241 research outputs found
Modelling double strand break susceptibility to interrogate structural variation in cancer
No full textStructural variants (SVs) are known to play important roles in a variety of cancers, but their origins and functional consequences are still poorly understood. The nonrandom distributions of these variants across tumour genomes are often assumed to reflect selective processes, but, as with single nucleotide variants, SV mutation rates often reflect the underlying chromatin and other features at a locus. Inferring which SVs may be under selection in tumourigenesis therefore remains challenging, though identifying such variants may lead to new diagnostic and therapeutic targets. Many SVs are thought to emerge via errors in the repair processes following DNA double strand breaks (DSBs) and a variety of studies have experimentally measured DSB frequencies across the genome in cell lines. Using these data we derive the first quantitative genome-wide models of DSB susceptibility, based upon underlying chromatin and sequence features. These models provide high predictive accuracy and novel insights into the mutational mechanisms generating DSBs. Models trained in one cell type can be successfully applied to others, but a substantial proportion of DSBs appear to reflect cell type specific processes. We also show that regions harboring unusually high tumour SV breakpoint frequencies occur within well modeled regions of the genome but often display DSB frequencies inconsistent with DSB model predictions. Using model predictions as a proxy for susceptibility to DSBs in tumours, many SV hotspots appear to be poorly explained by selectively neutral mutational bias alone. A substantial number of hotspots show unexpectedly high SV breakpoint frequencies given their predicted susceptibility to mutation, and are therefore credible targets of positive selection in tumours. These putatively positively selected hotspots are enriched for genes previously shown to be oncogenic. In contrast, several hundred regions across the genome show unexpectedly low levels of SVs, given their relatively high susceptibility to mutation. These novel ‘coldspot’ regions appear to be subject to purifying selection in tumours and are enriched for active promoters and enhancers. We conclude that models of DSB susceptibility offer a rigorous approach to the inference of SVs putatively subject to selection in tumours
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Analysis of genomic rearrangements in cancer from high throughput sequencing data
No full textIn the last century cancer has become increasingly prevalent and is the second largest killer in the United States, estimated to afflict 1 in 4 people during their life. Despite our long history with cancer and our herculean efforts to thwart the disease, in many cases we still do not understand the underlying causes or have successful treatments. In my graduate work, I’ve developed two approaches to the study of cancer genomics and applied them to the whole genome sequencing data of cancer patients from The Cancer Genome Atlas (TCGA). In collaboration with Dr. Ewing, I built a pipeline to detect retrotransposon insertions from paired-end high-throughput sequencing data and found somatic retrotransposon insertions in a fifth of cancer patients. My second novel contribution to the study of cancer genomics is the development of the CN-AVG pipeline, a method for reconstructing the evolutionary history of a single tumor by predicting the order of structural mutations such as deletions, duplications, and inversions. The CN-AVG theory was developed by Drs. Haussler, Zerbino, and Paten and samples potential evolutionary histories for a tumor using Markov Chain Monte Carlo sampling. I contributed to the development of this method by testing its accuracy and limitations on simulated evolutionary histories. I found that the ability to reconstruct a history decays exponentially with increased breakpoint reuse, but that we can estimate how accurately we reconstruct a mutation event using the likelihood scores of the events. I further designed novel techniques for the application of CN-AVG to whole genome sequencing data from actual patients and applied these techniques to search for evolutionary patterns in glioblastoma multiforme using sequencing data from TCGA. My results show patterns of two-hit deletions, as we would expect, and amplifications occurring over several mutational events. I also find that the CN-AVG method frequently makes use of whole chromosome copy number changes following by localized deletions, a bias that could be mitigated through modifying the cost function for an evolutionary history
KOME SMETA SLOVENSKI IDENTITET U TRŠĆANSKOME ZALJEVU? NEKE MISLI O ČLANKU PAMELE BALLINGER "CRTE U VODI, LJUDI NA KARTI: PREDOČAVANJE 'GRANICA' KULTURNIH SKUPINA NA SJEVERNOM JADRANU" (NARODNA UMJETNOST. HRVATSKI ČASOPIS ZA ETNOLOGIJU I FOLKLORISTIKU 43/1, 2006, STR. 15-39)
No full textThis aricle was written as a response to Pamela Ballinger's study of maritime museums in the Upper Adriatic and was based on the knowledge of this author on the museums in question, of places and circumstances of their origin, and of their broader historical context. It is this author's belief that Pamela Ballinger is insufficiently familiar with the area in question as well as with relevant publications from the field of social sciences. It seems that Ballinger's study had been written on the basis of preconceived, yet unsubstantiated conceptions that the museums, which help preserve and present cultural heritage of the people living along the Gulf of Trieste and which do not hide their Slovene identity, build walls between cultures. With her biased hints about their ties with nationalistic claims on the sea and on mainland territory Ballinger strayed far from scientific correctness.Članak je napisan kao odgovor na tekst Pamele Ballinger o maritimnim muzejima na sjeveru Jadranskoga mora. Temelji se na autoričinu poznavanju muzeja i mjesta koja su razmatrana u navedenome tekstu, na poznavanju okolnosti u kojima su ti muzeji nastali i širega povijesnoga konteksta u kojemu se zbivao cijeli proces. Autorica smatra da je Pamela Ballinger nedovoljno upoznata s tom regijom, kao i s relevantnim publikacijama o njoj iz područja društvenih znanosti. Pretpostavlja se da je Ballinger napisala svoj tekst na temelju nedovoljno argumentirane teze da muzeji koji pomažu očuvati i predstaviti kulturno naslijeđe ljudi u Tršćanskome zaljevu, a koji ne skrivaju svoj slovenski identitet, izgrađuju zidove među kulturama. Svojim pristranim tvrdnjama o njihovim vezama s nacionalističkim presizanjima nad morem i nad kopnom Ballinger se udaljila od znanstvene korektnosti
Drive-by requests… driving you nuts? Get out of email and into a bona fide ticket-tracking system… Spiceworks!
No full textIf you are keeping track of support issues through email, or worse sticky-notes, you need a ticketing system! The Delphi Center at UofL has been tracking all support request for Blackboard for the last three years. We will be discussing our experiences and help you get started
Chinese Ceramics: The Wong Collection
No full texttableOfContents: Preface Page iv
Introduction Page v
Notes Page xi
Chronology Page xiii
Collection Page 1
Acknowledgements Page 8
Lines in the Water, Peoples on the Map: Maritime Museums and the Representation of Cultural Boundaries in the Upper Adriatic
No full textThis article explores the relationship between political and symbolic borders in the Gulf of Trieste. The author inquires into the persistence of understandings that map peoples onto specific territories and terrains, such as the stereotypical association of Italians with the coast and Slavic peoples (Slovenes and Croats) with the rural interior. Focusing on representations of maritime culture along two contentious political borders – that between Italy and Slovenia and that between Slovenia and Croatia – the analysis demonstrates that museums become powerful sites for the reproduction of the coast/interior cultural boundary, even when the specific ethnic groups it maps onto change
Abstract A29: Searching for retrotransposon insertions from paired end sequencing of tumors
No full textPost trade liberalization policy and institutional challenges in Latin America and the Caribbean
No full textArgentina, Chile, Colombia, Jamaica, Trinidad and Tobago, and Uruguay undertook extensive trade reform at a time of crisis, at which time institutional reform was difficult to undertake. Many of the countries had become members of the General Agreement on Tariffs and Trade (GATT) in the late 1980s and anticipated institutional reform. Only later did they reform trade policymaking institutions to bring them somewhat in line with trade policy regimes and GATT rules. These countries have all used reference prices and antidumping provisions of GATT, rather than safeguards, to provide relief from import surges. They have all tried to centralize trade policy by moving it from different agencies into a single agency. Despite liberalization, some sectors -- including automobiles, textiles and agriculture -- remain protected. Lessons the author draws from experience in these coutries: 1) the deteriorating macroeconomic situations are the main challenge to maintaining open trade policy; 2) trade policymaking must be constantly reviewed to prevent reversals, and the costs of protection must be communicated to the public at large; 3) There must be short-run measures to help domestic activities adjust to short-run price movements and alleviate pressure for protection. The danger -- such measures (unrelated to long-run price trends) can become permanent. 4) external commitments (through WTO or customs unions) can be used to discourage a return to protection; 5) extending reform (to labor and capital markets and the regulatory framework) will help maintain and extend trade liberalization. Allowing factors of production to move smoothly from one activity to another could help prevent the buildup of pressures that lead to protection; 6) an institution to consider exceptional protection should be advisory (independent of day-to-day trade policymaking), so that it works steadily, free from administrative pressures and exigencies. Requests for protection must be handled openly and transparently, with the findings subject to public scrutiny. Procedures for granting relief through safeguards and similar mechanisms must reflect all interests, including those of consumers, exporters, and users of the product; and 7) the analysis to establish injury must conform to high technical standards. The criteria to consider trade policies must reflect national interests, not those of any particular sector.Economic Theory&Research,Common Carriers Industry,Trade Policy,Environmental Economics&Policies,Payment Systems&Infrastructure,TF054105-DONOR FUNDED OPERATION ADMINISTRATION FEE INCOME AND EXPENSE ACCOUNT,Economic Theory&Research,Trade Policy,Environmental Economics&Policies,Transport and Trade Logistics
EUCP Atlas of constrained climate projections
No full textWhat's Changed Change author order in citation.cff by @Peter9192 in https://github.com/eucp-project/atlas/pull/61 Full Changelog: https://github.com/eucp-project/atlas/compare/0.1.0...0.1.1Kalverla, P., Alidoost, F., Liu, Y., Verhoeven, S., Vreede, B., Booth, B., Coppola, E., Nogherotto, R., Brunner, L., Harris, G., Qasmi, S., Ballinger, A., Hegerl, G., McSweeney, C., O'Reilly, C., Palmer, T., Ribes, A., & de Vries, H. (2021). EUCP Atlas of constrained climate projections (0.1.1). Zenodo. https://doi.org/10.5281/zenodo.565474
Cultural Competency in Child Life: Is There a Gap Between Cultures in Pediatric Care That We Can Fill?
No full textabstract: Intercultural competency is becoming more crucial for effective communication as the world becomes more global and interconnected. This issue is particularly true in health care settings, where effective communication is essential for providing the best care possible. There is very little research about intercultural competence training for Child Life Specialists whose primary role is to communicate with the patients and parents. The purposes of this study was to investigate 1) the levels of cultural competency training Child Life Specialists (CLSs) report having received, as well as their interest in more training, 2) assessing the extent to which CLSs are providing culturally competent care (self-reported), 3) understanding the extent to which barriers to providing culturally competent care are present, 4) identifying relations between culturally competent practice, barriers, and perceived feelings of success, and 5) determining whether there are group differences on culturally competent practice, barriers, and perceived feelings of success between those who reported having received training and those who reported no training. A total of 42 Child Life Specialists completed an online survey. Results indicated a variety of training experiences, with those reporting more training perceiving fewer barriers to culturally competent care. A strong interest in more training was also revealed
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