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We investigate the phased evolution and variation of the South Asian monsoon and resulting weathering intensity and physical erosion in the Himalaya–Karakoram Mountains since late Pliocene time (c. 3.4 Ma) using a comprehensive approach. Neodymium and strontium isotopic compositions and single-grain zircon U–Pb age spectra reveal the sources of the deposits in the east Arabian Sea, and show a combination of sources from the Himalaya and the Karakoram–Kohistan–Ladakh Mountains, with sediments from the Indian Peninsula such as the Deccan Traps or Craton. We interpret shifts in the sediment sources to have been forced by sea-level changes that correlate with South Asian monsoon rainfall variation since late Pliocene time. We collected 908 samples from the International Ocean Discovery Program Hole U1456A, which was drilled in the east Arabian Sea. Time series of hematite content and grain size of the sediments were examined downcore. We found South Asian monsoon precipitation and weathering intensity experienced three phases from late Pliocene time. Lower monsoon precipitation, with a lower variability and strong weathering intensity, occurred during 3.4–2.4 Ma; an increased and more variable South Asian monsoon rainfall, along with strengthened but fluctuating weathering intensity, occurred at 1.8–1.1 Ma; and a reduced rainfall with lower South Asian monsoon precipitation variability and moderate weathering intensity marked the period 1.1–0.1 Ma. Maximum entropy spectral analysis and wavelet transform show that there were orbital-dominated cycles of periods c. 100 and c. 41 ka in these proxy-based time series. We propose that the monsoon, sea level, global temperature and insolation together forced the weathering and erosion in SW Asia.
The Arsenic (+3 oxidation state) methyltransferase (AS3MT) gene has been identified as a top risk gene for schizophrenia in several large-scale genome-wide association studies. A variable number tandem repeat (VNTR) of this gene is the most significant expression quantitative trait locus, but its role in brain activity in vivo is still unknown.
We first performed a functional magnetic resonance imaging (fMRI) scan of 101 healthy subjects during a memory span task, trained all subjects on an adaptive memory span task for 1 month, and finally performed another fMRI scan after the training. After excluding subjects with excessive head movements for one or more scanning sessions, data from 93 subjects were included in the final analyses.
The VNTR was significantly associated with both baseline brain activation and training-induced changes in multiple regions including the prefrontal cortex and the anterior and posterior cingulate cortex. Additionally, it was associated with baseline brain activation in the striatum and the parietal cortex. All these results were corrected based on the family-wise error rate method across the whole brain at the peak level.
This study sheds light on the role of AS3MT gene variants in neural plasticity related to memory span training.
Exosomes derived from hepatocellular carcinoma (HCC) cells are nanovesicles and are involved in the occurrence and development of HCC, they also serve as important carriers and drug targets of nanodrug delivery systems. The external shape and internal structure of exosomes are important indexes of identification, and isolated intact morphology is crucial to biological function integrity. However, given their susceptibility to various influencing factors, the external shape and internal structure of exosomes derived from HCC cells remain incompletely studied. In this study, exosomes purified from HCC cells were isolated at different centrifugation speeds and examined via multiple electron microscopy (EM) techniques. The results demonstrate that exosomes possess a nearly spherical shape and bilipid membranous vesicle with a concave cavity structure containing electron-dense and coated vesicles, suggesting the possible existence of subpopulations of exosomes with specific functions. The exosomes isolated at ultracentrifugation (UC) speed (≥110,000×g) presented irregular and diverse external morphologies, indicating the effect on the integrity of the exosomes. Transforming growth factor signaling bioactive substances (TGF-β1, S100A8, and S100A9) can be found in exosomes by performing Western blotting, showing that the internal content is associated with metastasis of HCC. These findings show that EMelectron microscopy and UC speed can affect exosome characteristics, including external shape, internal structure, and content of bioactive substances. The electron-dense and coated vesicles that had been discovered in exosomes might become new additional morphological features, which could help to improve the interpretation of experimental results and widen our understanding of exosome morphology.
Previous studies of amyloid diseases reported that the aggregating proteins share a similar conserved peptide sequence which can form the cross-β-sheet-containing nanostructures like nanofilaments. The template-assisted self-assembly (TASA) of peptides on inorganic substrates with different hydrophilicity could be an alternative approach to shed light on the fibrillization mechanism of proteins/peptides in vivo. To figure out the effect of interfaces on amyloid aggregation, we herein employed in situ atomic force microscopy (AFM) to investigate the self-assembling of a Parkinson disease-related core peptide sequence (TGV-9) on a hydrophobic liquid–solid interface via real-time observation of the dynamic fibrillization process. The results show that TGV-9 forms one-dimensional nanostructures on the surface of highly ordered pyrolytic graphite (HOPG) with three preferred growth orientations, which are consistent with the atomic lattice of HOPG, indicating an epitaxial growth or TASA. Conversely, the nanostructures formed in bulk solution can be free-standing nanofilaments, and the fibrillization mechanism is different from that on HOPG. These results could not only deepen the understanding of the protein/peptide aggregation mechanism but also benefit for the early diagnosis and clinic treatment of related diseases.
Combinational creativity is a significant element of design in supporting designers to generate creative ideas during the early phases of design. There exists three driven approaches to combinational creativity: problem-, similarity- and inspiration-driven. This study provides further insights into the three combinational creativity driven approaches, exploring which approach could lead to ideas that are more creative in the context of practical product design. The results from a case study reveal that the problem- driven approach could lead to more creative and novel ideas or products compared with the similarity- and inspiration-driven approach. Products originating from the similarity- and inspiration-driven approach are at comparable levels. This study provides better understanding of combinational creativity in practical design. It also delivers benefits to designers in improving creative idea generation, and supports design researchers in exploring future ideation methods and design support tools employing the concept of 'combination'.
This study proposes two multimodal frameworks to classify pathological voice samples by combining acoustic signals and medical records. In the first framework, acoustic signals are transformed into static supervectors via Gaussian mixture models; then, a deep neural network (DNN) combines the supervectors with the medical record and classifies the voice signals. In the second framework, both acoustic features and medical data are processed through first-stage DNNs individually; then, a second-stage DNN combines the outputs of the first-stage DNNs and performs classification. Voice samples were recorded in a specific voice clinic of a tertiary teaching hospital, including three common categories of vocal diseases, i.e. glottic neoplasm, phonotraumatic lesions, and vocal paralysis. Experimental results demonstrated that the proposed framework yields significant accuracy and unweighted average recall (UAR) improvements of 2.02–10.32% and 2.48–17.31%, respectively, compared with systems that use only acoustic signals or medical records. The proposed algorithm also provides higher accuracy and UAR than traditional feature-based and model-based combination methods.
Analogy is a core cognition process used to produce inferences as well as new ideas using previous knowledge and experience. Ontology is a formal representation of a set of domain concepts and their relationships. The use of analogy and ontology in design activities to support design creativity have previously been explored. This paper explores an approach to construct ontologies with sufficient richness and coverage to support reasoning over real-world datasets for prompting creative idea generation. This approach has been implemented into a computational tool for assisting designers in generating creative ideas during the early stages of design. The tool, called “the Retriever”, has been developed based on ontology by embracing the aspects of analogical reasoning. A case study has indicated that the tool can be effective and useful for idea generation. The results have indicated that the tool, in its current formulation, can significantly improve the fluency and flexibility of idea generation and the usefulness of ideas, as well as slightly increase the originality of ideas, for the case study concerned.
Idea generation is significant in design, but coming up with creative ideas is often challenging. This paper presents a computer-based tool, called the Combinator, for assisting designers to produce creative ideas. The tool is developed based on an approach simulating aspects of human cognition in achieving combinational creativity. It can generate combinational prompts in text and image forms through combining unrelated ideas. A case study has been conducted to evaluate the Combinator. The study results indicate that the Combinator, in its current formulation, has assisted the tool users involved in the case study in improving the fluency of idea generation, as well as increasing the originality, usefulness, and flexibility of the ideas generated. The results also indicate that the tool could benefit its users in generating high-novelty and high-quality ideas effectively. The Combinator is considered to be beneficial in expanding the design space, increasing better idea occurrence, improving design space exploration, and enhancing the design success rate.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Crystallized FeB and Fe2B powders were synthesized by a molten salt method with elemental Fe and B powders as starting materials. The results indicated that the presence of molten NaCl/KCl salts and the excess of Fe or B powders were essential to obtain pure FeB or Fe2B powders. The formation mechanism of iron borides was investigated by examining the phase compositions of the obtained products with different molar ratio of Fe/B. It was found that Fe powders firstly reacted with B powders to form Fe2B phase, and FeB phase formed from the reaction between Fe2B and excessive B. The as-synthesized FeB and Fe2B powders had a uniform short-rod and plate like morphology, respectively. Both FeB and Fe2B exhibited typical soft magnetic behavior. The saturation magnetization and the coercivity were 36.4 emu/g and 15.5 kA/m for FeB, 126.9 emu/g and 6.1 kA/m for Fe2B, respectively. The electrochemical performances of the as-synthesized FeB powders were evaluated by cyclic voltammetry, galvanostatic charge–discharge and electrochemical impedance test.
MnOx–CeO2/t-ZrO2 catalyst was prepared by impregnation of nanotetragonal zirconia. The NO conversion of 5 wt% MnOx–CeO2/t-ZrO2 catalyst was 68.1% at 100 °C while that of 30 wt% MnOx–CeO2/t-ZrO2 catalyst was 97.4%. The x-ray diffraction, Brunner–Emmet–Teller measurements (BET), and H2-TPR showed surface properties of the prepared catalysts were good for selective catalytic reduction reactions. X-ray photoelectron spectroscopy analysis indicated that Mn4+ and Ce4+ oxidation states were predominant on the surface of the catalyst and so was lattice oxygen which was conducive to Lewis acid sites. NH3-TPD test results demonstrated that Lewis acid sites are predominant on the surface of catalyst. The presence of SO2 reduced the catalyst activity. The realized conversion dramatically decreased to 47% from nearly 100% after 8 h. Characterization of fresh and spent catalysts indicated the deterioration of active component and deposition of NH4HSO4 or (NH4)2SO4 contribute to SO2 poisoning.
Arctic shipping routes attract more and more attention because of the increasing possibility to build commercial shipping routes which connect East Asia and Western Europe. To build profitable commercial shipping routes, shipping companies should study many issues about the Arctic carefully since it is a new and unfamiliar frontier. To find out key factors influencing the building of Arctic shipping routes, the authors applied the fuzzy Analytic Hierarchy Process (AHP) model in this study. Based on the AHP experts’ questionnaires, we applied the fuzzy AHP model to analyse the opinions of respondents. This article presents the results of an empirical survey conducted among shipping companies and academic researchers with ship captain experience to explore their attitudes toward the building of Arctic shipping routes. The findings showed that: ‘Safety and risk’ is the most important aspect affecting the building of Arctic shipping routes and in order of relative importance, the top six critical assessment factors are ‘navigation safety and risk analysis,’ ‘governance and cooperation,’ ‘navigation information,’ ‘cargo sources,’ ‘cost,’ and ‘navigator ability,’ respectively.
The present study was performed to identify the genotype of a hypertrophic cardiomyopathy family and investigate the clinicopathogenic characteristics and prognostic features of relevant genetic abnormalities. Target sequence capture sequencing was performed to screen for pathogenic alleles in a 32-year-old female patient (proband). Sanger sequencing was carried out to verify the results. Sanger sequencing was also performed on other family members to identify allele carriers. A survival analysis was carried out using published literature and our findings. We found that the proband and her son harboured a Gly716Arg sequence variant of the β-myosin heavy chain. Neither the proband’s father nor the mother were carriers of this sequence variant; thus, the mutation was classified as “de novo”. Further survival analysis revealed that female patients appear to have a longer life expectancy compared with males. Our study may provide an effective approach for the genetic diagnosis of hypertrophic cardiomyopathy.
Psychiatric disorders such as schizophrenia and major depressive disorder
(MDD) are likely to be caused by multiple susceptibility genes, each with
small effects in increasing the risk of illness. Identifying DNA variants
associated with schizophrenia and MDD is a crucial step in understanding
the pathophysiology of these disorders.
To investigate whether the SP4 gene plays a significant
role in schizophrenia or MDD in the Han Chinese population.
We focused on nine single nucleotide polymorphisms (SNPs) harbouring the
SP4 gene and carried out case–control studies in 1235
patients with schizophrenia, 1045 patients with MDD and 1235 healthy
controls recruited from the Han Chinese population.
We found that rs40245 was significantly associated with schizophrenia in
both allele and genotype distributions (Pallele = 0.0005, Pallele = 0.004 after Bonferroni correction; Pgenotype = 0.0023, Pgenotype = 0.0184 after Bonferroni correction). The rs6461563
SNP was significantly associated with schizophrenia in the allele
distributions (Pallele = 0.0033, Pallele = 0.0264 after Bonferroni correction).
Our results suggest that common risk factors in the SP4
gene are associated with schizophrenia, although not with MDD, in the Han
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
The microstructural evolution of spray-formed high speed steel during hot deformation was investigated as well as the effects of spray forming parameters on the porosity formation. Four distinct zones are identified in the as-deposited material, and interstitial porosity is present in the bottom and peripheral zones, while gas-related porosity is mainly found in the central zone. It can keep the porosity at a minimum value by using the optimum parameters, e.g., the average porosity of central zone is 3.7% for a superheat of 170 °C and a gas-to-metal flow rate of 0.7. During hot deformation at 1150 °C, the amount of porosity can be obviously decreased by increasing the height reduction which also plays a key role in breaking up eutectic carbides. The critical height reduction for the breakdown of the eutectic carbides is 50%, the dominant mechanism being mechanical fragmentation.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
To examine the vitamin D status, SNP of the vitamin D receptor gene (VDR) and the effects of vitamin D supplementation on parathyroid hormone and insulin secretion in adult males with obesity or normal weight in a subtropical Chinese city.
An intervention trial.
Shenzhen City, Guangdong Province, China.
From a cross-sectional survey conducted from June to July, eighty-two normal-weight and ninety-nine obese males (18–69 years) were screened to analyse their vitamin D status and for five SNP of VDR. From these individuals, in the same season of a different year, obese and normal-weight male volunteers (twenty-one per group) were included for an intervention trial with oral vitamin D supplementation at 1250 µg/week for 8 weeks.
For the survey, there was no significant difference (P>0·05) in baseline circulating 25-hydroxyvitamin D concentrations or in the percentages of participants in different categories of vitamin D status between the two groups. The VDR SNP, rs3782905, was significantly associated with obesity (P=0·043), but none of the examined SNP were correlated with serum 25-hydroxyvitamin D when adjusted for age, BMI and study group. After vitamin D supplementation, serum 25-hydroxyvitamin D concentration, hypersecretions of parathyroid hormone and insulin, and insulin resistance in the obese were changed beneficially (P<0·05); however, the increase in serum 25-hydroxyvitamin D was less than that of the normal-weight men.
For obese and normal-weight men of subtropical China, the summer baseline vitamin D status was similar. However, oral vitamin D supplementation revealed a decreased bioavailability of vitamin D in obese men and ameliorated their hypersecretion of parathyroid hormone and insulin resistance.
In the past 10 years, under the common problems of unemployment of people with a higher education and the devaluation of diplomas, the concepts and practices of higher education governance have emerged and have gradually been embedded in university operations. Higher education in Taiwan faces the same problems as the rest of the world. Thus, guided by policies of the Taiwanese Ministry of Education (TMOE) and fuelled by the media, the education-job gap is becoming a discursive truth. With this background, the TMOE has invested numerous resources to establish an information system (IS) that attempts to guide the direction of university education using information technology. If the IS is poorly designed, the scope of its side effects and harm will be magnified by a massive number of IS users and the characteristics of procedure standardisation. We suggest another form of action — IS competition, in which more positive social changes can be created. Based on the analysis of the available data, the action of IS competition does have a positive impact on society.