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In automotive digital development, 3D prototype creation is a team effort of designers and engineers, each contributing with ideas and technical evaluations through means of computer simulations. To support the team in the 3D design ideation and exploration task, we propose an interactive design system for assisted design explorations and faster performance estimations. We utilize the advantage of deep learning-based autoencoders to create a low-dimensional latent manifold of 3D designs, which is utilized within an interactive user interface to guide and strengthen the decision-making process.
The once-contiguous Ellesmere Ice Shelf, first reported in writing by European explorers in 1876, and now almost completely disintegrated, has rolling, wave-like surface topography, the origin of which we investigate using a viscous buckling instability analysis. We show that rolls can develop during a winter season (~ 100 d) if sea-ice pressure (depth-integrated horizontal stress applied to the seaward front of the Ellesmere Ice Shelf) is sufficiently large (1 MPa m) and ice thickness sufficiently low (1–10 m). Roll wavelength initially depends only on sea-ice pressure, but evolves over time depending on amplitude growth rate. This implies that a thinner ice shelf, with its faster amplitude growth rate, will have a shorter wavelength compared to a thicker ice shelf when sea-ice pressure is equal. A drawback of the viscous buckling mechanism is that roll amplitude decays once sea-ice pressure is removed. However, non-Newtonian ice rheology, where effective viscosity, and thus roll change rate, depends on total applied stress may constrain roll decay rate to be much slower than growth rate and allow roll persistence from year to year. Whether the viscous-buckling mechanism we explore here ultimately can be confirmed as the origin of the Ellesmere Ice Shelf rolls remains for future research.
We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.
We study the effects of fluid–particle and particle–particle interactions in a three-dimensional monodispersed reactor with unstable fluidization. Simulations were conducted using the immersed boundary method for particle Reynolds numbers of 20–70 with an Archimedes number of 23 600. Two different flow regimes were identified as a function of the particle Reynolds number. For low particle Reynolds numbers ($20 < Re_p < 40$), the porosity is relatively low and the particle dynamics are dominated by interparticle collisions that produce anisotropic particle velocity fluctuations. The relative importance of hydrodynamic effects increases with increasing particle Reynolds number, leading to a minimized anisotropy in the particle velocity fluctuations at an intermediate particle Reynolds number. For high particle Reynolds numbers ($Re_p > 40$), the particle dynamics are dominated by hydrodynamic effects, leading to decreasing and more anisotropic particle velocity fluctuations. A sharp increase in the anisotropy occurs when the particle Reynolds number increases from 40 to 50, corresponding to a transition from a regime in which collision and hydrodynamic effects are equally important (regime 1) to a hydrodynamic-dominated regime (regime 2). The results imply an optimum particle Reynolds number of roughly 40 for the investigated Archimedes number of 23 600 at which mixing in the reactor is expected to peak, which is consistent with reactor studies showing peak performance at a similar particle Reynolds number and with a similar Archimedes number. Results also show that maximum effective collisions are attained at intermediate particle Reynolds number. Future work is required to relate optimum particle Reynolds number to Archimedes number.
We study the effects of Archimedes number $Ar$ and volume fraction $\phi$ in three-dimensional, high concentration and monodispersed particle suspensions. Simulations were conducted using the immersed boundary method with direct forcing for triply periodic cases and with $Ar = 21 - 23\,600$ and $\phi = 0.22 - 0.43$. We find that cluster formation is strongly dependent on the Archimedes number but weakly dependent on the volume fraction for concentrated suspensions. Particles in low $Ar$ cases are characterized by less frequent but long-lived clusters, resulting in higher hindered settling, while high $Ar$ cases consist of more frequent but short-lived clusters, leading to reduced hindered settling. By quantifying the effects of collisions on the hydrodynamic fluctuations, we show that the lifespan of clusters for the low $Ar$ cases is longer because particles are subject to appreciable wake interactions without collisions. On the other hand, clusters for high $Ar$ cases are broken before being subject to appreciable wake interactions due to frequent collisions, leading to a shorter cluster lifespan. The results imply that there exists an $Ar$ for particles in fluidized bed reactors that can reduce short circuiting due to clustering and enhance performance by maximizing flow–particle interactions. This result is consistent with existing reactor studies demonstrating that optimal particle diameters and $Ar$ values correspond to cases with short-lived clusters, although more thorough experimental studies are needed.
Schizophrenia has been primarily conceptualized as a disorder of high-order cognitive functions with deficits in executive brain regions. Yet due to the increasing reports of early sensory processing deficit, recent models focus more on the developmental effects of impaired sensory process on high-order functions. The present study examined whether this pathological interaction relates to an overarching system-level imbalance, specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks.
We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state fMRI to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients v. 122 controls).
We demonstrated compression of the cortical hierarchy organization in schizophrenia, with a prominent compression from the sensorimotor region and a less prominent compression from the frontal−parietal region, resulting in a diminished separation between sensory and fronto-parietal cognitive systems. Further analyses suggested reduced differentiation related to atypical functional connectome transition from unimodal to transmodal brain areas. Specifically, we found hypo-connectivity within unimodal regions and hyper-connectivity between unimodal regions and fronto-parietal and ventral attention regions along the classical sensation-to-cognition continuum (voxel-level corrected, p < 0.05).
The compression of cortical hierarchy organization represents a novel and integrative system-level substrate underlying the pathological interaction of early sensory and cognitive function in schizophrenia. This abnormal cortical hierarchy organization suggests cascading impairments from the disruption of the somatosensory−motor system and inefficient integration of bottom-up sensory information with attentional demands and executive control processes partially account for high-level cognitive deficits characteristic of schizophrenia.
Dry wind-tunnel (DWT) flutter test systems model the unsteady distributed aerodynamic force using various electromagnetic exciters. They can be used to test the aeroelastic and aeroservoelastic stability of smart aircraft or high-speed flight vehicles. A new parameterised modelling method at the full system level based on the generalised force equivalence for DWT flutter systems is proposed herein. The full system model includes the structural dynamic model, electromechanical coupling model and fast aerodynamic computation model. An optimisation search method is applied to determine the best locations for measurement and excitation by introducing Fisher’s information matrix. The feasibility and accuracy of the proposed system-level numerical DWT modelling method have been validated for a plate aeroelastic model with four exciters/transducers. The effects of key parameters including the number of exciters, the control time delay, the noise interference and the electrical parameters of the electromagnetic exciter model have also been investigated. The numerical and experimental results indicate that the proposed modelling method achieves good accuracy (with deviations of less than 1.5% from simulations and 4.5% from experimental test results for the flutter speed) and robust performance even in uncertain environments with a 10% noise level.
The aim of this study was to explore the frequency and distribution of gene mutations that are related to isoniazid (INH) and rifampin (RIF)-resistance in the strains of the multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M.tb) in Beijing, China. In this retrospective study, the genotypes of 173 MDR-TB strains were analysed by spoligotyping. The katG, inhA genes and the promoter region of inhA, in which genetic mutations confer INH resistance; and the rpoB gene, in which genetic mutations confer RIF resistance, were sequenced. The percentage of resistance-associated nucleotide alterations among the strains of different genotypes was also analysed. In total, 90.8% (157/173) of the MDR strains belonged to the Beijing genotype. Population characteristics were not significantly different among the strains of different genotypes. In total, 50.3% (87/173) strains had mutations at codon S315T of katG; 16.8% (29/173) of strains had mutations in the inhA promoter region; of them, 5.5% (15/173) had point mutations at −15 base (C→T) of the inhA promoter region. In total, 86.7% (150/173) strains had mutations at rpoB gene; of them, 40% (69/173) strains had mutations at codon S531L of rpoB. The frequency of mutations was not significantly higher in Beijing genotypic MDR strains than in non-Beijing genotypes. Beijing genotypic MDR-TB strains were spreading in Beijing and present a major challenge to TB control in this region. A high prevalence of katG Ser315Thr, inhA promoter region (−15C→T) and rpoB (S531L) mutations was observed. Molecular diagnostics based on gene mutations was a useful method for rapid detection of MDR-TB in Beijing, China.
Metabolic syndrome induced by atypical antipsychotics is more prevalence in schizophrenic patients. Much less is known regarding paliperidone ER. The objective of this study was to compare matched paliperidone-ER- and olanzapine-treated schizophrenic patients on measures of glucose and lipid metabolism. Eighty hospitalized patients with schizophrenia (DSM-) were randomly assigned to treatment with paliperidone ER or olanzapine for 12 weeks. At baseline and every 4 weeks, we assessed weight, subcutaneous fat, waist and hip circumferences, fasting glucose, insulin, glycohemoglobin A1, cholesterol, triglycerides, high density level (HDL) cholesterol, low density level (LDL) cholesterol and prolactin. And we also evaluate the body mass index (BMI), homeostasis insulin resistance (HOMA-IR) and homeostasis β-cell function (HOMA-B). 33 patients randomly assigned to paliperidone ER and 23 patients randomly assigned to olanzapine completed the entire 12-week treatment. Within-group overall analysis showed that the fasting measures were increased in weight, BMI, waist circumferences, hip circumferences, subcutaneous fat, cholesterol, triglyceride and prolactin for two groups, and fasting glucose, LDL and HOMA-B were increased for olanzapine group. There was significantly difference in serum prolactin between paliperidone ER and olanzapine group. And there was a trend for HOMA-B to increase in olanzapine group over 12 weeks compared to paliperidone ER group. However, there were no overall differential drug effects over 12 weeks on the fasting measures of BMI, glucose, glycohemoglobin A1, insulin, HDL, LDL, cholesterol, triglyceride and HOMA-IR. The study further reinforces the necessity of regular monitoring the metabolic parameters in schizophrenic patients with atypical antipsychotics including paliperidone ER.
Recently, a triple-network model suggested the abnormal interactions between the executive-control network (ECN), default-mode network (DMN) and salience network (SN) are important characteristics of addiction, in which the SN plays a critical role in allocating attentional resources toward the ECN and DMN. Although increasing studies have reported dysfunctions in these brain networks in Internet gaming disorder (IGD), interactions between these networks, particularly in the context of the triple-network model, have not been investigated in IGD. Thus, we aimed to assess alterations in the inter-network interactions of these large-scale networks in IGD, and to associate the alterations with IGD-related behaviors.
DMN, ECN and SN were identified using group-level independent component analysis (gICA) in 39 individuals with IGD and 34 age and gender matched healthy controls (HCs). Then alterations in the SN-ECN and SN-DMN connectivity, as well as in the modulation of ECN versus DMN by SN, using a resource allocation index (RAI) developed and validated previously in nicotine addiction, were assessed. Further, associations between these altered network coupling and clinical assessments were also examined.
Compared with HCs, IGD had significantly increased SN-DMN connectivity and decreased RAI in right hemisphere (rRAI), and the rRAI in IGD was negatively associated with their scores of craving.
These findings suggest that the deficient modulation of ECN versus DMN by SN might provide a mechanistic framework to better understand the neural basis of IGD and might provide novel evidence for the triple-network model in IGD.
The diet of most adults is low in fish and, therefore, provides limited quantities of the long-chain, omega-3 fatty acids (LCn-3FAs), eicosapentaenoic and docosahexaenoic acids (EPA, DHA). Since these compounds serve important roles in the brain, we sought to determine if healthy adults with low-LCn-3FA consumption would exhibit improvements in neuropsychological performance and parallel changes in brain morphology following repletion through fish oil supplementation.
In a randomized, controlled trial, 271 mid-life adults (30–54 years of age, 118 men, 153 women) consuming ⩽300 mg/day of LCn-3FAs received 18 weeks of supplementation with fish oil capsules (1400 mg/day of EPA and DHA) or matching placebo. All participants completed a neuropsychological test battery examining four cognitive domains: psychomotor speed, executive function, learning/episodic memory, and fluid intelligence. A subset of 122 underwent neuroimaging before and after supplementation to measure whole-brain and subcortical tissue volumes.
Capsule adherence was over 95%, participant blinding was verified, and red blood cell EPA and DHA levels increased as expected. Supplementation did not affect performance in any of the four cognitive domains. Exploratory analyses revealed that, compared to placebo, fish oil supplementation improved executive function in participants with low-baseline DHA levels. No changes were observed in any indicator of brain morphology.
In healthy mid-life adults reporting low-dietary intake, supplementation with LCn-3FAs in moderate dose for moderate duration did not affect neuropsychological performance or brain morphology. Whether salutary effects occur in individuals with particularly low-DHA exposure requires further study.
Starch digestion in the small intestines of the dairy cow is low, to a large extent, due to a shortage of syntheses of α-amylase. One strategy to improve the situation is to enhance the synthesis of α-amylase. The mammalian target of rapamycin (mTOR) signalling pathway, which acts as a central regulator of protein synthesis, can be activated by leucine. Our objectives were to investigate the effects of leucine on the mTOR signalling pathway and to define the associations between these signalling activities and the synthesis of pancreatic enzymes using an in vitro model of cultured Holstein dairy calf pancreatic tissue. The pancreatic tissue was incubated in culture medium containing l-leucine for 3 h, and samples were collected hourly, with the control being included but not containing l-leucine. The leucine supplementation increased α-amylase and trypsin activities and the messenger RNA expression of their coding genes (P <0.05), and it enhanced the mTOR synthesis and the phosphorylation of mTOR, ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1 (P <0.05). In addition, rapamycin inhibited the mTOR signal pathway factors during leucine treatment. In sum, the leucine regulates α-amylase and trypsin synthesis in dairy calves through the regulation of the mTOR signal pathways.
Microorganisms are the most abundant organisms on Earth, and microbial abundance records preserved in ice cores have been connected to records of environmental change. As an alternative to high resolution abundance records, which can be difficult to recover, we used culture-dependent and culture-independent methods to examine bacteria in glacier ice from the Tibetan Plateau (TP). We recovered a total of 887 bacterial isolates from ice cores of up to 164 m in depth retrieved from seven glaciers, located across the TP. These isolates were related to 53 genera in the Actinobacteria, Firmicutes, Bacteroidetes, and Proteobacteria, with 13 major genera accounting for 78% of isolates. Most of the genera were common across the geographic region covered by our sampling, but there were differences in the genera recovered from different depths in the ice, with the deepest portions of the ice cores dominated by a single genus (Sporosarcina). Because microorganisms deposited on glaciers must survive atmospheric transport under a range of temperatures, temperature tolerance should be an important survival mechanism. We tested isolate growth across a range of temperatures (0–35 °C), and found psychrotolerance to be common. Together, our results show that ice depth, and by extension age, are characterized by different types of microorganisms, providing new information about microbial records in ice.
The 2017 plague outbreak in Madagascar was unprecedented in the African region, resulting in 2417 cases (498 confirmed, 793 probable and 1126 suspected) and 209 deaths by the end of the acute urban pneumonic phase of the outbreak. The Health Emergencies Programme of the WHO Regional Office for Africa together with the WHO Country Office and WHO Headquarters assisted the Ministry of Public Health of Madagascar in the rapid implementation of plague prevention and control measures while collecting and analysing quantitative and qualitative data to inform immediate interventions. We document the key findings of the evidence available to date and actions taken as a result. Based on the four goals of operational research – effective dissemination of results, peer-reviewed publication, changes to policy and practice and improvements in programme performance and health – we evaluate the use of evidence to inform response to the outbreak and describe lessons learned for future outbreak responses in the WHO African region. This article may not be reprinted or reused in any way in order to promote any commercial products or services.
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.
Objectives: Chemotherapy has adverse effects on cognitive performance in women treated for breast cancer, but less is known about the period before chemotherapy. Studies have focused on mean level of performance, yet there is increasing recognition that variability in performance within an individual is also an important behavioral indicator of cognitive functioning and underlying neural integrity. Methods: We examined intraindividual variability (IIV) before chemotherapy and surgery in women diagnosed with breast cancer (n=31), and a healthy control group matched on age and education (n=25). IIV was calculated across trials of a computerized Stroop task, including an examination of the slowest and fastest trials of reaction time (RT) responses. Results: The groups were equivalent on overall accuracy and speed, and participants in both groups were less accurate and slower on incongruent trials compared with congruent trials. However, women with breast cancer became more variable with increased task difficulty relative to healthy controls. Among the slowest RT responses, women with breast cancer were significantly more variable than healthy controls on incongruent trials. This suggests that a specific variability-producing process (e.g., attentional lapses) occurs in task conditions that require executive control (e.g., incongruent trials). Conclusions: Results are consistent with other evidence of executive dysfunction among women treated for breast cancer. These findings highlight the importance of pretreatment assessment and show that variability in performance provides information about cognition that measures of central tendency do not. (JINS, 2016, 23, 1–10)
The objective of the present study was to investigate the effect of feeding two transgenic corn lines containing the mCry1Ac gene from Bacillus thuringiensis strain (BT-799) and the maroACC gene from Agrobacterium tumefaciens strain (CC-2), respectively, on growth, egg quality and organ health indicators. Expression of the mCry1Ac gene confers resistance to Pyrausta nubilalis and the maroACC gene confers tolerance to herbicides. Healthy hens (n=96 placed in cages; 3 hens/cage) were randomly assigned to one of four corn–soybean meal dietary treatments (8 cages/treatment) formulated with the following corn: non-transgenic near-isoline control corn (control), BT-799 corn, CC-2 corn and commercially available non-transgenic reference corn (reference). The experiment was divided into three 4-week phases (week 1 to 4, week 5 to 8 and week 9 to 12), during which hens were fed mash diets. Performance (BW, feed intake and egg production) and egg quality were determined. Following slaughter at the end of 12 weeks of feeding (n=8/treatment), carcass yield and organ weights (heart, liver, spleen, lung, kidneys, stomach and ovary) were recorded; organs and intestines were sampled for histological analysis. Analysis of serum biochemistry parameters to assess the liver and kidney function were performed. No differences in BW, egg production and production efficiency were observed between hens consuming the control diet and hens consuming the BT-799 or CC-2 diet. Haugh unit measures and egg component weights were similar between the control and test groups. Carcass yield was not affected by the diet treatment. Similar organosomatic indices and serum parameters did not indicate the characteristics of organ dysfunction. All observed values of the BT-799 and CC-2 groups were within the calculated tolerance intervals. This research indicates that the performance, egg quality, organ health and carcass yield of laying hens fed diets containing the BT-799 or CC-2 corn line were similar to that of laying hens fed diets formulated with the non-transgenic near-isoline corn with comparable genetic backgrounds.
Bipolar disorder is a highly heritable polygenic disorder. Recent
enrichment analyses suggest that there may be true risk variants for
bipolar disorder in the expression quantitative trait loci (eQTL) in the
We sought to assess the impact of eQTL variants on bipolar disorder risk
by combining data from both bipolar disorder genome-wide association
studies (GWAS) and brain eQTL.
To detect single nucleotide polymorphisms (SNPs) that influence
expression levels of genes associated with bipolar disorder, we jointly
analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls)
and a genome-wide brain (cortical) eQTL (193 healthy controls) using a
Bayesian statistical method, with independent follow-up replications. The
identified risk SNP was then further tested for association with
hippocampal volume (n = 5775) and cognitive performance
(n = 342) among healthy individuals.
Integrative analysis revealed a significant association between a brain
eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes
factor = 5.48; bipolar disorder P =
5.85×10–5). Follow-up studies across multiple independent
samples confirmed the association of the risk SNP (rs6088662) with gene
expression and bipolar disorder susceptibility (P =
3.54×10–8). Further exploratory analysis revealed that
rs6088662 is also associated with hippocampal volume and cognitive
performance in healthy individuals.
Our findings suggest that 20q11.22 is likely a risk region for bipolar
disorder; they also highlight the informative value of integrating
functional annotation of genetic variants for gene expression in
advancing our understanding of the biological basis underlying complex
disorders, such as bipolar disorder.
Converging evidence has revealed both functional and structural abnormalities in adolescents with early-onset conduct disorder (EO-CD). The neurological abnormalities underlying EO-CD may be different from that of adolescent-onset conduct disorder (AO-CD) patients. However, the cortical structure in AO-CD patients remains largely unknown. The aim of the present study was to investigate the cortical alterations in AO-CD patients.
We investigated T1-weighted brain images from AO-CD patients and age-, gender- and intelligence quotient-matched controls. Cortical structures including thickness, folding and surface area were measured using the surface-based morphometric method. Furthermore, we assessed impulsivity and antisocial symptoms using the Barratt Impulsiveness Scale (BIS) and the Antisocial Process Screening Device (APSD).
Compared with the controls, we found significant cortical thinning in the paralimbic system in AO-CD patients. For the first time, we observed cortical thinning in the precuneus/posterior cingulate cortex (PCC) in AO-CD patients which has not been reported in EO-CD patients. Prominent folding abnormalities were found in the paralimbic structures and frontal cortex while diminished surface areas were shown in the precentral and inferior temporal cortex. Furthermore, cortical thickness of the paralimbic structures was found to be negatively correlated with impulsivity and antisocial behaviors measured by the BIS and APSD, respectively.
The present study indicates that AO-CD is characterized by cortical structural abnormalities in the paralimbic system, and, in particular, we highlight the potential role of deficient structures including the precuneus and PCC in the etiology of AO-CD.