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Research suggests that childhood adversity (CA) is associated with a wide range of repercussions, including an increased likelihood of interpersonal stress generation. This may be particularly true following interpersonal childhood adversity (ICA) and for youth with high hypothalamic-pituitary-adrenal (HPA) axis-related genetic risk. In the current study, we applied a multilocus genetic profile score (MGPS) approach to measuring HPA axis-related genetic variation and examined its interaction with ICA to predict interpersonal stress generation in a sample of adolescents aged 14–17 (N = 241, Caucasian subsample n = 192). MGPSs were computed using 10 single nucleotide polymorphisms from HPA axis-related genes (CRHR1, NRC31, NRC32, and FKBP5). ICA significantly predicted greater adolescent interpersonal dependent stress. Additionally, MGPS predicted a stronger association between ICA and interpersonal dependent (but not independent or noninterpersonal dependent) stress. No gene–environment interaction (G×E) effects were found for noninterpersonal CA and MGPS in predicting adolescent interpersonal dependent stress. Effects remained after controlling for current depressive symptoms and following stratification by race. Findings extend existing G×E research on stress generation to HPA axis-related genetic variation and demonstrate effects specific to the interpersonal domain.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
In the past four decades lipid vesicles (liposomes) have evolved from widely used biomembrane models into important drug and gene carriers. The phosphatidylcholine phospholipids PC used in the drug carriers are biocompatible and biodegradable but they function as a relatively inert shell and require the incorporation of cholesterol to maintain the drug encapsulated in the liposome; The PC are also incapable of associating with ligands and have very weak interactions with nucleic acids. Moreover, they are not particularly good for cytoplasmic delivery of the encapsulated cargo. Recently, we have devised three classes of new lipids and have improved the synthesis of a fourth class that enable the preparation of a bioresponsive targeted carrier with improved nucleic acid delivery. Class 1 are low pH sensitive and include a diortho ester PEG lipid or a di-orthoester PC. Class two are redox sensitive lipids and include thiocholesterol based and thio diacyl chain based lipids that can be used in a sequential assembly process to encapsulate nucleic acid drugs in a charge neutral or negatively charged nanolipid particle. Class 3 is a new family of lipids that provide increased in vivo bilayer stability without the need for crosslinking of the bilayer. Class 4 is an improved synthesis of a triNTA diacyl lipid. This lipid can be used to attach His-6 containing molecules to the bilayer vesicle after the liposomes have been prepared and loaded with drugs. These lipids form a tool kit that can be used to prepare a variety of targeted drug, protein and nucleic acid delivery vesicles with attached targeting ligands. The synthesis, characterization and use of these lipids in a variety of drug delivery applications will be described. Suported by NIH EB003008 & NIH GM061851.
Most compositional distributional semantic models represent sentence meaning with a single vector. In this paper, we propose a structured distributional model (SDM) that combines word embeddings with formal semantics and is based on the assumption that sentences represent events and situations. The semantic representation of a sentence is a formal structure derived from discourse representation theory and containing distributional vectors. This structure is dynamically and incrementally built by integrating knowledge about events and their typical participants, as they are activated by lexical items. Event knowledge is modelled as a graph extracted from parsed corpora and encoding roles and relationships between participants that are represented as distributional vectors. SDM is grounded on extensive psycholinguistic research showing that generalized knowledge about events stored in semantic memory plays a key role in sentence comprehension.We evaluate SDMon two recently introduced compositionality data sets, and our results show that combining a simple compositionalmodel with event knowledge constantly improves performances, even with dif ferent types of word embeddings.
Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
Guangxi, a province in southwestern China, has the second highest reported number of HIV/AIDS cases in China. This study aimed to develop an accurate and effective model to describe the tendency of HIV and to predict its incidence in Guangxi. HIV incidence data of Guangxi from 2005 to 2016 were obtained from the database of the Chinese Center for Disease Control and Prevention. Long short-term memory (LSTM) neural network models, autoregressive integrated moving average (ARIMA) models, generalised regression neural network (GRNN) models and exponential smoothing (ES) were used to fit the incidence data. Data from 2015 and 2016 were used to validate the most suitable models. The model performances were evaluated by evaluating metrics, including mean square error (MSE), root mean square error, mean absolute error and mean absolute percentage error. The LSTM model had the lowest MSE when the N value (time step) was 12. The most appropriate ARIMA models for incidence in 2015 and 2016 were ARIMA (1, 1, 2) (0, 1, 2)12 and ARIMA (2, 1, 0) (1, 1, 2)12, respectively. The accuracy of GRNN and ES models in forecasting HIV incidence in Guangxi was relatively poor. Four performance metrics of the LSTM model were all lower than the ARIMA, GRNN and ES models. The LSTM model was more effective than other time-series models and is important for the monitoring and control of local HIV epidemics.
Copy number variations (CNVs), as an important source of genetic variation, can affect a wide range of phenotypes by diverse mechanisms. The somatostatin receptor 2 (SSTR2) gene plays important roles in cell proliferation and apoptosis. Recently, this gene was mapped to a CNV region, which encompasses quantitative trait loci of cattle economic traits including body weight, marbling score, etc. Therefore, SSTR2 CNV may exhibit phenotypic effects on cattle growth traits. In the current study, distribution of SSTR2 gene CNVs was investigated in six Chinese cattle breeds (XN, QC, NY, JA, LX and PN), and the results showed higher CNV polymorphisms in XN, QC and NY cattle. Next, association analysis between growth traits and SSTR2 CNV was performed for XN, QC and NY cattle. In NY, individuals with fewer copies showed better performance than those with more copies. Further, the effects of SSTR2 CNV on the SSTR2 mRNA level were also investigated, but revealed no significant correlation in either muscle or adipose tissue of adult NY cattle. The results suggested the potential for use of SSTR2 CNV as a marker for the molecular breeding of NY cattle.
Solid state batteries are an emerging alternative to traditional liquid electrolyte cells that provide potential for safe and high-energy density power sources. This report describes a self-forming, solid state battery based on the Li/I2 couple using an LiI-rich LiI(3-hydroxypropionitrile)2 electrolyte (LiI–LiI(HPN)2). As the negative and positive active materials are generated in situ, the solid electrolyte–current collector interfaces play a critical role in determining the electrochemical response of the battery. Herein, we report the investigation of solid electrolyte–current collector interfaces with a self-forming LiI–LiI(HPN)2 solid electrolyte and the role of varying interface design in reducing resistance during cycling.
Results on least-squares refinement of X-ray reflectivity data obtained with a conventional powder diffractometer are reported. A model containing an oxygen contaminated surface on Pt was used to refine experimental data for a “500-Å” Pt film on Si. Values of layer thickness, density, and roughness determined by least-squares refinement agree with those obtained from highresolution reflectivity data. The results were found to be insensitive to the film-surface alignment. An agreement of ±2.3 Å for Pt thickness, 8% for density, and 2.5 Å for roughness was obtained when the surface was aligned to within the divergence of the incident X-ray beam. The least-squares refinement method was also used to analyze two sputtered “300-Å” Pt films deposited at 4 and 20 × 10-6 Torr Ar pressure. Results showed a significant increase in Pt thickness and a decrease in density for the 20 × 10-6 film probably caused by a large amount of Ar trapped in the film.
A tcchniquc for high-precision measurement of carbon thin-film thickness using X-ray fluorescence (XRF) is described. A quadratic calibration procedure is used for carbon thin films on silicon. Measurement of carbon-film thickness in a double-layer structure of carbon and CoCrX alloy is complicated by interference effects from the underlying layer. The dependence of the relative precision in measuring thickness (σT/T) on the counting time has been derived. It shows that a precision of 2% for a 25-nm carbon coating can be obtained using a W/C crystal and counting time of 4 minutes. Intensity and resolution advantages provided by the recently developed Ni/C and V/C multilayer synthetic crystals are also described.
As a result of interest in the characterization of materials with large d-spacings and layer periodicities, it has become necessary to develop a low-angle diffraction material which has welldefined diffraction peaks down to very small 2θ angles. The use of silver behenate, CH3(CH2)20COO-Ag, was introduced by one of the authors (TB) at the 1991 International Centre for Diffraction Data (ICDD) Annual Meeting and was shown to have a set of well-defined (001) diffraction peaks down to 1.5° 2θ when using CuKα radiation. The silver behenate diffraction peaks were observed to be slightly asymmetric with relatively long tails at the low angle side of the peaks. The average crystallite size along the c-axis was estimated using the Scherrer equation and was found to be 900 Å.
A task group of the JCPDS-ICJDD Data Collection and Analysis Subcommittee was established with the charge of investigating the use of silver behenate as a possible low-angle calibration material for diffraction applications. Utilizing several data collection and data analysis techniques, d001 long-period spacings in the range of 58.219-58.480 Å were obtained. Using the same collected data and one data analysis refinement calculation method resulted in long-period spacing with a range of 58.303-58.425 Å. Data collected using a silicon internal standard and the same singular data analysis calculation method provided d001 values with a range of 58.363-58.381 Å.
The formation of a full-range 2θ diffraction sample was also investigated. Silver behenate and inorganic powders were mixed with an epoxy binder to form a permanent sample which provides diffraction peaks over the entire 2θ range of a powder diffractometer.
Thin films containing periodic chemical or strain modulation (e.g. artificial superlattices or SL) are often characterized nondestructively by X-ray double-axis diffractometry. The satellite peaks from the modulated structure allow analysis of layer structure, elemental concentration and strain profile. This paper focuses on the effect of layer uniformity on the rocking curves of (001) GaAs/AlxGa1-xAsSL. Double-axis diffractometry for results from MBE samples with 800 Å SL periods and x=0.35 are compared for GaAs/AlGaAs layer thicknesses of 350/450, 400/400 and 450/350 Å. Symmetric (004) and asymmetric (315) diffraction planes are used to measure parallel and perpendicular misfit strains, layer periodicity and aluminum concentration. A modified kinematical scattering model, correcting for absorption and extinction, is used to calculate the satellite peak intensities and spacings. The relative thicknesses of GaAs and AlGaAs and the aluminum elemental concentration are optimized by matching with experimental results. The effect of nonuniform layer thickness on SL peak intensities is also investigated. The experimental results, the modified kinematical scattering calculations and dynamical theory agree closely for the 3-4 /zm thickness layers studied.
X-ray diffraction techniques have been used for the structure characterization of Y-Ba-Cu-O and Tl-Ca-Ba-Cu-O thin films. A powder diffraction analysis of Y-Ba-Cu-O films showed that the films deposited at 650°C on Si are polycrystalline and have an orthorhambic structure similar to that of the YBa2Cu3O7 bulk superconductors. In addition to the conventional powder diffraction technique, both the rocking curve and the grazing incidence diffraction methods were used to characterize a YBa2Cu3O7 film on (110) SrTiO3 substrate. Results showed that the film was epitaxially grown and aligned with its substrate in a true epitaxy. Phase identification and line broadening analyses of Tl-Ca-Ba-Cu-O films showed that the films are comprised of one or more superconducting phases and probably contain stacking faults.
Precise thin-film thicknesses have been obtained from X-ray specular and off-specular reflectivity data collected with a conventional powder diffractometer. An analysis of the specular reflectivity curve for a 565.9-Å thick pt film showed the results agreed with those determined previously from high-resolution reflectometer data to within 6.6 Å or 1.2%. An analysis of the off-specular reflectivity curves which have well-defined interference fringes showed that the results were insensitive to the surface alignment. Values of Pt thickness for the off-specular reflectivity curves agreed with that of the specular reflectivity curve to within 6.2 Å or 1.1%. The insensitivity in film-surface misalignment makes conventional powder diffractometer attractive for film-thickness determination and opens this techniques to many laboratories.
Unfavourable dietary habits, such as skipping breakfast, are common among ethnic minority children and may contribute to inequalities in cardiometabolic disease. We conducted a longitudinal follow-up of a subsample of the UK multi-ethnic Determinants of Adolescent Social well-being and Health cohort, which represents the main UK ethnic groups and is now aged 21–23 years. We aimed to describe longitudinal patterns of dietary intake and investigate their impact on cardiometabolic risk in young adulthood. Participants completed a dietary behaviour questionnaire and a 24 h dietary intake recall; anthropometry, blood pressure, total cholesterol and HDL-cholesterol and HbA1c were measured. The cohort consisted of 107 White British, 102 Black Caribbean, 132 Black African, 98 Indian, 111 Bangladeshi/Pakistani and 115 other/mixed ethnicity. Unhealthful dietary behaviours such as skipping breakfast and low intake of fruits and vegetables were common (56, 57 and 63 %, respectively). Rates of skipping breakfast and low fruit and vegetable consumption were highest among Black African and Black Caribbean participants. BMI and cholesterol levels at 21–23 years were higher among those who regularly skipped breakfast at 11–13 years (BMI 1·41 (95 % CI 0·57, 2·26), P=0·001; cholesterol 0·15 (95 % CI –0·01, 0·31), P=0·063) and at 21–23 years (BMI 1·05 (95 % CI 0·22, 1·89), P=0·014; cholesterol 0·22 (95 % CI 0·06, 0·37), P=0·007). Childhood breakfast skipping is more common in certain ethnic groups and is associated with cardiometabolic risk factors in young adulthood. Our findings highlight the importance of targeting interventions to improve dietary behaviours such as breakfast consumption at specific population groups.
Severe fever with thrombocytopaenia syndrome (SFTS) is an emerging infectious disease discovered in 2010 and has a case fatality as high as 30%. We intended to study the immune protection conferred by SFTS with natural infection. We collected and analysed 4-year follow-up data to study the characteristics of neutralising antibodies against SFTS virus (SFTSV). The 50% plaque reduction neutralisation test was used for the detection of neutralising antibodies against SFTSV. Geometric mean titres (GMTs) and proportions of patients with a protective titre were analysed, and the persistence of protection was predicted. The titre of antibodies declined yearly in the 4-year study period. Approximately 3 months after infection, the GMT was 143 (95% confidence interval (CI): 89–231), and 100% of patients had a protective titre. In the fourth year, the GMT declined to 53 (95% CI: 37–76), and 95% of patients had a protective titre. The titre was higher in females than in males. On average, the protection offered by neutralising antibodies against SFTSV could last as long as 9 years. The durations of protection were different for different initial titres. The characteristics of neutralising antibodies can be used as a reference for the vaccination doses and schedules of forthcoming vaccines.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
Research suggests that genetic variants linked to hypothalamic-pituitary-adrenal (HPA)-axis functioning moderate the association between environmental stressors and depression, but examining gene–environment interactions with single polymorphisms limits power. The current study used a multilocus genetic profile score (MGPS) approach to measuring HPA-axis–related genetic variation and examined interactions with acute stress, chronic stress, and childhood adversity (assessed using contextual threat interview methods) with depressive symptoms as outcomes in an adolescent sample (ages 14–17, N = 241; White subsample n = 192). Additive MGPSs were calculated using 10 single nucleotide polymorphisms within HPA-axis genes (CRHR1, NR3C2, NR3C1, FKBP5). Higher MGPS directly correlated with adolescent depressive symptoms. Moreover, MGPS predicted stronger associations between acute and chronic stress and adolescent depressive symptoms and also moderated the effect of interpersonal, but not noninterpersonal, childhood adversity. Gene–environment interactions individually accounted for 5%–8% of depressive symptom variation. All results were retained following multiple test correction and stratification by race. Results suggest that using MGPSs provides substantial power to examine gene–environmental interactions linked to affective outcomes among adolescents.
Rhizoctonia solani Kühn and Pythium aphanidermatum Edson cause cabbage seedling damping-off, resulting in severe yield losses. The current study demonstrates the production of toxic volatile organic compounds (VOCs) by two strains of Bacillus mycoides and the evaluation of a potential use of B. mycoides as a biocontrol agent to control cabbage damping-off. Two VOCs, dimethyl disulphide and ammonia, were found to reduce radial growth, cause hyphal deformation and result in organelle degeneration in both R. solani and P. aphanidermatum. Pathogen hyphae, after being exposed to VOCs, showed poor rigidity, shrinkage, curling and swelling. The amount of VOCs produced by B. mycoides and the antagonistic activity against plant pathogens varied, depending on the type of medium used to culture bacteria. Application of B. mycoides cell suspensions to cultivation medium promotes growth of five different plant species tested. Experiments conducted in greenhouses revealed that B. mycoides did not reduce damping-off incidence caused by R. solani. However, B. mycoides reduced damping-off incidence induced by P. aphanidermatum by as much as 45% on cabbage seedlings. The results provide valuable information on the feasibility of utilizing B. mycoides as a biocontrol agent in controlling cabbage damping-off.