Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Language
  • 1
    Keywords: RISK-FACTORS ; CUTANEOUS MALIGNANT-MELANOMA ; MELANOCYTE-STIMULATING HORMONE ; BASAL-CELL CARCINOMA ; POOLED-ANALYSIS ; LOGIC REGRESSION ; RED HAIR COLOR ; MC1R GENE ; MEDITERRANEAN POPULATION ; PIGMENTATION PHENOTYPE
    Abstract: BACKGROUND: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. DESIGN AND METHODS: Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. DISCUSSION: Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields.
    Type of Publication: Journal article published
    PubMed ID: 22862891
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2018-09-20
    Description: The growing and pruning radial basis function (GAP-RBF) network is a promising sequential learning algorithm for prediction analysis, but the parameter selection of such a network is usually a non-convex problem and makes it difficult to handle. In this paper, a hybrid bioinspired intelligent algorithm is proposed to optimize GAP-RBF. Specifically, the excellent local convergence of particle swarm optimization (PSO) and the extensive search ability of genetic algorithm (GA) are both considered to optimize the weights and bias term of GAP-RBF. Meanwhile, a competitive mechanism is proposed to make the hybrid algorithm choose the appropriate individuals for effective search and further improve its optimization ability. Moreover, a decoupled extended Kalman filter (DEKF) method is introduced in this study to reduce the size of error covariance matrix and decrease the computational complexity for performing real-time predictions. In the experiments, three classic forecasting issues including abalone age, Boston house price and auto MPG are adopted for extensive test, and the experimental results show that our method performs better than PSO and GA these two single bioinspired optimization algorithms. What is more, our method via DEKF achieves the better results in comparison with the state-of-art sequential learning algorithms, such as GAP-RBF, minimal resource allocation network, resource allocation network using an extended Kalman filter and resource allocation network.
    Keywords: hybrid computing
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2011-08-20
    Description: We investigated the association between a U.S. National Institutes of Health (NIH) R01 applicant's self-identified race or ethnicity and the probability of receiving an award by using data from the NIH IMPAC II grant database, the Thomson Reuters Web of Science, and other sources. Although proposals with strong priority scores were equally likely to be funded regardless of race, we find that Asians are 4 percentage points and black or African-American applicants are 13 percentage points less likely to receive NIH investigator-initiated research funding compared with whites. After controlling for the applicant's educational background, country of origin, training, previous research awards, publication record, and employer characteristics, we find that black applicants remain 10 percentage points less likely than whites to be awarded NIH research funding. Our results suggest some leverage points for policy intervention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412416/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412416/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ginther, Donna K -- Schaffer, Walter T -- Schnell, Joshua -- Masimore, Beth -- Liu, Faye -- Haak, Laurel L -- Kington, Raynard -- 1R01AG36820-01/AG/NIA NIH HHS/ -- HHSN276200800458U/PHS HHS/ -- HHSN276200900100U/PHS HHS/ -- R01 AG036820/AG/NIA NIH HHS/ -- Z99 OD999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Aug 19;333(6045):1015-9. doi: 10.1126/science.1196783.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Economics and Center for Science, Technology & Economic Policy, Institute for Policy & Social Research, University of Kansas, Lawrence, KS 66045, USA. dginther@ku.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21852498" target="_blank"〉PubMed〈/a〉
    Keywords: African Americans/statistics & numerical data ; African Continental Ancestry Group/statistics & numerical data ; Asian Continental Ancestry Group/statistics & numerical data ; *Biomedical Research ; *Continental Population Groups/statistics & numerical data ; Databases, Factual ; Education, Graduate ; *Ethnic Groups/statistics & numerical data ; European Continental Ancestry Group/statistics & numerical data ; Fellowships and Scholarships ; Financing, Government ; Hispanic Americans/statistics & numerical data ; Humans ; Likelihood Functions ; Models, Statistical ; National Institutes of Health (U.S.)/*economics ; Peer Review, Research ; Publishing ; *Research Personnel/economics/statistics & numerical data ; Research Support as Topic/*statistics & numerical data ; United States
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2011-08-13
    Description: Midbrain dopamine neurons regulate many important behavioral processes, and their dysfunctions are associated with several human neuropsychiatric disorders such as attention deficit hyperactivity disorder (ADHD) and schizophrenia. Here, we report that these neurons in mice selectively express guanylyl cyclase-C (GC-C), a membrane receptor previously thought to be expressed mainly in the intestine. GC-C activation potentiates the excitatory responses mediated by glutamate and acetylcholine receptors via the activity of guanosine 3',5'-monophosphate-dependent protein kinase (PKG). Mice in which GC-C has been knocked out exhibit hyperactivity and attention deficits. Moreover, their behavioral phenotypes are reversed by ADHD therapeutics and a PKG activator. These results indicate important behavioral and physiological functions for the GC-C/PKG signaling pathway within the brain and suggest new therapeutic targets for neuropsychiatric disorders related to the malfunctions of midbrain dopamine neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gong, Rong -- Ding, Cheng -- Hu, Ji -- Lu, Yao -- Liu, Fei -- Mann, Elizabeth -- Xu, Fuqiang -- Cohen, Mitchell B -- Luo, Minmin -- New York, N.Y. -- Science. 2011 Sep 16;333(6049):1642-6. doi: 10.1126/science.1207675. Epub 2011 Aug 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21835979" target="_blank"〉PubMed〈/a〉
    Keywords: Amphetamine/administration & dosage ; Animals ; Attention ; Attention Deficit Disorder with Hyperactivity/genetics/*metabolism ; Behavior, Animal/drug effects ; Cyclic GMP/metabolism ; Cyclic GMP-Dependent Protein Kinases/*metabolism ; Disease Models, Animal ; Dopamine/metabolism ; Enzyme Activation ; Gastrointestinal Hormones/metabolism/pharmacology ; Glycine/analogs & derivatives/metabolism/pharmacology ; Impulsive Behavior ; Ligands ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/drug effects ; Natriuretic Peptides/metabolism/pharmacology ; Neurons/*metabolism ; Patch-Clamp Techniques ; Receptors, Glutamate/metabolism ; Receptors, Guanylate Cyclase-Coupled/genetics/*metabolism ; Receptors, Muscarinic/metabolism ; Receptors, Peptide/genetics/*metabolism ; Resorcinols/metabolism/pharmacology ; Signal Transduction ; Substantia Nigra/cytology/*metabolism ; Ventral Tegmental Area/cytology/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2011-07-19
    Description: The chromosomal translocations found in acute myelogenous leukemia (AML) generate oncogenic fusion transcription factors with aberrant transcriptional regulatory properties. Although therapeutic targeting of most leukemia fusion proteins remains elusive, the posttranslational modifications that control their function could be targetable. We found that AML1-ETO, the fusion protein generated by the t(8;21) translocation, is acetylated by the transcriptional coactivator p300 in leukemia cells isolated from t(8;21) AML patients, and that this acetylation is essential for its self-renewal-promoting effects in human cord blood CD34(+) cells and its leukemogenicity in mouse models. Inhibition of p300 abrogates the acetylation of AML1-ETO and impairs its ability to promote leukemic transformation. Thus, lysine acetyltransferases represent a potential therapeutic target in AML.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251012/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251012/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Lan -- Gural, Alexander -- Sun, Xiao-Jian -- Zhao, Xinyang -- Perna, Fabiana -- Huang, Gang -- Hatlen, Megan A -- Vu, Ly -- Liu, Fan -- Xu, Haiming -- Asai, Takashi -- Xu, Hao -- Deblasio, Tony -- Menendez, Silvia -- Voza, Francesca -- Jiang, Yanwen -- Cole, Philip A -- Zhang, Jinsong -- Melnick, Ari -- Roeder, Robert G -- Nimer, Stephen D -- GM62437/GM/NIGMS NIH HHS/ -- R01 GM062437/GM/NIGMS NIH HHS/ -- R01 GM062437-12/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2011 Aug 5;333(6043):765-9. doi: 10.1126/science.1201662. Epub 2011 Jul 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21764752" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Cell Line ; Cell Line, Tumor ; *Cell Transformation, Neoplastic ; Core Binding Factor Alpha 2 Subunit/chemistry/*metabolism ; E1A-Associated p300 Protein/antagonists & inhibitors/*metabolism ; Fetal Blood/cytology ; Gene Expression Profiling ; Hematopoietic Stem Cells/*cytology/physiology ; Humans ; Leukemia, Myeloid, Acute/*metabolism/pathology ; Lysine/*metabolism ; Mice ; Mice, Inbred C57BL ; Mutant Proteins/metabolism ; Oncogene Proteins, Fusion/chemistry/*metabolism ; Preleukemia/metabolism/pathology ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Processing, Post-Translational ; Transcriptional Activation ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2015-12-19
    Description: Carbon-based supercapacitors can provide high electrical power, but they do not have sufficient energy density to directly compete with batteries. We found that a nitrogen-doped ordered mesoporous few-layer carbon has a capacitance of 855 farads per gram in aqueous electrolytes and can be bipolarly charged or discharged at a fast, carbon-like speed. The improvement mostly stems from robust redox reactions at nitrogen-associated defects that transform inert graphene-like layered carbon into an electrochemically active substance without affecting its electric conductivity. These bipolar aqueous-electrolyte electrochemical cells offer power densities and lifetimes similar to those of carbon-based supercapacitors and can store a specific energy of 41 watt-hours per kilogram (19.5 watt-hours per liter).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Tianquan -- Chen, I-Wei -- Liu, Fengxin -- Yang, Chongyin -- Bi, Hui -- Xu, Fangfang -- Huang, Fuqiang -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1508-13. doi: 10.1126/science.aab3798.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of High Performance Ceramics and Superfine Microstructure and CAS Key Laboratory of Materials for Energy Conversion, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, P.R. China. Beijing National Laboratory for Molecular Sciences and State Key Laboratory of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P.R. China. ; Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA. ; State Key Laboratory of High Performance Ceramics and Superfine Microstructure and CAS Key Laboratory of Materials for Energy Conversion, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, P.R. China. ; State Key Laboratory of High Performance Ceramics and Superfine Microstructure and CAS Key Laboratory of Materials for Energy Conversion, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, P.R. China. Beijing National Laboratory for Molecular Sciences and State Key Laboratory of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P.R. China. huangfq@mail.sic.ac.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680194" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Publication Date: 2018-11-06
    Description: MHC molecules are found in all jawed vertebrates and are known to present peptides to T lymphocytes. In mammals, peptides can hang out either end of the peptide-binding groove of classical class II molecules, whereas the N and C termini of peptides are typically tightly bound to specific pockets in classical class I molecules. The chicken MHC, like many nonmammalian vertebrates, has a single dominantly expressed classical class I molecule encoded by the BF2 locus. We determined the structures of BF2*1201 bound to two peptides and found that the C terminus of one peptide hangs outside of the groove with a conformation much like the peptides bound to class II molecules. We found that BF2*1201 binds many peptides that hang out of the groove at the C terminus, and the sequences and structures of this MHC class I allele were determined to investigate the basis for this phenomenon. The classical class I molecules of mammals have a nearly invariant Tyr (Tyr 84 in humans) that coordinates the peptide C terminus, but all classical class I molecules outside of mammals have an Arg in that position in common with mammalian class II molecules. We find that this invariant Arg residue switches conformation to allow peptides to hang out of the groove of BF2*1201, suggesting that this phenomenon is common in chickens and other nonmammalian vertebrates, perhaps allowing the single dominantly expressed class I molecule to bind a larger repertoire of peptides.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    facet.materialart.
    Unknown
    Springer Nature
    Publication Date: 2018-11-24
    Description: Control by cell size Control by cell size, Published online: 23 November 2018; doi:10.1038/s41563-018-0225-z Macrophage confinement reduces the ‘late’ inflammatory gene response to lipopolysaccharide through myocardin-related transcription factor, an actin-binding transcription factor.
    Print ISSN: 1476-1122
    Electronic ISSN: 1476-4660
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Natural Sciences in General , Physics
    Published by Springer Nature
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Publication Date: 2013-01-29
    Description: Insulin resistance is a fundamental pathogenic factor present in various metabolic disorders including obesity and type 2 diabetes. Although skeletal muscle accounts for 70-90% of insulin-stimulated glucose disposal, the mechanism underlying muscle insulin resistance is poorly understood. Here we show in mice that muscle-specific mitsugumin 53 (MG53; also called TRIM72) mediates the degradation of the insulin receptor and insulin receptor substrate 1 (IRS1), and when upregulated, causes metabolic syndrome featuring insulin resistance, obesity, hypertension and dyslipidaemia. MG53 expression is markedly elevated in models of insulin resistance, and MG53 overexpression suffices to trigger muscle insulin resistance and metabolic syndrome sequentially. Conversely, ablation of MG53 prevents diet-induced metabolic syndrome by preserving the insulin receptor, IRS1 and insulin signalling integrity. Mechanistically, MG53 acts as an E3 ligase targeting the insulin receptor and IRS1 for ubiquitin-dependent degradation, comprising a central mechanism controlling insulin signal strength in skeletal muscle. These findings define MG53 as a novel therapeutic target for treating metabolic disorders and associated cardiovascular complications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Ruisheng -- Peng, Wei -- Zhang, Yan -- Lv, Fengxiang -- Wu, Hong-Kun -- Guo, Jiaojiao -- Cao, Yongxing -- Pi, Yanbin -- Zhang, Xin -- Jin, Li -- Zhang, Mao -- Jiang, Peng -- Liu, Fenghua -- Meng, Shaoshuai -- Zhang, Xiuqin -- Jiang, Ping -- Cao, Chun-Mei -- Xiao, Rui-Ping -- England -- Nature. 2013 Feb 21;494(7437):375-9. doi: 10.1038/nature11834. Epub 2013 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23354051" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carrier Proteins/genetics/*metabolism ; Diabetes Mellitus, Type 2 ; Diet, High-Fat ; Dyslipidemias/metabolism ; Gene Deletion ; Hypertension/metabolism ; *Insulin/metabolism ; Insulin Receptor Substrate Proteins/metabolism ; Insulin Resistance/genetics/*physiology ; Male ; Metabolic Syndrome X/enzymology/genetics/*metabolism/prevention & control ; Mice ; Obesity/chemically induced/metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Receptor, Insulin/metabolism ; Signal Transduction ; Ubiquitin-Protein Ligases/*metabolism ; Ubiquitination
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Publication Date: 2013-11-29
    Description: There are two proposed explanations for ultraluminous X-ray sources (ULXs) with luminosities in excess of 10(39) erg s(-1). They could be intermediate-mass black holes (more than 100-1,000 solar masses, M sun symbol) radiating at sub-maximal (sub-Eddington) rates, as in Galactic black-hole X-ray binaries but with larger, cooler accretion disks. Alternatively, they could be stellar-mass black holes radiating at Eddington or super-Eddington rates. On its discovery, M 101 ULX-1 had a luminosity of 3 x 10(39) erg s(-1) and a supersoft thermal disk spectrum with an exceptionally low temperature--uncomplicated by photons energized by a corona of hot electrons--more consistent with the expected appearance of an accreting intermediate-mass black hole. Here we report optical spectroscopic monitoring of M 101 ULX-1. We confirm the previous suggestion that the system contains a Wolf-Rayet star, and reveal that the orbital period is 8.2 days. The black hole has a minimum mass of 5 M sun symbol, and more probably a mass of 20 M sun symbol-30 M sun symbol, but we argue that it is very unlikely to be an intermediate-mass black hole. Therefore, its exceptionally soft spectra at high Eddington ratios violate the expectations for accretion onto stellar-mass black holes. Accretion must occur from captured stellar wind, which has hitherto been thought to be so inefficient that it could not power an ultraluminous source.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Ji-Feng -- Bregman, Joel N -- Bai, Yu -- Justham, Stephen -- Crowther, Paul -- England -- Nature. 2013 Nov 28;503(7477):500-3. doi: 10.1038/nature12762.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of Optical Astronomy, National Astronomical Observatories, Chinese Academy of Sciences, 20A Datun Road, Chaoyang District, 100012 Beijing, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24284727" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...