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An efficient and scalable process for the synthesis of antihypercholesterolemic drug ezetimibe through chiral Evans auxiliary (S)-4-phenyl-2-oxazolidinone is described. The key steps in this process are the condensation of (S)-3-(5-(4-fluorophenyl)-5,5-dimethoxypentanoyl)-4-phenyloxazolidin-2-one and N-(4-((tert-butyldimethylsilyl)oxy)benzylidene)-4-fluoroaniline, and the stereoselective reduction of ezetimibe-ketone with NaBH4/I2, which is first applied in the synthesis of ezetimibe. The process is concise, mild, easy to operate, and highly stereoselective (99.6% of de value of ezetimibe). In addition, three diastereomers of ezetimibe are synthesized and served as the references in quality control of the product.

Obesity, a major health concern, results from an imbalance between energy intake and expenditure. Leptin-deficient ob/ob mice are paradigmatic of obesity, resulting from excess energy intake and storage. Mice lacking acyl-CoA oxidase 1 (Acox1), the first enzyme of the peroxisomal fatty acid β-oxidation system, are characterized by increased energy expenditure and a lean body phenotype caused by sustained activation of peroxisome proliferator-activated receptor α (PPARα) by endogenous ligands in liver that remain unmetabolized in the absence of Acox1. We generated ob/ob mice deficient in Acox1 (Acox1−/−) to determine how the activation of PPARα by endogenous ligands might affect the obesity of ob/ob mice. In contrast to Acox1−/− (14.3±1.2 g at 6 mo) and the Acox1-deficient (ob/ob) double-mutant mice (23.8±4.6 g at 6 mo), the ob/ob mice are severely obese (54.3±3.2 g at 6 mo) and had significantly more (P

Research highlights? We investigate the random surface defects on hot rolled steel bars and coils. ? Automatic image based inspection technique used for investigation. ? Defects classified based on process knowledge and image processing. ? Process knowledge leads to better classification scheme by support vector machines. Random surface defects occur during the hot bar rolling of steels and are identified either by manual or by automated inspection techniques. Manual inspection techniques are purely based on the process knowledge of the inspector such as the location, type and kind of defects, and the primary sources of these defects. The automated techniques, to identify and classify the defects, rely on machine vision technologies and image processing algorithms based on support vector machines, wavelets, image processing and statistical inference. Both these approaches have their own advantages and limitations. To improve the accuracy of classification of these defects a process knowledge based support vector classification scheme is proposed (called PK-MSVM) which combines feature extraction task of automated inspection with the process knowledge. The defect observation data from the imaging sensor is transformed to include this process knowledge. Three attributes of the defects - length to width ratio, longitudinal location and transverse location- are used for this transformation are they are closely related to the thermo-mechanics of the rolling process. Different formulations of the multi-class support vector machines (MSVMs) are compared for this classification with or without process knowledge based transformation: one-against-one, one-against-all and Hastie's algorithm of multi class SVM. It is found that the new approach (PK-MSVM) performs better than traditional MSVM for all the three formulations. For the best case, the performance sees a jump of more than 100%. Thus incorporating process knowledge in identification and classification does increase the reliability of inspection considerably.

Multidrug-resistant (MDR) and extensive drug-resistant (XDR) tuberculosis (TB) are significant health problems throughout the world. Although the main treatment is medical, adjunctive surgical resection may increase the chance of cure in selected patients with MDR-TB or XDR-TB. This study aimed to present a case series of patients who underwent surgical resection for MDR-TB. Between March 2008 and November 2011, surgical resection was performed on 54 patients including 34 with MDR-TB and 20 with XDR-TB at the Departments of Surgery of Shanghai Public Health Clinical Center (Shanghai), Henan Chest Hospital (Henan), and Anhui Chest Hospital (Henan). Preoperative sputum smear samples were positive for 28 patients and sputum quantitative polymerase chain reaction was positive for 32. Patients were treated according to a standard therapy protocol for a mean of 4.2 months before the operation. The variables that affected treatment outcomes were identified through multivariate regression analysis. Fifty-four patients were operated for MDR-TB with localized disease usually complicated by cavity formation or destroyed lung. Thirty-seven were males and 17 were females. Median age was 37.8 (range, 20–75) years. Lobectomy was performed in 46 patients and pneumonectomy in 8. Muscle flaps were used in 36 of the patients with lobectomy and 8 with pneumonectomy. Various complications occurred in 6 (11.1%) patients, including bronchopleural fistula in 1 patient, bleeding in 2 patients, and prolonged air leak in 2 patients. A favorable outcome was achieved in 47 patients (87%) who underwent surgical resection. Higher body mass index (BMI) was associated with better outcome (odds ratio = 0.537, 95% confidence interval: 0.310–0.928, P = .026). Patients with MDR-TB had good treatment outcomes after adjunctive pulmonary resection, and with few complications. Higher BMI was related to a favorable outcome.

A novel Friedel–Crafts alkylation of α- or β-naphthols with a variety of β-haloketones is described. The reaction was environmentally-friendly performed under mild conditions without any Lewis acid and in good to excellent yields.

Gastric cancer is one of the most common malignancies worldwide. Interleukin‐1‐beta (IL‐1β) is a pro‐inflammatory cytokine and potent inhibitor of gastric acid secretion. Some studies provided evidence of the association between IL‐1B 31 polymorphism and gastric cancer risk while other studies did not. Therefore, we conducted a comprehensive meta‐analysis to reassess the association. A systematic literature search of the PubMed and EMBASE databases identified 37 studies with 6108 cases and 8980 controls for this meta‐analysis. The crude odd ratios (ORs) and the 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Meta‐regression was used to determine the major source of heterogeneity across the studies. The pooled analysis did not suggest the significant association of IL‐1B 31 C>T polymorphism with gastric cancer risk. Stratified analysis was performed by ethnicity, source of control, genotype method, and indicated a significantly increased gastric cancer risk associated with IL‐1B 31T variant in the population‐based subgroup (heterozygous model: OR = 1.22, 95% CI = 1.03–1.45). Moreover, stratified analysis by Helicobacter pylori infection status indicated that IL‐1B 31 polymorphism increased gastric cancer risk in infection‐positive subgroup (homozygous model: OR = 1.35, 95% CI = 1.02–1.78; heterozygous model: OR = 1.31, 95% CI = 1.04–1.66; recessive model: OR = 1.29, 95% CI = 1.04–1.61). The study suggested that IL‐1B 31 polymorphism might confer susceptibility to gastric cancer in the presence of H. pylori infection, indicating a gene–environment interaction in gastric carcinogenesis.

We consider an M/GI/1 queue with two types of customers, positive and negative, which cancel each other out. The server provides service to either a positive customer or a negative customer. In such a system, the queue length can be either positive or negative and an arrival either joins the queue, if it is of the same sign, or instantaneously removes a customer of the opposite sign at the end of the queue or in service. This study is a generalization of Gelenbe's original concept of a queue with negative customers, where only positive customers need services and negative customers arriving at an empty system are lost or need no service. In this paper, we derive the transient and the stationary probability distributions for the major performance measures in terms of generating functions and Laplace transforms. It has been shown that the previous results for the system with negative arrivals of zero service time are special cases of our model. In addition, we obtain the stationary waiting time distribution of this system in terms of a Laplace transform.

Visible light communications (VLC) using multi-color light-emitting diodes (LEDs) can support simultaneous high-speed data rate and high-quality lighting. However, since the radiation spectrum of LEDs has a limited width, spectral overlapping will result in multi-color cross talk even when optical filters are applied at the receivers. Moreover, since LEDs are used for illumination and wireless data transmission in the meantime, both lighting quality and communication performance must be considered in VLC systems. In this paper, we consider a multiple-input-multiple-output with low-complexity linear minimum mean square error detection to collaboratively manage the cross talk by maximizing the minimum signal-to-interference-plus-noise ratio (SINR) subject to chromaticity constraint based on MacAdam ellipse, luminance constraint, and signal range constraint. A sub-optimal convex relaxation is proposed to attack the SINR maximization problem. Extensive simulations indicate that the proposed method provides very efficient solutions and outperforms the conventional wave-division multiplexing scheme under the illumination constraint.

The transmission rate of visible light communications (VLC) remains low as the low modulation bandwidth performance of light emitting diode (LED). This paper proposes a transmission system consisting of multiple LEDs and a photodiode (PD) to increase the transmission rate. We combines the radio superposition coded modulation (SCM), interleave division multiple access(IDMA) technology with VLC. To fit the driving voltage non-negative characteristics of LED and detect the mixed multi-LED light intensity signals, the VLC multi-LED parallel transmission based on OOK modulation scheme is proposed, which has about K (K is the number LED wicks) times the transmission rate of the traditional ways. Finally, we analyze the number of iterations, the different specific interleaver and the driving voltages that are the factors influence the transmission performance. The simulation also verifies the high speed transmission capability and the anti-nonlinearity performance of the proposed scheme.

Dietary intake of l-carnitine can promote cardiovascular diseases in humans through microbial production of trimethylamine (TMA) and its subsequent oxidation to trimethylamine N-oxide by hepatic flavin-containing monooxygenases. Although our microbiota are responsible for TMA formation from carnitine, the underpinning molecular and biochemical mechanisms remain unclear. In this study, using bioinformatics approaches, we first identified a two-component Rieske-type oxygenase/reductase (CntAB) and associated gene cluster proposed to be involved in carnitine metabolism in representative genomes of the human microbiota. CntA belongs to a group of previously uncharacterized Rieske-type proteins and has an unusual “bridging” glutamate but not the aspartate residue, which is believed to facilitate intersubunit electron transfer between the Rieske center and the catalytic mononuclear iron center. Using Acinetobacter baumannii as the model, we then demonstrate that cntAB is essential in carnitine degradation to TMA. Heterologous overexpression of cntAB enables Escherichia coli to produce TMA, confirming that these genes are sufficient in TMA formation. Site-directed mutagenesis experiments have confirmed that this unusual “bridging glutamate” residue in CntA is essential in catalysis and neither mutant (E205D, E205A) is able to produce TMA. Taken together, the data in our study reveal the molecular and biochemical mechanisms underpinning carnitine metabolism to TMA in human microbiota and assign the role of this novel group of Rieske-type proteins in microbial carnitine metabolism.

Methylocella silvestris, an alphaproteobacterium isolated from a forest soil, can grow on trimethylamine N-oxide (TMAO) as a sole nitrogen source; however, the molecular and biochemical mechanisms underpinning its growth remain unknown. Marker-exchange mutagenesis enabled the identification of several genes involved in TMAO metabolism, including Msil_3606, a permease of the amino acids-polyamine (APC) superfamily, and Msil_3603, consisting of an N-terminal domain of unknown function (DUF1989) and a C-terminal tetrahydrofolate-binding domain. Null mutants of Msil_3603 and Msil_3606 can no longer grow on TMAO. Purified Msil_3603 from recombinant Escherichia coli can convert TMAO to dimethylamine and formaldehyde (1 TMAO → 1 dimethylamine + 1 formaldehyde), confirming that it encodes a bona fide TMAO demethylase (Tdm). Tdm of M. silvestris and eukaryotic Tdms have no sequence homology and contrasting characteristics. Recombinant Tdm of M. silvestris appears to be hexameric, has a high affinity for TMAO (Km = 3.3 mM; Vmax = 21.7 nmol min(-1) mg(-1) ) and only catalyses demethylation of TMAO and a structural homologue, dimethyldodecylamine N-oxide. Our study has contributed to the understanding of the genetic and biochemical mechanisms for TMAO degradation in M. silvestris.

To describe the time-dependent behavior of soft clay, this paper extended one-dimensional Nishihara model to three-dimensional stress state based on the framework of Perzyna’s overstress theory and modified cam-clay model. The yield criterion of modified cam-clay model was used to describe the plastic properties of soft clay, and the overstress theory was used to describe the strain rate effect. Triaxial rheological tests were carried out on Ningbo soft clay and the rheological characteristics were studied. Based on laboratory results, the parameters of proposed model were determined by curve fitting, which show that this model is suitable for the rheological characteristics of Ningbo soft clay. The analysis of parameters shows that, the value of parameters changes slightly with different deviatoric stress when the confining pressure was constant, but changes notably with the increase of confining pressure. A user material subroutine of the proposed constitutive mode was coded on the platform of the FEM software ABAQUS and verified by triaxial compression of soil column. A plain strain problem was computed to analyze the rheological consolidation properties of soft clay, in which the rheological effect and the finite strain effect were considered.

We previously isolated and identified peroxisome proliferator-activated receptor (PPAR)-binding Protein (PBP) as a coactivator for PPARgamma. PBP has recently been identified as a component of the multiprotein complexes such as TRAP, DRIP, and ARC that appear to play an important role in the transcriptional activation by several transcriptional factors including nuclear receptors. To assess the biological significance of PBP, we disrupted the PBP gene (PBP/PPARBP) in mice by homologous recombination. PBP(+/-) mice are healthy, fertile, and do not differ significantly from PBP(+/+) control littermates. PBP null mutation (PBP(-/-)) is embryonically lethal at embryonic day 11.5, suggesting that PBP is an essential gene for mouse embryogenesis. The embryonic lethality is attributed, in part, to defects in the development of placental vasculature similar to those encountered in PPARgamma mutants. Transient transfection assays using fibroblasts isolated from PBP mutant embryos revealed a decreased capacity for ligand-dependent transcriptional activation of PPARgamma as compared with fibroblasts derived form the wild type embryos. These observations suggest that there is no functional redundancy between PBP and other coactivators such as steroid receptor coactivator-1 and that PBP plays a critical role in the signaling of PPARgamma and other nuclear receptors.

We previously isolated and identified steroid receptor coactivator-1 (SRC-1) and peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP/PPARBP) as coactivators for PPAR, using the ligand-binding domain of PPARgamma as bait in a yeast two-hybrid screening. As part of our continuing effort to identify cofactors that influence the transcriptional activity of PPARs, we now report the isolation of a novel coactivator from mouse, designated PRIP (peroxisome proliferator-activated receptor interacting protein), a nuclear protein with 2068 amino acids and encoded by 13 exons. Northern analysis showed that PRIP mRNA is ubiquitously expressed in many tissues of adult mice. PRIP contains two LXXLL signature motifs. The amino-terminal LXXLL motif (amino acid position 892 to 896) of PRIP was found to be necessary for nuclear receptor interaction, but the second LXXLL motif (amino acid position 1496 to 1500) appeared unable to bind PPARgamma. Deletion of the last 12 amino acids from the carboxyl terminus of PPARgamma resulted in the abolition of the interaction between PRIP and PPARgamma. PRIP also binds to PPARalpha, RARalpha, RXRalpha, ER, and TRbeta1, and this binding is increased in the presence of specific ligands. PRIP acts as a strong coactivator for PPARgamma in the yeast and also potentiates the transcriptional activities of PPARgamma and RXRalpha in mammalian cells. A truncated form of PRIP (amino acids 786-1132) acts as a dominant-negative repressor, suggesting that PRIP is a genuine coactivator.

Peroxisomes in liver parenchymal cells proliferate in response to structurally diverse nonmutagenic compounds designated as peroxisome proliferators (PP). Sustained induction of peroxisome proliferation and peroxisomal fatty acid beta-oxidation system in rats and mice leads to the development of liver tumors. Two mechanistic issues are important for consideration: elucidation of the upstream events responsible for the tissue and species specific induction of the characteristic pleiotropic responses by PPs; and delineation of the downstream events associated with peroxisome proliferation, and their role in the development of liver tumors in species that are sensitive to the induction of peroxisome proliferation. The induction of peroxisome proliferation is mediated by PP-activated receptor alpha (PPAR alpha), a member of a group of transcription factors that regulate the expression of genes associated with lipid metabolism and adipocyte differentiation. Three isotypes of this family of nuclear receptors, namely PPAR alpha, PPAR gamma, and PPAR delta (also called beta), have been identified as products of separate genes. Although PPAR alpha is responsible for the PP-induced pleiotropic responses, PPAR gamma seems to be involved in adipogenesis and differentiation, but the events associated with PPAR gamma do not directly involve peroxisomes and peroxisome proliferation. PPARs heterodimerize with 9-cis retinoic acid receptor (RXR), and bind to PP response element(s) (PPREs) on the target gene promoter to initiate inducible transcriptional activity. Tissue and species responses to PPs depend on pharmacokinetics, relative abundance of PPAR isotypes, nature of PPRE in the upstream regions of target genes, the extent of competition or cross-talk among nuclear transcription factors for PPAR heterodimerization partner retinoid X receptor and the modulating role of coactivators and corepressors on ligand-dependent transcription of PPARs. Using PPAR as bait in the yeast two-hybrid system, the authors recently cloned mouse steroid receptor coactivator-1 (SRC-1) and PPAR-binding protein (PBP), and identified them as PPAR coactivators. Both SRC-1 and PBP contain LXXLL signature motifs, considered necessary and sufficient for the binding of coactivators to nuclear receptors. A multifaceted approach, which includes the identification of additional coactivators that may be responsible for cell specific transcriptional activation of PPAR-mediated target genes, and generation of genetically modified animals (transgenic and gene disrupted), will be necessary to gain more insight into the upstream and downstream targets responsible for the induction of early and delayed PP-induced pleiotropic responses. In this context, it is important to note that mice deficient in fatty acyl-CoA oxidase, the first and rate-limiting enzyme of the peroxisomal beta-oxidation system, revealed that this enzyme is indispensable for the physiological regulation of PPAR alpha, and the absence of this enzyme leads to sustained transcriptional activation of genes regulated by this receptor.

Peroxisomes contain a classicall-hydroxy-specific peroxisome proliferator-inducible β-oxidation system and also a second noninducibled-hydroxy-specific β-oxidation system. We previously generated mice lacking fatty acyl-CoA oxidase (AOX), the first enzyme of the l-hydroxy-specific classical β-oxidation system; these AOX−/− mice exhibited sustained activation of peroxisome proliferator-activated receptor α (PPARα), resulting in profound spontaneous peroxisome proliferation in liver cells. These observations implied that AOX is responsible for the metabolic degradation of PPARα ligands. In this study, the function of enoyl-CoA hydratase/l-3-hydroxyacyl-CoA dehydrogenase (l-PBE), the second enzyme of this peroxisomal β-oxidation system, was investigated by disrupting its gene. Mutant mice (l-PBE−/−) were viable and fertile and exhibited no detectable gross phenotypic defects.l-PBE−/− mice showed no hepatic steatosis and manifested no spontaneous peroxisome proliferation, unlike that encountered in livers of mice deficient in AOX. These results indicate that disruption of classical peroxisomal fatty acid β-oxidation system distal to AOX step does not interfere with the inactivation of endogenous ligands of PPARα, further confirming that the AOX gene is indispensable for the physiological regulation of this receptor. The absence of appreciable changes in lipid metabolism also indicates that enoyl-CoAs, generated in the classical system inl-PBE−/− mice are diverted tod-hydroxy-specific system for metabolism byd-PBE. When challenged with a peroxisome proliferator,l-PBE−/− mice showed increases in the levels of hepatic mRNAs and proteins that are regulated by PPARα except for appreciable blunting of peroxisome proliferative response as compared with that observed in hepatocytes of wild type mice similarly treated. This blunting of peroxisome proliferative response is attributed to the absence of l-PBE protein inl-PBE−/− mouse liver, because all other proteins are induced essentially to the same extent in both wild type and l-PBE−/− mice.

In an attempt to identify cofactors that could possibly influence the transcriptional activity of peroxisome proliferator-activated receptors (PPARs), we used a yeast two-hybrid system with Gal4-PPARgamma as bait to screen a mouse liver cDNA library and have identified steroid receptor coactivator-1 (SRC-1) as a PPAR transcriptional coactivator. We now report the isolation of a cDNA encoding a 165-kDa PPARgamma-binding protein, designated PBP which also serves as a coactivator. PBP also binds to PPARalpha, RARalpha, RXR, and TRbeta1, and this binding is increased in the presence of specific ligands. Deletion of the last 12 amino acids from the carboxyl terminus of PPARgamma results in the abolition of interaction between PBP and PPARgamma. PBP modestly increased the transcriptional activity of PPARgamma, and a truncated form of PBP (amino acids 487-735) acted as a dominant-negative repressor, suggesting that PBP is a genuine coactivator for PPAR. In addition, PBP contains two LXXLL signature motifs considered necessary and sufficient for the binding of several coactivators to nuclear receptors. In situ hybridization and Northern analysis showed that PBP is expressed in many tissues of adult mice, including the germinal epithelium of testis, where it appeared most abundant, and during ontogeny, suggesting a possible role for this cofactor in cellular proliferation and differentiation.

In this paper, we propose two algorithms for verifying the existence of real solutions of positive-dimensional polynomial systems. The first one is based on the critical point method and the homotopy continuation method. It targets for verifying the existence of real roots on each connected component of an algebraic variety V ∩ Rn defined by polynomial equations. The second one is based on the low-rank moment matrix completion method and aims for verifying the existence of at least one real roots on V ∩ Rn. Combined both algorithms with the verification algorithms for zero-dimensional polynomial systems, we are able to find verified real solutions of positive-dimensional polynomial systems very efficiently for a large set of examples.

ObjectiveTo assess the effectiveness of nifedipine treatment in elderly hypertensives.MethodsA single-blind trial was conducted under the direction of the Shanghai Institute of Hypertension in 1632 subjects aged 60-79 years alternatively allocated to either nifedipine or placebo after a 4-week place

Massively parallel sequencing (MPS) combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs) by sequencing cell-free fetal DNA (cffDNA) from maternal plasma, so-called non-invasive prenatal testing (NIPT). However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR) and false positive rate (FPR) in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1%) in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples), suggesting that it is reliable and robust enough for clinical testing.

TMPRSS2-ERG translocation is involved in about 60% of prostate cancers. The translocation leads to overexpression of ERG which promotes cell proliferation and abrogates prostate epithelial differentiation. Suppression of ERG expression represents a major way to treat prostate cancers. However, there are no effective means to inhibit ERG expression. Although siRNA can deplete ERG expression, the big challenge is to deliver siRNA into prostate cancer cells. The mRNA stability, translation efficiency and protein stability of ERG are under strict control to maintain the ERG protein level. Here we report the establishment of a cell line which can be used to identify small molecules which inhibit ERG expression by targeting its post-transcriptional process. Using this cell line, we performed high-throughput screening and identified Gambogic acid which suppresses ERG expression in ERG-overexpressing prostate cancer cells.

In this paper a comprehensive analysis of the content of information education issues for Pudong, Shanghai Regional Network Support Teacher Learning Community Environmental Studies, is conducted through various survey data using grey relational analysis model. The results provide several insightful suggestions to improve the training-studying network. For example, it shows that the motivation for professional development of teachers age distribution curve and impact of male and female teachers in teacher training network of different factors are crucial factors as a platform for building and construction management team.

In this paper, grey multi-dimensional clustering analysis is used to investigate 37 lessons of middle schools from experts' observations. According to ten indicators of instruction effect, the grey multi-dimensional clustering analysis was applied to 37 lessons of 8 disciplines. Indicators were distinguished in three levels including high, medium and low by different contribution rates of instruction effect. The Analysis method suggested in this paper provided quantitative basis for classroom teaching assessment and curriculum construction in middle school.

One of the features of the digital ecosystem is the integration of human cognition and socio-economic themes into the process of new product development (NPD). In a socio-economic theme-based NPD, ranking a set of product prototypes that have been designed always requires the participation of multiple evaluators and consideration of multiple evaluation criteria. Using the well-being theme-based garment NPD as a background, this paper first presents a fuzzy hierarchical criteria group decision-making (FHCGDM) method which can effectively calculate final ranking results through fusing all assessment data from human beings and machines. It then presents a garment NPD comprehensive evaluation model with hierarchical criteria under the well-being theme through identifying a set of marketing tactics from a consumer acceptance survey. It further provides an establishment process for an NPD evaluation model under the digital ecosystem framework. Finally, a garment NPD case study further demonstrates the proposed well-being NPD comprehensive evaluation model and the FHCGDM method. The advantages of the proposed evaluation method include successfully handling criteria in a hierarchical structure, automatically processing both objective measurements from machines and subjective assessments from human evaluators, and using the most suitable type of fuzzy numbers to describe linguistic terms. © 2010 IEEE.

Denitrification is a microbial process that has received considerable attention during the past decade since it can result in losses of added nitrogen fertilisers from agricultural soils. Paddy soil has been known to have strong denitrifying activity, but the denitrifying microorganisms responsible for fertilisers in paddy soil are not well known. The objective of this study was to explore the impacts of 17-year application of inorganic and organic fertiliser (rice straw) on the abundance and composition of a nosZ-denitrifier community in paddy soil. Soil samples were collected from CK plots (no fertiliser), N (nitrogen fertiliser), NPK (nitrogen, phosphorus and potassium fertilisers) and NPK + OM (NPK plus organic matter). The nitrous oxide reductase gene (nosZ) community composition was analysed using terminal restriction fragment length polymorphism, and the abundance was determined by quantitative PCR.Both the largest abundance of nosZ-denitrifier and the highest potential denitrifying activity (PDA) occurred in the NPK + OM treatment with about four times higher than that in the CK and two times higher than that in the N and NPK treatments (no significant difference). Denitrifying community composition differed significantly among fertilisation treatments except for the comparison between CK and N treatments. Of the measured abiotic factors, total organic carbon was significantly correlated with the observed differences in community composition and abundance (P0.01 by Monte Carlo permutation).This study shows that the addition of different fertilisers affects the size and composition of the nosZ-denitrifier community in paddy soil.

The peroxisome proliferator-activated receptor- (PPAR) plays a key role in lipid metabolism and energy combustion. Chronic activation of PPAR in rodents leads to the development of hepatocellular carcinomas. The ability of PPAR to induce expression of its target genes depends on Mediator, an evolutionarily conserved complex of cofactors and, in particular, the subunit 1 (Med1) of this complex. Here, we report the identification and characterization of PPAR-interacting cofactor (PRIC)-295 (PRIC295), a novel coactivator protein, and show that it interacts with the Med1 and Med24 subunits of the Mediator complex. PRIC295 contains 10 LXXLL signature motifs that facilitate nuclear receptor binding and interacts with PPAR and five other members of the nuclear receptor superfamily in a ligand-dependent manner. PRIC295 enhances the transactivation function of PPAR, PPAR, and ER. These data demonstrate that PRIC295 interacts with nuclear receptors such as PPAR and functions as a transcription coactivator underin vitroconditions and may play an important role in mediating the effectsin vivoas a member of the PRIC complex with Med1 and Med24.

Fabric hand evaluation (FHE) is the main measure in textile material selection for fashion design and development. Fabric hand evaluation requires considering multiple evaluation aspects/criteria by a group of evaluators. Some fabric features can also be measured using instruments. The evaluation often uses linguistic terms in the weights of criteria, and the weights and judgments of evaluators. To support a FHE-based material selection, this study first develops a fabric hand-based textile material evaluation model. It then proposes a human-machine measure integrated fuzzy multi-criteria group decision-making method. A software tool is also developed, which implements the proposed method and is applied in fabric hand-based textile material evaluation. © 2009 Springer Science+Business Media, LLC.

Considering features of retrial, feedback and impatience in call centers, an M/M/s/k+G queue model with retrial, feedback and impatience is proposed in this paper for performance analysis of call centers. The queue model is solved by matrix iteration, and formulas for computing mean number of customers in waiting and service area, probability of blocking and probability of loss are derived. The indexes obtained by the model can be used for decision-making of management in call centers.

Given a multiple-antenna source and a multiple- antenna destination, a multiple-antenna relay between the source and the destination is desirable under useful circumstances. In this paper, a spatial multiplexing scheme and a cooperative beamforming scheme have been proposed for a non-regenerative MIMO relay system. In the spatial multiplexing scheme, the MIMO relay channel can be decomposed into several parallel channels each with the source to relay channel gain and the relay to destination channel gain. In the cooperative beamforming scheme, the transmitter uses all of its antennas to transmit one signal instead of multiplexing different signals simultaneously. It can be proved that the capacity of the spatial multiplexing scheme is smaller than that of the cooperative beamforming scheme in the low SNR regime. It is shown that for asymptotically large number of relays, the capacity of the spatial multiplexing scheme is converging to that of the beamforming scheme.

Metastasis, a process during which primary tumor disseminates into distal sites, likely occurs when primary tumor cells obtain additional genetic or epigenetic alteration. ERBP (estrogen receptor binding protein) is an estrogen receptor binding protein which potentiates the transcriptional activity of estrogen receptor. Unlike most coactivators which interact with AF2 domain of estrogen receptor, ERBP interacts with the DNA binding domain of estrogen receptor. The altered expression of ERBP could promote the metastasis through enhancing the expression of genes which are regulated by estrogen and are involved in the breast cancer metastasis. By overexpressing ERBP in breast cancer cells, we found ERBP overexpression enhanced the migration and invasion capability of tumor cells. ERBP overexpression also promoted the tumor formation in nude mice. We identified 8 estrogen inducible genes which were up-regulated by ERBP overexpression. Finally, we found that expression of ERBP is increased in about 30% of breast cancers.

Garment new product development (NPD) evaluation requires considering multiple criteria under a hierarchical structure. The evaluation process often involves uncertainty and fuzziness in both the relationships between criteria and the judgments of evaluators. This study first presents a garment NPD evaluation model under a well-being concept. It then proposes a fuzzy multi-criteria group decision-making (FMCGDM) method to evaluate garment NPD. The advantages of the FMCGDM method include handling criteria in a hierarchical structure, dealing with three kinds of uncertainties simultaneously, and using suitable types of fuzzy numbers to describe linguistic terms. A fuzzy multi-criteria group decision support system (FMCGDSS) is developed to implement the proposed method. Finally a garment NPD evaluation case study demonstrates the proposed method and software system. © 2008 Springer Berlin Heidelberg.

The objective of this project was to develop and implement innovative die material and surface coating strategies such as composite dies and lubricated coatings to increase die lives and to reduce environmental pollution. In this project approaches and software were developed for die life optimization and optimal design of lubrication systems for hot forging. In addition, LENS applied nickel-aluminide coatings were developed and validated in the industrial environment for significant improvements in die life.

Nuclear receptor coactivator PBP (peroxisome proliferator-activated receptor (PPAR)-binding protein) functions as a coactivator for PPARs and other nuclear receptors. PBP serves as an anchor for TRAP (thyroid hormone receptor-associated proteins)/mediator multisubunit cofactor transcription complex. Disruption of the PBP/TRAP220 gene results in embryonic lethality around embryonic day 11.5 by affecting placental, cardiac, hepatic, and bone marrow development. Because PPAR isoforms alpha, gamma, and beta/delta function as important regulators of lipid homeostasis in mammals, it becomes important to assess the requirement of coactivator PBP in the regulation of PPAR functions in vivo. Sustained activation of PPARalpha by structurally diverse classes of chemicals of biological importance, designated peroxisome proliferators, leads to proliferation of peroxisomes in liver, induction of PPARalpha target genes including those involved in fatty acid oxidation, and the eventual development of liver tumors. Here, we show that targeted deletion of PBP in liver parenchymal cells, using the Cre-loxP system, results in the near abrogation of PPARalpha ligand-induced peroxisome proliferation and liver cell proliferation, as well as the induction of PPARalpha-regulated genes in PBP-deficient liver cells. In contrast, scattered PBP(+/+) hepatocytes in these livers showed DNA synthesis and were markedly hypertrophic with peroxisome proliferation in response to PPARalpha ligands. Chromatin immunoprecipitation data suggest that in PBP conditional null livers, there appears to be reduced association of cofactors, especially of CBP and TRAP150, to the mouse enoyl-CoA hydratase/l-3-hydroxyacyl-CoA dehydrogenase gene promoter. These observations suggest that PBP is required for the stabilization of multiprotein cofactor complexes. In essence, the absence of PBP in hepatocytes in vivo appears to mimic the absence of PPARalpha, indicating that coactivator PBP is essential for PPARalpha-regulated gene expression in liver parenchymal cells.

Estrogen plays an important role in the normal breast and breast cancer development. Estrogens exert their cellular effects through ER that is a member of nuclear receptor superfamily. PRIP (Peroxisome proliferator receptor interacting protein) is a nuclear receptor coactivator that is amplified and overexpressed in breast cancer. The proposal was to investigate how the PRIP dysregulation contributes to abnormal growth and neoplastic development of breast. During the 3-year period, we dismpted PRIP gene in mice by homologous recombination. Mice nullizygous for PRIP died between embryonic day 11.5 and 12.5 (post coitum), indicating that PRIP like PBP, CBP, and p300 is an essential and nonredundant coactivator. We generated a conditional null mutation of PHP in mammary gland. Null mutation of PRIP in mammary gland causes defective mammopoiesis, demonstrating that PRIP is important for the normal mammary gland development. We isolated PIMT and PRMT2 as two components in the estrogen receptor transcriptional activation, advancing our understanding of estrogen signaling pathway. We found that PRIP overexpression occurs in about 60% and gene amplification occurs 10% of the breast cancers, suggesting that this coactivator plays an important role in the breast cancer development.

PAT5A [5-[4-[N-(2-pyridyl)-(2S)-pyrrolidine-2-methoxyl]phenylmethylene[thiazolidine-2,4-dione, malic acid salt]], a chemically distinct unsaturated thiazolidinedione, activates peroxisome proliferator-activated receptor gamma (PPARgamma) submaximally in vitro with the binding affinity approximately 10 times less than that of rosiglitazone, a highly potent thiazolidinedione. PAT5A reduces plasma glucose level and improves insulin sensitivity in insulin resistant db/db mice, similar to that of rosiglitazone, while exerting a relatively weak adipogenic effect. In contrast to rosiglitazone, PAT5A inhibits cholesterol and fatty acid biosynthesis suggesting that PAT5A possesses a unique receptor-independent non-PPAR related property. PAT5A induces qualitatively similar but quantitatively different protease digestion patterns and interacts with PPARgamma differently than rosiglitazone. PAT5A shows differential cofactor recruitment and gene activation than that of rosiglitazone. Thus, the partial agonism of PAT5A to PPARgamma together with its receptor independent effects may contribute to its antidiabetic potency similar to rosiglitazone in vivo despite reduced affinity for PPARgamma. These biological effects suggest that PAT5A is a PPARgamma modulator that activates some (insulin sensitization), but not all (adipogenesis), PPARgamma-signaling pathways.

PIMT (PRIP-interacting protein with methyltransferase domain), an RNA-binding protein with a methyltransferase domain capable of binding S-adenosylmethionine, has been shown previously to interact with nuclear receptor coactivator PRIP (peroxisome proliferator-activated receptor (PPAR)-interacting protein) and enhance its coactivator function. We now report that PIMT strongly interacts with transcriptional coactivators, CBP, p300, and PBP but not with SRC-1 and PGC-1alpha under in vitro and in vivo conditions. The PIMT binding sites on CBP and p300 are located in the cysteine-histidine-rich C/H1 and C/H3 domains, and the PIMT binding site on PBP is in the region encompassing amino acids 1101-1560. The N-terminal of PIMT (residues 1-369) containing the RNA binding domain interacts with both C/H1 and C/H3 domains of CBP and p300 and with the C-terminal portion of PBP that encompasses amino acids 1371-1560. The C-terminal of PIMT (residues 611-852), which binds S-adenosyl-l-methionine, interacts respectively with the C/H3 domain of CBP/p300 and with a region encompassing amino acids 1101-1370 of PBP. Immunoprecipitation data showed that PIMT forms a complex in vivo with CBP, p300, PBP, and PRIP. PIMT appeared to be co-localized in the nucleus with CBP, p300, and PBP. PIMT enhanced PBP-mediated transcriptional activity of the PPARgamma, as it did for PRIP, indicating synergism between PIMT and PBP. In contrast, PIMT functioned as a repressor of CBP/p300-mediated transactivation of PPARgamma. Based on these observations, we suggest that PIMT bridges the CBP/p300-anchored coactivator complex with the PBP-anchored coactivator complex but differentially modulates coactivator function such that inhibition of the CBP/p300 effect may be designed to enhance the activity of PBP and PRIP.

Peroxisome proliferator activator receptor (PPAR)-binding protein (PBP) is an important coactivator for PPARgamma and other nuclear receptors. It has been identified as an integral component of a multiprotein thyroid hormone receptor-associated protein/vitamin D(3) receptor-interacting protein/activator-recruited cofactor complexes required for transcriptional activity. Here, we show that PBP is critical for the development of placenta and for the normal embryonic development of the heart, eye, vascular, and hematopoietic systems. The primary functional cause of embryonic lethality at embryonic day11.5 observed with PBP null mutation was cardiac failure because of noncompaction of the ventricular myocardium and resultant ventricular dilatation. There was a paucity of retinal pigment, defective lens formation, excessive systemic angiogenesis, a deficiency in the number of megakaryocytes, and an arrest in erythrocytic differentiation. Some of these defects involve PPARgamma and retinoid-sensitive sites, whereas others have not been recognized in the PPAR-signaling pathway. Phenotypic changes in four organ systems observed in PBP null mice overlapped with those in mice deficient in members of GATA, a family of transcription factors known to regulate differentiation of megakaryocytes, erythrocytes, and adipocytes. We demonstrate that PBP interacts with all five GATA factors analyzed, GATA-1, GATA-2, GATA-3, GATA-4, and GATA-6, and show that the binding of GATA-1, GATA-4, and GATA-6 to PBP is not dependent on the nuclear receptor recognition sequence motif LXXLL (where L is leucine and X is any amino acid) in PBP. Coexpression of PBP with GATA-3 markedly enhanced transcriptional activity of GATA-3 in nonhematopoietic cells. These observations identify the GATA family of transcription factors as a new interacting partner of PBP and demonstrate that PBP is essential for normal development of vital organ systems.

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors, and it is assumed that the biological effects of these receptors depend on interactions with recently identified coactivators, including steroid receptor coactivator-1 (SRC-1). We assessed the in vivo function of SRC-1 on the PPARα-regulated gene expression in liver by generating mice in which the SRC-1 gene was inactivated by gene targeting. The homozygous (SRC-1 −/− ) mice were viable and fertile and exhibited no detectable gross phenotypic defects. When challenged with a PPARα ligand, such as ciprofibrate or Wy-14,643, the SRC-1 −/− mice displayed typical pleiotropic responses, including hepatomegaly, peroxisome proliferation in hepatocytes, and increased mRNA and protein levels of genes that are regulated by PPARα. These alterations were indistinguishable from those exhibited by SRC-1 +/+ wild-type mice fed either ciprofibrate- or Wy-14,643-containing diets. These results indicate that SRC-1 is not essential for PPARα-mediated transcriptional activation in vivo and suggest redundancy in nuclear receptor coactivators.

Peroxisome proliferator-activated receptors (PPARs) regulate genes involved in lipid metabolism and adipocyte differentiation. Steroid receptor coactivator-1 (SRC-1) and PPAR-binding protein (PBP) interact with PPARgamma and act as coactivators to enhance ligand-dependent transcription. We report here that PPARgamma, SRC-1, and PBP are differentially expressed in the brown fat, transitional epithelium of the urinary bladder, colonic mucosa, and mammary epithelium of the adult mouse. PPARgamma and PBP are expressed in the transitional epithelium of urinary bladder and in brown adipose tissue, but not SRC-1. In the colonic mucosa, PPARgamma expression occurs throughout the villi, whereas the expression of both SRC-1 and PBP is confined mostly to the crypts. The expression of both SRC-1 and PBP is prominent in the breast epithelium of nonpregnant, pregnant, and lactating mice, whereas PPARgamma expression appeared prominent during lactation. During early embryonic development, PPARgamma, SRC-1, and PBP are differentially expressed, with only limited cell types displaying overlapping expression. PPARgamma and PBP expression overlapped in the brown fat and urogenital sinus at stage E15.5 of embryogenesis, whereas SRC-1 expression occurred mostly in neuroepithelium and cartilage between stages E9.5 and E13.5 of embryogenesis.

To gain insight into the regulation of expression of peroxisome proliferator-activated receptor (PPAR) isoforms, we have determined the structural organization of the mouse PPAR gamma (mPPAR gamma) gene. This gene extends > 105 kb and gives rise to two mRNAs (mPPAR gamma 1 and mPPAR gamma 2) that differ at their 5' ends. The mPPAR gamma 2 cDNA encodes an additional 30 amino acids N-terminal to the first ATG codon of mPPAR gamma 1 and reveals a different 5' untranslated sequence. We show that mPPAR gamma 1 mRNA is encoded by eight exons, whereas the mPPAR gamma 2 mRNA is encoded by seven exons. Most of the 5' untranslated sequence of mPPAR gamma 1 mRNA is encoded by two exons, whereas the 5' untranslated sequence and the extra 30 N-terminal amino acids of mPPAR gamma 2 are encoded by one exon, which is located between the second and third exons coding for mPPAR gamma 1. The last six exons of mPPAR gamma gene code for identical sequences in mPPAR gamma 1 and mPPAR gamma 2 isoforms. The mPPAR gamma 1 and mPPAR gamma 2 isoforms are transcribed from different promoters. The mPPAR gamma gene has been mapped to chromosome 6 E3-F1 by in situ hybridization using a biotin-labeled probe. These results establish that at least one of the PPAR genes yields more than one protein product, similar to that encountered with retinoid X receptor and retinoic acid receptor genes. The existence of multiple PPAR isoforms transcribed from different promoters could increase the diversity of ligand and tissue-specific transcriptional responses.

Fabric selection plays an important role in fashion garment design. Designers often use both physical and normalized linguistic criteria for fabric selection. Perception and preference of consumers in their specific sociocultural context, expressed by fashion themes or emotional linguistic criteria, affect greatly new fashion product design. Modeling the relationship between linguistic design criteria and fashion themes of a brand image perceived by consumers becomes thus significant. For setting up this model, we first use fuzzy relations and correlation techniques to select the most relevant linguistic design criteria of fabric hand for each specific fashion theme. The selected criteria can then effectively reduce the complexity of the model and interpret consumer perception of fabrics. Finally, we use a weighted aggregation operator to predict the similarity degree between any new product and fashion themes. Compared with other models, the proposed method is more robust and easier to be interpreted with real data collected for design of senior T-shirt fabrics.