS teachers. CS4NorthCal will prepare and support high school teachers committed to CS education excellence throughout Northern California. This project will increase rigorous and engaging CS course offerings to all high school students. The retention of students in high school CS courses will increase, and these students will gain in-demand skills that allow them to enter the CS workforce. The strategies identified and tested in this project for improving teacher preparation and support will be of broad interest, as school districts throughout the country are facing, or will face, the same problems, as they ramp up their own CS offerings. Over the course of this project, the RPP will serve 200 teachers and support 25,000+ high school students. San Francisco State University, WestEd, and 20+ school districts will collaborate and launch CS4NorthCal to address the critical national need to broaden the availability of high-quality computer science (CS) education to all American students by creating a scalable and effective model for teacher preparation. The project has three main activities: (1) scaling a certification program for CS teacher preparation and professional development to increase the number of authorized high school CS teachers; (2) expanding Professional Learning Communities (PLCs) for newly certified high school CS teachers to provide continuous professional learning on CS curricula and effective pedagogical strategies; and (3) establishing and scaling a high school CS teacher mentorship program to offer ongoing, rigorous support to newly certified teachers to improve their retention and skills. The RPP has jointly developed research questions to investigate how best to design certification courses, PLCs, and teacher mentorship programs to prepare teachers of varying disciplinary and geographic backgrounds to teach high school CS: Research questions include: (1) How can online certification courses be designed to effectively prepare teachers with CS content knowledge and skills? (2) How can certification courses and ongoing support be designed to address the needs and readiness levels of teachers with different disciplinary backgrounds? (3) How do teachers engage in ongoing support (e.g., PLCs, mentoring) focused on the continuing development of their content knowledge and teaching skills, particularly in emerging areas such as artificial intelligence for workforce readiness? By focusing on building teacher capacity in high schools, this project creates new learning opportunities for all students, enabling them to pursue higher education and careers in high-demand STEM and AI-integrated fields. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIA - National Institute on Aging

PROJECT SUMMARY Artery Therapeutics, Inc. (ATI) is developing CS6253, a highly differentiated, cholesterol-transport focused treatment for the indication of hereditary APOE4-associated dementia including MCI-AD, targeting the ATP- Binding-Cassette-Transporter A1 (ABCA1). We now propose two sequential CS6253 studies to delineate mechanism and show Proof of Concept (PoC) in homozygous APOE4 early AD patients. In the recently performed Phase 1 SAD-MAD study in healthy men and women CS6253 showed favorable safety/tolerability and pharmacokinetics (PK), apoE target engagement and an amyloid-clearance signal consistent with previous mouse model (Boehm, 2016) and primate (Noveir, 2022) studies. In the Phase 1 study we also performed an exploratory IV-SC bioequivalence sub-study showing that a single CS6253 SC bolus injection of 1 mg/kg was safe with a 79% bioavailability (compared to IV injection) and within the exposure range of the successful targeted replacement mice studies (Boehm, 2016). We now need to show that multiple-fold higher exposure levels can be reached by SC route of administration prior to commencing Phase 2A mechanism/Proof of Concept (PoC) studies, covering a wider exposure range, to evaluate safety, PK, and pharmacodynamics (PD) effects. Thus, our objectives are to perform a subcutaneous (SC) injection PK feasibility study with the ABCA1 agonist CS6253, and provided prespecified drug exposure success criteria are met, then perform a 28-day Phase 2A mechanism/PoC study in 48 APOE4-carriers with Mild Cognitive Impairment (MCI), of which half are homozygous, to assess safety, tolerance, PK, plasma and CSF biomarker effects. We will assess; 1) CS6253’s ABCA1 target engagement by following change in CSF and plasma apoE (total and isomer specific protein and glycosylation levels) and lipidation (primary effect); 2) Test amyloid-clearance hypothesis by following CSF and plasma Aβ42, Aβ40, Aβ42/40-ratio (secondary); 3) ABCA1 cholesterol-transport salutary effects by following plasma and CSF changes in P-tau 181, 217, 231, GFAP, NfL, and TREM2 (tertiary); 4) Explore direct vs indirect CS6253 effect by assessing upregulation of natural ABCA1 agonists as apoE and small apoA-I particles in plasma and CSF (exploratory); 5) Inform on optimal dosing-regimen, patient population (homozygous vs heterozygous) and power for subsequent Phase 2-3 studies (trial preparatory). With a positive outcome from these important studies in the APOE4 carrier patient population the next regulatory- clinical development steps are to propose breakthrough designation with the FDA and assess CS6253 effects on cognition in a Phase 2-3, 9 month randomized controlled trial (RCT) in homozygous APOE4 carriers with AD/ADRD.

NSF

The Earth formed by a series of collisions between smaller rocky bodies. At some point during this process, the Earth also acquired the elements, known as volatiles, that make up its atmosphere and oceans. But how and when the Earth formed, and how and when it acquired its volatiles, are still very uncertain. This matters, because the volatile elements are essential for life as we know it; if we can understand how the Earth acquired its volatiles, that will help us understand how other planets did so, in this solar system and elsewhere. To solve this problem the investigators use two main tools. One is a series of natural “clocks”, derived from radioactive elements that decay; these tell us how fast things happened. The second is experiments to determine whether the volatile elements were sequestered into the Earth’s iron core, or whether they were left behind in the rocks and atmosphere. As part of this investigation the team will train graduate and undergraduate students in experimental and analytical techniques, adding to the technically-trained workforce. In this proposal the investigators explore the combined effects of volatile loss and core sequestration on a range of moderately volatile and refractory elements. They will use four isotopic chronometers (Hf-W, Pd-Ag, U-Pb and I-Pu-Xe), with different half-lives and chemical characteristics, to disentangle these two effects. The modeling efforts use N-body accretion models, allowing provenance to be tracked and isotopic evolution to be tracked; they also propose to carry out necessary experimental measurements on partitioning behavior and mantle Xe isotopic compositions. The team will use the four isotopic systems to answer three major questions: 1) are the Grand Tack or conventional accretion scenarios more consistent with the observations? 2) how did the composition of material added to the Earth change as accretion proceeded?; 3) how much volatile loss happened during and after accretion itself? In answering these questions the investigators will provide a more focused picture of the formation and earliest evolution of the Earth. The proposed research involves an inter-disciplinary collaboration between a modeler, an isotope geochemist and a high-pressure mineralogist. As such, it cuts across traditional disciplinary boundaries and will provide an opportunity for the three groups to educate each other and integrate experiments, measurements and modeling. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIGMS - National Institute of General Medical Sciences

Abstract Project Summary and Abstract. Over 17,000 new traumatic spinal cord injuries occur in the United States each year. Following the initial traumatic insult (i.e. primary injury), blood vessel disruption leads to pervasive hypoxic and inflammatory cell damage (i.e. secondary injury). Our inability to detect ongoing cell damage impairs our capacity to develop effective strategies to limit debilitating secondary injuries. The fundamental goal of this proposal is to test the hypothesis that cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA), serotonin’s primary metabolite, is a reliable biomarker of secondary cell damage. Descending raphe projections deliver and store serotonin near spinal sensory and motor synapses. Due to the proximity of raphe projections to sensory and motor fibers, insults that damage sensory and motor tracts inadvertently injure raphe fibers resulting in a transient release of stored serotonin into the extracellular spinal tissue. 5-HIAA is a highly stable serotonin metabolite with CSF levels mirroring extracellular serotonin levels. Building from well-published animal data, and recent human studies from our group, we further hypothesize 5-HIAA to be a reliable biomarker for structural injury to spinal sensory/motor tracts, therefore 5-HIAA is an important tool to acutely prognosticating long-term outcomes in humans with spinal cord injuries. This study represents the first step in developing strategies to limit secondary injuries that exacerbate disability and undermine recovery potential in humans with acute traumatic spinal cord injuries. Within the first phase of this proposal we have 1) refined our understanding of acute management strategies to preserve motor control in patients with acute traumatic spinal cord injuries (Swaroop et al., 2024), 2) demonstrated our capacity to reliably measure CSF metabolites in humans (Anand et al., 2024), and 3) demonstrated 5-HIAA to be a stable molecule with spinal levels NOT influenced by the circadian cycle (Anand et al., 2024). Within this second phase of the project (R00) we will perform a proof-of-concept study evaluating CSF 5-HIAA’s sensitivity in detecting secondary insults in humans with spinal cord injuries. This study will set the foundation for a future PHASE III study in which we will compare the accuracy of CSF 5-HIAA vs standard physical exams, to monitor ongoing secondary injuries and prognosticate long-term clinical outcomes for spinal cord injury patients.

NINDS - National Institute of Neurological Disorders and Stroke

SUMMARY The brain is bathed in cerebrospinal fluid (CSF), a medium rich in health- and growth-promoting factors, metabolites, nucleic acids, and more, whose composition changes profoundly throughout the lifespan and can be used to diagnose certain conditions. Most CSF is produced by the choroid plexus (ChP), a highly vascularized epithelium located in each ventricle of the brain. In addition, the sheet of tight junction-coupled ChP epithelial cells provides a critical blood-CSF barrier that protects the central nervous system from peripheral challenges such as bloodborne pathogens. The ChP detects and responds to changes in CSF composition. Abnormal levels of neurotransmitters in the CSF including glutamate have been reported in a wide range of neurologic and psychiatric disorders that are also characterized by ChP/barrier pathology and inflammation. We hypothesize a causal link between these observations. Specifically, we propose that excessive CSF-glutamate impairs ChP barrier integrity and that it does so through the metabotropic glutamate receptor 8 (mGluR8). Importantly, cAMP has been shown to enhance endothelial tight junctions at the blood-brain barrier (BBB), and experiments in cultured ChP cells suggest that cAMP may similarly regulate blood-CSF barrier permeability. Among the G-Protein Coupled Receptors (GPCRs) that we identified to be predominately and robustly expressed by mouse and human ChP epithelial cells, mGluR8 is coupled to the Gi/o-protein and therefore expected to inhibit cAMP/PKA signaling, consistent with negative regulation of barrier permeability. Our first set of experiments will test our hypothesis by studying cAMP regulation in ChP epithelial cells. Using methods we developed in collaboration with Mark Andermann (BIDMC/Harvard) for in vitro and in vivo two-photon imaging of ChP structure and function at subcellular resolution, we will visualize cAMP with a fluorescent indicator selectively expressed in ChP epithelial cells (cADDis). We will then use a newly generated mGluR8 knockout mouse (shared by Danny Winder, UMass), to test if mGluR8 is necessary and sufficient to mediate glutamate- evoked modulation of cAMP signaling (Aim 1). Next, we will test the hypothesis that CSF glutamate dose- dependently reduces barrier integrity in vivo and thereby causes ChP inflammation (Aim 2). To do so we will leverage technologies we recently developed based on GRAB-sensor technology for real-time tracking of neurotransmitters and neuromodulators in CSF. We will measure CSF glutamate levels with cell-based sensor iGluSnFR and correlate these levels with measurements of barrier permeability and inflammation.

NSF

Educate Maine, in collaboration with the Institute for Advancing Computing Education, will explore and plan resources to prepare and support core curriculum teachers integrating computer science and computational thinking (CS/CT) into their courses. Integration of CS/CT into required core disciplines (such as social studies, English language arts (ELA), math and science) holds great promise for fostering more participation and interest in CS and for increasing the general CS/CT skills and interest in the workforce. Integration is an especially important strategy in rural schools which often cannot afford a CS-specific teacher. This project partnership between interdisciplinary practitioners and researchers seek to support Maine teachers in developing CS skills that can prepare students for entering the modern workforce. This small High School Strand Research Practice Partnership (RPP) will implement exploratory research, RPP building, and pilot testing that results in stakeholder engagement, educator motivation, and research data that will underpin the future creation of resources to prepare and support teachers implementing CS/CT integration into core discipline topics in Maine’s rural high schools. The project will reach 140 teachers in rural Maine high schools while pilot testing a professional development series and engage teachers and community members from across the state in Listening Sessions and focus groups, as well as convening an 8-person RPP. This project will address three research questions: (1) What obstacles do high school teachers in rural Maine communities face in integrating CS/CT into their subjects? (2) What support structures and resources do rural Maine high school teachers need to effectively integrate CS/CT using the developed curriculum into other subjects? (3) How does preparing rural high school teachers to teach CS/CT through the developed curriculum in core subjects impact teachers' CS motivation (including self-efficacy in teaching CS and expectancy-value for learning CS), and interest in teaching CS? This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NCI - National Cancer Institute

Cancer is now recognized as an abnormal organ where multiple cell types cooperate during cancer initiation and metastatic progression. Enormous progress has been made on identifying genetic, epigenetic and metabolic alterations in tumor cells and characterizing the different cell types composing a tumor, understanding the mechanisms by which these cell types interact with each other, developing ways to image the changes in a tumor and exploring therapeutic opportunities that take into account the non-malignant cells. Thus, there is an emergence of a need for an integrative approach for controlling cancer. However, most cancer meetings are organized to focus on one or two aspects of the many aspects of the biology of tumor. The proposed meeting takes an integrative approach to create a platform and bring together world leaders in different aspects of cancer biology, genetics, epigenetics, metabolism, signaling, immunology, diagnostics, and therapeutics to discuss the latest findings and promote dialogue aimed at solving the chief problems that prevent durable responses in the clinic. We believe that such an integrative approach will trigger discussions and interactions that cross disciplinary borders and find new ways to develop and deliver novel therapeutic strategies for controlling cancer. The eighth rendition of this biennial conference will draw participants from academic labs, research institutes and biotech/pharmaceutical industries, and will include leaders in the field, established investigators, junior faculty, postdoctoral fellows, graduate students and corporate scientists. To ensure the presentation of the most cutting edge results many speakers will be chosen based on the quality of abstracts submitted to the meeting coordinators and session chairs several months prior to the meeting. Our emphasis will be on unpublished results. To maximize broad participation, efforts have been made to include outstanding scientists and scientists from abroad as session chairs and invited speakers. Each session will be chaired by two leading scientists in the field selected by the organizers. Oral presentations will be selected from submitted abstracts by the session chairs in consultation with the organizers. Selected speakers will include graduate students, postdoctoral fellows and junior faculty aiming for maximal inclusion of young investigators. In addition, to promote recognition of the next generation of scientists, a late breaking session will be assembled with invited early career investigators to discuss exciting advances in cancer biology. Of special importance are the two poster sessions and panel discussion. The poster session provides an opportunity for many participants to present their work in an atmosphere conducive to informal discussion and the panel discussion engages thought leaders and the participants on one highly debated topic on the role played by personalized cancer medicine in improving cancer treatment. The meeting will be of moderate size and we expect about 350 people to attend, the vast majority of whom will be presenting a poster or talk.

NINDS - National Institute of Neurological Disorders and Stroke

This proposal requests support for a unique international meeting, the biennial Neurobiology of Drosophila conference at Cold Spring Harbor, to be held in 2025, the 21st meeting in this series. For the 2025 edition, the organizers have focused the meeting on topics of direct bearing on the central goals of the NIH Neuroscience Blueprint and BRAIN initiative; it supports the mission of NINDS and also those of NICHD, NIDA, NIAAA, NIA, NIMH, and NIAID. The meeting will explore the latest advances being made in the highly successful model system of the fruit fly Drosophila melanogaster through the combined power of genetics, molecular biology, cell biology, electrophysiology, imaging, connectome, and behavioral analysis to address fundamental issues in neurobiology with direct relevance to human health and disease. The meeting will have nine oral sessions:1) Nervous System Evolution: Brain and Behavior; 2) Nervous System Disease and Injury Models 3) Technological Advances; 4) Connectome and Behavior; 5) Cell Biology of Neurons and Glia; 6) Diversity - from Cells to Individuals; 7) Circuit Construction and Remodeling; 8) Neuromodulation and Plasticity; and 9) Sensory Systems and Brain-body Interactions. There will be three poster sessions presenting work drawn from each of these areas and career development sessions on guidance for navigating careers in academia and alternate career trajectories. Finally, there will also be two special plenary presentations: the keynote Benzer Memorial Lecture and the Elkins Memorial Lecture, an honor awarded to the student who has written the best Ph.D. thesis since the previous meeting. The 2025 Benzer Memorial Lecture will be given by Dr. Scott Waddell (Oxford University), whose pioneering work has shed light on molecular and circuit mechanisms of learning and memory. The meeting will remain of moderate size (~450 participants) to facilitate in-person discussion, exchange of ideas and techniques, and promote new collaborations in rapidly evolving fields. In addition, virtual participation will be available to include those who cannot come in person. Roughly half the attendees have previously attended the meeting, highlighting its importance and relevance, and the new attendees bring fresh ideas and extend the meeting's reach. All applicants will be encouraged to submit an abstract; historically, over 75% present a talk or poster. Session leaders and meeting organizers will choose speakers from the most timely and interesting abstracts submitted a few months in advance of the conference; this ensures that late-breaking science is covered in all talks. This meeting has always attracted investigators across many career stages and has an excellent record of promoting young investigators' scientific development; most speakers are trainees. Special attention will be paid to running an energetic, and welcoming meeting that shares new findings and technological developments at the forefront of the rapidly moving and influential field of Drosophila neurobiology.

NIAID - National Institute of Allergy and Infectious Diseases

Cold Spring Harbor Laboratory Conference GENE EXPRESSION AND SIGNALING IN THE IMMUNE SYSTEM March 3-7,2026 ABSTRACT The proposed meeting on Gene Expression and Signaling in the Immune System, to be held in March, 2026, will focus on the most recent advances in this rapidly moving field. The meeting will be open, with attendance limited only by the facilities available to a maximum of ~425 participants. Oral presentations will be delivered by both invited speakers and those selected from submitted abstracts. This ensures the participation of junior and senior leaders in the field and the presentation of the most exciting results emerging at the time of the meeting. A particular emphasis will be made to ensure that a substantial number of speakers will be advanced trainees or junior PIs. The oral presentations will be complemented by poster presentations in two sessions, also selected from submitted abstracts. The areas to be covered in the 2026 meeting include 1) Regulation of gene expression; 2) Differentiation; 3) Signaling at the membrane; 4) Intracellular signaling; 5) Intercellular communication; 6) Host:microbe interactions; 7) Immune responses; and 8) Tissue-immune communication (immunophysiology). Rather than focusing on one particular type of immune cell or disease process, the meeting will highlight mechanistic approaches that aim to rigorously advance our knowledge of how the processes of signal transduction and gene regulation operate within the immune system at different scales. Ample opportunity is provided for the presentation of important, late-breaking findings. The meeting format ensures and encourages highly productive discussions, particularly during meals and in poster sessions. The meeting will foster interactions among immunologists working in related areas and provide a forum for the development of new ideas and approaches for current and future investigations of regulation of signaling and gene expression in the immune system.

NCI - National Cancer Institute

Cold Spring Harbor Laboratory Conference on The PARP Family and ADP-ribosylation March 25 to 28, 2026 ABSTRACT This proposal seeks support for a scientific meeting on “The PARP Family and ADP-ribosylation,” held at Cold Spring Harbor Laboratory (CSHL) on March 25–28, 2026. ADP-ribosylation is a reversible post- translational modification (PTM) of proteins, RNA, and DNA catalyzed by the enzymes of the PARP family— comprising 17 members in humans. PARPs utilize nicotinamide adenine dinucleotide (NAD⁺) as a substrate to transfer either a single ADP-ribose unit (mono-ADP-ribosylation, or MARylation) or multiple units in a chain (poly-ADP-ribosylation, or PARylation). Like other PTMs, ADP-ribosylation involves "writer," "eraser," and "reader" proteins. Initial research focused on the writers PARP1 and PARP2, which generate PAR chains in response to DNA damage, leading to the discovery of the synthetic lethal interaction between PARP1/2 and BRCA1/2 tumor-suppressing genes and the development of four FDA-approved dual PARP1/2 inhibitors for BRCA1/2-deficient cancers (breast, ovarian, pancreatic, and prostate), highlighting the contribution of fundamental discoveries to cancer therapeutics. Recent studies have expanded the functions of PARP1/2 beyond DNA repair and addressed the dose-limiting toxicity of PARP inhibitors in cancer therapy. There is also a growing knowledge of other PARP family members. PARP7 was recently identified in a synergistic lethal screen with histone demethylases mutated in cancer. Notably, > 50% of PARPs, including PARP7, are interferon-inducible. They, including PARP7, PARP11, and PARP14, play critical roles in modulating immune responses in cancer. Several PARP7 inhibitors are in clinical development for cancer therapy, reflecting the growing therapeutic potential of PARP family members beyond PARP1&2. Beyond the writers, recent studies have also expanded to erasers, such as PARG, in RNA ADP-ribosylation dynamics, driven by the development of potent and membrane-permeable selective PARG inhibitors. Marking a significant milestone in the field, PARG inhibitors are the first ADP-ribosylation eraser inhibitors to be evaluated in cancer clinical trials. The unique chemical composition of PAR with both sugar and ribose components renders innovations in chemical biology, structural biology, and mass spectrometry methods critical for studying ADP-ribosylation. This timely and unique meeting will bring together leading experts and emerging investigators to present and discuss cutting-edge research on PARPs and ADP-ribosylation. Sessions will span multiple disciplines, including genetics, chemical biology, and cell biology, and address topics such as DNA repair, immunity, synthetic lethality, and neurotoxicity. Each session will be co-chaired by two prominent scientists. Talks will include invited presentations from established leaders and rising stars and abstracts selected from submitted applications by graduate students, postdoctoral fellows, and junior faculty. We anticipate approximately 180 attendees, with most contributing a talk or poster. This premier meeting will promote innovation and strengthen the global ADP-ribosylation research community by integrating fundamental and translational perspectives and fostering interdisciplinary collaboration between academic and industry scientists.

NIA - National Institute on Aging

Cold Spring Harbor Laboratory Conference on Protein Homeostasis in Health and Disease April 21 - 25, 2026 ABSTRACT This proposal is a request for financial support for a meeting on PROTEIN HOMEOSTASIS IN HEALTH AND DISEASE to be held at Cold Spring Harbor Laboratory from April 21 - 25, 2026. This meeting is the premier international forum for presentation of new results in this exciting area across biology and medicine and is attended by representatives from virtually every major laboratory in the field. The explosion of new information on how the folded state of proteins is acquired and maintained in vivo and the relevance of this process to essentially all biological processes for healthy aging and risk for degenerative diseases of aging including neurodegeneration, cancer, and metabolism guarantees an excitement and urgency of this meeting. To honor the previous more-than-a-decade organizers and recognize their immense contributions to the field, Drs. Hartl and Morimoto, we will feature them in a keynote opening session. Because of the recent developments on stress signaling in aging and disease, we will next focus on cell stress response signaling, chaperone mechanisms and co-translational folding and ribosome quality control. We will then explore the roles of intrinsically disordered proteins and their roles in biological condensate formation, protein degradative mechanisms, and organellar proteostasis and spatial quality control in Aging and Disease. We will close with a session on protein misfolding and aggregation in aging as well as age-associated disorders, including Alzheimer's disease and ALS. The themes of aging, proteostasis failure, and diseases of protein misfolding are well integrated throughout each session, and emerging principles on protein client interactions and alternate protein conformations will be dominantly displayed. The diverse protein quality control strategies used by compartments of the cell to ensure the integrity of the secretory and organellar pathways during times of protein folding stress will be represented by emerging topics on spatial quality control within a cell. The field of heat shock proteins and molecular chaperones has grown exponentially and draws interest not only from traditional scientific disciplines in the basic sciences but also from diverse areas of biomedical research including neurodegenerative disease, infectious diseases, cancer, heart disease and aging. Overall, the meeting will have eight lecture sessions, two poster sessions, two lightning presentation sessions, a panel discussion on therapeutic approaches targeting proteostasis, and a daily lunch/mentoring session with the speakers. Each session will consist of eight to nine oral presentations. For each session, we have invited two speakers, who will also serve as co-chairs. The remaining speakers in each session will be selected from the submitted abstracts. All speakers will have 15 minutes talk time. In addition, each lightning sessions will have 10 pre-selected poster presenters, who will have the opportunity to highlight the key features of their work in 2-min talks. This balance of talks allows the meeting to feature presentations by leading scientists, to be responsive to exciting new developments, and to encourage participation from investigators new to this field.

NHGRI - National Human Genome Research Institute

Cold Spring Harbor Conference Systems Biology: Global Regulation of Gene Expression 2026-2030 ABSTRACT How cells control the expression of their genomes is a fundamental problem in biology. How the coordinate regulation of gene expression is affected by changes in the cellular and organismal environment is another fundamental question. Ever since the discovery that genes are encoded in the sequence of nucleotides that comprise the double strand DNA helix, there have been continuous investigations into these problems. The nuclear machineries that make transcripts as well as the many types of DNA sequences that serve to control gene expression have been discovered. Despite these efforts, many fundamental issues associated with the global regulation of gene expression remain unresolved. For example, the transcriptional regulatory sequences and the regulatory proteins for most genes in the human genome are still poorly defined. We cannot yet predict a human gene's expression pattern with high accuracy from the sequence of its surrounding regulatory DNA or the pattern of nearby epigenetic marks, or how these are affected by environmental change. Nor, in the majority of cases, can we make rational alterations to the DNA that result in specific, predefined changes in expression. It is clear that effective collaborations between experimental and computational biologists will be required to come to grips with the complex problems of gene regulation. Thus we propose to host meetings that foster the free cross-disciplinary exchange of existing ideas and expertise. It is hoped that these meetings will provide a mechanism for the establishment of new collaborations, and a forum for discussing new experimental, computational and AI-based approaches. This proposal seeks National Institutes of Health (NHGRI) funding to support the active participation of young scientists (graduate students, postdoctoral fellows and new faculty) in a continuing series of scientific meetings on systems biology, which have previously been held at Cold Spring Harbor Laboratory (CSHL) and in Puerto Rico. The 2026-2030 conferences will be managed by CSHL on the CSHL campus. These meetings are intended to foster cross- disciplinary exchange of ideas and expertise between experimentalists and computational biologists interested in the organization and control of complex transcription networks in eukaryotes. Key themes of the 2026 meeting include Mechanistic Genomics, which focuses on experimental and computational approaches to uncover causal relationships in gene regulation; Post- transcriptional Regulation, exploring RNA-based mechanisms that fine-tune gene expression; 3D Nuclear Organization, examining how chromatin architecture influences transcriptional dynamics; Single-cell Genomics, which has revolutionized our understanding of cellular heterogeneity and lineage dynamics. Additionally, advances in High Content Screening will be discussed, emphasizing large-scale perturbation and phenotypic profiling approaches. Lastly, the role of AI Embeddings and Computational Modeling in uncovering hidden biological patterns and improving regulatory sequence predictions will be explored. Oral presentations will be given by a group of distinguished invited speakers as well as speakers selected from submitted abstracts. Selected speakers will include graduate students, postdoctoral fellows and junior faculty aiming for maximal inclusion of young investigators. Of special importance are the two poster sessions, where many participants can present their work in an atmosphere conducive to informal discussion. The meeting will be of moderate size and we expect about 250-300 people to attend, the vast majority of whom will be presenting a poster or talk. This proposal seeks funding to support the participation of early career investigators in this important meeting.

Cambridge Symphony Orchestra

CSO Chamber Players Cambridge Outreach Series

Cambridge Symphony Orchestra

CSO Chamber Players Outreach Series 2013

NSF

Artificial Intelligence (AI) applications, such as ChatGPT, which can create digital content such as images, text, and video, have been considered promising for tasks like creative writing and software development. However, these AI applications’ complexity and demand for costly computational resources limit their access for many people and organizations. This project’s novelties are the creation of software-hardware solutions that enable these AI applications to run efficiently on smaller, less powerful computer systems. The project's broader significance and importance are making AI more available worldwide. This work also supports education by involving students in groundbreaking AI research and creating public AI-related tools to benefit society. This project addresses the critical challenge of running large foundation models, like those powering advanced AI applications, on smaller, resource-limited computer systems. By combining algorithmic and system-level innovations, the project seeks to improve efficiency, scalability, and resource utilization in foundation model inference, making AI more available. This project consists of three research thrusts. First, the project tackles data transfer bottlenecks between graphics processing units (GPUs) and central processing units (CPUs) by designing a sparsity-aware scheduling system. This approach prioritizes important data (tokens) and dynamically manages memory to reduce overhead. Second, the project optimizes how AI tasks are scheduled by introducing speculative execution for real-world workloads and adaptive memory management. Finally, the proposed solutions minimize GPU scheduling delays and cross-layer communication overhead using software-based solutions to improve kernel compilation. These innovations are expected to significantly reduce inference time and cut costs and energy consumption, while broadening access to AI tools for more people and organizations. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

Using ubiquitous Internet connectivity, it is possible to monitor and control the physical environment – from urban settings to rural communities to uninhabited wild lands – continuously, using digital technologies. Critical unsolved problems in the areas of extreme weather, agriculture, medicine, energy efficiency, education, sustainability, and other high-impact disciplines can be addressed through the creation and implementation of an always-on Internet of Things (IoT) that extends human perception and the ability to act at a distance using pervasively deployed and interconnected digital assets. This project develops a new unifying computer science and engineering approach to building and deploying IoT systems. This project’s novelties are a software environment and ecosystem that are operational ready using current digital technologies. The project’s broader significance is twofold. First, the project makes publicly available a new extensible IoT software infrastructure, enabling new cross-disciplinary discoveries and advances. Second, the project makes IoT more broadly accessible by unifying the technologies that are necessary to implement it as a new software capability. Scientifically, the project postulates a new, multi-scale set of computer science abstractions that are implementable on all devices from small-scale microcontrollers to the largest supercomputers. It does so as a full stack that can be implemented natively or as a guest of existing software infrastructure. It also includes a programming language approach that is general, highly concurrent (for efficiency) at large resource scales, and event-driven for implementation at embedded-system microscale. This combination of advances is integrable with existing development technologies and languages, thereby extending the accessibility of the research results that are required to achieve the project’s goals. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

The ubiquity of cameras and other sensors in our environment coupled with advances in computer vision and machine learning has enabled several novel situation awareness applications combining sensing, processing, and actuation. Many of these applications are latency sensitive, network bandwidth hungry, and geo-distributed. Edge computing has emerged as a new trend in catering to these computational needs by moving computers physically near the sensors, and is driven in part by low-cost processing resources such as Raspberry Pi and NVIDIA Jetson Nano. In the 5G/6G evolution, cell phone companies are moving network-level packet processing to geo-distributed edge data centers to amortize the computational cost of the proliferation of the wirelessly connected devices. Function-as-a-Service (FaaS) (which allows users to run code without managing server infrastructure) is an appropriate allocation paradigm to increase the utilization of resource-constrained Edge sites that host such applications, but to date its design has targeted Cloud datacenters. The project’s novelty rests in addressing the gap that exists in efficient system support for FaaS for a geo-distributed Edge ecosystem. The project’s broader significance and importance rest on the assertion that Edge computing could well be the next wave of disruption due to the emerging influence of AI and ML pervading all walks of future human endeavor. Thus, the technology nuggets from this project could spur such disruption in the technology landscape. The project is an end-to-end software system architecture for latency-sensitive situation awareness applications using the FaaS paradigm on geo-distributed Edge infrastructure. Specifically, the project makes the following advances to the state-of-the-art: programming idioms and associated runtime machinery that ensure the spatial and temporal correctness of the applications deployed on the Edge infrastructure without requiring distributed systems expertise which is largely unavailable to most developers; software control plane techniques for efficient federated orchestration across the Edge infrastructure while preserving the application’s service level objectives (SLOs) and ensuring spatio-temporal application correctness; data plane techniques for the efficient management of application state at each Edge site with respect to spatial and temporal correctness; and nimble execution environments to quickly launch application components while conserving limited Edge resources. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

This research project focuses on enhancing the performance and programmability of Field Programmable Gate Arrays(FPGAs), electronic devices whose behavior can be modified after manufacturing. Within the FPGA arena, the project further focuses on Compute-In-Memory (CIM) technology, which allows faster computing by merging memory and computer processing. The project’s novelties are the integration of CIM into specific memory blocks of FPGAs, which significantly increases computing power and energy efficiency. The project's broader significance and importance are in addressing the critical challenge of programmability in FPGAs, making them more accessible to a wider range of users, and in demonstrating the principles of open-source hardware design through prototyping CIM-enabled FPGAs. This research aims to accelerate the adoption of advanced FPGA architectures, ultimately leading to more energy-efficient and high-performance computing solutions, for processing modern workloads such as Machine Learning (ML) which require processing vast amounts of data, traditionally involving significant data movement between memory and processing units. Technically, the project employs a holistic approach that includes applications, programmability, architecture, and prototyping. It integrates CIM support into High-Level Synthesis (HLS) design frameworks, allowing for the use of high-level programming languages like C/C++ to program CIM blocks on FPGAs. Additionally, the project involves the physical design and prototyping of a CIM-enabled FPGA chip using open-source tools and technology, providing a proof-of-concept that can persuade industry vendors of its viability. Architectural enhancements in CIM blocks on FPGAs and additional applications for CIM-enabled FPGAs are also to be explored. The expected advances include a transformative impact on FPGA computing, making it a more viable alternative to accelerators like Application Specific Integrated Circuits (ASICs) for parallel workloads such as ML. The results of this research will be disseminated through educational modules, conference proceedings and journal papers, and with the release of open-source code. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

Digital platforms like cloud computing provide significant opportunities for services such as transaction processing and machine learning but also expose users to privacy risks. Fully Homomorphic Encryption (FHE) offers a promising solution by enabling computations directly on the encrypted data without the need to decrypt it, ensuring privacy and compliance with national regulations. However, while FHE guarantees confidentiality, it does not guarantee computation integrity and verifiability, leaving users vulnerable to errors or tampering. The project plans the development of a system for verifiable FHE that ensures both integrity and verifiability with low-performance overhead, enabling safer and broader applications in sensitive domains. The project's broader significance and importance are: (1) advancing the field of verifiable and private data sharing and analysis, as emphasized in the US national strategy to advance privacy-preserving data sharing and analytics; (2) deepening the understanding of interactions between verifiable algorithms, privacy-supporting computing, and trusted hardware design; and (3) enriching computer engineering curricula while encouraging STEM participation. The project develops system-level supports for efficient, verifiable, privacy-preserving data sharing and analysis with algorithm-hardware-system co-optimized solutions. It focuses on three coherent research thrusts: (1) designing near-zero-cost verifiable algorithms for linear operations in FHE-enabled encrypted computations; (2) integrating an integrity-only Trusted Execution Environment (TEE) with the first thrust to strategically support verification for both linear and non-linear FHE operations; and (3) redesigning hardware with a clean-slate TEE architecture to address side-channel vulnerabilities and minimize encryption overhead. These innovations aim to significantly enhance the scalability and trustworthy of privacy-preserving technologies in real-world applications. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

Modern Artificial Intelligence (AI)-based applications, such autonomous systems, traffic forecasting, social media, drug discovery, and chip design handle increasingly large and evolving graph-based data. Efficient processing of graph-based problems is challenging because they involve complex mathematical operations that incur performance overhead on hardware processing units. Researchers have recently leveraged methods that reduce this computational complexity via pruning redundant computational tasks, but many challenges related to computer memory and task parallelism persist. This project devises novel mathematical operators that address the bottlenecks of graph-based AI applications to increase their performance. The project also develops computer science curriculum and provides student training through integration of research results and education. Moreover, through semiconductor industry collaborations, the project engages in disseminating its research outcomes, ensuring practical adoption and deployment of emerging AI applications, such as semiconductor chip design and autonomous systems, thus improving the U.S. AI infrastructure, with significant benefits to the economy and society. Efficient processing of graph models is challenging since the underlying computations require graph-proportional matrix operators. The strong input graph dependence has led to performance scaling and sustainability challenges for massively parallel hardware processing units. Although the research community has been attempting to reduce the computational complexity of graph processing operations by introducing sparsity in the model inputs, the resulting graph-proportional operators face underutilization of vector-level parallelism, data locality, and indirect memory access patterns, resulting in diminished hardware parallelism. The aggressively sparsified matrix operators exacerbate the computational structures and patterns in already unstructured and ultra-sparse inputs. This project devises novel matrix operators tailored to efficiently exploit extreme sparsity on highly vectorized and high-core-count processors to unlock sustainable and scalable performance. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

Scientific research and engineering innovations increasingly depend on complex workflows that require coordination across many types of computing resources, ranging from small edge devices to powerful supercomputers. However, the growing complexity of these workflows and the distributed nature of the underlying computing and data cyberinfrastructure (CI) make it difficult for many researchers and engineers to fully access, manage, and benefit from these advanced technologies. The goal of iWMS is to apply new advancements in Artificial Intelligence (AI) techniques to design and implement a workflow management framework that empowers researchers, engineers, and educators to take advantage of the computing continuum for scientific discovery, innovation, and education. The framework promotes progress in science and engineering, powering applications that advance national priorities. The project designs and implements iWMS, an open, modular workflow management framework that integrates AI across the entire workflow lifecycle. In particular, iWMS incorporates AI models to support automated workflow composition, intelligent resource provisioning, performance prediction, real-time anomaly detection, and workflow adaptation. Techniques such as retrieval-augmented generation facilitate workflow discovery and assembly, while machine learning-based planning and monitoring services optimize execution and enhance system reliability. With the framework foundation built on a modular and integrated design, iWMS incorporates new AI methods as they are being developed in academia and industry. iWMS services feature documented APIs, enabling CI developers to contribute to and enhance iWMS over time. The framework is evaluated with real-world scientific applications and deployed across national testbeds and cyberinfrastructure platforms. In addition to delivering robust software tools and AI models, the project produces training materials, sample workflows, and public datasets to support adoption, foster community engagement, support AI research for enhancing CI, and advance the usability and resilience of the national cyberinfrastructure ecosystem. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

Arizona State University will investigate best practices for designing and implementing instructional coaching for computer science (CS) in the context of a large, urban school district: Clark County School District (CCSD), NV. Using a reciprocal learning approach, CSTransform seeks to advance progress in computer science education to benefit society by focusing on the overarching question: How does a large district leverage instructional coaching to develop the capacity of their high school CS teachers to teach CS in content-rich, and pedagogically engaging ways through a reciprocal learning approach? By expanding CS coaching resources and contextualizing and adapting the needs of a large school district, CSTransform will explore approaches to implement job-embedded CS coaching. The results of this study related to implementing a reciprocal lens to CS coaching and nurturing a coaching community of practice will be expanded to include professional development and implementation guidance. Moreover, this project team will co-construct a community of practice among CS coaches in CCSD while working in partnership with the Computer Science Teachers Association. Together, we will establish a national CS coaching community where instructional leaders and coaches can share their approaches, ideas, and resources with the larger community. This Small CSforAll High School Strand Research-Practice Partnership (RPP) explores the effectiveness of instructional coaching as a form of teacher professional development. Instructional coaching as a form of teacher professional development is just emerging within CS education. Research underpinning the design and implementation of CS coaching is in its nascent stage. Opportunities for CS teachers to refine their teaching and further develop their CS content, knowledge, and pedagogy beyond initial exposure is lacking. Preservice teacher programs dedicated to developing a future generation of CS teachers are also rare. This proposal will contribute to a critical domain of research to explore how a research-practitioner partnership can support and sustain job-embedded CS coaching for high school teachers and inform further scaling of such efforts. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.