A5031489667- Radiology practices and education
- Breast Cancer Treatment Studies
- Renal Transplantation Outcomes and Treatments
- Topic Modeling
- Radiation Dose and Imaging
- Cell Adhesion Molecules Research
- Natural Language Processing Techniques
- Advances in Oncology and Radiotherapy
- Organ Donation and Transplantation
- Breast Lesions and Carcinomas
- Endoplasmic Reticulum Stress and Disease
- Ultrasound in Clinical Applications
- Innovations in Medical Education
- Monoclonal and Polyclonal Antibodies Research
- Complement system in diseases
- Radiomics and Machine Learning in Medical Imaging
- Cancer-related Molecular Pathways
- Online and Blended Learning
- Education and Technology Integration
- Immune Response and Inflammation
- AI in cancer detection
- Education and Critical Thinking Development
- Protein Degradation and Inhibitors
- Renal Diseases and Glomerulopathies
- Medical Malpractice and Liability Issues
Google (United States)
2022-2025
University of Colorado Boulder
2022-2025
The University of Texas MD Anderson Cancer Center
2018-2024
University of Connecticut
2019-2024
Molecular Oncology (United States)
2024
Massachusetts General Hospital
2024
DeepMind (United Kingdom)
2024
Anaheim University
2024
University of Colorado System
2024
MRC Weatherall Institute of Molecular Medicine
2023
Masked language modeling (MLM) pre-training methods such as BERT corrupt the input by replacing some tokens with [MASK] and then train a model to reconstruct original tokens. While they produce good results when transferred downstream NLP tasks, generally require large amounts of compute be effective. As an alternative, we propose more sample-efficient task called replaced token detection. Instead masking input, our approach corrupts it plausible alternatives sampled from small generator...
Voltage-gated sodium (Nav) channels propagate action potentials in excitable cells. Accordingly, Nav are therapeutic targets for many cardiovascular and neurological disorders. Selective inhibitors have been challenging to design because the nine mammalian channel isoforms share high sequence identity remain recalcitrant high-resolution structural studies. Targeting human Nav1.7 involved pain perception, we present a protein-engineering strategy that has allowed us determine crystal...
In many of the secondary classrooms across country, students are passively engaged in mathematics content, and academic performance can be described, at best, as mediocre. This research study sought to bring about improvements student engagement classroom through implementation flipped model instruction compared interaction with a traditional format. The is relatively new teaching strategy attempting improve by moving lecture outside via technology homework exercises concepts inside learning...
Recent artificial intelligence (AI) systems have reached milestones in "grand challenges" ranging from Go to protein-folding. The capability retrieve medical knowledge, reason over it, and answer questions comparably physicians has long been viewed as one such grand challenge. Large language models (LLMs) catalyzed significant progress question answering; Med-PaLM was the first model exceed a "passing" score US Medical Licensing Examination (USMLE) style with of 67.2% on MedQA dataset....
Large language models (LLMs) have shown promise in medical question answering, with Med-PaLM being the first to exceed a 'passing' score United States Medical Licensing Examination style questions. However, challenges remain long-form answering and handling real-world workflows. Here, we present 2, which bridges these gaps combination of base LLM improvements, domain fine-tuning new strategies for improving reasoning grounding through ensemble refinement chain retrieval. 2 scores up 86.5% on...
The angiopoietin family of secreted factors is functionally defined by the C-terminal fibrinogen (FBN)-like domain, which mediates binding to Tie2 receptor and thereby facilitates a cascade events ultimately regulating blood vessel formation. By screening expressed sequence tag data bases for homologies consensus FBN-like motive, we have identified ANGPTL3, liver-specific, factor consisting an N-terminal coiled-coil domain domain. Co-immunoprecipitation experiments, however, failed detect...
Inhibition of the bromodomain transcriptional regulator CBP/P300 is an especially interesting new therapeutic approach in oncology. We recently disclosed vivo chemical tool 1 (GNE-272) for CBP that was moderately potent and selective over BRD4(1). In pursuit a more inhibitor, we used structure-based design. Constraining aniline into tetrahydroquinoline motif maintained potency increased selectivity 2-fold. Structure–activity relationship studies coupled with further design targeting LPF...
Multiple myeloma (MM) arises from malignant immunoglobulin (Ig)-secreting plasma cells and remains an incurable, often lethal disease despite therapeutic advances. The unfolded-protein response sensor IRE1α supports protein secretion by deploying a kinase-endoribonuclease module to activate the transcription factor XBP1s. MM may co-opt IRE1α-XBP1s pathway; however, validity of as potential target is controversial. Genetic disruption or XBP1s, pharmacologic kinase inhibition, attenuated...
The protein-protein interaction between leukocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte immune system function. Here, we report on the transfer of contiguous, nonlinear epitope ICAM-1, responsible for its association with LFA-1, a small-molecule framework. These LFA-1 antagonists bound blocked binding inhibited mixed reaction (MLR) potency significantly greater than that cyclosporine A. Furthermore, in comparison an antibody...
Beginning with promiscuous COT inhibitors, which were found to inhibit CDK8, a series of 6-aza-benzothiophene containing compounds developed into potent, selective CDK8 inhibitors. When cocrystallized and cyclin C, these exhibit an unusual binding mode, making single hydrogen bond the hinge residue A100, second K252, key cation-π interaction R356. Structure-based drug design resulted in tool 13 32, are highly kinase selective, permeable free fraction >2% no measurable efflux. Despite...
Summary— Of 161 flexible cystoscopies performed in an out‐patient endoscopy suite, the incidence of urinary tract infection was 7.5%. Infection rates were higher patients with a history previous or where additional procedure also performed. No difference noted between men and women.
Using Sorafenib as a starting point, series of potent and selective inhibitors CDK8 was developed. When cocrystallized with cyclin C, these compounds exhibit Type-II (DMG-out) binding mode.
Barriers exist in access to kidney transplantation, where minority and patients with low socioeconomic status are less likely complete transplant evaluation. The purpose of this study was examine the effectiveness a center-based patient navigator helping at high risk dropping out evaluation process waiting list.We conducted randomized, controlled trial 401 (n=196 intervention n=205 control) referred for (January 2013 August 2014; followed through May 2016) single center. A trained assisted...
The migration, adhesion, and subsequent extravasation of leukocytes into inflamed tissues contribute to the pathogenesis a variety inflammatory diseases including asthma, rheumatoid arthritis, bowel disease, multiple sclerosis. integrin adhesion receptor alpha 4 beta 1 expressed on binds extracellular matrix protein fibronectin cytokine inducible vascular cell molecule-1 (VCAM-1) at sites. Binding VCAM-1 initiates firm leukocyte endothelium followed by tissue. Monoclonal antibodies generated...
Abstract Inositol-Requiring Enzyme 1 (IRE1) is an essential component of the Unfolded Protein Response. IRE1 spans endoplasmic reticulum membrane, comprising a sensory lumenal domain, and tandem kinase endoribonuclease (RNase) cytoplasmic domains. Excess unfolded proteins in ER lumen induce dimerization oligomerization IRE1, triggering trans-autophosphorylation RNase activation. Known ATP-competitive small-molecule inhibitors either allosterically disrupt or stabilize active dimeric unit,...
Endoplasmic-reticulum resident inositol-requiring enzyme 1α (IRE1) supports protein homeostasis via its cytoplasmic kinase-RNase module. Known cancer dependency on IRE1 entails enzymatic activation of the transcription factor XBP1s and regulated RNA decay. We discovered that some cells surprisingly require but not activity. knockdown inhibition or XBP1 disruption attenuated cell cycle progression tumor growth. silencing led to TP53 CDKN1A/p21 in conjunction with increased DNA damage...
Abstract: The Spring 2025 Issue. Ploughshares is an award-winning journal of new writing. Since 1971, has discovered and cultivated the freshest voices in contemporary American literature, now provides readers with thoughtful entertaining literature a variety formats. Find out why New York Times named "the Triton among minnows." Issue, edited by Peggy Schumaker, features poetry prose Naomi Shihab Nye, Felicia Zamora, Tim Seibles, Lena Khalaf Tuffaha, Lia Purpura, Sonja Livingston, Marjorie...