Xin-Yong Yuan - Profile on Academia.edu (original) (raw)
Papers by Xin-Yong Yuan
Molecular immunology, 2005
The availability of monoclonal antibodies (mAbs) specific for the SARS-coronavirus (SARS-CoV) is ... more The availability of monoclonal antibodies (mAbs) specific for the SARS-coronavirus (SARS-CoV) is important for the development of both diagnostic tools and treatment of infection. A molecular characterization of nine monoclonal antibodies raised in immune mice, using highly purified, inactivated SARS-CoV as the inoculating antigen, is presented in this report. These antibodies are specific for numerous viral protein targets, and six of them are able to effectively neutralize SARS-CoV in vitro, including one with a neutralizing titre of 0.075 nM. A phylogenetic analysis of the heavy and light chain sequences reveals that the mAbs share considerable homology. The majority of the heavy chains belong to a single Ig germline V-gene family, while considerably more sequence variation is evident in the light chain sequences. These analyses demonstrate that neutralization ability can be correlated with specific murine V(H)-gene alleles. For instance, one evident trend is high sequence conser...
FEMS Immunology & Medical Microbiology, 2006
Antibodies against the protective antigen (PA) of Bacillus anthracis play a key role in response ... more Antibodies against the protective antigen (PA) of Bacillus anthracis play a key role in response to infection by this important pathogen. The aim of this study was to produce and characterize monoclonal antibodies (mAbs) specific for PA and to identify novel neutralizing epitopes. Three murine mAbs with high specificity and nanomolar affinity for B. anthracis recombinant protective antigen (rPA) were produced and characterized. Western immunoblot analysis, coupled with epitope mapping using overlapping synthetic peptides, revealed that these mAbs recognize a linear epitope within domain 2 of rPA. Neutralization assays demonstrate that these mAbs effectively neutralize lethal toxin in vitro.
Aeroelastic Analysis of Oscillatory Blowing Control of the Airfoil’s Flutter at Large Attack Angle
It is known that oscillatory blowing on the back of an airfoil can delay the flow separation and ... more It is known that oscillatory blowing on the back of an airfoil can delay the flow separation and the stall. The purpose of the present paper is to apply the oscillatory blowing technique to the control of the airfoil’s flutter. High accuracy, high solution fluid-structure coupling numerical method is used in the study. The numerical results show that the steady blowing will weaken the flutter, but at the same time the excess blowing will make the lift coefficient to drop. The best blowing velocity can be found by the present numerical method. The influence of the frequency and the amplitude of the oscillatory blowing on the airfoil’s vibration is studied in the paper. The numerical results show that the oscillatory blowing is more efficient in the cases of flutter than steady blowing.
2011 IEEE International Symposium on Parallel and Distributed Processing Workshops and Phd Forum, 2011
Trends in Biotechnology, 2010
The Prostate, 2008
BACKGROUND. PAK6 is a member of the p21-activated kinase (PAK) family of serine/ threonine kinase... more BACKGROUND. PAK6 is a member of the p21-activated kinase (PAK) family of serine/ threonine kinases that was originally cloned from prostate cancer (PCa) cells as an androgen receptor interacting protein, but its cellular distribution and functions have not been established.
Proceedings of the National Academy of Sciences, 1994
Enterokinase is a protease of the intestinal brush border that specifically cleaves the acidic pr... more Enterokinase is a protease of the intestinal brush border that specifically cleaves the acidic propeptide from trypsinogen to yield active trypsin. This cleavage initiates a cascade of proteolytic reactions leading to the activation of many pancreatic zymogens. The full-length cDNA sequence for bovine enterokinase and partial cDNA sequence for human enterokinase were determined. The deduced amino acid sequences indicate that active two-chain enterokinase is derived from a single-chain precursor. Membrane association may be
Proceedings of the National Academy of Sciences, 2006
Androgen receptors (ARs) are phosphorylated at multiple sites in response to ligand binding, but ... more Androgen receptors (ARs) are phosphorylated at multiple sites in response to ligand binding, but the kinases mediating AR phosphorylation and the importance of these kinases in AR function have not been established. Here we show that cyclin-dependent kinase 1 (Cdk1) mediates AR phosphorylation at Ser-81 and increases AR protein expression, and that Cdk1 inhibitors decrease AR Ser-81 phosphorylation, protein expression, and transcriptional activity in prostate cancer (PCa) cells. The decline in AR protein expression mediated by the Cdk inhibitor roscovitine was prevented by proteosome inhibitors, indicating that Cdk1 stabilizes AR protein, although roscovitine also decreased AR message levels.
Atom transfer radical polymerization of styrene initiated by 2-(4-chloromethyl-phenyl)-benzoxazole with high activity and fluorescent property
Polymer, 2005
Functionalized polystyrene (PSt) was synthesized utilizing atom transfer radical polymerization (... more Functionalized polystyrene (PSt) was synthesized utilizing atom transfer radical polymerization (ATRP), which was conducted by using 2-(4-chloromethyl-phenyl)-benzoxazole (CMPB) as initiator, CuCl/PMDETA as catalyst, and cyclohexanone as solvent. The mechanism of ATRP was proved by characterizing the structure of PSt via 1H NMR and preparing of PSt-b-PMMA block copolymer. The polymerization showed first order with respect to monomer concentration and relatively
Nature Genetics, 2008
We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified ... more We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified a newly associated locus at chromosome 20p11.22, confirmed in three independent cohorts (n = 1,650; OR = 1.60, P = 1.1 × 10 -14 for rs1160312). The one man in seven who harbors risk alleles at both 20p11.22 and AR (encoding the androgen receptor) has a sevenfold-increased odds of androgenic alopecia (OR = 7.12, P = 3.7 × 10 -15 ). Androgenic alopecia is a common disorder affecting 40% of adult men and women1. Men and women with hair loss experience negative body-image perceptions2. Moreover, the mechanisms involved in androgenic alopecia may influence common medical disorders, such as coronary heart disease and metabolic syndrome3. Underscoring the social
Journal of Virological Methods, 2004
There is a global need to elucidate protective antigens expressed by the SARS-coronavirus (SARS-C... more There is a global need to elucidate protective antigens expressed by the SARS-coronavirus (SARS-CoV). Monoclonal antibody reagents that recognise specific antigens on SARS-CoV are needed urgently. In this report, the development and immunochemical characterisation of a panel of murine monoclonal antibodies (mAbs) against the SARS-CoV is presented, based upon their specificity, binding requirements, and biological activity. Initial screening by ELISA, using highly purified virus as the coating antigen, resulted in the selection of 103 mAbs to the SARS virus. Subsequent screening steps reduced this panel to seventeen IgG mAbs. A single mAb, F26G15, is specific for the nucleoprotein as seen in Western immunoblot while five other mAbs react with the Spike protein. Two of these Spike-specific mAbs demonstrate the ability to neutralise SARS-CoV in vitro while another four Western immunoblot-negative mAbs also neutralise the virus. The utility of these mAbs for diagnostic development is demonstrated. Antibody from convalescent SARS patients, but not normal human serum, is also shown to specifically compete off binding of mAbs to whole SARS-CoV. These studies highlight the importance of using standardised assays and reagents. These mAbs will be useful for the development of diagnostic tests, studies of SARS-CoV pathogenesis and vaccine development.
Journal of Polymer Science Part A: Polymer Chemistry, 2007
Two functional monomers, methacrylic acid 4-(2-benzoxazol)-benzyl ester (MABE) containing the ben... more Two functional monomers, methacrylic acid 4-(2-benzoxazol)-benzyl ester (MABE) containing the benzoxazole group and 4-(2-(9-anthryl))-vinyl-styrene (AVS) containing the anthracene group were synthesized by rational design. The MABE was polymerized via atom transfer radical polymerization (ATRP) using ethyl 2-bromoisobutyrate (EBIB) as initiator in CuBr/N,N,N 0 ,N 00 ,N 00 -pentamethyldiethylenetriamine (PMDETA) catalyst system; block copolymers poly(MABE-b-AVS) was obtained, which was conducted by using poly(MABE) as macro-initiator, AVS as the second monomer, and CuBr/PMDETA as catalyst. The constitute of two monomers in block copolymers poly(MABE-b-AVS) by ATRP could be adjusted, that is the constitute of the benzoxazole group and the anthracene group could be controlled in ABtype block copolymers. Moreover, the fluorescent properties of homopolymers poly (MABE) and block copolymers poly(MABE-b-AVS) were discussed herein. With the excitation at k ex ¼ 330 nm, the fluorescent emission spectrum of poly(MABE) solution showed emission at 375 nm corresponding to the benzoxazole-based part; with the same excitation, the fluorescent emission spectrum of poly(MABE-b-AVS) solution showed a broad peek at 330-600 nm when the monomer AVS to the total monomers mole ratio was 0.31, and the fluorescent emission spectrum of poly(MABE-b-AVS) in film state only showed one peak at 525 nm corresponding to the anthracene-based unit that indicated a complete energy transfer from the benzoxazole group to the anthracene group. V V C 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3894-3901, 2007
Journal of Chemical Technology & Biotechnology, 2010
BACKGROUND: In the presence of light, micro-algae convert CO 2 and nutrients to biomass that can ... more BACKGROUND: In the presence of light, micro-algae convert CO 2 and nutrients to biomass that can be used as a biofuel. In closed photo-bioreactors, however, light and CO 2 availability often limit algae production and can be difficult to control using traditional diffuser systems. In this research, a hollow fiber membrane photo-bioreactor (HFMPB) was investigated to: (1) increase the interfacial contact area available for gas transfer, (2) treat high nutrient strength (412 mg NO 3 − -N L −1 ) wastewater, and (3) produce algal biomass that can be used as a biofuel.
IEEE/ACM Transactions on Networking, 2000
Fat-tree based system area networks have been widely adopted in high performance computing cluste... more Fat-tree based system area networks have been widely adopted in high performance computing clusters. In such systems, the routing is often deterministic and the traffic demand is usually uncertain and changing. In this paper, we study routing performance on fat-tree based system area networks with deterministic routing under the assumption that the traffic demand is uncertain. The performance of a routing algorithm under uncertain traffic demands is characterized by the oblivious performance ratio that bounds the relative performance of the routing algorithm and the optimal routing algorithm for any given traffic demand. We consider both single path routing where the traffic between each source-destination pair follows one path, and multipath routing where multiple paths can be used for the traffic between a source-destination pair. We derive lower bounds of the oblivious performance ratio of any single path routing scheme for fat-tree topologies and develop single path oblivious routing schemes that achieve the optimal oblivious performance ratio for commonly used fat-tree topologies. These oblivious routing schemes provide the best performance guarantees among all single path routing algorithms under uncertain traffic demands. For multi-path routing, we show that it is possible to obtain a scheme that is optimal for any traffic demand (an oblivious performance ratio of 1) on the fat-tree topology. These results quantitatively demonstrate that single path routing cannot guarantee high routing performance while multi-path routing is very effective in balancing network loads on the fat-tree topology.
Genome-wide association study identifies loci affecting blood copper, selenium and zinc
Human Molecular Genetics, 2013
ABSTRACT Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide... more ABSTRACT Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N r 71,225 European ancestry, N r 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N ¼ 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P ¼ 7 10 24), CYP1A2 (P ¼ 1 10 23), FGF5 (P ¼ 1 10 21), SH2B3 (P ¼ 3 10 18), MTHFR (P ¼ 2 10 13), c10orf107 (P ¼ 1 10 9), ZNF652 (P ¼ 5 10 9) and PLCD3 (P ¼ 1 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease
BMC Cardiovascular Disorders, 2008
Background: Cardiovascular diseases and their associated risk factors remain the main cause of mo... more Background: Cardiovascular diseases and their associated risk factors remain the main cause of mortality in western societies. In order to assess the prevalence of cardiovascular risk factors (CVRFs) in the Caucasian population of Lausanne, Switzerland, we conducted a population-based study (Colaus Study). A secondary aim of the CoLaus study will be to determine new genetic determinants associated with CVRFs. Methods: Single-center, cross-sectional study including a random sample of 6,188 extensively phenotyped Caucasian subjects (3,251 women and 2,937 men) aged 35 to 75 years living in Lausanne, and genotyped using the 500 K Affymetrix chip technology. Results: Obesity (body mass index ≥ 30 kg/m 2 ), smoking, hypertension (blood pressure ≥ 140/90 mmHg and/or treatment), dyslipidemia (high LDL-cholesterol and/or low HDL-cholesterol and/or high triglyceride levels) and diabetes (fasting plasma glucose ≥ 7 mmol/l and/or treatment) were present in 947 (15.7%), 1673 (27.0%), 2268 (36.7%), 2113 (34.2%) and 407 (6.6%) of the participants, respectively, and the prevalence was higher in men than in women. In both genders, the prevalence of obesity, hypertension and diabetes increased with age. The prevalence of major CVRFs is high in the Lausanne population in particular in men. We anticipate that given its size, the depth of the phenotypic analysis and the availability of dense genome-wide genetic data, the CoLaus Study will be a unique resource to investigate not only the epidemiology of isolated, or aggregated CVRFs like the metabolic syndrome, but can also serve as a discovery set, as well as replication set, to identify novel genes associated with these conditions.
Microplasma Technology and Its Applications in Analytical Chemistry
Applied Spectroscopy Reviews, 2011
This review paper describes some existing microplasma sources and their applications in analytica... more This review paper describes some existing microplasma sources and their applications in analytical chemistry. These microplasmas mainly include direct current glow discharge (DC), microhollow cathode discharge (MCHD) or microstructure electrode (MSE), dielectric barrier discharge (DBD), capacitively coupled microplasmas (CCμPs), miniature inductively coupled plasmas (mICPs) and microwave-induced plasmas (MIPs). The historical development and recent advance in these microplasma techniques are presented. Fundamental properties of the microplasmas, the unique features of the reduced size and volume, as well as the advantageous device structures for chemical analysis are discussed in detail, with the emphasis towards detection of gaseous samples. The analytical figures of merit obtained using these microplasmas as molecular/elemental-selective detectors for emission spectrometry and as ionization sources for mass spectrometry are also given in this review paper.
Effects of transactional leadership, psychological empowerment and empowerment climate on creative performance of subordinates: A cross-level study
Frontiers of Business Research in China, 2010
This research surveyed 101 teams, involving 497 team members and 101 team leaders, in a large mul... more This research surveyed 101 teams, involving 497 team members and 101 team leaders, in a large multinational company in China. A hierarchical linear model is used to examine the hypothesized mediated moderation model. It is found that: (1) individual psychological empowerment is positively related to creative performance; (2) the relationship between transactional leadership and subordinates’ creative performance is moderated by
Nature, 2010
Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lip... more Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in .100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P , 5 3 10 28 ), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD. Plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) are heritable risk factors for cardiovascular disease and targets for therapeutic intervention 1 . Genomewide association studies (GWASs) involving up to 20,000 individuals of European ancestry have identified .30 genetic loci contributing to inter-individual variation in plasma lipid concentrations [2] . Half of these loci harboured genes previously known to influence plasma lipid concentrations, establishing the technical validity of the lipid GWAS. Nevertheless, the practical value of the GWAS approach remains a subject of debate . Here we focus on three key questions motivated by recent progress in genetic mapping: (1) are loci identified in populations of European descent important in non-European groups, suggesting relevance in different global populations; (2) are these loci of clinical relevance, providing the framework to identify potential novel drug targets for the treatment of extreme lipid phenotypes and prevention of CAD; and (3) do these loci harbour genes with biological relevance, that is, which are directly involved in lipid regulation and metabolism? We address these questions using several approaches: a genomewide association screen for plasma lipids in .100,000 individuals of European ancestry; evaluation of mapped variants in East Asians, South Asians and African Americans; association testing in individuals with and without CAD; evaluation of genetic variants in patients with extreme plasma lipid concentrations; and genetic manipulation in mouse models.
PLoS Genetics, 2012
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly her... more Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5610 28 -1.2610 243 ). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p,3610 24 ). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3610 23 , n = 22,044), increased triglycerides (p = 2.6610 214 , n = 93,440), increased waist-to-hip ratio (p = 1.8610 25 , n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4610 23 , n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDLcholesterol concentrations (p = 4.5610 213 , n = 96,748) and decreased BMI (p = 1.4610 24 , n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
Molecular immunology, 2005
The availability of monoclonal antibodies (mAbs) specific for the SARS-coronavirus (SARS-CoV) is ... more The availability of monoclonal antibodies (mAbs) specific for the SARS-coronavirus (SARS-CoV) is important for the development of both diagnostic tools and treatment of infection. A molecular characterization of nine monoclonal antibodies raised in immune mice, using highly purified, inactivated SARS-CoV as the inoculating antigen, is presented in this report. These antibodies are specific for numerous viral protein targets, and six of them are able to effectively neutralize SARS-CoV in vitro, including one with a neutralizing titre of 0.075 nM. A phylogenetic analysis of the heavy and light chain sequences reveals that the mAbs share considerable homology. The majority of the heavy chains belong to a single Ig germline V-gene family, while considerably more sequence variation is evident in the light chain sequences. These analyses demonstrate that neutralization ability can be correlated with specific murine V(H)-gene alleles. For instance, one evident trend is high sequence conser...
FEMS Immunology & Medical Microbiology, 2006
Antibodies against the protective antigen (PA) of Bacillus anthracis play a key role in response ... more Antibodies against the protective antigen (PA) of Bacillus anthracis play a key role in response to infection by this important pathogen. The aim of this study was to produce and characterize monoclonal antibodies (mAbs) specific for PA and to identify novel neutralizing epitopes. Three murine mAbs with high specificity and nanomolar affinity for B. anthracis recombinant protective antigen (rPA) were produced and characterized. Western immunoblot analysis, coupled with epitope mapping using overlapping synthetic peptides, revealed that these mAbs recognize a linear epitope within domain 2 of rPA. Neutralization assays demonstrate that these mAbs effectively neutralize lethal toxin in vitro.
Aeroelastic Analysis of Oscillatory Blowing Control of the Airfoil’s Flutter at Large Attack Angle
It is known that oscillatory blowing on the back of an airfoil can delay the flow separation and ... more It is known that oscillatory blowing on the back of an airfoil can delay the flow separation and the stall. The purpose of the present paper is to apply the oscillatory blowing technique to the control of the airfoil’s flutter. High accuracy, high solution fluid-structure coupling numerical method is used in the study. The numerical results show that the steady blowing will weaken the flutter, but at the same time the excess blowing will make the lift coefficient to drop. The best blowing velocity can be found by the present numerical method. The influence of the frequency and the amplitude of the oscillatory blowing on the airfoil’s vibration is studied in the paper. The numerical results show that the oscillatory blowing is more efficient in the cases of flutter than steady blowing.
2011 IEEE International Symposium on Parallel and Distributed Processing Workshops and Phd Forum, 2011
Trends in Biotechnology, 2010
The Prostate, 2008
BACKGROUND. PAK6 is a member of the p21-activated kinase (PAK) family of serine/ threonine kinase... more BACKGROUND. PAK6 is a member of the p21-activated kinase (PAK) family of serine/ threonine kinases that was originally cloned from prostate cancer (PCa) cells as an androgen receptor interacting protein, but its cellular distribution and functions have not been established.
Proceedings of the National Academy of Sciences, 1994
Enterokinase is a protease of the intestinal brush border that specifically cleaves the acidic pr... more Enterokinase is a protease of the intestinal brush border that specifically cleaves the acidic propeptide from trypsinogen to yield active trypsin. This cleavage initiates a cascade of proteolytic reactions leading to the activation of many pancreatic zymogens. The full-length cDNA sequence for bovine enterokinase and partial cDNA sequence for human enterokinase were determined. The deduced amino acid sequences indicate that active two-chain enterokinase is derived from a single-chain precursor. Membrane association may be
Proceedings of the National Academy of Sciences, 2006
Androgen receptors (ARs) are phosphorylated at multiple sites in response to ligand binding, but ... more Androgen receptors (ARs) are phosphorylated at multiple sites in response to ligand binding, but the kinases mediating AR phosphorylation and the importance of these kinases in AR function have not been established. Here we show that cyclin-dependent kinase 1 (Cdk1) mediates AR phosphorylation at Ser-81 and increases AR protein expression, and that Cdk1 inhibitors decrease AR Ser-81 phosphorylation, protein expression, and transcriptional activity in prostate cancer (PCa) cells. The decline in AR protein expression mediated by the Cdk inhibitor roscovitine was prevented by proteosome inhibitors, indicating that Cdk1 stabilizes AR protein, although roscovitine also decreased AR message levels.
Atom transfer radical polymerization of styrene initiated by 2-(4-chloromethyl-phenyl)-benzoxazole with high activity and fluorescent property
Polymer, 2005
Functionalized polystyrene (PSt) was synthesized utilizing atom transfer radical polymerization (... more Functionalized polystyrene (PSt) was synthesized utilizing atom transfer radical polymerization (ATRP), which was conducted by using 2-(4-chloromethyl-phenyl)-benzoxazole (CMPB) as initiator, CuCl/PMDETA as catalyst, and cyclohexanone as solvent. The mechanism of ATRP was proved by characterizing the structure of PSt via 1H NMR and preparing of PSt-b-PMMA block copolymer. The polymerization showed first order with respect to monomer concentration and relatively
Nature Genetics, 2008
We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified ... more We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified a newly associated locus at chromosome 20p11.22, confirmed in three independent cohorts (n = 1,650; OR = 1.60, P = 1.1 × 10 -14 for rs1160312). The one man in seven who harbors risk alleles at both 20p11.22 and AR (encoding the androgen receptor) has a sevenfold-increased odds of androgenic alopecia (OR = 7.12, P = 3.7 × 10 -15 ). Androgenic alopecia is a common disorder affecting 40% of adult men and women1. Men and women with hair loss experience negative body-image perceptions2. Moreover, the mechanisms involved in androgenic alopecia may influence common medical disorders, such as coronary heart disease and metabolic syndrome3. Underscoring the social
Journal of Virological Methods, 2004
There is a global need to elucidate protective antigens expressed by the SARS-coronavirus (SARS-C... more There is a global need to elucidate protective antigens expressed by the SARS-coronavirus (SARS-CoV). Monoclonal antibody reagents that recognise specific antigens on SARS-CoV are needed urgently. In this report, the development and immunochemical characterisation of a panel of murine monoclonal antibodies (mAbs) against the SARS-CoV is presented, based upon their specificity, binding requirements, and biological activity. Initial screening by ELISA, using highly purified virus as the coating antigen, resulted in the selection of 103 mAbs to the SARS virus. Subsequent screening steps reduced this panel to seventeen IgG mAbs. A single mAb, F26G15, is specific for the nucleoprotein as seen in Western immunoblot while five other mAbs react with the Spike protein. Two of these Spike-specific mAbs demonstrate the ability to neutralise SARS-CoV in vitro while another four Western immunoblot-negative mAbs also neutralise the virus. The utility of these mAbs for diagnostic development is demonstrated. Antibody from convalescent SARS patients, but not normal human serum, is also shown to specifically compete off binding of mAbs to whole SARS-CoV. These studies highlight the importance of using standardised assays and reagents. These mAbs will be useful for the development of diagnostic tests, studies of SARS-CoV pathogenesis and vaccine development.
Journal of Polymer Science Part A: Polymer Chemistry, 2007
Two functional monomers, methacrylic acid 4-(2-benzoxazol)-benzyl ester (MABE) containing the ben... more Two functional monomers, methacrylic acid 4-(2-benzoxazol)-benzyl ester (MABE) containing the benzoxazole group and 4-(2-(9-anthryl))-vinyl-styrene (AVS) containing the anthracene group were synthesized by rational design. The MABE was polymerized via atom transfer radical polymerization (ATRP) using ethyl 2-bromoisobutyrate (EBIB) as initiator in CuBr/N,N,N 0 ,N 00 ,N 00 -pentamethyldiethylenetriamine (PMDETA) catalyst system; block copolymers poly(MABE-b-AVS) was obtained, which was conducted by using poly(MABE) as macro-initiator, AVS as the second monomer, and CuBr/PMDETA as catalyst. The constitute of two monomers in block copolymers poly(MABE-b-AVS) by ATRP could be adjusted, that is the constitute of the benzoxazole group and the anthracene group could be controlled in ABtype block copolymers. Moreover, the fluorescent properties of homopolymers poly (MABE) and block copolymers poly(MABE-b-AVS) were discussed herein. With the excitation at k ex ¼ 330 nm, the fluorescent emission spectrum of poly(MABE) solution showed emission at 375 nm corresponding to the benzoxazole-based part; with the same excitation, the fluorescent emission spectrum of poly(MABE-b-AVS) solution showed a broad peek at 330-600 nm when the monomer AVS to the total monomers mole ratio was 0.31, and the fluorescent emission spectrum of poly(MABE-b-AVS) in film state only showed one peak at 525 nm corresponding to the anthracene-based unit that indicated a complete energy transfer from the benzoxazole group to the anthracene group. V V C 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3894-3901, 2007
Journal of Chemical Technology & Biotechnology, 2010
BACKGROUND: In the presence of light, micro-algae convert CO 2 and nutrients to biomass that can ... more BACKGROUND: In the presence of light, micro-algae convert CO 2 and nutrients to biomass that can be used as a biofuel. In closed photo-bioreactors, however, light and CO 2 availability often limit algae production and can be difficult to control using traditional diffuser systems. In this research, a hollow fiber membrane photo-bioreactor (HFMPB) was investigated to: (1) increase the interfacial contact area available for gas transfer, (2) treat high nutrient strength (412 mg NO 3 − -N L −1 ) wastewater, and (3) produce algal biomass that can be used as a biofuel.
IEEE/ACM Transactions on Networking, 2000
Fat-tree based system area networks have been widely adopted in high performance computing cluste... more Fat-tree based system area networks have been widely adopted in high performance computing clusters. In such systems, the routing is often deterministic and the traffic demand is usually uncertain and changing. In this paper, we study routing performance on fat-tree based system area networks with deterministic routing under the assumption that the traffic demand is uncertain. The performance of a routing algorithm under uncertain traffic demands is characterized by the oblivious performance ratio that bounds the relative performance of the routing algorithm and the optimal routing algorithm for any given traffic demand. We consider both single path routing where the traffic between each source-destination pair follows one path, and multipath routing where multiple paths can be used for the traffic between a source-destination pair. We derive lower bounds of the oblivious performance ratio of any single path routing scheme for fat-tree topologies and develop single path oblivious routing schemes that achieve the optimal oblivious performance ratio for commonly used fat-tree topologies. These oblivious routing schemes provide the best performance guarantees among all single path routing algorithms under uncertain traffic demands. For multi-path routing, we show that it is possible to obtain a scheme that is optimal for any traffic demand (an oblivious performance ratio of 1) on the fat-tree topology. These results quantitatively demonstrate that single path routing cannot guarantee high routing performance while multi-path routing is very effective in balancing network loads on the fat-tree topology.
Genome-wide association study identifies loci affecting blood copper, selenium and zinc
Human Molecular Genetics, 2013
ABSTRACT Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide... more ABSTRACT Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N r 71,225 European ancestry, N r 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N ¼ 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P ¼ 7 10 24), CYP1A2 (P ¼ 1 10 23), FGF5 (P ¼ 1 10 21), SH2B3 (P ¼ 3 10 18), MTHFR (P ¼ 2 10 13), c10orf107 (P ¼ 1 10 9), ZNF652 (P ¼ 5 10 9) and PLCD3 (P ¼ 1 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease
BMC Cardiovascular Disorders, 2008
Background: Cardiovascular diseases and their associated risk factors remain the main cause of mo... more Background: Cardiovascular diseases and their associated risk factors remain the main cause of mortality in western societies. In order to assess the prevalence of cardiovascular risk factors (CVRFs) in the Caucasian population of Lausanne, Switzerland, we conducted a population-based study (Colaus Study). A secondary aim of the CoLaus study will be to determine new genetic determinants associated with CVRFs. Methods: Single-center, cross-sectional study including a random sample of 6,188 extensively phenotyped Caucasian subjects (3,251 women and 2,937 men) aged 35 to 75 years living in Lausanne, and genotyped using the 500 K Affymetrix chip technology. Results: Obesity (body mass index ≥ 30 kg/m 2 ), smoking, hypertension (blood pressure ≥ 140/90 mmHg and/or treatment), dyslipidemia (high LDL-cholesterol and/or low HDL-cholesterol and/or high triglyceride levels) and diabetes (fasting plasma glucose ≥ 7 mmol/l and/or treatment) were present in 947 (15.7%), 1673 (27.0%), 2268 (36.7%), 2113 (34.2%) and 407 (6.6%) of the participants, respectively, and the prevalence was higher in men than in women. In both genders, the prevalence of obesity, hypertension and diabetes increased with age. The prevalence of major CVRFs is high in the Lausanne population in particular in men. We anticipate that given its size, the depth of the phenotypic analysis and the availability of dense genome-wide genetic data, the CoLaus Study will be a unique resource to investigate not only the epidemiology of isolated, or aggregated CVRFs like the metabolic syndrome, but can also serve as a discovery set, as well as replication set, to identify novel genes associated with these conditions.
Microplasma Technology and Its Applications in Analytical Chemistry
Applied Spectroscopy Reviews, 2011
This review paper describes some existing microplasma sources and their applications in analytica... more This review paper describes some existing microplasma sources and their applications in analytical chemistry. These microplasmas mainly include direct current glow discharge (DC), microhollow cathode discharge (MCHD) or microstructure electrode (MSE), dielectric barrier discharge (DBD), capacitively coupled microplasmas (CCμPs), miniature inductively coupled plasmas (mICPs) and microwave-induced plasmas (MIPs). The historical development and recent advance in these microplasma techniques are presented. Fundamental properties of the microplasmas, the unique features of the reduced size and volume, as well as the advantageous device structures for chemical analysis are discussed in detail, with the emphasis towards detection of gaseous samples. The analytical figures of merit obtained using these microplasmas as molecular/elemental-selective detectors for emission spectrometry and as ionization sources for mass spectrometry are also given in this review paper.
Effects of transactional leadership, psychological empowerment and empowerment climate on creative performance of subordinates: A cross-level study
Frontiers of Business Research in China, 2010
This research surveyed 101 teams, involving 497 team members and 101 team leaders, in a large mul... more This research surveyed 101 teams, involving 497 team members and 101 team leaders, in a large multinational company in China. A hierarchical linear model is used to examine the hypothesized mediated moderation model. It is found that: (1) individual psychological empowerment is positively related to creative performance; (2) the relationship between transactional leadership and subordinates’ creative performance is moderated by
Nature, 2010
Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lip... more Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in .100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P , 5 3 10 28 ), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD. Plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) are heritable risk factors for cardiovascular disease and targets for therapeutic intervention 1 . Genomewide association studies (GWASs) involving up to 20,000 individuals of European ancestry have identified .30 genetic loci contributing to inter-individual variation in plasma lipid concentrations [2] . Half of these loci harboured genes previously known to influence plasma lipid concentrations, establishing the technical validity of the lipid GWAS. Nevertheless, the practical value of the GWAS approach remains a subject of debate . Here we focus on three key questions motivated by recent progress in genetic mapping: (1) are loci identified in populations of European descent important in non-European groups, suggesting relevance in different global populations; (2) are these loci of clinical relevance, providing the framework to identify potential novel drug targets for the treatment of extreme lipid phenotypes and prevention of CAD; and (3) do these loci harbour genes with biological relevance, that is, which are directly involved in lipid regulation and metabolism? We address these questions using several approaches: a genomewide association screen for plasma lipids in .100,000 individuals of European ancestry; evaluation of mapped variants in East Asians, South Asians and African Americans; association testing in individuals with and without CAD; evaluation of genetic variants in patients with extreme plasma lipid concentrations; and genetic manipulation in mouse models.
PLoS Genetics, 2012
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly her... more Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5610 28 -1.2610 243 ). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p,3610 24 ). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3610 23 , n = 22,044), increased triglycerides (p = 2.6610 214 , n = 93,440), increased waist-to-hip ratio (p = 1.8610 25 , n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4610 23 , n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDLcholesterol concentrations (p = 4.5610 213 , n = 96,748) and decreased BMI (p = 1.4610 24 , n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.