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Previous studies have inferred a strong genetic component in schizophrenia. However, the genetic variants involved in the susceptibility to schizophrenia remain unclear.
To detect potential gene pathways and networks associated with schizophrenia, and to explore the relationship between common and rare variants in these pathways and abnormal white matter integrity in schizophrenia.
The analysis included 100 first-episode treatment-naïve patients with schizophrenia and 140 healthy controls. A network-based analysis was carried out on the data collected from the Psychiatric Genomics Consortium Phase I (PGC-I). Based on our genome-wide association study and whole-exome sequencing data-sets, we performed a gene-set analysis to detect associations between the combining effects of common and rare genetic variants and abnormal white matter integrity in schizophrenia.
Patients had significantly reduced functional anisotropy in the left and right anterior cingulate cortex, left and right precuneus and extra-nuclear (t = 4.61–5.10, PFDR < 0.01), compared with controls. Generated from co-expression network analysis of the PGC-1 summary statistics of schizophrenia, a subnetwork of 207 genes associated with schizophrenia was identified (P < 0.01), and 176 genes were co-expressed in four gene modules. Functional enrichment analysis for genes in each module revealed that the yellow module was enriched with highly co-expressed, innate immune response genes. Furthermore, rare variants of enriched genes in the yellow module were associated with reduced functional anisotropy in the left anterior cingulate cortex (P = 0.006; Padjusted = 0.024) in patients only.
The pathogenesis of schizophrenia may be substantially influenced by genes involved in the immune system, via both pathway and network.
Drag reduction at the external surface of a cylinder in turbulent flows along the axial direction by circumferential wall motion is studied by direct numerical simulations. The circumferential wall oscillation can lead to drag reduction due to the formation of a Stokes layer, but it may also result in centrifugal instability, which can enhance turbulence and increase drag. In the present work, the Reynolds number based on the reference friction velocity and the nominal thickness of the boundary layer is 272. A map describing the relationship between the drag-reduction rate and the control parameters, namely, the angular frequency
and the streamwise wavenumber
, is obtained at the oscillation amplitude of
is the friction velocity of the uncontrolled flow and
is the kinematic viscosity of the fluid. The maximum drag-reduction rate and the maximum drag-increase rate are both approximately 48 %, which are respectively attained at
(0.0126, 0.0148) and (0.0246, 0.0018). The drag-reduction rate can be scaled well with the help of the effective thickness of the Stokes layer. The drag increase is observed in a narrow triangular region in the frequency–wavenumber plane. The vortices induced by the centrifugal instability become the primary coherent structure in the near-wall region, and they are closely correlated with the high skin friction. In these drag-increase cases, the effective control frequency or wavenumber is crucial in scaling the drag-increase rate. As the wall curvature normalised by the boundary layer thickness becomes larger, the drag-increase region in the
plane as well as the maximum drag-increase rate also become larger. Net energy saving with a considerable drag-reduction rate is possible when reducing the oscillation amplitude. At
, a net energy saving of 18 % can be achieved with a drag-reduction rate of 25 % if only the power dissipation due to viscous stress is taken into account in an ideal actuation system.
Plasma levels of very-long-chain SFA (VLCSFA) are associated with the metabolic syndrome (MetS). However, the associations may vary by different biological activities of individual VLCSFA or population characteristics. We aimed to examine the associations of VLCSFA and MetS risk in Chinese adults. Totally, 2008 Chinese population aged 35–59 years were recruited and followed up from 2010 to 2012. Baseline MetS status and plasma fatty acids data were available for 1729 individuals without serious diseases. Among 899 initially metabolically healthy individuals, we identified 212 incident MetS during the follow-up. Logistic regression analysis was used to estimate OR and 95 % CI. Cross-sectionally, each VLCSFA was inversely associated with MetS risk; comparing with the lowest quartile, the multivariate-adjusted OR for the highest quartile were 0·18 (95 % CI 0·13, 0·25) for C20 : 0, 0·26 (95 % CI 0·18, 0·35) for C22 : 0, 0·19 (95 % CI 0·13, 0·26) for C24 : 0 and 0·16 (0·11, 0·22) for total VLCSFA (all Pfor trend<0·001). The associations remained significant after further adjusting for C16 : 0, C18 : 0, C18 : 3n-3, C22 : 6n-3, n-6 PUFA and MUFA, respectively. Based on follow-up data, C20 : 0 or C22 : 0 was also inversely associated with incident MetS risk. Among the five individual MetS components, higher levels of VLCSFA were most strongly inversely associated with elevated TAG (≥1·7 mmol/l). Plasma levels of VLCSFA were significantly and inversely associated with MetS risk and individual MetS components, especially TAG. Further studies are warranted to confirm the findings and explore underlying mechanisms.
Assertive Community Treatment (ACT) is an evidence-based treatment program for people with severe mental illness developed in high-income countries. We report the first randomized controlled trial of ACT in mainland China.
Sixty outpatients with schizophrenia with severe functional impairments or frequent hospitalizations were randomly assigned to ACT (n = 30) or standard community treatment (n = 30). The severity of symptoms and level of social functioning were assessed at baseline and every 3 months during the 1-year study. The primary outcome was the duration of hospital readmission. Secondary outcomes included a pre-post change in symptom severity, the rates of symptom relapse and gainful employment, social and occupational functioning, and quality of life of family caregivers.
Based on a modified intention-to-treat analysis, the outcomes for ACT were significantly better than those of standard community treatment. ACT patients were less likely to be readmitted [3.3% (1/30) v. 25.0% (7/28), Fisher's exact test p = 0.023], had a shorter mean readmission time [2.4 (13.3) v. 30.7 (66.9) days], were less likely to relapse [6.7% (2/30) v. 28.6% (8/28), Fisher's exact test p = 0.038], and had shorter mean time in relapse [3.5 (14.6) v. 34.4 (70.6) days]. The ACT group also had significantly longer times re-employed and greater symptomatic improvement and their caregivers experienced a greater improvement in their quality of life.
Our results show that culturally adapted ACT is both feasible and effective for individuals with severe schizophrenia in urban China. Replication studies with larger samples and longer duration of follow up are warranted.
A series of CoCrFeNiMox (x = 0.2, 0.4, 0.6, 0.8, 1.0, and 1.2) high-entropy alloys were designed to develop a eutectic high-entropy alloy system and to acquire a superfine eutectic structure. The results show that for the CoCrFeNiMox alloys, with the increase of Mo content from 0.2 to 1.2, the microstructures shift from a typical dendrite structure to a hypoeutectic microstructure (x = 0.6), and then to a fully eutectic microstructure (x = 0.8) with a lamellar spacing only 110 nm, and finally culminate in the hypereutectic structure (x = 1.0, x = 1.2). The XRD results show that CoCrFeNiMox alloys have a single FCC phase when x is 0.2 or 0.4. When Mo content is over 0.6, it begins to separate Cr9Mo21Ni20 intermetallic compounds. The hardness of the CoCrFeNiMox alloys is increasing significantly from 172.8 to 763.7 HV with the increase of Mo content. Meanwhile, the fracture strength increased but the ductility decreases. Among these alloys, the CoCrFeNiMo0.6 alloy shows excellent integrated mechanical properties of compressive fracture strength and strain, which are 2051 Mpa and 23%, respectively.
Fingerprint-based indoor localisation suffers from influences such as fingerprint pre-collection, environment changes and expending a lot of manpower and time to update the radio map. To solve the problem, we propose an efficient radio map updating algorithm based on K-Means and Gaussian Process Regression (KMGPR). The algorithm builds a Gaussian Process Regression (GPR) predictive model based on a Gaussian mean function and realises the update of the radio map using K-Means. We have conducted experiments to evaluate the performance of the proposed algorithm and results show that GPR using the Gaussian mean function improves localisation accuracy by about 13·76% compared with other functions and KMGPR can reduce the computational complexity by about 7% to 20% with no obvious effects on accuracy.
An analytical method is proposed to reduce the memory effects and third-order intermodulation distortions for improving the linearity of wideband power amplifier (PA). An excellent linearity can be obtained by reducing the second-harmonic output power levels and reducing the envelope voltage components in the megahertz range. An improved wideband Chebyshev low-pass matching network including the bias network is analyzed and designed to validate the proposed method. The measured results indicate that a wideband high-efficiency linearized PA is realized from 1.35 to 2.45 GHz (fractional bandwidth = 58%) with power added efficiency of 60–78%, power gain of 10.8–12.3 dB, and output power of 40.0–41.2 dBm. For a 20 MHz LTE modulated signal, the adjacent channel leakage ratios (ACLRs) of the proposed PA with digital pre-distortion (DPD) linearization are −55.7 ~ −53.9 dBc across 1.5–2.4 GHz at an average output power of 32.4–33.6 dBm. For a 40 MHz two-carrier LTE modulated signal, the ACLRs of the proposed PA with DPD linearization are −51.1 ~ −48.2 dBc at an average output power of ~30.5 dBm in the frequency range from 1.5 GHz to 2.4 GHz.
Stimulated Brillouin scattering (SBS) effect is currently the major limitation for the power scaling of single-frequency/narrow linewidth fiber laser systems. A single-mode linearly polarized all-fiber amplifier system is set up to investigate SBS effect in triple-frequency high-power amplifiers. With this amplifier, up to 302 W output power with 83% slope efficiency is achieved and the SBS threshold is scaled up to 12 dB. To the best of our knowledge, this is the highest output power of multifrequency laser from a single-mode polarization maintaining fiber. Good spectral properties and high brightness make this laser source available for the application of second harmonic generation, coherent beam combining.
Glacier surface melting can be described using energy-balance models. We conducted a surface energy budget experiment to quantify surface energy fluxes and to identify factors affecting glacial melt in the ablation zone of Laohugou glacier No. 12, western Qilian mountains. The surface energy budget was calculated based on data from an automatic weather station, and turbulent fluxes calculated using the bulk-aerodynamic approach were corrected using measurements from an eddy-covariance system. Simulated mass balances were validated by stake observations. Net shortwave radiation was the primary component of the surface energy balance (126Wm–2), followed by sensible heat flux. Net longwave radiation (–45Wm–2) and latent heat flux (–12.8 Wm–2) represented heat sinks. The bulk-aerodynamic method underestimated sensible and latent heat fluxes by 3.4 and 1.2 W m–2, respectively. The simulated total mass balance of –1703mmw.e. exceeded the observed total by 90 mm w.e. Daily positive accumulated temperature and low albedo were the main factors accelerating glacier melt. An uncertainty assessment showed that mass balance was very sensitive to albedo and varied by 36% when albedo changed by 0.1.
Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs.
SG-III laser facility is now the largest laser driver for inertial confinement fusion research in China. The whole laser facility can deliver 180 kJ energy and 60 TW power ultraviolet laser onto target, with power balance better than 10%. We review the laser system and introduce the SG-III laser performance here.
To investigate the potential influence of dietary Se intake on mortality among Chinese populations.
We prospectively evaluated all-cause, CVD and cancer mortality risks associated with dietary Se intake in participants of the Shanghai Women’s Health Study (SWHS) and the Shanghai Men’s Health study (SMHS). Dietary Se intake was assessed by validated FFQ during in-person interviews. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95 % CI.
Urban city in China.
Chinese adults (n 133 957).
During an average follow-up of 13·90 years in the SWHS and 8·37 years in the SMHS, 5749 women and 4217 men died. The mean estimated dietary Se intake was 45·48 μg/d for women and 51·34 μg/d for men, respectively. Dietary Se intake was inversely associated with all-cause mortality and CVD mortality in both women and men, with respective HR for the highest compared with the lowest quintile being 0·79 (95 % CI 0·71, 0·88; Ptrend<0·0001) and 0·80 (95 % CI 0·66, 0·98; Ptrend=0·0268) for women, and 0·79 (95 % CI 0·70, 0·89; Ptrend=0·0001) and 0·66 (95 % CI 0·54, 0·82; Ptrend=0·0002) for men. No significant associations were observed for cancer mortality in both women and men. Results were similar in subgroup and sensitivity analyses.
Dietary Se intake was inversely associated with all-cause and cardiovascular mortality in both sexes, but not cancer mortality.
Porpidia hypostictica is described as a new species; it has a white to grey-white thallus with yellow, oxidized patches near the margin, and contains hypostictic acid as the only major compound. A phylogenetic analysis is provided which is based on ITS sequences using ML and Bayesian analyses. The phylogeny supported the separation of the new species from other species. A key to all known Chinese Porpidia species is provided.
The genetic influences in human brain structure and function and impaired functional connectivities are the hallmarks of the schizophrenic brain. To explore how common genetic variants affect the connectivities in schizophrenia, we applied genome-wide association studies assaying the abnormal neural connectivities in schizophrenia as quantitative traits.
We recruited 161 first-onset and treatment-naive patients with schizophrenia and 150 healthy controls. All the participants underwent scanning with a 3 T-magnetic resonance imaging scanner to acquire structural and functional imaging data and genotyping using the HumanOmniZhongHua-8 BeadChip. The brain-wide association study approach was employed to account for the inherent modular nature of brain connectivities.
We found differences in four abnormal functional connectivities [left rectus to left thalamus (REC.L–THA.L), left rectus to right thalamus (REC.L–THA.R), left superior orbital cortex to left thalamus (ORBsup.L–THA.L) and left superior orbital cortex to right thalamus (ORBsup.L–THA.R)] between the two groups. Univariate single nucleotide polymorphism (SNP)-based association revealed that the SNP rs6800381, located nearest to the CHRM3 (cholinergic receptor, muscarinic 3) gene, reached genomic significance (p = 1.768 × 10−8) using REC.L–THA.R as the phenotype. Multivariate gene-based association revealed that the FAM12A (family with sequence similarity 12, member A) gene nearly reached genomic significance (nominal p = 2.22 × 10–6, corrected p = 0.05).
Overall, we identified the first evidence that the CHRM3 gene plays a role in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia. Identification of these genetic variants using neuroimaging genetics provides insights into the causes of variability in human brain development, and may help us determine the mechanisms of dysfunction in schizophrenia.
The late Quaternary sedimentary sequence in the northwestern part of the Sichuan Basin consists of five lithological units and with increasing depth include the: Chengdu Clay; Brown Clay; Red Clay; Sandy Silt; and basal Muddy Gravel. The genesis, provenance and age of the sediments, as well as the possible presence of hiatuses within this sequence are debated. Measurements of grain-size, magnetic susceptibility, quartz content, quartz δ18O values, element composition, and Sr–Nd isotopic concentrations of samples from a typical sedimentary sequence in the area provides new insights into the genesis and history of the sequence. The new data confirm that the sediments in study site are alluvial–aeolian in origin, with basal alluvial deposits overlain by aeolian deposits. Like the uppermost Chengdu Clay, the underlying Brown Clay and Red Clay are aeolian in origin. In contrast, the Silty Sand, like the basal Muddy Gravel, is an alluvial deposit and not an aeolian deposit as previously thought. Moreover, the succession of the aeolian deposits very likely contains two significant sedimentary hiatuses. Sedimentological analysis demonstrates that the source materials for the aeolian deposits in the northwestern part of the Sichuan Basin and those on the eastern Tibetan Plateau are different. Furthermore, the loess deposits on the eastern Tibetan Plateau are derived from heterogeneous local sources.
Iron is an essential trace element that plays important roles in the cellular function of all organs and systems. However, the function of Fe(II) in mammalian embryo development is unknown. In this study, we investigated the role of Fe(II) during preimplantation embryo development. Depletion of Fe(II) using thiosemicarbazone-24 (TSC24), a specific Fe(II) chelator, rescued quenching of the Fe(II)-sensitive fluorophore phen green-SK. After in vitro fertilization, TSC24 significantly reduced the cleavage rate as well as blastocyst formation. The hatch rate of blastocysts was also reduced with 1 pM TSC24 treatment (20.25±1.86 versus 42.28±12.96%, p<0.05). Blastocysts were cultured in leukemia inhibitory factor-free mouse embryonic stem cell culture medium with or without TSC24, and those with depleted Fe(II) displayed delayed attachment and lost the ability to induce embryoid body formation. To further explore the mechanism of Fe(II) in embryo development, we assessed the expression of 5-hydroxymethylcytosine (5hmC) and OCT4 in the pronuclear and blastocyst stages, respectively. We observed that Fe(II) reduced 5hmC and OCT4 expression, which could be explained by low ten-eleven translocation (TET) enzyme activity induced by TSC24 treatment. These findings demonstrate that Fe(II) is required for mammalian embryo development and that it facilitates the process via regulation of TET activity.
A large schizophrenia genome-wide association study (GWAS) and a
subsequent extensive replication study of individuals of European
ancestry identified eight new loci with genome-wide significance and
suggested that the MIR137-mediated pathway plays a role
in the predisposition for schizophrenia.
To validate the above findings in a Han Chinese population.
We analysed the single nucleotide polymorphisms (SNPs) in the newly
identified schizophrenia candidate loci and predicted
MIR137 target genes based on our published Han
Chinese populations (BIOX) GWAS data. We then analysed 18 SNPs from the
candidate regions in an independent cohort that consisted of 3585
patients with schizophrenia and 5496 controls of Han Chinese
We replicated the associations of five markers
(P<0.05), including three that were located in the
predicted MIR137 target genes. Two loci
(ITIH3/4: rs2239547, P
=1.17×10–10 and CALN1: rs2944829,
P=9.97×10–9) exhibited genome-wide
significance in the Han Chinese population.
The ITIH3/4 locus has been reported to be of genome-wide
significance in the European population. The successful replication of
this finding in a different ethnic group provides stronger evidence for
the association between schizophrenia and ITIH3/4. We
detected the first genome-wide significant association of schizophrenia
with CALN1, which is a predicted target of
MIR137, and thus provide new evidence for the
associations between MIR137 targets and
Dislocations are line defects in crystalline materials. The Peierls-Nabarro models are hybrid models that incorporate atomic structure of dislocation core into continuum framework. In this paper, we present a numerical method for a generalized Peierls-Nabarro model for curved dislocations, based on the fast multipole method and the iterative grid redistribution. The fast multipole method enables the calculation of the long-range elastic interaction within operations that scale linearly with the total number of grid points. The iterative grid redistribution places more mesh nodes in the regions around the dislocations than in the rest of the domain, thus increases the accuracy and efficiency. This numerical scheme improves the available numerical methods in the literature in which the long-range elastic interactions are calculated directly from summations in the physical domains; and is more flexible to handle problems with general boundary conditions compared with the previous FFT based method which applies only under periodic boundary conditions. Numerical examples using this method on the core structures of dislocations in Al and Cu and in epitaxial thin films are presented.