515 research outputs found
A Proposal for a Comprehensive Restructuring of the Public Information System
After more than ten years of legislative, judicial and bureaucratic tinkering, the public information system created by the Freedom of Information Act (FOIA) is still far from satisfactory. The present public information system has not been successful because its drafters lacked imagination and failed to do the basic work necessary to create a sound foundation for such a comprehensive program. They failed to analyze the realistic goals of a public information system; they ignored the ultimate goals of improved government performance; they misrepresented the system\u27s costs, both in monetary expense to taxpayers and in diminished government performance. They considered neither alternative techniques nor the problem of designing the public information system as an integral part of the total governmental structure. Actual open government for the benefit of the general populace will be possible only if the basic weaknesses of the present system are explored in depth. This Article is an appeal to Congress to undertake the careful analysis necessary to construct a workable, useful public information system
Tuberculosis
Asserts that despite progress in controlling tuberculosis (TB), the decline in incidence has been disappointing, pointing to the need for new strategies and more effective tools. HIV/AIDS is one factor that challenges effective control of TB, especially in Southern African countries. Three key elements are needed to achieve effective TB control and to meet the Sustainable Development Goals: (1) early and accurate diagnosis and drug-sensitivity testing, (2) patient access to and completion of effective treatment, and (3) prevention of progression from latent infection to disease. Prevention requires vaccination and screening of individual at high risk as well as interventions such as air disinfection and the use of masks and respirators in hospitals and other congregate settings. Recommendations stress the need to strengthen health systems in high-burden countries by emphasizing community-based care over hospital care; to improve information systems to ensure patient adherence and manage medication supply chains; and to invest in research to develop the necessary interventions. Fundamentally, current global TB control strategies must undergo revision and receive significant research funding
Photoproduction of phi(1020) mesons on the proton at large momentum transfer
The cross section for meson photoproduction on the proton has been
measured for the first time up to a four-momentum transfer -t = 4 GeV^2, using
the CLAS detector at the Thomas Jefferson National Accelerator Facility. At low
four-momentum transfer, the differential cross section is well described by
Pomeron exchange. At large four-momentum transfer, above -t = 1.8 GeV^2, the
data support a model where the Pomeron is resolved into its simplest component,
two gluons, which may couple to any quark in the proton and in the .Comment: 5 pages; 7 figure
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images
of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL
maps are derived through computational staining using a convolutional neural network trained to
classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and
correlation with overall survival. TIL map structural patterns were grouped using standard
histopathological parameters. These patterns are enriched in particular T cell subpopulations
derived from molecular measures. TIL densities and spatial structure were differentially enriched
among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial
infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic
patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for
the TCGA image archives with insights into the tumor-immune microenvironment
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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The Internal-External Security Nexus and EU Police/Rule of Law Missions in the Western Balkans
Common Security and Defence Policy (CSDP) police/rule of law missions in the Western Balkans are increasingly guided by externally imposed normative agendas that respond primarily to EU internal security needs rather than functional imperatives or local realities. In line with these needs, EU police reform efforts tend to prioritise effectiveness and crime fighting over longer- term democratic policing and good governance reforms. In practice this means that police reform initiatives are technocratically oriented, yet value ridden fitting EU security concerns and needs. As a result, the police reform process can be—and often is—disconnected from the political and socio-economic reforms necessary for long-term stability and sustainable peace. Police assistance in Bosnia and Herzegovina has been shaped by a determined albeit questionable focus on organised crime and corruption. The focus of EU police reform in Macedonia on primarily crime-fighting aspects of policing has compromised the functioning of the Macedonian police. Similarly, the politics of (non-)recognition of Kosovo's self-proclaimed independence and the intrusiveness of EULEX Kosovo's executive mandate contravene meeting local challenges
Deeply virtual and exclusive electroproduction of omega mesons
The exclusive omega electroproduction off the proton was studied in a large
kinematical domain above the nucleon resonance region and for the highest
possible photon virtuality (Q2) with the 5.75 GeV beam at CEBAF and the CLAS
spectrometer. Cross sections were measured up to large values of the
four-momentum transfer (-t < 2.7 GeV2) to the proton. The contributions of the
interference terms sigma_TT and sigma_TL to the cross sections, as well as an
analysis of the omega spin density matrix, indicate that helicity is not
conserved in this process. The t-channel pi0 exchange, or more generally the
exchange of the associated Regge trajectory, seems to dominate the reaction
gamma* p -> omega p, even for Q2 as large as 5 GeV2. Contributions of handbag
diagrams, related to Generalized Parton Distributions in the nucleon, are
therefore difficult to extract for this process. Remarkably, the high-t
behaviour of the cross sections is nearly Q2-independent, which may be
interpreted as a coupling of the photon to a point-like object in this
kinematical limit.Comment: 15 pages,19 figure
Clinical Camel: An Open Expert-Level Medical Language Model with Dialogue-Based Knowledge Encoding
We present Clinical Camel, an open large language model (LLM) explicitly
tailored for clinical research. Fine-tuned from LLaMA-2 using QLoRA, Clinical
Camel achieves state-of-the-art performance across medical benchmarks among
openly available medical LLMs. Leveraging efficient single-GPU training,
Clinical Camel surpasses GPT-3.5 in five-shot evaluations on all assessed
benchmarks, including 64.3% on the USMLE Sample Exam (compared to 58.5% for
GPT-3.5), 77.9% on PubMedQA (compared to 60.2%), 60.7% on MedQA (compared to
53.6%), and 54.2% on MedMCQA (compared to 51.0%). In addition to these
benchmarks, Clinical Camel demonstrates its broader capabilities, such as
synthesizing plausible clinical notes. This work introduces dialogue-based
knowledge encoding, a novel method to synthesize conversational data from dense
medical texts. While benchmark results are encouraging, extensive and rigorous
human evaluation across diverse clinical scenarios is imperative to ascertain
safety before implementation. By openly sharing Clinical Camel, we hope to
foster transparent and collaborative research, working towards the safe
integration of LLMs within the healthcare domain. Significant challenges
concerning reliability, bias, and the potential for outdated knowledge persist.
Nonetheless, the transparency provided by an open approach reinforces the
scientific rigor essential for future clinical applications.Comment: for model weights, see https://huggingface.co/wanglab
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