Publications

Cellular senescence is a tumor suppressive mechanism that can paradoxically contribute to aging pathologies. Despite evidence of immune clearance in mouse models, it is not known how senescent cells (SnCs) persist and accumulate with age or in tumors in individuals. Here, we identify cooperative mechanisms that orchestrate the immunoevasion and persistence of normal and cancer human SnCs through extracellular targeting of natural killer receptor signaling. Damaged SnCs avoid immune recognition through MMPs-dependent shedding of NKG2D-ligands reinforced via paracrine suppression of NKG2D receptor-mediated immunosurveillance. These coordinated immunoediting processes are evident in residual, drug-resistant tumors from cohorts of >700 prostate and breast cancer patients treated with senescence-inducing genotoxic chemotherapies. Unlike in mice, these reversible senescence-subversion mechanisms are independent of p53/p16 and exacerbated in oncogenic RAS-induced senescence. Critically, the p16INK4A tumor suppressor can disengage the senescence growth arrest from the damage-associated immune senescence program, which is manifest in benign nevi lesions where indolent SnCs accumulate over time and preserve a non-pro-inflammatory tissue microenvironment maintaining NKG2D-mediated immunosurveillance. Our study shows how subpopulations of SnCs elude immunosurveillance, and reveals secretome-targeted therapeutic strategies to selectively eliminate -and restore the clearance of- the detrimental SnCs that actively persist after chemotherapy and accumulate at sites of aging pathologies.

Current state of the art Na-ion battery cathodes are selected from the broad chemical space of layered first row transition metal (TM) oxides. Unlike their lithium ion counterparts, seven first row layered TM oxides can intercalate Na ions reversibly. Their voltage curves also indicate significant and numerous reversible phase transformations during electrochemical cycling. These transformations are not yet fully understood, but arise from Na-ion vacancy ordering and metal oxide slab glide. In this study, we investigate the nature of vacancy ordering transformations within the O3, P3 and P2 lattice frameworks. We generate predicted electrochemical voltage curves for each of the Na-ion intercalating layered single TM oxides using a high-throughput framework of density functional theory (DFT) calculations. We determine a set of vacancy ordered phases appearing as ground states in all Na\textsubscript{x}MO\textsubscript{2} systems, and investigate the effect of ordering interactions between adjacent layers. We further investigate the role of TM choice and TM mixing in mitigating phase transformations and synthesis of O3 and P2 type materials.

Even with the renaissance in gamma-ray burst (GRB) research fostered by the Swift satellite, few bursts have both contemporaneous observations at long wavelengths and exquisite observations at later times across the electromagnetic spectrum. We present here contemporaneous imaging with the KAIT robotic optical telescope, dense optical sampling with Lulin, supplemented with infrared data from PAIRITEL and radio to gamma-ray data from the literature. For the first time, we can test the constancy of microphysical parameters in the internal-external shock paradigm and carefully trace the flow of energy from the GRB to the surrounding medium. KAIT data taken ≤1 minute after the start of GRB 051111 and coinciding with the fading gamma-ray tail of the prompt emission indicate a smooth reinjection of energy into the shock. No color change is apparent in observations beginning ∼ 1.5 minutes after the GRB and lasting for the first hour after the burst. There are achromatic flux modulations about the best-fit model at late (t ≈ 104 s) times, possibly due to variations in the external density. We find that the host galaxy extinction is well fit by a curve similar to that of the Small Magellanic Cloud. Low visual extinction, AV ≈ 0.2 mag, combined with high column densities determined from the X-ray and optical spectroscopy (NH > 10 21 cm-2), indicate a low dust-to-metals ratio and a possible overabundance of the light metals. An apparent small ratio of total to selective extinction (RV ≈ 2) argues against dust destruction by the GRB. Time constancy of both the IR/optical/UV spectral energy distribution and the soft X-ray absorption suggests that the absorbing material is not local to the GRB. © 2006. The American Astronomical Society. All rights reserved.

State-of-the-art approaches to ObjectGoal navigation (ObjectNav) rely on reinforcement learning and typically require significant computational resources and time for learning. We propose Potential functions for ObjectGoal Navigation with Interaction-free learning (PONI), a modular approach that disentangles the skills of 'where to look?' for an object and 'how to navigate to <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$(x,\ y)$</tex> ?'. Our key insight is that 'where to look?' can be treated purely as a perception problem, and learned without environment interactions. To address this, we propose a network that predicts two complementary potential functions conditioned on a semantic map and uses them to decide where to look for an unseen object. We train the potential function network using supervised learning on a passive dataset of top-down semantic maps, and integrate it into a modular framework to perform ObjectNav. Experiments on Gibson and Matterport3D demonstrate that our method achieves the stateof-the-art for ObjectNav while incurring up to <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$1,600\times less$</tex> computational cost for training. Code and pre-trained models are available. <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> Website: https://vision.cs.utexas.edu/projects/poni/

Novel microcavities are fabricated that consist of GaAs microdisks (-3 l m diameter) sandwiched betwecn AlAs cladding, bounded by a circular grating of deeply etched air trenches.An enutting layer of I d s quantum dots is insend in GaAs.The prating acts as a 4thorder Bragg reflector for the in-plane cavity, so that some 2nd-order diffraclion towards air can occur.This allows to Microdirks modes usually requlre lugh azimuthal number 1 to be confined through toral internal reflection, while drum-like modes with low-azimuthal number I only see the poorer norms1 reflection at the semiconductor-air interface (30%).In our cavity, the circular Bragg mirror ic

Pretraining Large Language Models (LLMs) on large corpora of textual data is now a standard paradigm. When using these LLMs for many downstream applications, it is common to additionally bake in new knowledge (e.g., time-critical news, or private domain knowledge) into the pretrained model either through RAG-based-prompting, or fine-tuning. However, the optimal methodology for the model to gain such new knowledge remains an open question. In this paper, we present Retrieval Augmented FineTuning (RAFT), a training recipe that improves the model's ability to answer questions in a "open-book" in-domain settings. In RAFT, given a question, and a set of retrieved documents, we train the model to ignore those documents that don't help in answering the question, which we call, distractor documents. RAFT accomplishes this by citing verbatim the right sequence from the relevant document that would help answer the question. This coupled with RAFT's chain-of-thought-style response helps improve the model's ability to reason. In domain-specific RAG, RAFT consistently improves the model's performance across PubMed, HotpotQA, and Gorilla datasets, presenting a post-training recipe to improve pre-trained LLMs to in-domain RAG. RAFT's code and demo are open-sourced at github.com/ShishirPatil/gorilla.

Core competencies have been used to redefine curricula across the major health professions in recent decades. In 2006, the Association of Schools of Public Health identified core competencies for the master of public health degree in graduate schools and programs of public health. We provide an overview of the model development process and a listing of 12 core domains and 119 competencies that can serve as a resource for faculty and students for enhancing the quality and accountability of graduate public health education and training. The primary vision for the initiative is the graduation of professionals who are more fully prepared for the many challenges and opportunities in public health in the forthcoming decade.

Streptomyces genomes have a high G + C content and typically use an ATG or GTG codon to initiate protein synthesis. Although gene-finding tools perform well in low GC genomes, it is known that the accuracy in predicting a translational start site (TSS) is much less for high GC genomes. LipPks1 is a Streptomyces-derived, well-characterized modular polyketide synthase (PKS). Using this enzyme as a model, we experimentally investigated the effects of alternative TSSs using a heterologous host, Streptomyces venezuelae. One of the TSSs employed boosted the protein level by 59-fold and the product yield by 23-fold compared to the originally annotated start codon. Interestingly, a structural model of the PKS indicated the presence of a structural motif in the N-terminus, which may explain the observed different protein levels together with a proline and arginine-rich sequence that may inhibit translational initiation. This structure was also found in six other modular PKSs that utilize noncarboxylated starter substrates, which may guide the selection of optimal TSSs in conjunction with start-codon prediction software.