An Integrative Genomic and Epigenomic Approach for the Study of Transcriptional Regulation

The molecular heterogeneity of acute leukemias and other tumors constitutes a major obstacle towards understanding disease pathogenesis and developing new targeted-therapies. Aberrant gene regulation is a hallmark of cancer and plays a central role in determining tumor phenotype. We predicted that integration of different genome-wide epigenetic regulatory marks along with gene expression levels would provide greater power in capturing biological differences between leukemia subtypes. Gene expression, cytosine methylation and histone H3 lysine 9 (H3K9) acetylation were measured using high-density oligonucleotide microarrays in primary human acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) specimens. We found that DNA methylation and H3K9 acetylation distinguished these leukemias of distinct cell lineage, as expected, but that an integrative analysis combining the information from each platform revealed hundreds of additional differentially expressed genes that were missed by gene expression arrays alone. This integrated analysis also enhanced the detection and statistical significance of biological pathways dysregulated in AML and ALL. Integrative epigenomic studies are thus feasible using clinical samples and provide superior detection of aberrant transcriptional programming than single-platform microarray studies

Electroweak production of two jets in association with a Z boson in proton-proton collisions root s =13 TeV

A measurement of the electroweak (EW) production of two jets in association with a Z boson in proton-proton collisions at root s = 13 TeV is presented, based on data recorded in 2016 by the CMS experiment at the LHC corresponding to an integrated luminosity of 35.9 fb(-1). The measurement is performed in the lljj final state with l including electrons and muons, and the jets j corresponding to the quarks produced in the hard interaction. The measured cross section in a kinematic region defined by invariant masses m(ll) > 50 GeV, m(jj) > 120 GeV, and transverse momenta P-Tj > 25 GeV is sigma(EW) (lljj) = 534 +/- 20 (stat) fb (syst) fb, in agreement with leading-order standard model predictions. The final state is also used to perform a search for anomalous trilinear gauge couplings. No evidence is found and limits on anomalous trilinear gauge couplings associated with dimension-six operators are given in the framework of an effective field theory. The corresponding 95% confidence level intervals are -2.6 <cwww/Lambda(2) <2.6 TeV-2 and -8.4 <cw/Lambda(2) <10.1 TeV-2. The additional jet activity of events in a signal-enriched region is also studied, and the measurements are in agreement with predictions.Peer reviewe

The landscape of tolerated genetic variation in humans and primates.

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases

Animal Welfare: Perceptions of Nonmetropolitan Nebraskans: 2011 Nebraska Rural Poll Results

The manner in which food animals are produced, shipped and processed has been in the news lately. Specifically at question is whether or not current livestock practices adequately ensure the welfare of food animals. With a sizable animal agriculture production sector in the state of Nebraska, this is an important issue. How do rural Nebraskans feel about animal welfare issues? Do their opinions differ by age, education or their experience with livestock production? This paper provides a detailed analysis of these questions. This report details 2,490 responses to the 2011 Nebraska Rural Poll, the sixteenth annual effort to understand rural Nebraskans’ perceptions. Respondents were asked a series of questions about animal welfare. For all questions, comparisons are made among different respondent subgroups, that is, comparisons by age, occupation, region, etc. Based on these analyses, some key findings emerged: -Almost all rural Nebraskans recognize the importance of livestock and poultry production to the state’s economy. -Most rural Nebraskans are familiar with livestock care practices. Many rural Nebraskans have experience raising beef cattle, poultry and swine. They have less experience with dairy production. -Most rural Nebraskans believe animal welfare means providing adequate exercise, space and social activities for the animals in addition to food, water and shelter. -Most rural Nebraskans trust livestock farmers, especially on family farms, and their veterinarians to care for their animals. -Most rural Nebraskans believe that current regulation of the state’s livestock practices is adequate to ensure animal welfare. Persons with agriculture occupations are more likely than persons with different occupations to agree that current regulation of Nebraska livestock practices is adequate to ensure the welfare of food animals. Persons with agriculture occupations are more likely than persons with different occupations to disagree with the statement that more regulation of livestock practices is needed to ensure the welfare of food animals. -Most rural Nebraskans believe regulation will impact the cost of food. Persons working in agriculture are more likely than persons with different occupations to believe regulation will impact food prices

Animal Welfare: Perceptions of Nonmetropolitan Nebraskans: 2011 Nebraska Rural Poll Results

The manner in which food animals are produced, shipped and processed has been in the news lately. Specifically at question is whether or not current livestock practices adequately ensure the welfare of food animals. With a sizable animal agriculture production sector in the state of Nebraska, this is an important issue. How do rural Nebraskans feel about animal welfare issues? Do their opinions differ by age, education or their experience with livestock production? This paper provides a detailed analysis of these questions. This report details 2,490 responses to the 2011 Nebraska Rural Poll, the sixteenth annual effort to understand rural Nebraskans’ perceptions. Respondents were asked a series of questions about animal welfare. For all questions, comparisons are made among different respondent subgroups, that is, comparisons by age, occupation, region, etc. Based on these analyses, some key findings emerged: -Almost all rural Nebraskans recognize the importance of livestock and poultry production to the state’s economy. -Most rural Nebraskans are familiar with livestock care practices. Many rural Nebraskans have experience raising beef cattle, poultry and swine. They have less experience with dairy production. -Most rural Nebraskans believe animal welfare means providing adequate exercise, space and social activities for the animals in addition to food, water and shelter. -Most rural Nebraskans trust livestock farmers, especially on family farms, and their veterinarians to care for their animals. -Most rural Nebraskans believe that current regulation of the state’s livestock practices is adequate to ensure animal welfare. Persons with agriculture occupations are more likely than persons with different occupations to agree that current regulation of Nebraska livestock practices is adequate to ensure the welfare of food animals. Persons with agriculture occupations are more likely than persons with different occupations to disagree with the statement that more regulation of livestock practices is needed to ensure the welfare of food animals. -Most rural Nebraskans believe regulation will impact the cost of food. Persons working in agriculture are more likely than persons with different occupations to believe regulation will impact food prices

Community Life in Nonmetropolitan Nebraska: Current Perceptions and Future Strategies: 2011 Nebraska Rural Poll Results

Recent community level Census data show that most small communities in Nebraska experienced population decline since 2000. However, most of the larger communities experienced population growth during this same time period. Various economic development strategies could be employed by communities to grow their population and economies. Given these conditions, how do rural Nebraskans feel about their community? Are they satisfied with the services provided by their community? Are they planning to move from their community in the next year? Have these views changed over the past sixteen years? How do rural Nebraskans believe various economic development strategies would impact their community? This paper provides a detailed analysis of these questions. This report details 2,490 responses to the 2011 Nebraska Rural Poll, the sixteenth annual effort to understand rural Nebraskans\u27 perceptions. Respondents were asked a series of questions about their community and economic development strategies. Trends for some of these questions are examined by comparing data from the fifteen previous polls to this year’s results. In addition, comparisons are made among different respondent subgroups, that is, comparisons by age, occupation, region, etc. Based on these analyses, some key findings emerged: -By many different measures, rural Nebraskans are positive about their community. Many rural Nebraskans rate their community favorably on its social dimensions. Over one-half of rural Nebraskans say it would be difficult to leave their community. Most rural Nebraskans disagree that their community is powerless to control its future. -Residents of smaller communities are more likely than residents of larger communities to rate their community favorably on its social dimensions and to have positive sentiments about their community. Persons living in or near smaller communities are more likely than persons living in or near larger communities to rate their community as friendly, trusting and supportive. Persons living in or near smaller communities are more likely than persons living in or near larger communities to say it would be difficult to leave their community. -Residents of larger communities are more likely than residents of smaller communities to say their community has changed for the better during the past year and will be a better place to live ten years from now. Persons living in or near larger communities are more likely than persons living in or near smaller communities to say their community has changed for the better during the past year. Persons living in or near larger communities are more likely than persons living in or near smaller communities to say their community will be a better place to live ten years from now. -Except for a few services that are largely unavailable in rural communities, rural Nebraskans are generally satisfied with basic community services and amenities. -Few rural Nebraskans are planning to move from their community in the next year, but most of those who do plan to move expect to leave the state. -Most rural Nebraskans believe strategies that assist small businesses and entrepreneurs would have a positive impact on their community

Quality of Life in Nonmetropolitan Nebraska: 2011 Nebraska Rural Poll Results

Nebraska appeared to survive the recent economic recession better than most other states. The state\u27s unemployment rate has been one of the lowest in the nation in recent years. The agricultural economy has also been strong. Farm income levels reached record levels in 2010 and are expected to remain strong this year. Given the challenges and uncertainties of recent years, how do rural Nebraskans believe they are doing and how do they view their future? Have these views changed over the past sixteen years? How satisfied are they with various items that influence their well-being? How happy are rural Nebraskans? Do they believe they are entrepreneurial or leaders in various areas of their lives? This paper provides a detailed analysis of these questions. This report details 2,490 responses to the 2011 Nebraska Rural Poll, the sixteenth annual effort to understand rural Nebraskans\u27 perceptions. Respondents were asked a series of questions about their individual well-being. Trends for some of the questions are examined by comparing data from the fifteen previous polls to this year\u27s results. In addition, comparisons are made among different respondent subgroups, that is, comparisons by age, occupation, region, etc. Based on these analyses, some key findings emerged: -Most rural Nebraskans believe they are better off than they were five years ago. -Rural Nebraskans continue to be generally positive about their future. -Most rural Nebraskans disagree that people are powerless to control their own lives. -Following trends in previous years, rural Nebraskans are most satisfied with their marriage, family, friends, religion/spirituality and the outdoors. They continue to be less satisfied with job opportunities, current income level and financial security during retirement. -Persons with the highest household incomes are more likely than persons with lower incomes to feel they are better off compared to five years ago, are better off compared to their parents when they were their age, and will be better off ten years from now. -Persons with lower education levels are more likely than persons with more education to believe that people are powerless to control their own lives. -The majority of younger persons are dissatisfied with their job opportunities. -Most rural Nebraskans say they are very happy or fairly happy. -Persons living in the Southeast region are more likely than persons living in other regions of the state to report being very happy. -Most rural Nebraskans rate themselves as entrepreneurial. -Persons living in or near smaller communities are more likely than persons living in or near larger communities to report being entrepreneurial. -Most rural Nebraskans consider themselves a leader in their family and their work/career