Toward Monodisperse Poly(γ-benzyl α,L-glutamate): Uniform, Polar, Molecular Rods

Poly(γ-benzyl α,L-glutamate) (PBLG) has been widely used in studies of the physics of rod-like polymer chains. The helical structure of PBLG gives rise to considerable chain stiffness, such that the persistence length of the chain is on the order of 70 nm in helicogenic solvents. This feature, coupled with the ease of synthesis and good solubility of the polymer has made PBLG the system of choice for the study of both isotropic and liquid crystalline solutions of rod-like macromolecules

Electromagnetic design and loss calculations of a 1.12-MW high-speed permanent-magnet motor for compressor applications

Electromagnetic design of a 1.12-MW, 18 000-r/min high-speed permanent-magnet motor (HSPMM) is carried out based on the analysis of pole number, stator slot number, rotor outer diameter, air-gap length, permanent magnet material, thickness, and pole arc. The no-load and full-load performance of the HSPMM is investigated in this paper by using 2-D finite element method (FEM). In addition, the power losses in the HSPMM including core loss, winding loss, rotor eddy current loss, and air friction loss are predicted. Based on the analysis, a prototype motor is manufactured and experimentally tested to verify the machine design

Partitioning overstory and understory evapotranspiration in a semiarid savanna woodland from the isotopic composition of water vapor

Abstract The relative contributions of overstory and understory plant transpiration and soil evaporation to total evapotranspiration (ET) in a semiarid savanna woodland were determined from stable isotope measurements of atmospheric water vapor. The savanna overstory was dominated by the deeply rooted, woody legume Prosopis velutina ("mesquite"), and the understory was dominated by a perennial C 4 grass, Sporobolus wrightii. "Keeling plots" (turbulent mixing relationships) were generated from isotope ratios (␦D and ␦ 18 O) of atmospheric water vapor collected within the tree (3-14 m) and understory (0.1-1 m) canopies during peak (July) and post-monsoon (September) periods of 2001. The unique regression intercepts from upper and lower profiles were used to partition the ET flux from the understory layer separately from that of the whole ecosystem. Although ET partitioning was problematic during the first sampling period in July, our results in September provided support to the validity of this method for measuring and understanding the dynamic behavior of water balance components in this semiarid savanna woodland. During the post-monsoon period (22nd September), transpiration accounted for 85% of ecosystem ET. Transpiration by the grass layer accounted for 50% of the understory ET over the same period. The total ecosystem ET estimated by eddy covariance (EC) on 22nd September was 3.5 mm per day. Based on partitioning by the isotope method, 2.5 mm per day (70%) was from tree transpiration and 0.5 mm per day (15%) was from transpiration by the grass layer. Independent estimates of overstory and understory ET partitioning from distributed understory EC measurements were remarkably consistent with our isotope approach

Journey to the east: Diverse routes and variable flowering times for wheat and barley en route to prehistoric China.

Today, farmers in many regions of eastern Asia sow their barley grains in the spring and harvest them in the autumn of the same year (spring barley). However, when it was first domesticated in southwest Asia, barley was grown between the autumn and subsequent spring (winter barley), to complete their life cycles before the summer drought. The question of when the eastern barley shifted from the original winter habit to flexible growing schedules is of significance in terms of understanding its spread. This article investigates when barley cultivation dispersed from southwest Asia to regions of eastern Asia and how the eastern spring barley evolved in this context. We report 70 new radiocarbon measurements obtained directly from barley grains recovered from archaeological sites in eastern Eurasia. Our results indicate that the eastern dispersals of wheat and barley were distinct in both space and time. We infer that barley had been cultivated in a range of markedly contrasting environments by the second millennium BC. In this context, we consider the distribution of known haplotypes of a flowering-time gene in barley, Ppd-H1, and infer that the distributions of those haplotypes may reflect the early dispersal of barley. These patterns of dispersal resonate with the second and first millennia BC textual records documenting sowing and harvesting times for barley in central/eastern China

Identification of Sequence Variants in Genetic Disease-Causing Genes Using Targeted Next-Generation Sequencing

Identification of gene variants plays an important role in research on and diagnosis of genetic diseases. A combination of enrichment of targeted genes and next-generation sequencing (targeted DNA-HiSeq) results in both high efficiency and low cost for targeted sequencing of genes of interest.To identify mutations associated with genetic diseases, we designed an array-based gene chip to capture all of the exons of 193 genes involved in 103 genetic diseases. To evaluate this technology, we selected 7 samples from seven patients with six different genetic diseases resulting from six disease-causing genes and 100 samples from normal human adults as controls. The data obtained showed that on average, 99.14% of 3,382 exons with more than 30-fold coverage were successfully detected using Targeted DNA-HiSeq technology, and we found six known variants in four disease-causing genes and two novel mutations in two other disease-causing genes (the STS gene for XLI and the FBN1 gene for MFS) as well as one exon deletion mutation in the DMD gene. These results were confirmed in their entirety using either the Sanger sequencing method or real-time PCR.Targeted DNA-HiSeq combines next-generation sequencing with the capture of sequences from a relevant subset of high-interest genes. This method was tested by capturing sequences from a DNA library through hybridization to oligonucleotide probes specific for genetic disorder-related genes and was found to show high selectivity, improve the detection of mutations, enabling the discovery of novel variants, and provide additional indel data. Thus, targeted DNA-HiSeq can be used to analyze the gene variant profiles of monogenic diseases with high sensitivity, fidelity, throughput and speed

Long-Term Exposure to Ambient Air Pollution and Mortality Due to Cardiovascular Disease and Cerebrovascular Disease in Shenyang, China

BACKGROUND: The relationship between ambient air pollution exposure and mortality of cardiovascular and cerebrovascular diseases in human is controversial, and there is little information about how exposures to ambient air pollution contribution to the mortality of cardiovascular and cerebrovascular diseases among Chinese. The aim of the present study was to examine whether exposure to ambient-air pollution increases the risk for cardiovascular and cerebrovascular disease. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective cohort study among humans to examine the association between compound-air pollutants [particulate matter <10 µm in aerodynamic diameter (PM(10)), sulfur dioxide (SO(2)) and nitrogen dioxide (NO(2))] and mortality in Shenyang, China, using 12 years of data (1998-2009). Also, stratified analysis by sex, age, education, and income was conducted for cardiovascular and cerebrovascular mortality. The results showed that an increase of 10 µg/m(3) in a year average concentration of PM(10) corresponds to 55% increase in the risk of a death cardiovascular disease (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.51 to 1.60) and 49% increase in cerebrovascular disease (HR, 1.49; 95% CI, 1.45 to 1.53), respectively. The corresponding figures of adjusted HR (95%CI) for a 10 µg/m(3) increase in NO(2) was 2.46 (2.31 to 2.63) for cardiovascular mortality and 2.44 (2.27 to 2.62) for cerebrovascular mortality, respectively. The effects of air pollution were more evident in female that in male, and nonsmokers and residents with BMI<18.5 were more vulnerable to outdoor air pollution. CONCLUSION/SIGNIFICANCE: Long-term exposure to ambient air pollution is associated with the death of cardiovascular and cerebrovascular diseases among Chinese populations

A Better Anti-Diabetic Recombinant Human Fibroblast Growth Factor 21 (rhFGF21) Modified with Polyethylene Glycol

As one of fibroblast growth factor (FGF) family members, FGF21 has been extensively investigated for its potential as a drug candidate to combat metabolic diseases. In the present study, recombinant human FGF21 (rhFGF21) was modified with polyethylene glycol (PEGylation) in order to increase its in vivo biostabilities and therapeutic potency. At N-terminal residue rhFGF21 was site-selectively PEGylated with mPEG20 kDa-butyraldehyde. The PEGylated rhFGF21 was purified to near homogeneity by Q Sepharose anion-exchange chromatography. The general structural and biochemical features as well as anti-diabetic effects of PEGylated rhFGF21 in a type 2 diabetic rat model were evaluated. By N-terminal sequencing and MALDI-TOF mass spectrometry, we confirmed that PEG molecule was conjugated only to the N-terminus of rhFGF21. The mono-PEGylated rhFGF21 retained the secondary structure, consistent with the native rhFGF21, but its biostabilities, including the resistance to physiological temperature and trypsinization, were significantly enhanced. The in vivo immunogenicity of PEGylated rhFGF21 was significantly decreased, and in vivo half-life time was significantly elongated. Compared to the native form, the PEGylated rhFGF21 had a similar capacity of stimulating glucose uptake in 3T3-L1 cells in vitro, but afforded a significantly long effect on reducing blood glucose and triglyceride levels in the type 2 diabetic animals. These results suggest that the PEGylated rhFGF21 is a better and more effective anti-diabetic drug candidate than the native rhFGF21 currently available. Therefore, the PEGylated rhFGF21 may be potentially applied in clinics to improve the metabolic syndrome for type 2 diabetic patients

Human Disease-Drug Network Based on Genomic Expression Profiles

BACKGROUND: Drug repositioning offers the possibility of faster development times and reduced risks in drug discovery. With the rapid development of high-throughput technologies and ever-increasing accumulation of whole genome-level datasets, an increasing number of diseases and drugs can be comprehensively characterized by the changes they induce in gene expression, protein, metabolites and phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: We performed a systematic, large-scale analysis of genomic expression profiles of human diseases and drugs to create a disease-drug network. A network of 170,027 significant interactions was extracted from the approximately 24.5 million comparisons between approximately 7,000 publicly available transcriptomic profiles. The network includes 645 disease-disease, 5,008 disease-drug, and 164,374 drug-drug relationships. At least 60% of the disease-disease pairs were in the same disease area as determined by the Medical Subject Headings (MeSH) disease classification tree. The remaining can drive a molecular level nosology by discovering relationships between seemingly unrelated diseases, such as a connection between bipolar disorder and hereditary spastic paraplegia, and a connection between actinic keratosis and cancer. Among the 5,008 disease-drug links, connections with negative scores suggest new indications for existing drugs, such as the use of some antimalaria drugs for Crohn's disease, and a variety of existing drugs for Huntington's disease; while the positive scoring connections can aid in drug side effect identification, such as tamoxifen's undesired carcinogenic property. From the approximately 37K drug-drug relationships, we discover relationships that aid in target and pathway deconvolution, such as 1) KCNMA1 as a potential molecular target of lobeline, and 2) both apoptotic DNA fragmentation and G2/M DNA damage checkpoint regulation as potential pathway targets of daunorubicin. CONCLUSIONS/SIGNIFICANCE: We have automatically generated thousands of disease and drug expression profiles using GEO datasets, and constructed a large scale disease-drug network for effective and efficient drug repositioning as well as drug target/pathway identification