The Chinese white pine beetle Dendroctonus armandi (Coleoptera: Scolytinae) typically displays bivoltinism at altitudes below 1700 m in the Qinling Mountains, China. The periods of host colonization and larval overwintering are two important phases in the life cycle of bark beetles, as it is during these periods that they have to contend with host plant defences and periods of intense cold, respectively. Although during different seasons, the females and males of Chinese white pine beetles show varying tolerances to host plant terpenoids, the sex ratio and survival physiology condition of the two beetle generations are unknown. We investigated the sex ratio of individuals, and also examined the body mass, energy stores, and detoxication enzymes of males and females in each of the two generations in order to determine the overall population stability of each generation. We identified a female-biased sex ratio among adults in both generations. Furthermore, patterns of body mass, energy stores, and detoxication enzymes were found to differ between the two sexes and two seasons. Compared with the males, the females have a larger body mass and higher amounts of stored lipids, which are assumed to be adaptations designed to overcome host resistance and facilitate subsequent oviposition.

The very high temperature reactor (VHTR) is a development of the high-temperature gas-cooled reactors (HTGRs) and one of the six proposed Generation IV reactor concept candidates. The 10 MW high temperature gas-cooled reactor (HTR-10) is the first pebble-bed gas-cooled test reactor in China. A sampling system for the measurement of carbon-14 (14C) was established in the helium purification system of the HTR-10 primary loop, which could sample 14C from the coolant at three locations. The results showed that activity concentration of 14C in the HTR-10 primary coolant was 1.2(1) × 102 Bq/m3 (STP). The production mechanisms, distribution characteristics, reduction routes, and release types of 14C in HTR-10 were analyzed and discussed. A theoretical model was built to calculate the amount of 14C in the core of HTR-10 and its concentration in the primary coolant. The activation reaction of 13C has been identified to be the dominant 14C source in the core, whereas in the primary coolant, it is the activation of 14N. These results can supplement important information for the source term analysis of 14C in HTR-10 and promote the study of 14C in HTGRs.

OBJECTIVES/SPECIFIC AIMS: Dopamine transporter (DAT1) gene variation is associated with reward-related phenotypes including alcohol response. There is also evidence for a potential moderating role for mu-opioid receptor (OPRM1) gene variation on the relationship between DAT1 variation and alcohol response measures. We aimed at studying the interaction between the DAT1 VNTR and OPRM1 A118G polymorphisms on alcohol consumption and subjective responses among non-dependent drinkers. METHODS/STUDY POPULATION: We employed a progressive ratio (PR) paradigm of intravenous alcohol self-administration (IV-ASA) using the Computer-Assisted Infusion System (CAIS) to assess the motivation for alcohol seeking and consumption in a sample of nondependent drinkers. We used the Drug Effects Questionnaire (DEQ) and Biphasic Alcohol Effects Questionnaire (BAES) to assess subjective response. IV-ASA measures included average breath alcohol concentration (BrAC) and total ethanol infused. Peripheral blood samples were collected for genotyping. Ethics approval was obtained from the NIH Addictions Institutional Review Board. RESULTS/ANTICIPATED RESULTS: Fifty participants completed the PR IV-ASA session after informed consent. There were significant interactions between the DAT1 and OPRM1 genotypes in subjective effects of alcohol. Simple main effects analysis showed that DAT1 10a allele carriers that were also OPRM1 G allele carriers had significantly higher scores for several measures: “feel the drug effects” (F (1,46)=6.573, P = 0.014), “feel intoxicated”(F(1,46)=8.613, P = 0.005) and “feeling high” (F(1,46)=10.889, P = 0.002) in DEQ and higher sedation (F(1,46)=4.575, P = 0.038) in BAES. The genotypes statistically significantly predicted average breath alcohol (F (1,61) =3.295, p=0.044) and total ethanol infused(F(1,61)=3.632, p=0.032. DAT1 VNTR and OPRM1 A118G polymorphisms taken together accounted for 6.9 and 7.8% of variations in average breath alcohol and total ethanol infused respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Polymorphic variations in DAT1 and OPRM1 interact with each other in determining subjective effects of alcohol in intravenous alcohol infusion assessing motivation for alcohol seeking and consumption in nondependent drinkers. These epistatic interactions in subjective effects of alcohol are salient in the context of predicting and understanding neurobiological effects of alcohol and thereby the therapeutic responses in treating alcohol use disorders.

OBJECTIVES/SPECIFIC AIMS: The objective of this exploratory study is to evaluate the relationship between the individual genetic variants in COMTrs4680 and DRDrs1076560 and relevant alcohol use behaviors (i.e. alcohol consumption and reward processing behaviors) in non-dependent drinkers within experimentally controlled IV-ASA CAIS sessions. The overall goal of this study is to begin gathering data on the influence of individual genetic variants on alcohol consumption and other drinking-related behaviors. This will aid in the creation of a polygenic model of risk for AUD which will provide more insight into how the mesolimbic pathway is affected by alcohol use. METHODS/STUDY POPULATION: Study population: The sample included male and female non-dependent drinkers (N=149). Genotypes for functional polymorphisms in COMT (rs4680) and DRD2 (rs1076560) genes were determined for all subjects from blood samples obtained during screening. Alcohol consumption was assessed using the 90-day Timeline Followback Interviews (TLFB). Study population demographics: Self-reported gender (53.5% identified as male); Self-reported race (61.2% identified as white); Age ranged from 21-46 years old, with 22 years being the mode. Experiment: Free access (open-bar) intravenous alcohol self-administration (IV-ASA) using the computer-assisted alcohol infusion system (CAIS) paradigm; Subjects had the choice of pressing a button ad libitum for IV alcohol infusions during the session, neurobehavioral questionnaires were collected throughout the 2.5-hr alcohol infusion session. Primary outcome measures included: Total Rewards, Peak breath alcohol concentration (BrAC) achieved, and Total Ethanol consumed. Statistical Analyses: Conducted using SPSS IBM Statistics Versions 1.0.0-2482; non-dependent drinkers were organized into two groups based on their genotypes, minor allele carriers and major allele homozygotes. Outcome measures were compared between genotype groups using analysis of variance or non-parametric Mann-Whitney U-test as appropriate. RESULTS/ANTICIPATED RESULTS: -We expect the genetic makeup of the sample to be reflective of larger genome samples that are publically available (e.g. e!Ensembl) - Initial analysis for COMTrs4680 did not reveal significant effects on IV-ASA measures. Specifically, the majo DISCUSSION/SIGNIFICANCE OF IMPACT: Alcohol Use Disorder (AUD) affects millions of men and women globally. The heterogeneity within AUD individuals has made it difficult to identify biological and/or psychological factors that could be targeted for the development of treatments. By using the human laboratory model of free access IV-ASA, this study evaluated the relationship between dopaminergic genetic variants, COMTrs4680 and DRDrs1076560, and alcohol consumption in non-dependent drinkers within a controlled experimental environment. This study will begin to evaluate genetic and behavioral data that can be used to create a polygenic model of risk for AUD, which will provide more insight as to how the mesolimbic reward pathway is affected by alcohol use and contributes to risk for AUD.

Hepatitis E is an important zoonosis that is prevalent in China. Hepatitis E virus (HEV) is a pathogen that affects humans and animals and endangers public health in China. In this study, the detection of HEV epidemics in swine in Sichuan Province, China, was carried out by nested real-time PCR. A total of 174 stool samples and 160 bile samples from swine in Sichuan Province were examined. In addition, software was used to analyse the biological evolution of HEV. The results showed that within 2 years of swine HEV (SHEV) infection in China, SHEV was first detected in Sichuan Province. HEV was endemic in Sichuan; the positive rate for pig farms was 11.1%, and the total positive sample rate was 10.5%. The age of swine with the highest positive rate (17.9%) was 5–9 weeks. The examined swine species in order of highest to lowest HEV infection rates were Chenghua pig, Large White, Duroc, Pietrain, Landrace and Hampshire. Nucleotide and amino acid sequence analysis showed that the HEV epidemic in swine in Sichuan Province was related to genotype IV, which had the highest homology to HEV in Beijing. Sichuan strains have greater variation than Chinese representative strains, which may indicate the presence of new HEV strains.

The viscoelastic properties of magnetorheological elastomers (MREs) are tunable with an external magnetic field, which provides them with greater functionality than conventional reinforced polymers. Despite the abundant amount of literature studying the complex micromechanics of MREs, the effect of filler morphology (including particle size, shape and superficial texture) is an aspect that has been recurrently overlooked. This paper presents a multiscale experimental investigation of the microscopic mechanisms governing the macroscopic viscoelastic behavior of PDMS-silicone-based MREs, with an emphasis on the effect of filler morphology on both the microstructure and the overall dynamic shear response of MREs. Sixteen different MREs were produced using four different iron powders of varying average particle size, shape and texture. The morphology of iron particles and the microstructure of the fabricated materials were analyzed via X-ray computed nanotomography and scanning electron microscopy. In addition, the shear moduli of the specimens were monitored under coupled magneto-mechanical loading via dynamic mechanical analysis. This study shows that the particle size affects the strength of the magnetic interparticle interactions, which produce a confining effect on the rubber matrix, while the particle shape and texture have a great influence on the rubber-filler mechanical adhesion.

A nonlinear station-keeping control method for a multi-vectored propeller airship under unknown wind field with thrust saturation is developed, which is composed of three modules: nonlinear model predictive controller (NMPC), disturbance observer (DOB) and tracking differentiator (TD). The nonlinear kinematics and dynamics models are introduced, and the wind effect is considered by the wind-induced aerodynamic force. Based on both models, an explicit NMPC is designed. Then a nonlinear DOB is introduced to estimate the wind disturbance. A TD, showing the relationship between the maximum propulsion force and the maximum flight acceleration, is proposed to handle the thrusts’ amplitude saturation. Stability analysis shows that the closed-loop system is globally asymptotically stable. Simulations for a multi-vectored propeller airship are conducted to demonstrate the robustness and effectiveness of the proposed method.

Hydrogen is an important intermediate that is produced during carbohydrate fermentation to volatile fatty acid and utilized by methanogens to produce methane in the rumen. Ruminal volatile fatty acid and dissolved methane concentrations are more than 500 times greater than dissolved hydrogen concentration. Therefore, we hypothesized that dissolved hydrogen might have a higher sensitivity in response to dietary changes compared with volatile fatty acid and dissolved methane. Using goats, we investigated the effects of increasing dietary starch content (maize replaced with wheat bran) and supplementing with rhubarb rhizomes and roots on the relationships among dissolved hydrogen, dissolved methane and other fermentation end products. The study was conducted in a replicated 4×4 Latin square with a 2×2 factorial arrangement of four treatments: two starch levels (220 v. 320 g/kg dry matter (DM)), without and with rhubarb supplement (0% v. 2.8% of total mixed ration). Increased dietary starch and rhubarb supplementation did not alter volatile fatty acid concentrations or methane emissions in terms of g/day, g/g DM intake and g/g organic matter digested. However, goats fed the high-starch diet had greater dissolved hydrogen (P=0.005) and relative abundance of Selenomonas ruminantium (P<0.01), and lower (P=0.02) copy number of protozoa than those fed the low-starch diet. Rhubarb increased ruminal dissolved H2 (P=0.03) and total volatile fatty acid concentration (P<0.001), but decreased copies of bacteria (P=0.002). In conclusion, dissolved hydrogen appears to be more sensitive to dietary changes with starch content and rhubarb supplementation, when compared with volatile fatty acid concentrations and methane production.

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.

The response of soil microbial communities to soil quality changes is a sensitive indicator of soil ecosystem health. The current work investigated soil microbial communities under different fertilization treatments in a 31-year experiment using the phospholipid fatty acid (PLFA) profile method. The experiment consisted of five fertilization treatments: without fertilizer input (CK), chemical fertilizer alone (MF), rice (Oryza sativa L.) straw residue and chemical fertilizer (RF), low manure rate and chemical fertilizer (LOM), and high manure rate and chemical fertilizer (HOM). Soil samples were collected from the plough layer and results indicated that the content of PLFAs were increased in all fertilization treatments compared with the control. The iC15:0 fatty acids increased significantly in MF treatment but decreased in RF, LOM and HOM, while aC15:0 fatty acids increased in these three treatments. Principal component (PC) analysis was conducted to determine factors defining soil microbial community structure using the 21 PLFAs detected in all treatments: the first and second PCs explained 89.8% of the total variance. All unsaturated and cyclopropyl PLFAs except C12:0 and C15:0 were highly weighted on the first PC. The first and second PC also explained 87.1% of the total variance among all fertilization treatments. There was no difference in the first and second PC between RF and HOM treatments. The results indicated that long-term combined application of straw residue or organic manure with chemical fertilizer practices improved soil microbial community structure more than the mineral fertilizer treatment in double-cropped paddy fields in Southern China.

Objectives: The aim of this study was to investigate alterations in functional connectivity, white matter integrity, and cognitive abilities due to sports-related concussion (SRC) in adolescents using a prospective longitudinal design. Methods: We assessed male high school football players (ages 14–18) with (n=16) and without (n=12) SRC using complementary resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) along with cognitive performance using the Immediate Post-Concussive Assessment and Cognitive Testing (ImPACT). We assessed both changes at the acute phase (<7 days post-SRC) and at 21 days later, as well as, differences between athletes with SRC and age- and team-matched control athletes. Results: The results revealed rs-fMRI hyperconnectivity within posterior brain regions (e.g., precuneus and cerebellum), and hypoconnectivity in more anterior areas (e.g., inferior and middle frontal gyri) when comparing SRC group to control group acutely. Performance on the ImPACT (visual/verbal memory composites) was correlated with resting state network connectivity at both time points. DTI results revealed altered diffusion in the SRC group along a segment of the corticospinal tract and the superior longitudinal fasciculus in the acute phase of SRC. No differences between the SRC group and control group were seen at follow-up imaging. Conclusions: Acute effects of SRC are associated with both hyperconnectivity and hypoconnectivity, with disruption of white matter integrity. In addition, acute memory performance was most sensitive to these changes. After 21 days, adolescents with SRC returned to baseline performance, although chronic hyperconnectivity of these regions could place these adolescents at greater risk for secondary neuropathological changes, necessitating future follow-up. (JINS, 2018, 24, 781–792)

Extensive insecticide use has led to the resistance of mosquitoes to these insecticides, posing a major barrier to mosquito control. Previous Solexa high-throughput sequencing of Culex pipiens pallens in the laboratory has revealed that the abundance of a novel microRNA (miRNA), miR-13664, was higher in a deltamethrin-sensitive (DS) strain than a deltamethrin-resistant (DR) strain. Real-time quantitative PCR revealed that the miR-13664 transcript level was lower in the DR strain than in the DS strain. MiR-13664 oversupply in the DR strain increased the susceptibility of these mosquitoes to deltamethrin, whereas inhibition of miR-13664 made the DS strain more resistant to deltamethrin. Results of bioinformatic analysis, quantitative reverse-transcriptase polymerase chain reaction, luciferase assay and miR mimic/inhibitor microinjection revealed CpCYP314A1 to be a target of miR-13664. In addition, downregulation of CpCYP314A1 expression in the DR strain reduced the resistance of mosquitoes to deltamethrin. Taken together, our results indicate that miR-13664 could regulate deltamethrin resistance by interacting with CpCYP314A1, providing new insights into mosquito resistance mechanisms.

Wave loading on marine structures is the major external force to be considered in the design of such structures. The accurate prediction of the nonlinear high-order components of the wave loading has been an unresolved challenging problem. In this paper, the nonlinear harmonic components of hydrodynamic forces on a bottom-mounted vertical cylinder are investigated experimentally. A large number of experiments were conducted in the Danish Hydraulic Institute shallow water wave basin on the cylinder, both on a flat bed and a sloping bed, as part of a European collaborative research project. High-quality data sets for focused wave groups have been collected for a wide range of wave conditions. The high-order harmonic force components are separated by applying the ‘phase-inversion’ method to the measured force time histories for a crest focused wave group and the same wave group inverted. This separation method is found to work well even for locally violent nearly-breaking waves formed from bidirectional wave pairs. It is also found that the $n$ th-harmonic force scales with the $n$ th power of the envelope of both the linear undisturbed free-surface elevation and the linear force component in both time variation and amplitude. This allows estimation of the higher-order harmonic shapes and time histories from knowledge of the linear component alone. The experiments also show that the harmonic structure of the wave loading on the cylinder is virtually unaltered by the introduction of a sloping bed, depending only on the local wave properties at the cylinder. Furthermore, our new experimental results reveal that for certain wave cases the linear loading is actually less than 40 % of the total wave loading and the high-order harmonics contribute more than 60 % of the loading. The significance of this striking new result is that it reveals the importance of high-order nonlinear wave loading on offshore structures and means that such loading should be considered in their design.

Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.

Superior and inferior rice grains have different weights and are located on the upper primary branch and lower secondary branches of the panicle, respectively. To study differences in germination vigour of these two types of grain, a number of factors were investigated from 0 to 48 h of germination. The present study demonstrated that in inferior grains the starch granule structure was looser at 0 h, with full water absorption at 48 h, while in superior grains the structure was tight and dense. Relative water content increased, and dry matter decreased, more rapidly in inferior grains than in superior ones. Abscisic acid and gibberellin levels, as well as α-amylase activity, also changed more rapidly in inferior grains, while soluble sugar content and amylase coding gene expression increased more rapidly in inferior than superior grains during early germination. The expression of OsGAMYB was higher in inferior grains at 24 h but higher in superior grains at 48 h. The phenotypic index of seedlings was higher in seedlings from superior grains at the two-leaf stage. However, the thousand-grain weight and yield per plant in superior and inferior plants showed no significant difference at harvest. The present study indicates that inferior grains germinate faster than superior ones in the early germination stage. Although inferior grains produced weaker seedlings, it is worthwhile using them in rice production due to their comparative yield potential over that of superior grains.