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Identification of treatment-specific predictors of drug therapies for bipolar disorder (BD) is important because only about half of individuals respond to any specific medication. However, medication response in pediatric BD is variable and not well predicted by clinical characteristics.
Methods
A total of 121 youth with early course BD (acute manic/mixed episode) were prospectively recruited and randomized to 6 weeks of double-blind treatment with quetiapine (n = 71) or lithium (n = 50). Participants completed structural magnetic resonance imaging (MRI) at baseline before treatment and 1 week after treatment initiation, and brain morphometric features were extracted for each individual based on MRI scans. Positive antimanic treatment response at week 6 was defined as an over 50% reduction of Young Mania Rating Scale scores from baseline. Two-stage deep learning prediction model was established to distinguish responders and non-responders based on different feature sets.
Results
Pre-treatment morphometry and morphometric changes occurring during the first week can both independently predict treatment outcome of quetiapine and lithium with balanced accuracy over 75% (all p < 0.05). Combining brain morphometry at baseline and week 1 allows prediction with the highest balanced accuracy (quetiapine: 83.2% and lithium: 83.5%). Predictions in the quetiapine and lithium group were found to be driven by different morphometric patterns.
Conclusions
These findings demonstrate that pre-treatment morphometric measures and acute brain morphometric changes can serve as medication response predictors in pediatric BD. Brain morphometric features may provide promising biomarkers for developing biologically-informed treatment outcome prediction and patient stratification tools for BD treatment development.
Protein content (PC) and oil content (OC) are important breeding traits of soybean [Glycine max (L.) Merr.]. Quantitative trait locus (QTL) mapping for PC and OC is important for molecular breeding in soybean; however, the negative correlation between PC and OC influences the accuracy of QTL mapping. In the current study, a four-way recombinant inbred lines (FW-RILs) population comprising 160 lines derived from the cross (Kenfeng14 × Kenfeng15) × (Heinong48 × Kenfeng19) was planted in eight different environments and PC and OC measured. Conditional and unconditional QTL analyses were carried out by interval mapping (IM) and inclusive complete IM based on linkage maps of 275 simple sequences repeat markers in a FW-RILs population. This analysis revealed 59 unconditional QTLs and 52 conditional QTLs among the FW-RILs. An analysis of additive effects indicated that the effects of 13 protein QTLs were not related to OC, whereas OC affected the expression of 13 and eight QTLs either partially or completely, respectively. Eight QTLs affecting OC were not influenced by PC, whereas six and 26 QTLs were partially and fully affected by PC, respectively. Among the QTLs detected in the current study, two protein QTLs and five oil QTLs had not been previously reported. These findings will facilitate marker-assisted selection and molecular breeding of soybean.
LiMnxCoyNi1−x−yO2 (LMCNO) has been broadly investigated and commercialized primarily as lithium ion battery (LIB) cathodes, owing to its high operating voltage, large energy density, and superior electronic conductivity. However, poor cycling stability induced by the rapid structure degradation limits their further development. Coating is regarded as a very effective strategy to address the problem of structure degradation. Regrettably, the coating layers obtained by traditional methods are usually thick, which is not appropriate for delivering of integrated performance. As an emerging coating technology, atomic layer deposition (ALD) demonstrates immeasurable advantages in deposition of ultrathin coating materials because of its atomic-level precision, and has been widely applied in construction of the coating layers on LMCNO substrate materials. Herein, we firstly outline the development and mechanism of ALD technology, and then systematically summarize intrinsic reasons for the enhanced electrochemical performance. Finally, we propose new insights toward designing and preparing the coating structure of LMCNO cathodes by controllable ALD for the next-generation LIBs.
We describe the use of a terrestrial laser scanner (TLS) to monitor the net mass balance of Urumqi Glacier No. 1, eastern Tien Shan. We used an ultra-long-range Riegl VZ®-6000 TLS, which is specially designed for surveying snow- and ice-covered terrain, to create repeated high spatiotemporal resolution DEMs, focusing on the monthly-scale (25 April–28 May 2015) net mass balance. According to the TLS-derived DEMs, the area of Urumqi Glacier No. 1 was 1.558 km2 on 25 April 2015 and the average surface elevation change was 0.225 m. By comparing the results from the use of TLS with the conventional glaciological mass-balance method, the correlation coefficient (R2) between glaciological elevation changes of individual stakes and the TLS-derived geodetic elevation change of corresponding points was 0.85. Considering the uncertainty of both methods, this is a promising result. Using the in situ measured snow densities (snow pits) of the glacier surface, the geodetic net mass balance was 0.074 m w.e., which is slightly positive. The mean uncertainty in the TLS-derived monthly net mass balance was 0.018 m w.e., showing that the TLS surveying system presented accurate and relevant results and is therefore suitable to monitor mass-balance evolution of mountain glaciers.
In this study, the effects of Ag variations on dynamic recrystallization (DRX), texture, and mechanical properties of ultrafine-grained Mg–3Al–1Zn alloys are investigated. The results suggest that Ag segregation and Al–Zn–Ag clusters form in the Mg matrix with Ag addition less than 1 wt%, which retard DRX and the growth of the DRXed grains. The resulting grain size decreases from 513 to 316 nm. As the Ag addition increases to 2 wt%, the Mg54Ag17 phase precipitates along the grain boundary, which plays an important role in restricting DRXed grain growth via grain boundary pinning effect. The resulting grain size is 375 nm with a bimodal grain size distribution. The extrusion texture of the investigated alloys is in fairly scattered orientation distribution. The weak basal texture and ultrafine grain size lead to the high yield asymmetry ratio. The Ag-containing extruded alloys exhibit an increase in the tensile and compressive properties. The strengthening mechanisms due to grain refinement, dislocations, solid solution, precipitates, solute clusters, and segregation are discussed.
In this paper, a novel wideband right-angle transition between thin substrate integrated waveguide (SIW) and rectangular waveguide (RWG) based on multi-section structure operating at center frequency 31.5 GHz is presented. A multi-section SIW with a rectangular aperture etched on the broad wall and two stepped ridges embedded in the RWG flange are introduced to obtain a wide impedance matching. The simulations show that the bandwidth with return loss better than 20 dB is about 17 GHz. In order to verify our designs, two back-to-back transitions with different lengths are fabricated and measured. The experimental results agree well with simulations. The proposed component shows an insertion loss less than 0.44 dB and a return loss better than 14.5 dB over 12.15 GH, which corresponds to 38.57% bandwidth.
In the preparation process for scanning electron microscopy (SEM), flexed silkworm embryos typically assume several curled shapes with irregular postures that obscure morphological details during SEM observation. We describe a preparation technique based on glycerol substitution for better SEM visualization of straight and flat silkworm embryos. Glycerol has high viscosity, low vapor pressure, and sufficient electrical conductivity. Silkworm embryos were infiltrated with glycerol and arranged in a straight posture or flattened using a cover slip. Samples were directly observed by SEM without additional dehydration, drying, or coating procedures. The complete ventral side could be easily viewed in one image. Recoating alleviated the charging phenomenon. This represents a simple method for preparation of straight and flat samples from curled biological specimens for SEM observation.
Seed filling rate of soybean has been shown to be a dynamic process in different developmental stages affected by both genotype and environment. The objective of the present study was to determine additive, epistatic and quantitative trait loci (QTLs)×environment interaction (QE) effects of the QTL underlying a seed filling rate of soybean. One hundred and forty-three recombinant inbred lines (RILs) derived from the cross of Charleston and Dongnong 594 were used with 2 years of field data (2004 and 2005). Eleven QTLs with significantly unconditional and conditional additive (a) effect and/or additive×environment interaction (ae) effect at different filling stages were identified. Of them six QTLs showed positive a effects and four QTLs had negative a effects on the seed filling rate during seed development. aa and aae effects of 12 pairs of QTLs were identified by unconditional mapping from the initial stage to the final stage. Thirteen pairs of QTLs underlying the seed filling rate with aa and aae effects were identified by conditional mapping. QTLs with aa and aae (additive×additive×environment) effects appeared to vary at different filling stages. Our results demonstrated that the mass filling rate in soybean seed were under genetic and environmental control.
Cerebral white matter injury in premature infants, known as periventricular leukomalacia (PVL), is common after hypoxia–ischemia (HI). While ionotropic glutamate receptors (iGluRs) can mediate immature white matter injury, we have previously shown that excitotoxic injury to premyelinating oligodendrocytes (preOLs) in vitro can be attenuated by group I metabotropic glutamate receptor (mGluR) agonists. Thus, we evaluated mGluR expression in developing white matter in rat and human brain, and tested the protective efficacy of a central nervous system (CNS)-penetrating mGluR agonist on injury to developing oligodendrocytes (OLs) in vivo. Group I mGluRs (mGluR1 and mGluR5) were strongly expressed on OLs in neonatal rodent cerebral white matter throughout normal development, with highest expression early in development on preOLs. Specifically at P6, mGluR1 and mGLuR5 were most highly expressed on GalC-positive OLs compared to neurons, axons, astrocytes and microglia. Systemic administration of (1S,3R) 1-aminocyclopentane-trans-1,3,-dicarboxylic acid (ACPD) significantly attenuated the loss of myelin basic protein in the white matter following HI in P6 rats. Assessment of postmortem human tissue showed both mGluR1 and mGluR5 localized on immature OLs in white matter throughout development, with mGluR5 highest in the preterm period. These data indicate group I mGluRs are highly expressed on OLs during the peak period of vulnerability to HI and modulation of mGluRs is protective in a rodent model of PVL. Group I mGluRs may represent important therapeutic targets for protection from HI-mediated white matter injury.
The accumulation of seed mass in soybean is affected by both genotype and environment. The aim of the present study was to measure additive, epistatic and quantitative trait locus (QTL)×environment (QE) interaction effects of QTLs on the development of 100-seed weight in a population of 143 F5 derived recombinant inbred lines (RILs) developed from the cross between the soybean cultivars ‘Charleston’ and ‘Dong Nong 594’. Broad-sense heritability of 100-seed weight from 30 days (30D) to 80D stages was 0·58, 0·52, 0·62, 0·60, 0·66 and 0·57, respectively. A total of 17 QTLs with conditional additive (a) effect and/or conditional additive×environment interaction (ae) effect at specific stages were identified in ten linkage groups by conditional mapping. Of them, only 4 QTLs had significant a effect or ae effect at different stages of seed development. Among QTLs with significant a effect, five acted positively and six acted negatively on seed development. A total of 35 epistatic pairwise QTLs of 100-seed weight were identified by conditional mapping at different developmental stages. Five pairs of QTL showed the additive×additive epistatic (aa) effect and 16 QTLs showed the aa×environment interaction (aae) effect at the different developmental stages. QTLs with aa effect as well with their environmental interaction effect appeared to vary at different developmental stages. Overall, the results indicated that 100-seed weight in soybean is under developmental, genetic and environmental control.
Investigation into the depositional and post-depositional processes of atmospheric NH4+ on Ürümqi glacier No. 1 (UG1), China, was implemented within the Program for Glacier Processes Investigation (PGPI) campaign. Aerosol and surface snow samples were collected concurrently on a weekly basis from March 2004 to March 2005 in the UG1 accumulation zone at the headwaters of the Ürümqi river, eastern Tien Shan. All samples were analyzed for NH4+ and other chemical species. This paper investigates the seasonal variations of NH4+. A significant linear relationship (R2 = 0.70, N = 21, P < 0.01) between NH4+ concentrations in surface snow and aerosol was found during spring and summer, indicating that the warm–wet condition facilitates the air–snow exchange of NH4+. Humidity was found to be a significant meteorological factor influencing NH4+ in deposition in autumn and winter. The NH4+ concentration in aerosol clearly shows a trend similar to that in surface snow, suggesting that the variation of atmospheric NH4+ might have been preserved in the surface snow. The possible source of NH4+ is discussed in this paper.
To investigate the environmental and climatic significance of the ice-core records from the Tien Shan, central Asia, the characteristics of ionic concentration and oxygen isotopic ratio (δ18O) as well as their variability are assessed from surface-snow samples as well as old-snow samples collected year-round at weekly intervals from November 2002 to October 2005 on Ürümqi glacier No. 1, eastern Tien Shan. The results indicate that the δ18O in surface-snow samples is reversely coincident with air temperature and insignificantly affected by post-depositional processes. Ionic concentrations in the wet-season (1 November to 31 March) snow are overall higher than those in dry-season (1 April to 31 October) snow, while the variability of relative ionic composition between dry seasons is slightly less than that between wet seasons. During dry seasons, surface-snow chemistry was mostly controlled by the chemical content entrained in some sporadic precipitations. When precipitation is absent, the effect of all post-depositional processes together elevated the ionic concentrations in surface snow. During wet seasons, the snow chemistry is determined mainly by the input of aerosols entrained in precipitation and the elution process from percolation of meltwater.
We report on the development of depth hoar and its relation to stable oxygen isotopic content in snow–firn stratigraphy in the percolation zone of Ürümqi glacier No. 1, eastern Tien Shan, China, during the period September 2004–August 2006. The essential condition for the development of depth hoar in the snow–firn pack is the temperature gradient. When the temperature gradient of the snow–firn pack reaches a maximum value of 13.0˚Cm–1 in mid-October, depth hoar begins to develop. By the end of March, the depth hoar might account for 25% of the total snow–firn pack depth. From April to June, as the weather becomes warm, the transport of water vapor diminishes and melting– regelation metamorphism replaces metamorphism caused by the temperature gradient. As a result, the depth hoar turns into coarse-grained firn. Fractionation of the oxygen isotopic content also occurs during formation of the depth hoar. The bottom 15 cm of the depth-hoar δ18O values were depleted in the lighter isotopic species as the snow sublimated from the lower to the upper crystals, and the δ values increased from –9.4% to –7.0% from 8 September 2004 to 25 January 2005. The upper 10 cm of the depth-hoar δ18O values were enriched in the lighter isotopic species and the δ values decreased from –6.8% to –9.3% during the same period.
The improved effects of dietary chickpeas on visceral adiposity, dyslipidaemia and insulin resistance were examined. Rats were fed a normal-fat diet (NFD), a high-fat diet (HFD) or a high-fat plus chickpea diet (HFD+CP) for 8 months. The epididymal fat pad weight v. total body weight of rats was higher in the HFD group (0·032 (sd 0·0042) g/g) than in the NFD group (0·015 (sd 0·0064) g/g) and smaller in the HFD+CP group (0·023 (sd 0·0072) g/g) compared with the HFD group (P < 0·05). Chickpea treatment also induced a favourable plasma lipid profile reflecting decreased TAG, LDL-cholesterol (LDL-C) and LDL-C:HDL-cholesterol levels (P < 0·05). HFD-fed rats had higher TAG concentration in muscle and liver, whereas the addition of chickpeas to the HFD drastically lowered TAG concentration (muscle, 39 %; liver, 23 %). The activities of lipoprotein lipase (LPL) in epididymal adipose tissue and hepatic TAG lipase in liver recorded a 40 and 23 % increase respectively in HFD rats compared with those in NFD rats; dietary chickpeas completely normalised the levels. Furthermore, chickpea-treated obese rats also showed a markedly lower leptin and LPL mRNA content in epididymal adipose tissue. An insulin tolerance test, oral glucose tolerance test and insulin-releasing test showed that chickpeas significantly improved insulin resistance, and prevented postprandial hyperglycaemia and hyperinsulinaemia induced by the chronic HFD. The present findings provide a rational basis for the consumption of chickpeas as a functional food ingredient, which may be beneficial for correcting dyslipidaemia and preventing diabetes.
The coalescence process of poly (ethylene-co-vinyl acetate) (EVA) and poly (ethylene-co-octene) (EO) dispersion particles was monitored in situ using tapping-mode atomic force microscopy (TMAFM) equipped with a miniature hot stage. This work describes the effect of particle size on the film formation temperature based on direct experimental observation, clarifying further the debate about particle size effect on minimum film formation temperature (MFFT). The results suggest that semicrystalline polyolefin particles have similar deformation temperature dependence. Smaller particles tend to deform faster than larger particles, which is attributed to their smaller mass. Furthermore, morphology changes and mechanical property development associated with the film formation process are also discussed. The TMAFM technique is shown to be very useful in gaining insight into the film formation mechanism, which will provide guidance in future practical applications with polyolefin dispersions.
The mechanism for combustion synthesis (CS) of AlN was investigated in the present paper. A novel quenching technique was developed to retain the high-temperature structure formed in the sample during the combustion process. Based on the microstructural observation of the quenched specimen and thermodynamic analysis, a two-step reaction mechanism for CS AlN, i.e., vaporization of Al and subsequent reaction with N2, is proposed.
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