6365 results for "11+1双色球多少钱一注"

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• Environmental Influences on Child Health Outcomes (ECHO) - PATHWAYS - Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE)

  Pregnant women are exposed daily to multiple chemical and non-chemical stressors, including air pollutants, phthalates, and psychosocial stress. The Developmental Origins of Health and Disease model (DOHaD) states that exposure to these stressors in pregnancy affects fetal development in a manner that impacts offspring health across the life course. Yet epidemiologic data in these areas is limited, particularly with U.S. samples. It is also poorly understood whether these exposures prenatally affect childhood neurodevelopment and airway health in an independent or combined manner, and likely moderators of effects, such as the sex of the child, are infrequently addressed. We propose to unify three diverse extant pregnancy cohorts: TIDES (N=717, 2010-12), GAPPS (N=1133, 2012-16), and CANDLE (N=1385, 2007-11), for a combined sample size of 3235 mother-child dyads in the PATHWAYS study. PATHWAYS will investigate how chemical (air pollutants and phthalates) and non-chemical (psychosocial stress) exposures during pregnancy are related to placental gene expression (transcriptome) and childhood neurodevelopment and airway health (at ages 4-6, 8-9, and 10-11 years). Each cohort has rich resources of prenatal data and banked specimens (urine, blood, and placenta) that will be harmonized for the PATHWAYS study and will contribute to the ECHO consortium. We will develop a national model with high spatiotemporal resolution of key air pollutants and assess urinary markers of maternal exposure. A composite measure will capture multilevel maternal psychosocial stress across pregnancy, and urinary phthalate and blood stress hormone [Corticotropin-releasing hormone (CRH)] levels in the second and third trimesters will provide individual assessment of those exposures in potential critical periods. We will characterize the placental transcriptome using RNA sequencing (RNA-Seq) and will assess neurodevelopment and airway health prospectively into middle childhood. PATHWAYS will examine how these prenatal exposures are related to the placental transcriptome and child health outcomes in main effect and interactive models, with emphasis on sex-specific associations. For both neurodevelopment and airway health, we propose to measure both phenotypic precursors of health outcomes (i.e. fluid cognition, lung function growth), which yield dimensional tests of proposed associations, as well as clinically meaningful and policy relevant outcomes (i.e. asthma, mental health). Our study is powered to assess interactive effects of chemical and non-chemical stressors and will be the first study to characterize how prenatal environmental exposures relate to placental transcriptome pathways in relation to childhood health outcomes. This represents a significant scientific advance in testing DOHaD hypotheses. Major contributions to the ECHO Consortium include: 1) the development of a state of the art national model of air pollution, 2) a large, diverse pregnancy cohort with extensive biorepositories and extant prenatal and postnatal biomarkers, placental transcriptome, psychosocial and environmental data, and 3) an experienced, interdisciplinary team that will contribute meaningfully to the ECHO program of work.The sequencing data in this submission pertains only to the 794 subjects from the CANDLE study for whom placental tissue transcriptomics was performed.

  Study phs003619

• Environmental Influences on Child Health Outcomes (ECHO) - PATHWAYS - Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)

  Pregnant women are exposed daily to multiple chemical and non-chemical stressors, including air pollutants, phthalates, and psychosocial stress. The Developmental Origins of Health and Disease model (DOHaD) states that exposure to these stressors in pregnancy affects fetal development in a manner that impacts offspring health across the life course. Yet epidemiologic data in these areas is limited, particularly with U.S. samples. It is also poorly understood whether these exposures prenatally affect childhood neurodevelopment and airway health in an independent or combined manner, and likely moderators of effects, such as the sex of the child, are infrequently addressed. We propose to unify three diverse extant pregnancy cohorts: TIDES (N=717, 2010-12), GAPPS (N=1133, 2012-16), and CANDLE (N=1385, 2007-11), for a combined sample size of 3235 mother-child dyads in the PATHWAYS study. PATHWAYS will investigate how chemical (air pollutants and phthalates) and non-chemical (psychosocial stress) exposures during pregnancy are related to placental gene expression (transcriptome) and childhood neurodevelopment and airway health (at ages 4-6, 8-9, and 10-11 years). Each cohort has rich resources of prenatal data and banked specimens (urine, blood, and placenta) that will be harmonized for the PATHWAYS study and will contribute to the ECHO consortium. We will develop a national model with high spatiotemporal resolution of key air pollutants and assess urinary markers of maternal exposure. A composite measure will capture multilevel maternal psychosocial stress across pregnancy, and urinary phthalate and blood stress hormone [Corticotropin-Releasing Hormone (CRH)] levels in the second and third trimesters will provide individual assessment of those exposures in potential critical periods. We will characterize the placental transcriptome using RNA sequencing (RNA-Seq) and will assess neurodevelopment and airway health prospectively into middle childhood. PATHWAYS will examine how these prenatal exposures are related to the placental transcriptome and child health outcomes in main effect and interactive models, with emphasis on sex-specific associations. For both neurodevelopment and airway health, we propose to measure both phenotypic precursors of health outcomes (i.e., fluid cognition, lung function growth), which yield dimensional tests of proposed associations, as well as clinically meaningful and policy relevant outcomes (i.e., asthma, mental health). Our study is powered to assess interactive effects of chemical and non-chemical stressors and will be the first study to characterize how prenatal environmental exposures relate to placental transcriptome pathways in relation to childhood health outcomes. This represents a significant scientific advance in testing DOHaD hypotheses. Major contributions to the ECHO Consortium include: 1) the development of a state of the art national model of air pollution, 2) a large, diverse pregnancy cohort with extensive biorepositories and extant prenatal and postnatal biomarkers, placental transcriptome, psychosocial and environmental data, and 3) an experienced, interdisciplinary team that will contribute meaningfully to the ECHO program of work.The sequencing data in this submission pertain only to the 408 subjects from the GAPPS study for whom placental tissue transcriptomics was performed.

  Study phs003620

• Gene expression profiles of single disseminated breast cancer cells

  A set of 56 EpCAM-positive cells derived from bone marrow aspirates of breast cancer patients or patients without a cancererous disease (30 cells from 21 M0-stage and 11 cells from five M1-stage breast cancer patients, 15 cells from seven non-cancer patients serving as controls). EpCAM-positive cells from breast cancer patients were considered disseminated tumor cells as they harbored copy number alterations and showed high expression of the epithelial marker EpCAM and the mammary luminal progenitor marker KIT in comparison to EpCAM-positive bone marrow cells from non-cancer patients. Paired-end RNA-Sequencing of the samples was performed on Illumina NovaSeq6000, raw data are provided in the Fastq format.

  Dataset EGAD00001006359

• Unravelling the contribution of HIF pathway and its therapeutic potential in human AML leukemia-initiating cells

  We performed single cell RNA sequencing (scRNA-seq) from bone marrow on 11 pediatric (0-14 years-old) and adolescent and young adult (AYA) (15-39 years-old) de novo AML samples (Dx) (4 inv(16), 3 t(8;21) and 4 rMLL). In addition, for some patients also relapse sample was sequenced (2 inv(16), 2 t(8;21) and 3 rMLL). Cells were sorted into CD34+/CD38- and CD34-/CD38+ and sequenced separately.

  Dataset EGAD00001008514

• The Role of E2F4 in Controlling Resistance to Irinotecan (CPT-11) in Human Colon Cancer

  This study reports the results of RNA sequencing (RNA-seq) experiments performed on three isogenic clones of the human HT29 colon cancer cell line, genetically engineered to achieve the selective inactivation of the adenovirus early 2 (E2) gene transcription factor 4 (E2F4) protein, a key functional component of the multimeric transcriptional repression complex known as the dimerization partner (DP), retinoblastoma-like (RB-like), E2F and multi-vulva class B (MuvB) complex (DREAM). In previous studies, we identified E2F4 as a key regulator of colorectal cancer (CRC) resistance to irinotecan (CPT-11), a cytotoxic agent that stands at the backbone of multiple chemotherapy regimens for the treatment of metastatic CRCs. The molecular mechanisms linking E2F4 to irinotecan resistance, however, remain poorly understood. The present study was designed to identify which genes are under the transcriptional control of E2F4, either at baseline or following exposure to SN38 (i.e., the active metabolite of irinotecan, generated in vivo by biotransformation in the liver) in order to clarify the role played by E2F4 in shaping colon cancer resistance to chemotherapy. The cell line used for this study (HT29) is aneuploid and contains three copies of the E2F4 gene, because of a trisomy of chromosome 16, where the E2F4 gene is located (Kawai et al., Genes, Chromosomes & Cancer, 34:1-8, 2002; PMID: 11921276). HT29 cells were infected with lentivirus vectors encoding for CRISPR/Cas9 constructs designed to selectively inactivate the E2F4 gene, using three distinct guide-RNAs (gRNAs), each targeting a different sequence within the proximal exons of the E2F4 gene (exon 1, exon 2). Lentivirus-infected cells were sub-cloned by single-cell fluorescence-activated cell sorting (FACS), based on the differential expression of a fluorescent reporter (EGFP) expressed in tandem with the gRNAs. Isogenic clones (EGFP+) were then screened to identify those with a tri-allelic knock-out, as revealed by both genetic sequencing of the E2F4 gene (revealing the presence of three distinct frameshift mutations) and Western blot (revealing complete loss of E2F4 protein expression). The study includes twelve (n=12) RNA-seq experiments, representative of 3 experimental replicates (i.e., three distinct isogenic clones of the HT29 cell line, each displaying complete loss of E2F4 expression) and 3 negative controls (i.e., three independent preparations of the parent HT29 cell line, infected with a lentivirus vector encoding for a non-targeting gRNA) exposed to 2 distinct in vitro cell culture conditions: a) treatment with SN38 resuspended in dimethyl sulfoxide (DMSO); or b) treatment with DMSO alone (negative control). The in vitro treatment regimen used for SN38 (32 nM, 24 hours) was designed so that the exposure to SN38 experienced in vitro by HT29 cells would mirror the exposure to SN38 experienced in vivo by malignant tissues, as measured, for example, in metastatic CRC patients receiving a standard dose of irinotecan (180 mg/m2) administered by intravenous infusion over 90 minutes (Deyme et al., Cancer Chemotherapy and Pharmacology, 88:247-258, 2021; PMID: 33912999).

  Study phs003560

• NHLBI GO-ESP Family Studies: Idiopathic Bronchiectasis of unknown etiology that is not related to cystic fibrosis or classic primary ciliary dyskinesia or immune deficiency or any other known causes

  The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO. The major goal of this project is to apply next generation resequencing technology to identify disease-causing variants that cause bronchiectasis of unknown etiology (e.g. non cystic fibrosis (CF), classic primary ciliary dyskinesia (PCD), immune deficiency, or any other known cause of bronchiectasis), i.e., "idiopathic bronchiectasis." As part of our ongoing efforts to define the genetic cause of rare lung diseases, we have also studied families in whom diagnosis of PCD or other known etiologies could not be confirmed. We have systematically collected and stored the DNA and phenotypic data on each of the families in our cohort. The phenotypic data includes age, gender, ethnicity information, clinical data pertaining to the airways disease, including neonatal respiratory distress, otitis media, sinusitis and bronchiectasis, ciliary ultrastructure analysis, and microbial colonization (status of nontuberculosis mycobacterium). During the course of our study, we have acquired 98 unrelated patients in whom bronchiectasis seemed to be of unknown causes. We will be using 11 unrelated patients, 5 unrelated affected sib-pairs, and 3 affected sibs from a family from this cohort, based on 1) development of bronchiectasis in the absence of smoking, 2) a good family pedigree with available DNA, and 3) a family history of bronchiectasis and/or occurrence of airways disease in a sibling. Classic CF, PCD and immune deficiency were ruled out, based on the tests described above. Alpha-1 antiprotease deficiency work up was negative and none of the patients were tobacco users or smokers.

  Study phs000518

• GEX CITE-Seq performance dataset

  To understand the impact of enzymatic treatments on gene expression and epitope preservation on major immune cell populations, skin dissociation (SkinD) and solid soft tumor dissociation (TumorD) were tested on three healthy PBMC samples in triplicate (D1, D2, D3), against an untreated control. CITE-seq performance was assessed on a solid biopsy cohort of 11 samples (5 healthy skin samples, 3 primary melanoma samples, 3 melanoma metastasis samples) as well as on a liquid biopsy PBMC cohort consisting of three healthy donors and three immunotherapy-treated melanoma patients. This dataset contains the GEX data for each sample. Data is provided in the form of pooled BAM files. Linkage between samples, BAM files and hashtags is provided in a separate linkage file.

  Dataset EGAD00001008418

• ADT/SPEX CITE-Seq performance dataset

  To understand the impact of enzymatic treatments on gene expression and epitope preservation on major immune cell populations, skin dissociation (SkinD) and solid soft tumor dissociation (TumorD) were tested on three healthy PBMC samples in triplicate (D1, D2, D3), against an untreated control. CITE-seq performance was assessed on a solid biopsy cohort of 11 samples (5 healthy skin samples, 3 primary melanoma samples, 3 melanoma metastasis samples) as well as on a liquid biopsy PBMC cohort consisting of three healthy donors and three immunotherapy-treated melanoma patients. This dataset contains the ADT/SPEX data for each sample. Data is provided in the form of pooled BAM files. Linkage between samples, BAM files and hashtags is provided in a separate linkage file.

  Dataset EGAD00001008419

• Targeted Validation Samples

  The dataset consists of targeted sequencing data obtained from an independent cohort of 11 patients to validate discriminative DMRs (differentially methylated regions) for Acute coronary syndrome (ACS) subtypes. The cohort includes 2 healthy subjects, 4 STEMI (ST-segment elevation myocardial infarction), 3 NSTEMI (non-ST-segment elevation myocardial infarction), and 2 UA (unstable angina) patients. The sequencing panel targeted 18,831 CpGs for analysis, reaching at least 5 reads coverage for 75% of the targeted CpGs in each sample. The sequencing was performed using the NEBNext Enzymatic Methyl-seq Module and the Nonacus Cell3TMTarget: Library Preparation kit, followed by probe hybridization, capture enrichment, and sequencing on the Novaseq 6000 platform, generating 400 million reads. The dataset is in raw fastq format.

  Dataset EGAD00001010934

• Structure and Diversity of Urinary Cell-Free DNA Informative of Host-Pathogen Interactions in Human Urinary Tract Infection

  The risk of acquiring urinary tract infection (UTI) is very high for patients who have received kidney transplants; nearly half will develop bacteriuria and an eighth viruria via BK polyomavirus in the first three years following transplantation. Current methodology for diagnosing viral and bacterial infections, while well practiced, is often limited in scope. The advent of next generation sequencing of cell-free DNA has shown promise in its ability to capture multiple perspectives of human health from discovering the origin of cell-free DNA in plasma; such a diagnostic has not been readily applied to urinary cell-free DNA. In this study, we selected 141 urine samples from a cohort of kidney transplant patients, which were collected and stored at Weill Cornell Medical College - New York Presbyterian Hospital. Of these samples, 43 samples were determined to be culture positive (> 10,000 CFU) for one or more bacterial species, including E. coli, Enterococcus, Klebsiella, Haemophilus, and Raoultella. A separate 23 samples were confirmed for BK virus nephropathy, with presence of BK polyomavirus confirmed via qPCR. We also included 29 samples from 14 patients who did not develop UTIs in the first three months following transplantation, and 11 samples that were negative for BK virus nephropathy. For a full description of samples, please see the Supplementary Data 1 in https://pubmed.ncbi.nlm.nih.gov/29925834/. From these urine samples, we aimed to capture and sequence urinary cell-free DNA using a single-stranded library preparation. In addition, we performed whole-genome bisulfite sequencing to 170 plasma samples collected from 27 hematopoietic cell transplant patients who developed graft-versus host disease and BK polyomavirus infection. We also performed Sample-Intrinsic microbial DNA Found by Tagging and sequencing (SIFT-seq) on 196 cell-free DNA (cfDNA) samples (154 plasma and 42 urine) collected from five groups of subjects. For a full description of samples, please see publications in PMID: 35864089 and PMID: 35058359.

  Study phs001564