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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The development of preferred orientation, by powder compaction was studied in several single phase, two-phase and three-phase powders. It was found that texture formation depends strongly on the properties of the powder particles and the preparation technique. In powder mixtures strong interaction effects were observed which either enhanced or reduced the degree of the preferred orientation. The required degree of series expansion of the texture function ranged from zero up to about fourteen.
OBJECTIVES/SPECIFIC AIMS: We have reported that radiofrequency renal denervation (RF-RDN) in SHR at 20-weeks of age, decreased blood pressure (BP) and fibrosis in kidney cortex and medulla when rats were sacrificed at 6 months. However, whether RF-RDN can have similar benefits in older rats remains unknown. This study examined whether performing RF-RDN in older rats also has a beneficial effect on BP and renal fibrosis. METHODS/STUDY POPULATION: Baseline systolic and diastolic BP (SBP/DPB) was measured (telemetry) in nine-month-old SHR and Wistar Kyoto rats (WKY). Groups of rats then received bilateral RF-RDN or Sham-RDN (SHR-RDN, n=9; SHR-Sham, n=10; WKY-RDN, n=5; WKY-Sham, n=8). Rats were then sacrificed at 12-months of age. Kidneys were harvested, sectioned, and assessed for fibrosis by Masson’s trichrome stain. A pathologist, who was blinded to treatment groups, evaluated each kidney section for fibrosis. RESULTS/ANTICIPATED RESULTS: Compared to SHR with Sham-RDN, RF-RDN prevented a further increase in systolic and diastolic BP from baseline (9-month) in SHR as they aged to 12-months (SHR-Sham mmHg: 9-month 193±4/127±4; 12-month 207±3/142±5; SHR-RDN mmHg: 9-month 197±3/132±2; 12-month 197±4/132±3). RF-RDN did not alter SBP or DBP in aged WKY. One-year-old SHR with prior Sham-RDN showed extensive renal fibrosis in kidney cortex and medulla. In contrast, RF-RDN significantly decreased renal fibrosis in the medulla, but not cortex. There was no fibrosis in kidneys of age matched WKY. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that RF-RDN may be a potential therapy for halting progression of hypertension and decreasing medullary fibrosis in the aged population.
Latrophilin (LPH) is known as an adhesion G-protein-coupled receptor which involved in multiple physiological processes in organisms. Previous studies showed that lph not only involved the susceptibility to anticholinesterase insecticides but also affected fecundity in Tribolium castaneum. However, its regulatory mechanisms in these biological processes are still not clear. Here, we identified two potential downstream carboxylesterase (cce) genes of Tclph, esterase4 and esterase6, and further characterized their interactions with Tclph. After treatment of T. castaneum larvae with carbofuran or dichlorvos insecticides, the transcript levels of Tcest4 and Tcest6 were significantly induced from 12 to 72 h. RNAi against Tcest4 or Tcest6 led to the higher mortality compared with the controls after the insecticides treatment, suggesting that these two genes play a vital role in detoxification of insecticides in T. castaneum. Furthermore, with insecticides exposure to Tclph knockdown beetles, the expression of Tcest4 was upregulated but Tcest6 was downregulated, indicating that beetles existed a compensatory response against the insecticides. Additionally, RNAi of Tcest6 resulted in 43% reductions in female egg laying and completely inhibited egg hatching, which showed the similar phenotype as that of Tclph knockdown. These results indicated that Tclph affected fecundity by positively regulating Tcest6 expression. Our findings will provide a new insight into the molecular mechanisms of Tclph involved in physiological functions in T. castaneum.
Aiming at three-dimensional (3D) terminal guidance problem, a novel guidance model is established in this paper, in which line-of-sight (LOS) range is treated as an independent variable, describing the relative motion between the vehicle and the target. The guidance model includes two differential equations that describe LOS’s pitch and yaw motions in which the pitch motion is separately decoupled. This model avoids the inaccuracy of simplified two-dimensional (2D) guidance model and the complexity of 3D coupled guidance model, which not only maintains the accuracy but also simplifies the guidance law design. The application of this guidance model is studied for optimal re-entry guidance law with impact angle constraint, which is presented in the form of normal overload. Compared with optimal guidance laws based on traditional guidance model, the proposed one based on novel guidance model is implemented with the LOS range instead of time-to-go, which avoids the problem of the time-to-go estimation of traditional optimal guidance laws. Finally, the correctness and validity of the guidance model and guidance law are verified by numerical simulation. The guidance model and guidance law proposed in this paper provide a new way for the design of terminal guidance.
While most papers on high-entropy alloys (HEAs) focus on the microstructure and mechanical properties for structural materials applications, there has been growing interest in developing high-entropy functional materials. The objective of this paper is to provide a brief, timely review on select functional properties of HEAs, including soft magnetic, magnetocaloric, physical, thermoelectric, superconducting, and hydrogen storage. Comparisons of functional properties between HEAs and conventional low- and medium-entropy materials are provided, and examples are illustrated using computational modeling and tuning the composition of existing functional materials through substitutional or interstitial mixing. Extending the concept of high configurational entropy to a wide range of materials such as intermetallics, ceramics, and semiconductors through the isostructural design approach is discussed. Perspectives are offered in designing future high-performance functional materials utilizing the high-entropy concepts and high-throughput predictive computational modeling.
Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.
SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.
SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
The overwhelming majority of galaxies in the Universe are dwarf galaxies. But although they are important components in understanding galaxy evolution, these systems are typically too faint to be observed at high redshifts. However, we are able to obtain an unobscured view of early star formation and chemical enrichment in these galaxies at low redshift and low-redshift analogs at high redshift. In this talk, I will review the mass-metallicity relation, the mass-star formation rate relation of galaxies, the classifications of dwarf galaxies, and the importance of dwarf galaxies for both astronomy and physics. Then I will introduce some work in our group on connections among between different types of dwarf galaxies,the mass-metallicity relations and the main sequence relations of dwarf galaxies, using the deep optical and near infrared images and spectra of large dwarf galaxy sample. At the end, I will talk about some projects of dwarf galaxies we are working on, including the spectroscopic survey for compact dwarf galaxies using the LAMOST.
OBJECTIVES/SPECIFIC AIMS: The goal of this study was to investigate whether RF-RDN attenuates renal fibrosis and inflammation in SHR with established hypertension. METHODS/STUDY POPULATION: Twenty-two-week-old SHR received bilateral RF-RDN or Sham-RDN (Biosense Webster Stockert 70 generator and RF-probe). Four weeks later, SHR were sacrificed and paraffin sections of kidneys were stained for fibrosis by Masson’s trichrome staining. Kidney tissue were homogenized for measurement of cytokines levels by ELISA. RESULTS/ANTICIPATED RESULTS: The results showed that Sham-RDN treated SHR had extensive fibrosis as demonstrated by moderate thickening of Bowman’s capsule, collagen deposition in glomerulus, extensive tubulointerstitial fibrosis, and segmental glomerulosclerosis. In contrast, RF-RDN significantly reduced each of these pathological components of fibrosis in kidney cortex and medulla as compared with Sham-RDN treated kidneys. In other studies, RF-RDN decreased B cells, CD4+ T cells, and CD8+ T cells in the kidney of SHR as measured by flow cytometry. Meanwhile, kidney tissue levels of IL-17, INF-γ, MIP-3a, TNF-α, and TGF-β were decreased as compared with respective levels in Sham-RDN. DISCUSSION/SIGNIFICANCE OF IMPACT: Together, these findings demonstrate that removal of the influence of heightened renal sympathetic activity by RF-RDN decreases kidney inflammatory markers and attenuates renal fibrosis in hypertensive SHR.
Using the data from APOGEE, WISE, and GLIMPSE, we explored the variation of the near-infrared (NIR) and mid-infrared (MIR) interstellar extinction laws of the Milky Way. We derived the IR extinction laws towards a number of different sightlines, including 24 bins along Galactic latitude (b) and 592 plates observed by APOGEE. Our results indicate that E(J-H)/E(J-K) show only subtle variation along b, Galactic longitude (l), or the depth of E(J-K). This suggests that the NIR extinction law can be considered as universal. Similarly, E(K-W1, W2, W3, [3.6], [4.5], [5.8], [8.0])/E(J-K) also show only small variation along b, l, or the extinction depth. The MIR extinction curve is flat, indicating that the MIR extinction law is likely universal.
Large numbers of high quality graphene transistors were fabricated by chemical vapor deposition and packaged into a standard electronics assembly, enabling the readout of graphene properties on the benchtop. After chemical functionalization, these sensors demonstrate sensitivity into the pM range to inflammation (IL6) and Zika virus (ZIKV NS1) biomarkers. Signal-to-noise ratio (SNR) of graphene biosensors is over an order of magnitude greater than established diagnostic and biophysical assays, namely ELISA and BLI respectively. High precision measurements of protein kinetics captured using this technology, commercially available as the AGILE R100, are comparable to both clinical diagnostic and state-of-the-art biomolecule characterization tools. These results demonstrate that graphene-based platforms are highly attractive biological sensors for next generation diagnostics.
In individuals with latent tuberculosis (TB) infection, those living with human immunodeficiency virus (HIV) had a 20–37 times higher risk of developing active TB compared to those without HIV infection. Systematic testing and treatment of latent TB infection are priorities in HIV-infected persons. In China, the prevalence of HIV infection in men who have sex with men (MSM) has gradually increased in the past decade. However, the prevalence of TB infection has been studied sparsely in HIV-infected MSM. Hence, we conducted a pilot study in MSM living with HIV infection in Xi'an city to evaluate TB infection status by means of interferon-γ release assay (IGRA). A total of 182 HIV-infected MSM were included in this study, the prevalence of IGRA positivity was observed to be 8·79% (16/182). IGRA quantitative results were not statistically influenced by the CD4 cell counts of the study participants. However, IGRA positivity was found to be lower than our previously reported data from the general population. This suggests that immunological deficiency might decrease the sensitivity of IGRA and thus increase the number of false negatives. Our primary results, suggesting systematic testing and treatment of latent TB infection together with active case-finding, were equally important for TB control in persons living with HIV infection.
Foxtail millet (Setaria italica (L.) P. Beauv.) is a naturally stress-tolerant plant, a major reserve crop and a model for panicoid grasses. The recent completion of the S. italica genome facilitates identification and characterization of WRKY transcription factor family proteins that are important regulators of major plant processes, including growth, development and stress response. The present study identified 103 WRKY transcription factor-encoding genes in the S. italica genome. The genes were named SiWRKY1–SiWRKY103 according to their order on the chromosomes. A comprehensive expression analysis of SiWRKY genes among four different tissues was performed using publicly available RNA sequencing data. Eighty-four SiWRKY genes were more highly expressed in root tissue than in other tissues and nine genes were only expressed in roots. Additionally, real-time quantitative polymerase chain reaction was performed to comprehensively analyse the expression of all SiWRKY genes in response to dehydration. Results indicated that most SiWRKY genes (over 0.8) were up-regulated by drought stress. In conclusion, genome-wide identification and expression profiling of SiWRKY genes provided a set of candidates for cloning and functional analyses in plants’ response to drought stress.
Studies of schizophrenia at drug-naive state and on antipsychotic medication have reported a number of regions of gray-matter (GM) abnormalities but the reports have been inconsistent. The aim of this study was to conduct multimodal meta-analysis to compare the cross-sectional voxel-based morphometry studies of brain GM in antipsychotic-naive first-episode schizophrenia (AN-FES) and those with antipsychotic treatment within 1 year (AT-FES) to determine the similarities and differences in these groups. We conducted two separate meta-analyses containing 24 studies with a sample size of 801 patients and 957 healthy controls. A multimodal meta-analysis method was used to compare the findings between AN-FES and AT-FES. Meta-regression analyses were done to determine the influence of different variables including age, duration of illness, and positive and negative symptom scores. Finally, jack-knife analyses were done to test the robustness of the results. AN-FES and AT-FES showed common patterns of GM abnormalities in frontal (gyrus rectus), superior temporal, left hippocampal and insular cortex. GM in the left supramarginal gyrus and left middle temporal gyrus were found to be increased in AN-FES but decreased in AT-FES, whereas left median cingulate/paracingulate gyri and right hippocampus GM was decreased in AN-FES but increased in AT-FES. Findings suggest that both AN-FES and AT-FES share frontal, temporal and insular regions as common anatomical regions to be affected indicating these to be the primary regions of GM abnormalities in both groups.
The service life of aircraft structure includes the fatigue life and calendar life. The Aircraft Structural Life Envelop (ASLE) is a safe and reliable life scope of aircraft structures in service. The specific steps to establish the ASLE are developed, and a residual life prediction method for aircraft structure under service environments is established by combining the ASLE with the Miner theory. Furthermore, a service life extension method of aircraft structure is proposed based on a scope extension of the ASLE, including methods based on reliability analysis and structural repair. Finally, an application example of the ASLE is presented.
Social networks facilitate the transmission of hepatitis C virus (HCV) in people who inject drugs (PWID). The aim of this study was to assess how certain network structural characteristics are related to HCV infections in PWID and to determine the most susceptible individuals for HCV transmission in a network of PWID. PWID (N = 80) from central China were recruited from a previous follow-up case-control study. Demographic and behavioural information was obtained from a computerized database for each group. HCV RNA was extracted from blood specimens. Sequences were used to construct a phylogenetic tree and to determine genetic distances. Socio-metric social links were established between participants. Network measures were calculated using UCINET. Three HCV genotypes were identified, covering five subtypes. The density of the social networks for the whole sample (N = 80), case group (n = 31) and control group (n = 49) was 0.038, 0.054 and 0.008, respectively. PWID infected with HCV were in frequent contact with others within their group. There were four pairs of nodes with genotypic distances of 0.000 that were identified and clustered in subtypes 6a and 1b; each subject pair was linked and found in one clique. Three of the five most active nodes were infected with HCV. These three nodes served as a bridge, contributing to the connection of other nodes. These findings identify susceptible individuals for HCV transmission in PWID based on their frequent contact with others in the network. These results provide data that could be used for modelling HCV transmission patterns and in public health policies.
The current study aimed to examine the relationship between floods and the three enteric infectious diseases, namely bacillary dysentery (BD), hand-foot-mouth disease (HFMD) and other infectious diarrhoea (OID) in Qingdao, China. Relative risks (RRs) and 95% confidence intervals (CIs) of floods on BD, HFMD and OID were calculated using a quasi-Poisson generalized linear model, adjusting for daily average temperature, daily average relative humidity, and seasonal and long-term temporal trends. Two separate models within two different periods were designed. Model 1 for the summer period showed that floods were positively associated with BD for 4- to 12-day lags, with the greatest effects for 7-day (RR 1·41, 95% CI 1·22–1·62) and 11-day (RR 1·42, 95% CI 1·22–1·64) lags. Similar findings were found in model 2 for the whole study period for 5- to 12-day lags. However, HFMD and OID were not significantly associated with floods in both models. Results from this study will provide insight into the health risks associated with floods and may help inform public health precautionary measures for such disasters.
In October 2013, public health authorities were notified of a suspected outbreak of gastroenteritis in students and guests following a catered function at a university residential college. A retrospective cohort study was undertaken to examine whether foods served at the function caused illness. A total of 56 cases of gastroenteritis, including seven laboratory-confirmed cases of Campylobacter jejuni infection, were identified in 235 eligible respondents. Univariate analysis showed a significant association with a chicken liver pâté entrée [relative risk (RR) 3·64, 95% confidence interval (CI) 2·03–6·52, P < 0·001], which retained significance after adjustment for confounding via multivariable analysis (adjusted RR 2·80, 95% CI 1·26–6·19, P = 0·01). C. jejuni and C. coli were also isolated in chicken liver pâté recovered from the college's kitchen. Subsequent whole genome multilocus sequence typing (wgMLST) of clinical and food-derived C. jejuni isolates showed three genetically distinct sequence types (STs) comprising ST528, ST535 (both clinically derived) and ST991 (food derived). The study demonstrates the value of utilizing complementary sources of evidence, including genomic data, to support public health investigations. The use of wgMLST highlights the potential for significant C. jejuni diversity in epidemiologically related human and food isolates recovered during outbreaks linked to poultry liver.
Heteroepitaxial growth of high-quality II-VI-alloy materials on Si substrates is a well-established commercial growth process for infrared (IR) detector devices. However, it has only recently been recognized that these same processes may have important applications for production of high-efficiency photovoltaic devices. This submission reviews the process developments that have enabled effective heteroepitaxy of II-VI alloy materials on lattice-mismatched Si for IR detectors as a foundation to describe recent efforts to apply these insights to the fabrication of multijunction Si/CdZnTe devices with ultimate conversion efficiencies >40%. Reviewed photovoltaic studies include multijunction Si/CdZnTe devices with conversion efficiency of ∼17%, analysis of structural and optoelectrical quality of undoped CdTe epilayer films on Si, and the effect that a Te-rich growth environment has on the structural and optoelectronic quality of both undoped and As-doped heteroepitaxial CdTe.