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  • 1
    Article
    Article
    2012
    ISSN: 0006-341X 
    Language: English
    In: Biometrics, 2012-03, Vol.68 (1), p.1-11
    Description: RNA-seq may replace gene expression microarrays in the near future. Using RNA-seq, the expression of a gene can be estimated using the total number of sequence reads mapped to that gene, known as the total read count (TReC). Traditional expression quantitative trait locus (eQTL) mapping methods, such as linear regression, can be applied to TReC measurements after they are properly normalized. In this article, we show that eQTL mapping, by directly modeling TReC using discrete distributions, has higher statistical power than the two-step approach: data normalization followed by linear regression. In addition, RNA-seq provides information on allele-specific expression (ASE) that is not available from microarrays. By combining the information from TReC and ASE, we can computationally distinguish eis-and trans-eQTL and further improve the power of czs-eQTL mapping. Both simulation and real data studies confirm the improved power of our new methods. We also discuss the design issues of RNA-seq experiments. Specifically, we show that by combining TReC and ASE measurements, it is possible to minimize cost and retain the statistical power of ds-eQTL mapping by reducing sample size while increasing the number of sequence reads per sample. In addition to RNA-seq data, our method can also be employed to study the genetic basis of other types of sequencing data, such as chromatin immunoprecipitation followed by DNA sequencing data. In this article, we focus on eQTL mapping of a single gene using the association-based method. However, our method establishes a statistical framework for future developments of eQTL mapping methods using RNA-seq data (e. g., linkage-based eQTL mapping), and the joint study of multiple genetic markers and/or multiple genes.
    Subject(s): Total read count (TReC) ; eQTL ; RNA-seq ; Allele-specific expression (ASE) ; Haplotypes ; Quantitative trait loci ; Biometrics ; Sample size ; Linear regression ; Binomial distributions ; Genes ; Alleles ; P values ; BIOMETRIC METHODOLOGY ; Genotypes ; RNA‐seq ; Allele‐specific expression (ASE) ; Sequence Analysis, RNA - methods ; Data Interpretation, Statistical ; Algorithms ; Base Sequence ; Computer Simulation ; Humans ; Molecular Sequence Data ; Models, Genetic ; Models, Statistical ; Quantitative Trait Loci - genetics ; RNA - genetics ; Anopheles ; Chromatin ; Analysis ; Nucleotide sequencing ; Gene expression ; DNA sequencing ; Quantitative genetics ; Genetic markers ; Ribonucleic acid--RNA ; Genomics ; Index Medicus ; Allele-specific Expression (ASE) ; Total Read Count (TReC)
    ISSN: 0006-341X
    E-ISSN: 1541-0420
    Source: JSTOR Arts & Sciences II
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: SPORTDiscus with Full Text
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  • 2
    Language: English
    In: Human reproduction (Oxford), 2018-03-01, Vol.33 (3), p.353-356
    Subject(s): Female ; Endometriosis - pathology ; Fibrosis - pathology ; Endometrium - pathology ; Hemorrhage - pathology ; Humans ; Index Medicus
    ISSN: 0268-1161
    E-ISSN: 1460-2350
    Source: Alma/SFX Local Collection
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  • 3
    Article
    Article
    2009
    ISSN: 1355-4786 
    Language: English
    In: Human reproduction update, 2009, Vol.15 (4), p.441-461
    Description: BACKGROUND Although surgery is currently the treatment of choice for managing endometriosis, recurrence poses a formidable challenge. To delay or to eliminate the recurrence is presently an unmet medical need in the management of endometriosis. To this end, proposals to investigate patterns of recurrence, to develop biomarkers for recurrence and to carry out biomarker-based intervention have been made. METHODS Publications pertaining to the recurrence of endometriosis and its related yet unaddressed issues were identified through MEDLINE. The reported recurrence rates, risk factors for recurrence, the effects of post-operative medication and causes of recurrence were reviewed and synthesized. In addition, several poorly explored issues such as time hazard function and mechanisms of recurrence were reviewed. Approaches to the development of biomarkers for recurrence and future intervention are discussed. RESULTS The reported recurrence rate was high, estimated as 21.5% at 2 years and 40–50% at 5 years. Few risk factors for recurrence have been consistently identified, and the evidence on the efficacy of the post-operative use of medication was scanty. The investigation on the patterns of recurrence may provide us with new insight into the possible mechanisms of recurrence and its control. The attempt to identify biomarkers for recurrence has started only very recently. CONCLUSIONS Much research is needed to better understand the patterns of recurrence and risk factors, and to develop biomarkers. One top priority is to develop biomarkers for recurrence, which may provide much needed clues to the possible mechanisms underlying recurrence and would allow the identification of patients with high recurrence risk, and permit for targeted intervention.
    Subject(s): recurrence ; endometriosis ; control ; biomarker ; hazard ; Biomarkers - metabolism ; Endometriosis - diagnosis ; Humans ; Risk Factors ; Secondary Prevention ; Endometriosis - drug therapy ; Randomized Controlled Trials as Topic ; Estrogen Antagonists - therapeutic use ; Time Factors ; Cyclooxygenase 2 - metabolism ; Female ; Endometriosis - epidemiology ; Endometriosis - prevention & control ; Gonadotropin-Releasing Hormone - agonists ; Danazol - therapeutic use ; Index Medicus
    ISSN: 1355-4786
    E-ISSN: 1460-2369
    Source: Alma/SFX Local Collection
    Source: Oxford Journals 2016 Current and Archive A-Z Collection
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  • 4
    Language: English
    In: Communications on pure and applied mathematics, 2017-01, Vol.70 (1), p.172-199
    Description: We study a class of fully nonlinear elliptic equations on closed Hermitian manifolds. Under the assumption of the cone condition, we derive the L∞ estimate directly. As an application, we solve the complex quotient equations on closed Kähler manifolds. © 2016 Wiley Periodicals, Inc.
    Subject(s): Topological manifolds ; Estimates ; Mathematics
    ISSN: 0010-3640
    E-ISSN: 1097-0312
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
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  • 5
    Language: English
    In: Nature genetics, 2011, Vol.43 (9), p.897-901
    Description: Graves' disease is a common autoimmune disorder characterized by thyroid stimulating hormone receptor autoantibodies (TRAb) and hyperthyroidism. To investigate the genetic architecture of Graves' disease, we conducted a genome-wide association study in 1,536 individuals with Graves' disease (cases) and 1,516 controls. We further evaluated a group of associated SNPs in a second set of 3,994 cases and 3,510 controls. We confirmed four previously reported loci (in the major histocompatibility complex, TSHR, CTLA4 and FCRL3) and identified two new susceptibility loci (the RNASET2-FGFR1OP-CCR6 region at 6q27 (P(combined) = 6.85 × 10(-10) for rs9355610) and an intergenic region at 4p14 (P(combined) = 1.08 × 10(-13) for rs6832151)). These newly associated SNPs were correlated with the expression levels of RNASET2 at 6q27, of CHRNA9 and of a previously uncharacterized gene at 4p14, respectively. Moreover, we identified strong associations of TSHR and major histocompatibility complex class II variants with persistently TRAb-positive Graves' disease.
    Subject(s): Fundamental and applied biological sciences. Psychology ; Classical genetics, quantitative genetics, hybrids ; Human ; Non tumoral diseases. Target tissue resistance. Benign neoplasms ; Thyroid. Thyroid axis (diseases) ; Biological and medical sciences ; Endocrinopathies ; Genetics of eukaryotes. Biological and molecular evolution ; Medical sciences ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Receptors, Thyrotropin - genetics ; Autoantibodies - blood ; Humans ; Molecular Sequence Data ; Male ; Risk ; Genetic Loci ; Receptors, Thyrotropin - immunology ; Graves Disease - genetics ; Graves Disease - immunology ; Female ; Graves Disease - epidemiology ; Histocompatibility Antigens Class II - genetics ; Polymerase chain reaction ; Usage ; Graves' disease ; Physiological aspects ; Genomes ; Genetic aspects ; Research ; Gene expression ; Risk factors ; Index Medicus
    ISSN: 1061-4036
    E-ISSN: 1546-1718
    Source: Single Journals
    Source: Academic Search Ultimate
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  • 6
    Language: English
    In: Cancer science, 2018-10, Vol.109 (10), p.3129-3138
    Description: The sensitivity of breast cancer cells to epirubicin (EPI) is closely related to the efficacy of the drug and the prognosis of patients. A growing body of research has suggested that autophagy is involved in the treatment of a variety of cancers, including breast cancer, and modifies the sensitivity of anticancer drugs. However, the mechanism by which autophagy participates in cancer therapy and modulates drug sensitivity has not been fully elucidated. In this study, we showed that the expression of Autophagy/Beclin 1 regulator 1 (Ambra1), a key protein of autophagy, was negatively correlated with EPI sensitivity in breast cancer cells. In addition, it altered the sensitivity of breast cancer cells to EPI by regulating EPI‐induced autophagy. As a potential mechanism, we demonstrated that autophagy‐related protein 12 (ATG12) was a downstream protein that Ambra1‐regulated EPI‐induced autophagy. Therefore, Ambra1 plays an important role in regulating the sensitivity of breast cancer cells to EPI. And the regulatory effect of Ambra1 on EPI sensitivity is achieved through the regulation of autophagy by targeting ATG12. Overall, we propose a novel mechanism by which autophagy modulates the sensitivity of breast cancer cells to EPI. ATG12 is a novel targeting protein of Ambra1 in regulating EPI‐induced autophagy. In addition, the important role of Ambra1 in modulating the sensitivity of breast cancer cells to EPI is confirmed in vivo. This finding indicates that Ambra1 might be a target for developing breast cancer treatments. Ambra1 plays an important role in regulating the sensitivity of breast cancer cells to Epirubicin (EPI). ATG12 is a novel targeting protein of Ambra1 in regulating EPI‐induced autophagy .
    Subject(s): breast cancer ; epirubicin ; autophagy ; Ambra1 ; ATG12 ; Cell Survival - drug effects ; Autophagy-Related Protein 12 - genetics ; Antibiotics, Antineoplastic - pharmacology ; Humans ; Drug Resistance, Neoplasm ; Autophagy-Related Protein 12 - metabolism ; Breast Neoplasms - drug therapy ; Autophagy - drug effects ; Xenograft Model Antitumor Assays ; Animals ; Antibiotics, Antineoplastic - therapeutic use ; MCF-7 Cells ; Breast Neoplasms - pathology ; Mice, Nude ; Adaptor Proteins, Signal Transducing - genetics ; Beclin-1 - genetics ; Epirubicin - therapeutic use ; Mice, Inbred BALB C ; Adaptor Proteins, Signal Transducing - metabolism ; Beclin-1 - metabolism ; Apoptosis ; Epirubicin - pharmacology ; RNA, Small Interfering - metabolism ; Development and progression ; Anthracyclines ; Breast cancer ; Cancer cells ; Studies ; Proteins ; Immunoglobulins ; Chemotherapy ; Antitumor agents ; Cytotoxicity ; Epirubicin ; Autophagy ; Cancer therapies ; Phagocytosis ; Index Medicus ; Original
    ISSN: 1347-9032
    E-ISSN: 1349-7006
    Source: PubMed Central
    Source: ProQuest Central
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  • 7
    Language: English
    In: Fertility and sterility, 2014, Vol.101 (1), p.183-190.e4
    Description: Objective To examine and compare differences, if any, between industry- and nonindustry-sponsored clinical trials on endometriosis and to evaluate the effect of prior published positive preclinical results, or lack thereof, on trial status. Design Cross-sectional study of clinical trials on endometriosis that evaluate drugs/biologicals registered at ClinicalTrials.gov as of July 3, 2013. Setting University-affiliated hospital. Patient(s) None. Intervention(s) None. Main Outcome Measure(s) Trial status, size, phase, and duration; use of comparator groups; drug classes, number of arms, targeting conditions; and presence or absence of prior positive preclinical results before the launch of the trial. Result(s) Eighty trials were identified. The trials sponsored by industry and non-industry have distinct features, differing in trial status, phase, comparator, drug classes, number of arms, trial size, and duration. The phase II/III trials are predominantly industry supported, but these trials frequently use placebo as the comparator. Trials launched without prior published preclinical results do not seem to fare well, although the presence of such studies is no guarantee for success. Conclusion(s) Questions as to whether the drug on trial is truly superior to the best available drug or of its cost-benefit profile are overlooked in most cases. There seems to be a deluge of “me-too” drugs with equivocal superiority over existing drugs and cost-benefit profiles. Because clinical trials are time-consuming, no blockbuster drug for endometriosis seems to be on the horizon yet.
    Subject(s): Internal Medicine ; Obstetrics and Gynecology ; Clinical trials ; endometriosis ; sponsorship ; issues ; drug ; status ; Cross-Sectional Studies ; Endometriosis - diagnosis ; Humans ; Female ; Hormone Antagonists - therapeutic use ; Clinical Trials as Topic - methods ; Clinical Trials as Topic - standards ; Endometriosis - drug therapy ; Endometriosis - epidemiology ; Aromatase Inhibitors - therapeutic use ; Endometriosis ; Index Medicus
    ISSN: 0015-0282
    E-ISSN: 1556-5653
    Source: Alma/SFX Local Collection
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  • 8
    Language: English
    In: British journal of pharmacology, 2018-01, Vol.175 (2), p.181-191
    Description: Infectious diseases account for nearly one fifth of the worldwide death toll every year. The continuous increase of drug‐resistant pathogens is a big challenge for treatment of infectious diseases. In addition, outbreaks of infections and new pathogens are potential threats to public health. Lack of effective treatments for drug‐resistant bacteria and recent outbreaks of Ebola and Zika viral infections have become a global public health concern. The number of newly approved antibiotics has decreased significantly in the last two decades compared with previous decades. In parallel with this, is an increase in the number of drug‐resistant bacteria. For these threats and challenges to be countered, new strategies and technology platforms are critically needed. Drug repurposing has emerged as an alternative approach for rapid identification of effective therapeutics to treat the infectious diseases. For treatment of severe infections, synergistic drug combinations using approved drugs identified from drug repurposing screens is a useful option which may overcome the problem of weak activity of individual drugs. Collaborative efforts including government, academic researchers and private drug industry can facilitate the translational research to produce more effective new therapeutic agents such as narrow spectrum antibiotics against drug‐resistant bacteria for these global challenges. Linked Articles This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc
    Subject(s): Drug Synergism ; Anti-Bacterial Agents - therapeutic use ; Drug Therapy, Combination - methods ; Communicable Diseases - drug therapy ; Humans ; Drug Repositioning - methods ; Drugs ; Virus diseases ; Ebola virus infections ; Drug therapy, Combination ; Drug resistance ; Pharmaceutical industry ; Health aspects ; Drug approval ; Index Medicus ; Themed Section ; Review
    ISSN: 0007-1188
    E-ISSN: 1476-5381
    Source: Academic Search Ultimate
    Source: Wiley Online Library All Journals
    Source: PubMed Central
    Source: Alma/SFX Local Collection
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  • 9
    Article
    Article
    2020
    ISSN: 0028-0836 
    Language: English
    In: Nature (London), 2020-01, Vol.577 (7791), p.477-478
    Description: Two-dimensional materials have potential uses in flexible electronics, biosensors and water purification. A method for producing air-stable 2D materials on an industrial scale, now reported, is a key step in bringing them to market.
    Subject(s): Usage ; Transition metal compounds ; Chemical synthesis ; Production processes ; Methods ; Monomolecular films
    ISSN: 0028-0836
    E-ISSN: 1476-4687
    Source: Alma/SFX Local Collection
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  • 10
    Language: English
    In: Scientific reports, 2013-05-07, Vol.3 (1), p.1776
    Description: Rare Earth Elements (REE) are essential to modern society but the origins of many large REE deposits remain unclear. The U-Th-Pb ages, chemical compositions and C, O and Mg isotopic compositions of Bayan Obo, the world's largest REE deposit, indicate a protracted mineralisation history with unusual chemical and isotopic features. Coexisting calcite and dolomite are in O isotope disequilibrium; some calcitic carbonatite samples show highly varied δ26 Mg which increases with increasing Si and Mg; and ankerite crystals show decreases in Fe and REE from rim to centre, with highly varied REE patterns. These and many other observations are consistent with an unusual mineralisation process not previously considered; protracted fluxing of calcitic carbonatite by subduction-released high-Si fluids during the closure of the Palaeo-Asian Ocean. The fluids leached Fe and Mg from the mantle wedge and scavenged REE, Nb and Th from carbonatite, forming the deposit through metasomatism of overlying sedimentary carbonate.
    Subject(s): Mineralization ; Isotopes ; Calcite ; Crystals
    ISSN: 2045-2322
    E-ISSN: 2045-2322
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
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