KAP1 Is a Chromatin Reader that Couples Steps of RNA Polymerase II Transcription to Sustain Oncogenic Programs

Precise control of the RNA polymerase II (RNA Pol II) cycle, including pausing and pause release, maintains transcriptional homeostasis and organismal functions. Despite previous work to understand individual transcription steps, we reveal a mechanism that integrates RNA Pol II cycle transitions. Surprisingly, KAP1/TRIM28 uses a previously uncharacterized chromatin reader cassette to bind hypo-acetylated histone 4 tails at promoters, guaranteeing continuous progression of RNA Pol II entry to and exit from the pause state. Upon chromatin docking, KAP1 first associates with RNA Pol II and then recruits a pathway-specific transcription factor (SMAD2) in response to cognate ligands, enabling gene-selective CDK9-dependent pause release. This coupling mechanism is exploited by tumor cells to aberrantly sustain transcriptional programs commonly dysregulated in cancer patients. The discovery of a factor integrating transcription steps expands the functional repertoire by which chromatin readers operate and provides mechanistic understanding of transcription regulation, offering alternative therapeutic opportunities to target transcriptional dysregulation

Technical note: Extension of CERR for computational radiomics: a comprehensive MATLAB platform for reproducible radiomics research

PurposeRadiomics is a growing field of image quantitation, but it lacks stable and high-quality software systems. We extended the capabilities of the Computational Environment for Radiological Research (CERR) to create a comprehensive, open-source, MATLAB-based software platform with an emphasis on reproducibility, speed, and clinical integration of radiomics research. MethodThe radiomics tools in CERR were designed specifically to quantitate medical images in combination with CERR's core functionalities of radiological data import, transformation, management, image segmentation, and visualization. CERR allows for batch calculation and visualization of radiomics features, and provides a user-friendly data structure for radiomics metadata. All radiomics computations are vectorized for speed. Additionally, a test suite is provided for reconstruction and comparison with radiomics features computed using other software platforms such as the Insight Toolkit (ITK) and PyRadiomics. CERR was evaluated according to the standards defined by the Image Biomarker Standardization Initiative. CERR's radiomics feature calculation was integrated with the clinically used MIM software using its MATLAB((R)) application programming interface. ResultsThe CERR provides a comprehensive computational platform for radiomics analysis. Matrix formulations for the compute-intensive Haralick texture resulted in speeds that are superior to the implementation in ITK 4.12. For an image discretized into 32 bins, CERR achieved a speedup of 3.5 times over ITK. The CERR test suite enabled the successful identification of programming errors as well as genuine differences in radiomics definitions and calculations across the software packages tested. ConclusionThe CERR's radiomics capabilities are comprehensive, open-source, and fast, making it an attractive platform for developing and exploring radiomics signatures across institutions. The ability to both choose from a wide variety of radiomics implementations and to integrate with a clinical workflow makes CERR useful for retrospective as well as prospective research analyses

Identification of chemosensory receptor genes in Manduca sexta and knockdown by RNA interference

Insects detect environmental chemicals via a large and rapidly evolving family of chemosensory receptor proteins. Although our understanding of the molecular genetic basis for Drosophila chemoreception has increased enormously in the last decade, similar understanding in other insects remains limited. The tobacco hornworm, Manduca sexta, has long been an important model for insect chemosensation, particularly from ecological, behavioral, and physiological standpoints. It is also a major agricultural pest on solanaceous crops. However, little sequence information and lack of genetic tools has prevented molecular genetic analysis in this species. The ability to connect molecular genetic mechanisms, including potential lineage-specific changes in chemosensory genes, to ecologically relevant behaviors and specializations in M. sexta would be greatly beneficial. Here, we sequenced transcriptomes from adult and larval chemosensory tissues and identified chemosensory genes based on sequence homology. We also used dsRNA feeding as a method to induce RNA interference in larval chemosensory tissues. We report identification of new chemosensory receptor genes including 17 novel odorant receptors and one novel gustatory receptor. Further, we demonstrate that systemic RNA interference can be used in larval olfactory neurons to reduce expression of chemosensory receptor transcripts. Together, our results further the development of M. sexta as a model for functional analysis of insect chemosensation

Synthesis report of the IPCC Sixth Assessment Report (AR6), Longer report. IPCC.

This Synthesis Report (SYR) of the IPCC Sixth Assessment Report (AR6) summarises the state of knowledge of climate change, its widespread impacts and risks, and climate change mitigation and adaptation, based on the peer-reviewed scientific, technical and socio-economic literature since the publication of the IPCC’s Fifth Assessment Report (AR5) in 2014. The assessment is undertaken within the context of the evolving international landscape, in particular, developments in the UN Framework Convention on Climate Change (UNFCCC) process, including the outcomes of the Kyoto Protocol and the adoption of the Paris Agreement. It reflects the increasing diversity of those involved in climate action. This report integrates the main findings of the AR6 Working Group reports1 and the three AR6 Special Reports. It recognizes the interdependence of climate, ecosystems and biodiversity, and human societies; the value of diverse forms of knowledge; and the close linkages between climate change adaptation, mitigation, ecosystem health, human well-being and sustainable development. Building on multiple analytical frameworks, including those from the physical and social sciences, this report identifies opportunities for transformative action which are effective, feasible, just and equitable using concepts of systems transitions and resilient development pathways. Different regional classification schemes are used for physical, social and economic aspects, reflecting the underlying literature. After this introduction, Section 2, ‘Current Status and Trends’, opens with the assessment of observational evidence for our changing climate, historical and current drivers of human-induced climate change, and its impacts. It assesses the current implementation of adaptation and mitigation response options. Section 3, ‘Long-Term Climate and Development Futures’, provides a long-term assessment of climate change to 2100 and beyond in a broad range of socio-economic futures. It considers long-term characteristics, impacts, risks and costs in adaptation and mitigation pathways in the context of sustainable development. Section 4, ‘Near-Term Responses in a Changing Climate’, assesses opportunities for scaling up effective action in the period up to 2040, in the context of climate pledges, and commitments, and the pursuit of sustainable development. Based on scientific understanding, key findings can be formulated as statements of fact or associated with an assessed level of confidence using the IPCC calibrated language5 . The scientific findings are drawn from the underlying reports and arise from their Summary for Policymakers (hereafter SPM), Technical Summary (hereafter TS), and underlying chapters and are indicated by {} brackets. Figure 1.1 shows the Synthesis Report Figures Key, a guide to visual icons that are used across multiple figures within this report

IPCC, 2023: Climate Change 2023: Synthesis Report, Summary for Policymakers. Contribution of Working Groups I, II and III to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change [Core Writing Team, H. Lee and J. Romero (eds.)]. IPCC, Geneva, Switzerland.

This Synthesis Report (SYR) of the IPCC Sixth Assessment Report (AR6) summarises the state of knowledge of climate change, its widespread impacts and risks, and climate change mitigation and adaptation. It integrates the main findings of the Sixth Assessment Report (AR6) based on contributions from the three Working Groups1 , and the three Special Reports. The summary for Policymakers (SPM) is structured in three parts: SPM.A Current Status and Trends, SPM.B Future Climate Change, Risks, and Long-Term Responses, and SPM.C Responses in the Near Term.This report recognizes the interdependence of climate, ecosystems and biodiversity, and human societies; the value of diverse forms of knowledge; and the close linkages between climate change adaptation, mitigation, ecosystem health, human well-being and sustainable development, and reflects the increasing diversity of actors involved in climate action. Based on scientific understanding, key findings can be formulated as statements of fact or associated with an assessed level of confidence using the IPCC calibrated language

The Effects of Financial Liberalization on the Growth of the Jamaican Economy

(Statement of Responsibility) by Aditi Shukla(Thesis) Thesis (B.A.) -- New College of Florida, 2009(Electronic Access) RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE(Bibliography) Includes bibliographical references.(Source of Description) This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.(Local) Faculty Sponsor: Khemraj, Tarro

Extracting Knowledge from User Access Logs

Abstract- As the size of web increases along with number of users, it is very much essential for the website owners to better understand their customers so that they can provide better service, and also enhance the quality of the website. To achieve this they depend on the web access log files.. It is is a file to which the Web server writes information each time a user requests a resource from that particular site. In this paper we will study web access log files and the information we can mine from logs which is useful in understanding user behavior. This information is used in restructuring and redesigning of the website. Index Terms- web mining, usage mining, server logs, pattern mining. I I