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Background: The incidence of preserved ejection fraction heart failure has significantly increased in persons with type 2 diabetes mellitus (T2DM). Left ventricular (LV) diastolic dysfunction is an early and important manifestation of preserved ejection fraction heart failure. The onset of heart failure in persons with diabetes is associated with diabetic neuropathy. However, the relationship among sudomotor function, which is an early manifestation of small fiber neuropathy, and LV diastolic function remains unclear. This study aimed to explore the association between sudomotor function and LV diastolic function in persons with T2DM. Methods: In total, 699 persons with T2DM were enrolled and divided into three groups according to electrochemical skin conductance (ESC) assessed using the SUDOSCAN device: “no dysfunction” group (NSF), “moderate dysfunction” group (MDF), and “severe dysfunction” group (SDF). LV diastolic function was assessed using Doppler echocardiography. To evaluate the relationship between ESC and echocardiographic parameters, Pearson’s correlation analysis was performed. Additionally, logistic regression analysis was used to determine the association between LV diastolic function and ESC. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of sudomotor function indicators in detecting impaired cardiac diastolic function. Results: There were 301 persons (43.06%) in the NSF group, 232 (33.19%) in the MDF group, and 166 (23.75%) in the SDF group. Compared to the NSF group, the MDF and SDF groups had higher Aand E/e′ and lower e′ values (all p< 0.05). Pearson’s correlation analysis showed that Aand E/e′ were negatively associated with foot ESC (FESC) and hand ESC (HESC), whereas e′ was positively associated with FESC and HESC (all p< 0.05). After adjusting for confounding factors, binary logistic regression analysis showed that ESC was independently associated with impaired LV diastolic function (p= 0.003). The area under the ROC curve values for FESC and HESC were 0.621 and 0.635, respectively (both p< 0.05). Conclusions: Deteriorating sudomotor function was associated with reduced diastolic function indicators. ESC can be used as a biomarker for detecting LV diastolic impairment.

X-ray bursts are among the brightest stellar objects frequently observed in the sky by space-based telescopes. A type-I X-ray burst is understood as a violent thermonuclear explosion on the surface of a neutron star, accreting matter from a companion star in a binary system. The bursts are powered by a nuclear reaction sequence known as the rapid proton capture process (rp process), which involves hundreds of exotic neutron-deficient nuclides. At so-called waiting-point nuclides, the process stalls until a slower β+decay enables a bypass. One of the handful of rp process waiting-point nuclides is 64Ge, which plays a decisive role in matter flow and therefore the produced X-ray flux. Here we report precision measurements of the masses of 63Ge, 64,65As and 66,67Se—the relevant nuclear masses around the waiting-point 64Ge—and use them as inputs for X-ray burst model calculations. We obtain the X-ray burst light curve to constrain the neutron-star compactness, and suggest that the distance to the X-ray burster GS 1826–24 needs to be increased by about 6.5% to match astronomical observations. The nucleosynthesis results affect the thermal structure of accreting neutron stars, which will subsequently modify the calculations of associated observables.

Background: Multiple studies have established a strong relationship between circRNA and cancer progression. Cervical lymph node metastasis is a key factor influencing the surgical approach and distant metastasis of papillary thyroid cancer (PTC). However, the role of circNDST1 in PTC has not been investigated. Our research focused on revealing the function and mechanism of action of circNDST1 in PTC. Methods: High-throughput sequencing and qPCR were used to assess the expression of circRNA in PTC tissues with extensive cervical lymph node metastasis and circNDST1 in cell lines, respectively. The proliferative effects of circNDST1 in vitro and in vivo were analyzed using CCK8, clone formation assay, EdU, and nude mouse tumorigenesis assay. The transwell scratch assay was employed in the scrutiny of the effect of circNDST1 on the migration and invasion abilities of thyroid cancer cells, while circNDST1’s influence on the PI3K–Akt pathway and the Epithelial–Mesenchymal Transition (EMT) key protein expression was evaluated utilizing RNA sequencing and western blot. RNA pull-down and RIP were used to examine the binding of circNDST1 to CSNK2A1. Results: CircNDST1 was highly expressed in PTC cell lines, but knocking it down inhibited the proliferation, migration, and invasive abilities of TPC1 and KTC1 cell lines. CircNDST1 bonded with CSNK2A1 and promoted the interaction between CSNK2A1 and Akt, leading to the activation of the PI3K–Akt pathway and EMT. Conclusion: CircNDST1’s high expression boosted thyroid cancer progression through the activation of the PI3K–Akt pathway and EMT in a CSNK2A1-dependent manner

J Med Genet 2003;40:825-831 Human height is a complex trait determined by both genetic and environmental factors. An initial whole genome study showed several genomic regions with suggestive linkage to [...]

J Med Genet 2003;40:918-924 Obesity, defined as a body mass index (BMI) of greater than 30 kg/[m.sup.2], has become a worldwide public health problem. (1) About 250 million adults, roughly [...]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).

El prúrigo nodular (PN), una dermatosis crónica prurítica e hiperplásica, induce respuestas psicológica y fisiológicamente estresantes. Las respuestas inducidas por PN en los ejes hipotalámico-pituitario-adrenal e hipotalámico-pituitario-gonadal y en el sistema endocannabinoide son anómalas. En cierta medida, los estudios sobre la patogenia de PN se centran sobre todo en sus respuestas psicológicas. Hasta la fecha no se han revelado plenamente las respuestas fisiológicas.

Inflammation is a critical player in the development and progression of colon cancer. Basic leucine zipper transcription factor ATF-like 3 (BATF3) plays an important role in infection and tumor immunity through regulating the development of conventional type 1 dendritic cells (cDC1s). However, the function of BATF3 in colitis and colitis-associated colon cancer (CAC) remains unclear. Here, BATF3 wild-type and knockout mice were used to construct an AOM/DSS-induced CAC model. In addition, DSS-induced chronic colitis, bone marrow cross-transfusion (BMT), neutrophil knockout, and other animal models were used for in-depth research. We found that BATF3 deficiency in intestinal epithelial cells rather than in cDC1s inhibited CAC, which was depended on inflammatory stimulation. Mechanistically, BATF3 directly promoted transcription of CXCL5 by forming a heterodimer with JunD, and accelerated the recruitment of neutrophils through the CXCL5-CXCR2 axis, ultimately increasing the occurrence and development of CAC. Tissue microarray and TCGA data also indicated that high expression of BATF3 was positively correlated with poor prognosis of colorectal cancer and other inflammation-related tumors. In summary, our results demonstrate that intestinal epithelial-derived BATF3 relies on inflammatory stimulation to promote CAC, and BATF3 is expected to be a novel diagnostic indicator for colitis and CAC.

Background: Polydactyly, characterized by supernumerary digits in the upper or lower extremities, is the most common congenital digital abnormalities. It derives from the defective patterning of anteroposterior axis of the developing limb, with various etiology and clinical heterogeneity. The patients with post-axial polydactyly type A (PAPA) have the typical symptom of a well-formed supernumerary digit outside the fifth digit. Objective: The aim of present study was to identify the causative mutations of two unrelated Han Chinese patients with non-syndromic PAPA. Methods: Two unrelated Han Chinese patients and 100 ethnicity-matched, unrelated normal controls were recruited for this study. BGISEQ-500 exome sequencing was performed in the two patients, followed by validation in the patients and 100 controls by using Sanger sequencing. Results: Two mutations in the GLI family zinc finger 3 gene (GLI3), including a frameshift mutation c.3437_3453delTCGAGCAGCCCTGCCCC (p.L1146RfsX95) and a nonsense mutation c.3997C>T (p.Q1333X), were identified in two patients but were absent in the 100 healthy controls. Conclusion: The two GLI3 mutations, p.L1146RfsX95 and p.Q1333X, may account for non-syndromic PAPA in the two patients, respectively. The findings of this study may expand the mutational spectrum of GLI3-PAPA and provide novel insights into the genetic basis of polydactyly.

To determine the association between serum periostin and the presence of diabetic retinopathy (DR). Serum periostin was detected in 114 healthy subjects, 122 patients with type 2 diabetes mellitus (T2DM) and 159 patients with DR and compared among groups. Clinical data and other laboratory measurements such as glycated hemoglobin (HbA1c), lipid profiles, serum creatinine (Cr) and high-sensitivity CRP (hsCRP) were also collected and compared among groups. For subgroup analysis, patients with DR were divided into a non-proliferated diabetic retinopathy (NPDR) group and a proliferated diabetic retinopathy (PDR) group. Multivariate analysis was performed using logistic regression models. The serum periostin level was significantly higher in patients with diabetic retinopathy compared with healthy subjects and patients with T2DM (both P< 0.001, respectively). Also, the periostin level was significantly higher in the PDR group compared to the NPDR group (P= 0.044). Multivariate logistic regression revealed that serum periostin was independently associated with the presence of DR in patients with T2DM (P< 0.001). The receiver operating characteristic (ROC) curves for DR development using serum periostin showed that the area under the receiver operating characteristic curves (AUC) was 0.838 (P< 0.001). The current study demonstrated that serum periostin is significantly associated with the presence of DR in patients with T2DM and is an independent risk factor of DR.

•MCM-41 has been synthesized from pulverized coal fly ash and rice husk ash.•Obtained MCM-41 has been impregnated by polyethyleneimine (PEI) for CO2capture.•At the maximum 60 Wt.% PEI loading even 90% of the equilibrium uptake was obtained.

To detect plasma vascular endothelial growth factor B (VEGF-B) in individuals with different glucose tolerance and investigate the relationship between plasma VEGF-B levels and the first phase of glucose-stimulated insulin secretion. A cross-sectional study was conducted involving 45 patients with newly diagnosed type 2 diabetes mellitus (T2DM), 37 patients with impaired glucose regulation (IGR), and 39 Normal glucose tolerance (NGT) subjects, all of whom underwent intravenous glucose tolerance test. Plasma VEGF-B levels were assayed by ELISA. The first phase of insulin secretion was evaluated by acute insulin response (AIR), the area under the curve of the first-phase (0–10 min) insulin secretion (AUC) and glucose disposition index (GDI). The T2DM and IGR groups had higher plasma VEGF-B levels than the NGT group (P< 0.01). Plasma VEGF-B levels were negatively correlated with AIR, AUC, GDI, HOMA-β (P< 0.01), and positively correlated with plasma glucose, HbA1c, triglyceride, free fatty acid (FFA), fasting insulin, and HOMA-IR (P< 0.01). Logistic regression analysis revealed that higher VEGF-B levels [145.59–180.07 pg/ml, OR 3.55 (95% CI 1.05–12.02) and >180.07 pg/ml, OR 3.64 (95% CI 1.16–11.42)] were related to a greater probability of β-cell hypofunction, compared with low VEGF-B levels (<145.59 pg/ml). After adjusting for triglyceride or FFA, the association between VEGF-B levels and β-cell hypofunction disappeared (P> 0.05). Our study provides evidence that plasma VEGF-B levels were higher in patients with newly diagnosed T2DM, and were strongly associated with glucose and lipid metabolism and the first-phase insulin secretion function of β-cells. VEGF-B may be involved in the mechanism of β-cell dysfunction in T2DM.

Gene therapy has shown great potential for the treatment of diseases that previously were either untreatable or treatable but not curable with conventional schemes. Recent progress in clinical gene therapy trials has emerged in various severe diseases, including primary immunodeficiencies, leukodystrophies, Leber’s congenital amaurosis, haemophilia, as well as retinal dystrophy. The clinical transformation and industrialization of gene therapy in Asia have been remarkable and continue making steady progress. A total of six gene therapy-based products have been approved worldwide, including two drugs from Asia. This review aims to highlight recent progress in gene therapy clinical trials and discuss the prospects for the future in China and wider Asia.

The three-dimensional porous structure, excellent mechanical properties, rapid preparation process, and low cost of nonwovens lay a foundation for the fabrication of superhydrophobic nonwovens. Among them, the protogenous three-dimensional structure of nonwovens simplifies the preparation process of superhydrophobic nonwovens to a certain extent. Superhydrophobic nonwoven is one of researches of functional nonwovens due to their high selectivity contraposing to oil and water, water and pollution resistance, self-cleaning performance, and antibacterial property. This review summarizes the effects of fiber fineness and micro-nano hierarchical structure on superhydrophobicity of nonwovens, in particular, overhanging structure and re-entrant structure; discusses the construction methods of superhydrophobic materials, describes in detail the preparation methods of superhydrophobic nonwovens, containing dip-coating method, chemical vapor deposition method, electrospinning, and others; and enumerates their applications in the fields of oil–water separation, self-cleaning, air filter material, and self-healing waterproof material. At the same time, the effects of structure control, interface fabrication, and nonwovens self-structure on superhydrophobicity are prospected.

Axial loading test was performed to investigate the S–Ncharacteristics and the failure mechanisms of a high carbon chromium bearing steel under very high cycle fatigue (VHCF). Compared with the experimental results under rotating bending, the bearing steel under axial loading also exhibited two failure modes including surface failure and interior inclusion-induced failure. In the life regime beyond about 106cycles, the fine granular area can occur around the inclusion. But under the axial loading with the uniform stress distribution on the cross-section of specimen, the duplex S–Ncharacteristics of bearing steel was not so distinct. In view of the limitation of common statistical method, a statistical method based on mixed Weibull distribution and parameter optimisation was proposed to evaluate the VHCF property of bearing steel corresponding to two failure modes. Based on the proposed statistical method, the P–S–Ncurves of bearing steel under axial loading can be better established.This paper is part of a Themed Issue on Recent developments in bearing steels.

Objectives:: With ENCODE epigenomic data and results from published genome-wide association studies (GWASs), we aimed to find regulatory signatures of obesity genes and discover novel susceptibility genes. Methods:: Obesity genes were obtained from public GWAS databases and their promoters were annotated based on the regulatory element information. Significantly enriched or depleted epigenomic elements in the promoters of obesity genes were evaluated and all human genes were then prioritized according to the existence of the selected elements to predict new candidate genes. Top-ranked genes were subsequently applied to validate their associations with obesity-related traits in three independent in-house GWAS samples. Results:: We identified RAD21 and EZH2 as over-represented, and STAT2 (signal transducer and activator of transcription 2) and IRF3 (interferon regulatory transcription factor 3) as depleted transcription factors. Histone modification of H3K9me3 and chromatin state segmentation of 'poised promoter' and 'repressed' were over-represented. All genes were prioritized and we selected the top five genes for validation at the population level. Combining results from the three GWAS samples, rs7522101 in ESRRG(estrogen-related receptor-?) remained significantly associated with body mass index after multiple testing corrections (P=7.25 × 10-5). It was also associated with ß-cell function (P=1.99 × 10-3) and fasting glucose level (P&lt;0.05) in the meta-analyses of glucose and insulin-related traits consortium (MAGIC) data set. Cnoclusions:: In summary, we identified epigenomic characteristics for obesity genes and suggested ESRRGas a novel obesity-susceptibility gene.

A vital step in the development of heart failure is the transition from compensatory cardiac hypertrophy to decompensated dilated cardiomyopathy (DCM) during cardiac remodeling under mechanical or pathological stress. However, the molecular mechanisms underlying the development of DCM and heart failure remain incompletely understood. In the present study, we investigate whether Gab1, a scaffolding adaptor protein, protects against hemodynamic stress-induced DCM and heat failure. We first observed that the protein levels of Gab1 were markedly reduced in hearts from human patients with DCM and from mice with experimental viral myocarditis in which DCM developed. Next, we generated cardiac-specific Gab1 knockout mice (Gab1-cKO) and found that Gab-cKO mice developed DCM in hemodynamic stress-dependent and age-dependent manners. Under transverse aorta constriction (TAC), Gab1-cKO mice rapidly developed decompensated DCM and heart failure, whereas Gab1 wild-type littermates exhibited adaptive left ventricular hypertrophy without changes in cardiac function. Mechanistically, we showed that Gab1-cKO mouse hearts displayed severe mitochondrial damages and increased cardiomyocyte apoptosis. Loss of cardiac Gab1 in mice impaired Gab1 downstream MAPK signaling pathways in the heart under TAC. Gene profiles further revealed that ablation of Gab1 in heart disrupts the balance of anti- and pro-apoptotic genes in cardiomyocytes. These results demonstrate that cardiomyocyte Gab1 is a critical regulator of the compensatory cardiac response to aging and hemodynamic stress. These findings may provide new mechanistic insights and potential therapeutic target for DCM and heart failure.

Bone mineral content (BMC) and/or bone mineral density (BMD, i.e. BMC scaled by bone size) are major determinants for osteoporosis, which is a serious health problem. The major determinant of variation in BMD/BMC is genetic. The few studies now available are inconsistent in the identification and/or even in the existence of major gene(s) for BMD/BMC. In 51 human pedigrees with 941 individuals (526 measured for phenotypes) identified via probands with extreme BMD values, we performed complex segregation analyses to test the existence of a genetic locus with a major effect on BMD/BMC variation. We analyzed BMD and BMC at the spine, hip and wrist jointly by employing, as the study phenotype, factor scores (FS) of the principle component that explains ∼75% of the total BMD/BMC variation at the three sites. The results indicate that a major gene exists with a codominant effect that is responsible for ∼16% of the FS variation when adjusted for significant effects of sex, body weight and age. A significant genotype-×-sex-×-age interaction was found, which may explain ∼14% of the FS variation after adjusting for body weight. Testing of various models did not provide support for shared familial environmental effects but suggested the existence of residual polygenic effects, which may explain ∼50% of the FS variation when adjusting for sex, body weight and age. This study indicates a promising aspect of studies to identify a major gene for BMD/BMC variation in our pedigrees identified via extreme probands.

To efficiently manipulate large amounts of genotype data generated with fluorescently labeled dinucleotide markers, we developed a Microsoft database management system, named. offers several advantages. First, it accommodates the dynamic nature of the accumulations of genotype data during the genotyping process; some data need to be confirmed or replaced by repeat lab procedures. By using, the raw genotype data can be imported easily and continuously and incorporated into the database during the genotyping process that may continue over an extended period of time in large projects. Second, almost all of the procedures are automatic, including autocomparison of the raw data read by different technicians from the same gel, autoadjustment among the allele fragment-size data from cross-runs or cross-platforms, autobinning of alleles, and autocompilation of genotype data for suitable programs to perform inheritance check in pedigrees. Third, provides functions to track electrophoresis gel files to locate gel or sample sources for any resultant genotype data, which is extremely helpful for double-checking consistency of raw and final data and for directing repeat experiments. In addition, the user-friendly graphic interface of renders processing of large amounts of data much less labor-intensive. Furthermore, has built-in mechanisms to detect some genotyping errors and to assess the quality of genotype data that then are summarized in the statistic reports automatically generated by. The can easily handle >500,000 genotype data entries, a number more than sufficient for typical whole-genome linkage studies. The modules and programs we developed for the can be extended to other database platforms, such as Microsoft SQL server, if the capability to handle still greater quantities of genotype data simultaneously is desired.

The Mingantu Ultrawide Spectral Radioheliograph (MUSER) is a synthetic-aperture radio interferometer built in Ming'antu, Inner Mongolia, China. As a solar-dedicated interferometric array, the MUSER can produce high-quality radio images in a frequency range of 400 MHz-15 GHz with high temporal, spatial, and spectral resolution. Implementing of the data processing system for the MUSER is a major challenge to performing high-cadence imaging in wideband and obtaining more than two orders of higher multiple frequencies. There is an urgent need to build a pipeline for processing the massive amount of MUSER data generated each day. In this article, we present a high-performance distributed data processing pipeline (DDPP) built on the OpenCluster infrastructure for processing MUSER observational data, including data storage, preprocessing, image reconstruction, deconvolution, archiving, and real-time monitoring. We comprehensively elaborate the system architecture of the pipeline and the implementation of each subsystem. The DDPP is automatic, robust, scalable, and manageable. The processing performance under a parallel CPU/GPU hybrid system meets the requirements of MUSER data processing.

The aim of this study was to evaluate the effects of antibacterial peptide (ABP) sufficiency on cellular immune functions by determining the spleen cell cycle and apoptosis, peripheral blood T cell subsets, and T cell proliferation function in weaned piglets. A total of 90 piglets (Duroc × Landrace × Yorkshire) of both sexes were randomly allotted to 5 dietary treatments. Each treatment consisted of 3 replicates with 6 piglets per replicate. The dietary treatments consisted of the negative control (NC; basal diet), positive control (PC; basal diet supplemented with 400 mg/kg Astragaluspolysaccharide), and ABP (basal diet mixed with 250, 500, and 1,000 mg/kg ABP). The experimental lasted for 28 d. Two piglets from each replicate were selected randomly for blood samples extraction from the jugular vein to obtain peripheral blood T cell subsets, and T cell proliferation function analysis was performed on d 32, 39, 46, and 53. Two piglets from each replicate were selected and euthanized to observe the spleen cell cycle and apoptosis on d 39 and 53. In ABP-sufficient piglets, the G0/G1phase of the spleen cell cycle was much lower (P< 0.05) and the S and G2+ M phases and proliferation index (PI) were greater (P< 0.05) than in NC piglets. The percentage of apoptotic cells in the spleen significantly decreased under ABP sufficiency (P< 0.05). The proliferation function of peripheral blood T cells increased (P< 0.05) in ABP-sufficient piglets. Percentages of CD3+and CD3+CD4+ratios (d 39, 46, and 53) and CD4+CD8+ratios (d 32, 39, 46, and 53) increased remarkably (P< 0.05) under ABP sufficiency compared with NC. These results suggest that ABP sufficiency could increase the T cell population and proliferation function of T cells and could induce decreased percentages of apoptotic cells. Overall, the cellular immune function was evidently improved in weaned piglets. We suggest optimal dosages of 500 mg/kg ABP for 4-wk addition and 1,000 mg/kg ABP for 2-wk addition.

This randomized, placebo‐controlled trial demonstrates that cinacalcet effectively and safely corrects hypercalcemia in adult patients with persistent hyperparathyroidism after successful kidney transplantation. See editorial by Coyne and Delos Santos on page 2446.

The Square Kilometre Array (SKA) project is an international cooperation project to build the largest radio telescope worldwide. Data processing is one of the biggest challenges of building the SKA telescope. As a distributed execution framework, the Data Activated Liu Graph Engine (DALiuGE) was proposed to be one of the candidates for addressing the massive data of the SKA. DALiuGE has many distinctive features, but its actual ability to handle scientific data is still not clear. In this paper, we perform an objective evaluation of the usability of DALiuGE for the execution performance, developer workload, and implementation difficulty of porting the SAGECal to DALiuGE. The evaluation results show that the DALiuGE enables fast integration of astronomical software, but there are significant differences in the efficiency of different parallel granularities. Even with the deep optimization of the program, there is still a gap between the current DALiuGE and the traditional MPI in execution performance. Therefore, we come to a preliminary conclusion that the DALiuGE has no performance advantage in batch processing of massive data. At the same time, it may be more suitable for application scenarios with more customized computational tasks, such as SKA science regional centers.

Chemical figuring and finishing techniques using atmospheric pressure plasma were proposed for realizing damage free processing of a reaction sintered SiC substrate. Open-air type plasma chemical vaporization machining (PCVM) utilizing He based CF4/O2 mixture process gas demonstrated good linearity of the relationship between removal volume and plasma irradiation time which required in numerically controlled figuring. However, the surface roughness of the substrate processed by PCVM increased with an increase in removal depth by forming pores on the surface because etching rate of residual Si was about 3 times greater than that of SiC.

In this paper, the dynamic model of a two-link rigid-flexible manipulator was established by using the theory of Lagrange equation. Due to the model is a distributed-parameter system, we present a simple, efficient method for model reduction based on spectral approximation method such that a model-based scheme can be implemented. The method was illustrated by comparing with the simulation results of the reduced-order model and the virtual reduced model based on finite element method.

In this study, the effect of different dimple shapes on the tribological performance of surface texture has been investigated. First, a numerical model was developed to study the effect of dimple shapes on hydrodynamic pressure generation. The selected dimple shapes include circle, square, and ellipse, and the flow direction of lubricant is perpendicular to the major axis of elliptical dimples or the sides of square dimples. The results showed that the dimple shape can be optimized for greater hydrodynamic pressure generation. Then, the reciprocating sliding tests were carried out under oil lubrication and face-contact conditions. Tests were conducted for rotational speeds in the range 50–500 r/min and test loads of 200 and 400 N. Surface texture patterns with different dimple shapes were used, the dimple shapes and orientations were the same as those used in the numerical model, and the dimple depth and dimple area ratio were varied under fixed dimple area conditions. The test results indicated that a better friction reduction effect compared with untextured specimens can be obtained by selecting a suitable dimple area ratio and dimple depth for each dimple shape. Comparing the friction reduction effect, the elliptical dimples showed the best performance, the square dimples showed the second best results, and the circular dimples performed worst. However, as the test load increased, the friction reduction effect of all dimple shapes decreased; moreover, the differences between the shapes became smaller.

To improve understanding of TRPV4-associated axonal Charcot-Marie-Tooth (CMT) neuropathy phenotypes and their debated pathologic mechanism.

A series of area temperature maps were obtained from the upper surface of a moving thermomechanical controlled processed (TMCP) microalloyed steel skelp following laminar cooling using an infrared video camera. In addition, an emissivity probe was used to obtain both the emissivity and temperature at the mid-face of the moving skelp. Properly sampled infrared camera temperature measurements correlated well with both the measured probe temperature and with the process control pyrometer. A finite element thermal model of the system, in conjunction with the transverse skelp temperature profiles obtained from the infrared camera, was used to quantify the size and shape of the laminar cooling water jet’s direct impact zone on the skelp. The region experiencing direct water impact was found to be constrained by the residual water present on the moving skelp.

Amyotrophic lateral sclerosis (ALS) is a progressive paralytic disorder caused by degeneration of motor neurons. Mutations in the FUSgene were identified in patients with familial ALS (FALS) and patients with sporadic ALS (SALS) from a variety of genetic backgrounds. This work further explores the spectrum of FUSmutations in patients with FALS and patients with FALS with features of frontotemporal dementia (FALS/FTD) or parkinsonism and dementia (FALS/PD/DE).

Abstract: We discuss a continuum model for the absorption and redistribution of fluid in swollen elastomers due to mechanical loading; and in particular distinguish between systems that are saturated with liquid and those that are not. To this end we consider a boundary value problem of radial displacement combined with azimuthal shear for an annular cylinder consisting of a fluid infused hyperelastic media. In the absence of load the elastomer deforms by free swelling, giving a homogeneous expansion in which the imbibed fluid is uniformly distributed. This free swelling is described by the theory of Flory and Rehner. We then consider the effect of various boundary displacements and tractions so as to study how this alters the uniform fluid distribution. This problem was previously considered by Wineman and Rajagopal for the case in which the lateral surfaces maintained the radius associated with free swelling. Here we consider certain generalizations in which the lateral surfaces may undergo not only a prescribed relative twist, but also radial displacement. This permits fluid to either enter or exit the cylinder. A numerical method is invoked to solve these boundary value problems using representative material parameters. Certain boundary tractions generate an overall volume increase after the free swelling. If the amount of available fluid is limited, this gives rise to the possibility of complete fluid absorption, whereupon the system is no longer saturated. It is found that the overall mechanical response after loss of saturation is stiffer than it would be if the system had remained saturated. [Copyright &y& Elsevier]

Accurate and integrated modelling and optimisation of 2½ - axis end milling using standard tools and novel approaches is presented here. The resulting system provides a practical bridge between current state-of-the-art CAD/CAM and optimised CNC production. First, a novel and generic approach for extracting the in-cut geometry is implemented using ACIS® open architecture solid modeller. Next, an ANN (artificial neural network) model is designed and implemented for force prediction. Finally, a new technique for optimising the cutting parameters is applied and verified. The technique is based on reverse mapping of the ANN model for cutting force estimation. As such, the machining process is optimised directly using the learned neural network model by adjusting the net inputs to optimal values that minimise a specified objective function subject to cutting constraints. The optimisation results are used to update the initial CL (cutter location) data file to produce an optimum NC (numerically controlled) code. The proposed approach is demonstrated and verified through a case study to show its validity, practicality, and applicability.

The alanine to valine mutation at codon 4 (A4V) of SOD1causes a rapidly progressive dominant form of amyotrophic lateral sclerosis (ALS) with exclusively lower motor neuron disease and is responsible for 50% of SOD1mutations associated with familial ALS in North America. This mutation is rare in Europe. The authors investigated the origin (geographic and time) of the A4V mutation.

Mg-doped (≤15at%) ZnO thin films were prepared on quartz glass substrates by sol-gel method using a spinning-techniques. The films were charactered by X-ray diffraction , UV Vis-NIR double beam spectrophotometer and a SHIMADZU fluorespectrometer. It was found that optimally crystallized when the Mg concentration is 9at% were obtained. A photoluminescence study at room temperature revealed a blue shift in the near band edge emission peak with increasing of Mg content , which is agreement with the observation from the optical transmittance measurement. The photoconductive UV detectors based on these films were investigated, and the result showed that highest response was obtained from the photodecters fabricated by films with 15at% Mg concentration.

Interconnected microstructural ZnO:Al thin films with low doping concentration (Al/Zn ?1%) were deposited on (0001) sapphire substrates by the sol-gel technique. The effects of low doping concentration on the structural, optical and electrical properties of the films were investigated. Scanning electron microscope?(SEM), X-ray diffraction (XRD), photoluminescence (PL), and four-point probe method were used to characterize the structural, optical and electrical properties. We found that with increasing the dopant concentration the interconnected thread becomes thinner, the (002) diffraction peak and the near band edge (NBE) emission are enhanced while the deep level emission (DLE) and the resistivity are decreased.

The Gaojiacun mafic-ultramafic intrusive complex in the Yanbian area, Sichuan Province, Southwest China, is a layered intrusive body that underwent intensive magmatic differentiation during two cumulative cycles. SHRIMP (sensitive high-resolution ion microprobe) zircon U-Pb data show that the Gaojiacun complex was formed at 825 ± 12 Ma. These mafic-ultramafic rocks are relatively enriched in light rare-earth elements (LREE) and large-ion lithophile elements (LILE), but are relatively depleted in high-field-strength elements (HFSE). They are characterized by low initial 87Sr/86Sr (0.7045 to 0.7050) and positive εNd(t) values (+1.3 to +4.5). The geochemical data indicate that the parental magma of the mafic/ultramafic rocks was derived from a depleted mantle source, and underwent fractional crystallization and crustal contamination. We suggest that the Gaojiacun complex was formed in a continental rift related to mantle superplume activity beneath the Neoproterozoic supercontinent Rodinia.

The clinical diagnosis of ALS is based entirely on clinical features. Identification of biomarkers for ALS would be important for diagnosis and might also provide clues to pathogenesis.

A series of novel aminoalkylindoles was synthesized in an effort to develop compounds that are potent agonists at the CB1 cannabinoid receptor and that are also easily labeled with radioisotopes of iodine for biochemical and imaging studies. 2-Iodophenyl-[1-(1-methylpiperidin-2-ylmethyl)-1H-indol-3-yl]methanone (8, AM2233) had a very high affinity for the rat CB1 receptor, with most of the affinity residing with the (R)-enantiomer. Radioiodinated 8, (R)-8, and (S)-8 were prepared by radioiododestannylation of the tributyltin analogues in high yields, radiochemical purities, and specific radioactivities. In a mouse hippocampal membrane preparation with [¹³¹I](R)-8 as radioligand, racemic 8 exhibited a Ki value of 0.2 nM compared with 1.6 nM for WIN55212-2. In autoradiographic experiments with mouse brain sections, the distribution of radioiodinated 8 was consistent with that of brain CB1 receptors. Again, very little specific binding was seen with the (S)-enantiomer [¹³¹I](S)-8 and none occurred with the (R)-enantiomer [¹³¹I](R)-8 in sections from CB1 receptor knockout mice. Radioiodinated 8 thus appears to be a suitable radioligand for studies of CB1 cannabinoid receptors.

Meeting ProgrammeProf David O'Hagan [University of St Andrews, UK]—Enzymatic C–18F Bond Synthesis: A New Strategy for PET Synthesis.Dr Michael Carroll [University of Newcastle, UK]—Studies Towards 6‐[18F]Fluoro‐m‐tyramine using Iodonium Salts.Dr John Gardiner [University of Manchester, UK]—Methods Towards Isotopomer‐Versatile Synthesis of 13C‐Labelled Carbohydrates.Prof William Lockley [University of Surrey, UK]—Some New Catalytic Systems for Isotope‐Exchange Labelling.Dr David Rustidge [Scynexis Europe, UK]—14C‐Synthesis—Not Always as Easy as it Looks.Dr Richard Hartley [University of Glasgow, UK]—The Potential for using Titanium Alkylidene Chemistry in Solid‐Phase Radiochemical Synthesis.Dr Ian Wilson [Turku Imanet, Finland]—Transition of PET Tracers from Clinical Research Tools to Commercial Diagnostics.Dr Simon Harwood [GlaxoSmithKline, UK]—The Synthesis of Stable Labelled Ketamine.Dr John Herbert [Sanofi‐Aventis, UK]—Towards Robust Conditions for Iridium‐mediated Exchange.Dr Conor Barry [University of Bristol, UK]—Total Synthesis of Clavosolide A.

Efforts have recently been made toward the study of interactions of phospholipid with various enzymes. It seems that phospholipids may be directly involved in regulating the enzyme activity. In this work, three phospholipid analogous polymers (PAPs), containing hydrophobic octyloxy, dodecyloxy, and octadecyloxy groups (abbreviated as 8-PAP, 12-PAP, and 18-PAP, respectively), were tethered on polypropylene hollow fiber microfiltration membrane (PPHFMM) to create a biocompatible interface for lipase immobilization. Lipase from Candida rugosa was immobilized on these PPHFMMs by adsorption. The adsorption capacity, activity, and thermal stability of enzyme on the PAP-modified PPHFMMs were compared with those of enzyme on the nascent ones. It was found that, as for the PAP-modified PPHFMMs, the adsorption capacities of lipase are lower than that of the nascent ones, while the activity retention of immobilized lipase increases from 57.5% to 74.1%, 77.5%, and 83.2% respectively for the 8-PAP-, 12-PAP-, and 18-PAP-modified PPHFMMs. In addition, the experimental results of thermal stability show that the residual activity of the immobilized lipase at 50 °C for 2 h is 62% for the 8-PAP-modified PPHFMM, 59% for the 12-PAP-modified PPHFMM, and 66% for the 18-PAP-modified PPHFMM, which are also higher than that of the nascent ones.

The adsorption characteristics and tribological properties of the perfluoropolyether (PFPE) lubricants Zdol and Z-Tetraol on amorphous nitrogenated CNxcarbon are investigated as a function of solvent used to apply the lubricants. The solvents used in these studies include perfluorohexane, CF3CHFCHFCF2CF3and C4F9OCH3. Deposition studies indicate that the applied thickness of PFPE films is strongly solvent-dependent that can be related to differences in the solubility parameters between the various lubricants and solvents. The results of ab initio computations on the molecular electronic structure of the solvent molecules show that their solvent power is correlated to their polarity and in particular to the acidity of the protons on the CF3CHFCHFCF2CF3and C4F9OCH3molecules. Tribological reliability, as measured by contact start-stop testing, slider-disk clearance, lubricant pickup by the slider, lubricant smearing on the disk surface, etc., is independent of solvent and is limited to the physical properties of the adsorbed lubricant film. The kinetics of lubricant mobility are charateristic of confined liquids that are independent of solvent as shown by lubricant flow profiles, bonding kinetics, and contact angle goniometry.

AbstractHardy-Weinberg disequilibrium (HWD) measures have been proposed using dense markers to fine map a quantitative trait locus (QTL) to regions &lt; ~ 1 cM. Earlier HWD measures may introduce bias in the fine mapping because they are dependent on marker allele frequencies across loci. Hence, HWD indices that do not depend on marker allele frequencies are desired for fine mapping. Based on our earlier work, here we present four new HWD indices that do not depend on marker allele frequencies. Two are for use when marker allele frequencies in a study population are known, and two are for use when marker allele frequencies in a study population are not known and are only known in the extreme samples. The new measures are a function of the genetic distance between the marker locus and a QTL. Through simulations, we investigated and compared the fine mapping performance of the new HWD measures with that of the earlier ones. Our results show that when marker allele frequencies vary across loci, the new measures presented here are more robust and powerful.Copyright © 2003 S. Karger AG, Basel

We have investigated the tribological properties of a novel perfluoropolyether (PFPE) lubricant truncated on one end by a hydroxyl group and on the other end by a cyclotriphosphazene derivative. A measurement of the friction force as a function of molecular weight indicates that the dynamic clearance between the slider and the disk can be reduced by ∼1.5 nm by decreasing the molecular weight from 5300 to 2400 g/mol. However, the thermodynamic film stability of the novel PFPE lubricants, as determined by surface energy measurements and ellipsometric imaging of lubricant dewetting, becomes increasingly unstable at lower film thicknesses with decreasing molecular weight. Measurements conducted on lubricant mobility indicate that the novel PFPE lubricants are relatively immobile compared to the Zdol perfluoropolyether lubricants and hence resist film thinning to a greater degree. These data provide the direction for the optimization of the molecular weight of these novel PFPE lubricants.