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Across Eurasia, horse transport transformed ancient societies. Although evidence for chariotry is well dated, the origins of horse riding are less clear. Techniques to distinguish chariotry from riding in archaeological samples rely on elements not typically recovered from many steppe contexts. Here, the authors examine horse remains of Mongolia's Deer Stone-Khirigsuur (DSK) Complex, comparing them with ancient and modern East Asian horses used for both types of transport. DSK horses demonstrate unique dentition damage that could result from steppe chariotry, but may also indicate riding with a shallow rein angle at a fast gait. A key role for chariots in Late Bronze Age Mongolia helps explain the trajectory of horse use in early East Asia.
ABSTRACT IMPACT: Screening the effect of thousands of non-coding genetic variants will help identify variants important in the etiology of diseases OBJECTIVES/GOALS: Massively parallel reporter assays (MPRAs) can experimentally evaluate the impact of genetic variants on gene expression. In this study, our objective was to systematically evaluate the functional activity of 3’-UTR SNPs associated with neurological disorders and use those results to help understand their contributions to disease etiology. METHODS/STUDY POPULATION: To choose variants to evaluate with the MPRA, we first gathered SNPs from the GWAS Catalog that were associated with any neurological disorder trait with p-value < 10-5. For each SNP, we identified the region that was in linkage disequilibrium (r2 > 0.8) and retrieved all the common 3’-UTR SNPs (allele-frequency > 0.05) within that region. We used an MPRA to measure the impact of these 3’-UTR variants in SH-SY5Y neuroblastoma cells and a microglial cell line. These results were then used to train a deep-learning model to predict the impact of variants and identify features that contribute to the predictions. RESULTS/ANTICIPATED RESULTS: Of the 13,515 3’-UTR SNPs tested, 400 and 657 significantly impacted gene expression in SH-SY5Y and microglia, respectively. Of the 84 SNPs significantly impacted in both cells, the direction of impact was the same in 81. The direction of eQTL in GTEx tissues agreed with the assay SNP effect in SH-SY5Y cells but not microglial cells. The deep-learning model predicted sequence activity level correlated with the experimental activity level (Spearman’s corr = 0.45). The deep-learning model identified several predictive motifs similar to motifs of RNA-binding proteins. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study demonstrates that MPRAs can be used to evaluate the effect of non-coding variants, and the results can be used to train a machine learning model and interpret its predictions. Together, these can help identify causal variants and further understand the etiology of diseases.
The rotating instability in a contra-rotating axial flow compressor is investigated by experiments. Twenty-four pressure sensors were installed on the casing to capture the unsteady flow in the rotor tip region simultaneously. A double-phase-locking technique suitable for the contra-rotating compressor was proposed to characterise the static pressure contours of the rotor tip. The mean and root-mean-square pressure contours indicate that rotating instability occurs before the rotating stall happened, and the rotor tip clearance vortex is located upstream of the rear rotor leading edge plane before stall. Fourier spectrum shows that rotating instability and rotating stall both happened under the stall condition, and the frequency band of rotating instability does not change with the flow rate. In the front rotor, the frequency of rotating instability is half of the blade passing frequency. It is verified that the modal estimation method can be implemented by using the average azimuthal phase velocity, which significantly reduced the number of pressure sensors required. Modal estimation results show that each peak of the rotating instability frequency band corresponds to a unique dominant circumferential mode. By optimising average azimuthal phase velocity, an improved modal estimation method is obtained, which can further improve the reliability of the modal estimation results.
This study investigated the latent factor structure of the NIH Toolbox Cognition Battery (NIHTB-CB) and its measurement invariance across clinical diagnosis and key demographic variables including sex, race/ethnicity, age, and education for a typical Alzheimer’s disease (AD) research sample.
The NIHTB-CB iPad English version, consisting of 7 tests, was administered to 411 participants aged 45–94 with clinical diagnosis of cognitively unimpaired, dementia, mild cognitive impairment (MCI), or impaired not MCI. The factor structure of the whole sample was first examined with exploratory factor analysis (EFA) and further refined using confirmatory factor analysis (CFA). Two groups were classified for each variable (diagnosis or demographic factors). The confirmed factor model was next tested for each group with CFA. If the factor structure was the same between the groups, measurement invariance was then tested using a hierarchical series of nested two-group CFA models.
A two-factor model capturing fluid cognition (executive function, processing speed, and memory) versus crystalized cognition (language) fit well for the whole sample and each group except for those with age < 65. This model generally had measurement invariance across sex, race/ethnicity, and education, and partial invariance across diagnosis. For individuals with age < 65, the language factor remained intact while the fluid cognition was separated into two factors: (1) executive function/processing speed and (2) memory.
The findings mostly supported the utility of the battery in AD research, yet revealed challenges in measuring memory for AD participants and longitudinal change in fluid cognition.
To evaluate the validity and reproducibility of a 152-item semi-quantitative FFQ (SFFQ) for estimating flavonoid intakes.
Over a 1-year period, participants completed two SFFQ and two weighed 7-d dietary records (7DDR). Flavonoid intakes from the SFFQ were estimated separately using Harvard (SFFQHarvard) and Phenol-Explorer (SFFQPE) food composition databases. 7DDR flavonoid intakes were derived using the Phenol-Explorer database (7DDRPE). Validity was assessed using Spearman’s rank correlation coefficients deattenuated for random measurement error (rs), and reproducibility was assessed using rank intraclass correlation coefficients.
This validation study included primarily participants from two large observational cohort studies.
Six hundred forty-one men and 724 women.
When compared with two 7DDRPE, the validity of total flavonoid intake assessed by SFFQPE was high for both men and women (rs = 0·77 and rs = 0·74, respectively). The rs for flavonoid subclasses ranged from 0·47 for flavones to 0·78 for anthocyanins in men and from 0·46 for flavonols to 0·77 for anthocyanins in women. We observed similarly moderate (0·4–0·7) to high (≥0·7) validity when using SFFQHarvard estimates, except for flavonesHarvard (rs = 0·25 for men and rs = 0·19 for women). The SFFQ demonstrated high reproducibility for total flavonoid and flavonoid subclass intake estimates when using either food composition database. The intraclass correlation coefficients ranged from 0·69 (flavonolsPE) to 0·80 (proanthocyanidinsPE) in men and from 0·67 (flavonolsPE) to 0·77 (flavan-3-ol monomersHarvard) in women.
SFFQ-derived intakes of total flavonoids and flavonoid subclasses (except for flavones) are valid and reproducible for both men and women.
Thermal barrier coating is a high-temperature protective technology widely used in industrial gas turbines. However, the failure of coating peeling because of the generation of thermally grown oxide (TGO) at the interface during service hinders its further application. In this study, Raman spectroscopy and wedge indentation are used to determine the TGO residual stress and the interface energy release rate, respectively. The effect of TGO on the interfacial fracture toughness during the growth process was discussed. Raman spectroscopy test results show that the residual stress of TGO is about 0.5 GPa. Wedge indentation test results illustrate that high-temperature heat treatment could accelerate the interface degradation of thermal barrier coatings. Stress analysis and test research demonstrate that the microcracks induced by compressive stress of TGO will propagate with increasing heating time, ending with failure of barrier coatings.
Schizophrenia is one of the most severe and chronic forms of mental illness. Quantum resonance spectrometer (QRS) test may be useful as a biological marker for the clinical diagnosis of psychiatric disorders of Schizophrenia.
To evaluate reliability and psychiatric clinical value of QRS via thought disorder detection.
We studied 1014 schizophrenic patients, 155 patients with bipolar disorders patient, and 100 normal controls. Thought disorder symptoms of same subjects obtained from QRS test and psychiatrists' diagnoses were compared. Also Thought disorder symptoms of renumbered 65 schizophrenia patient and 100 normal controls were discriminated using QRS test.
Kappa values of thought disorders detection and diagnosed were more than 65% in 6/9 symptoms of schizophrenia, and more than 74% in all 3 symptoms of bipolar disorder. Same consistency could also be seen in Pearson R value, and ROC AUC. In the discriminated analysis, sensitivity, specificity, positive predictive value and negative predictive of delusion, looseness of thought and paralogism thinking detected utilizing QRS are more than 70% same compared with psychiatrists diagnoses.
QRS in thought disorder detection seem to have a predictable value for outcome in schizophrenia and bipolar disorder, would become an objective identification and diagnosis instrument, and might promote psychiatric clinical diagnosis.
Major depressive disorder (MDD) is the second leading cause of disability in China.
To analyze functioning during the course of treating MDD in China, Taiwan and Hong Kong.
To study the influence of pain and clinical remission on functioning.
This was a post-hoc analysis of a 6-month, prospective, observational study (n = 909) with 422 patients enrolled from China (n = 205; 48.6%), Taiwan (n = 199; 47.2%) and Hong Kong (n = 18; 4.2%). Functioning was measured with the Sheehan Disability Scale (SDS), pain with the Somatic Symptom Inventory, and severity of depression with the Quick Inventory of Depressive Symptomatology-Self Report 16 (QIDS). Patients were classified as having no pain, persistent pain (pain at any visit) or remitted pain (pain only at baseline). A mixed model with repeated measures was fitted to analyze the relationship between pain and functioning.
At baseline, 40% of the patients had painful physical symptoms. Patients with pain had a higher QIDS and lower SDS (P < 0.05) at baseline. At 6 months, patients with persistent pain had lower functioning (P < 0.05). The regression model confirmed that clinical remission was associated with higher functioning at endpoint and that patients with persistent pain had lower functioning at endpoint when compared with the no pain group.
Patients presenting with pain symptoms had lower functioning at baseline. At 6 months, pain persistence was associated with significantly lower functioning as measured by the SDS. Clinical remission was associated with better functional outcomes. The course of pain was related to the likelihood of achieving remission.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Muscle fiber characteristics comprise a set of complex traits that influence the meat quality and lean meat production of livestock. However, the genetic and biological mechanisms regulating muscle fiber characteristics are largely unknown in pigs. Based on a genome-wide association study (GWAS) performed on 421 Large White × Min pig F2 individuals presenting well-characterized phenotypes, this work aimed to detect genome variations and candidate genes for five muscle fiber characteristics: percentage of type I fibers (FIB1P), percentage of type IIA fibers (FIB2AP), percentage of type IIB fibers (FIB2BP), diameter of muscle fibers (DIAMF) and number of muscle fibers per unit area (NUMMF). The GWAS used the Illumina Porcine SNP60K genotypic data, which were analyzed by a mixed model. Seven and 10 single nucleotide polymorphisms (SNPs) were significantly associated with DIAMF and NUMMF, respectively (P < 1.10E-06); no SNP was significantly associated with FIB1P, FIB2AP or FIB2B. For DIAMF, the significant SNPs on chromosome 4 were located in the previously reported quantitative trait loci (QTL) interval. Because the significant SNPs on chromosome 6 were not mapped in the previously reported QTL interval, a putative novel QTL was suggested for this locus. None of the previously reported QTL intervals on chromosomes 6 and 14 harbored significant SNPs for NUMMF; thus, new potential QTLs on these two chromosomes are suggested in the present work. The most significant SNPs associated with DIAMF (ALGA0025682) and NUMMF (MARC0046984) explained 12.02% and 11.59% of the phenotypic variation of these traits, respectively. In addition, both SNPs were validated as associated with DIAMF and NUMMF in Beijing Black pigs (P < 0.01). Some candidate genes or non-coding RNAs, such as solute carrier family 44 member 5 and miR-124a-1 for DIAMF, and coiled-coil serine rich protein 2 for NUMMF, were identified based on their close location to the significant SNPs. This study revealed some genome-wide association variants for muscle fiber characteristics, and it provides valuable information to discover the genetic mechanisms controlling these traits in pigs.
Determine the effectiveness of a personal protective equipment (PPE)-free zone intervention on healthcare personnel (HCP) entry hand hygiene (HH) and PPE donning compliance in rooms of patients in contact precautions.
Quasi-experimental, multicenter intervention, before-and-after study with concurrent controls.
All patient rooms on contact precautions on 16 units (5 medical-surgical, 6 intensive care, 5 specialty care units) at 3 acute-care facilities (2 academic medical centers, 1 Veterans Affairs hospital). Observations of PPE donning and entry HH compliance by HCP were conducted during both study phases. Surveys of HCP perceptions of the PPE-free zone were distributed in both study phases.
A PPE-free zone, where a low-risk area inside door thresholds of contact precautions rooms was demarcated by red tape on the floor. Inside this area, HCP were not required to wear PPE.
We observed 3,970 room entries. HH compliance did not change between study phases among intervention units (relative risk [RR], 0.92; P = .29) and declined in control units (RR, 0.70; P = .005); however, the PPE-free zone did not significantly affect compliance (P = .07). The PPE-free zone effect on HH was significant only for rooms on enteric precautions (P = .008). PPE use was not significantly different before versus after the intervention (P = .15). HCP perceived the zone positively; 65% agreed that it facilitated communication and 66.8% agreed that it permitted checking on patients more frequently.
HCP viewed the PPE-free zone favorably and it did not adversely affect PPE or HH compliance. Future infection prevention interventions should consider the complex sociotechnical system factors influencing behavior change.
Two phases of diabase-sill-forming magmatism are recorded within the Badu anticline where magmas were emplaced into upper Palaeozoic carbonates and clastic rocks of the Youjiang fold-and-thrust belt in the SW South China Block, China. Zircons from these diabase units yield weighted mean U–Pb ages of 249.2±2.0 Ma and 187.1±3.3 Ma, and magmatic oxygen fugacity values from ‒20 to ‒6 (average of ‒12, equating to FMQ +5) and ‒20 to ‒10 (average of ‒15, equating to FMQ +2), respectively. These data indicate that the sills were emplaced during Early Triassic and Early Jurassic times. The discovery of c. 250 Ma mafic magmatism in this area was probably related to post-flood-basalt extension associated with the Emeishan mantle plume or rollback of the subducting Palaeo-Tethys slab. The c. 190 Ma diabase sills indicate that the southwestern South China Block records Early Jurassic mafic magmatism and lithospheric extension that was likely associated with a transition from post-collisional to within-plate tectonic regimes. The emplacement of diabase intrusions at depth may have driven hydrothermal systems, enabling the mobilization of elements from sedimentary rocks and causing the formation of a giant epigenetic metallogenic domain. The results indicate that high-oxygen-fugacity materials within basement rocks caused crustal contamination of the magmas, contributing to the wide range of oxygen fugacity conditions recorded by the Au-bearing Badu diabase. In addition, data from inherited xenocrystic zircons within the Badu diabase and detrital zircons from basement rocks suggest that the Neoproterozoic Jiangshao suture extends to the south of the Badu anticline.
This article focus on the rigid-liquid coupling dynamics of the spacecraft with arbitrary axisymmetrical tanks with curved walls and top. The carrier velocity potential function was obtained according to the motion equations of a representative point in the tank of spacecraft, and the relative velocity potential function can be expressed as Gauss hypergeometric series. The Hamilton's variational principle was applied to derive the governing equations of liquid sloshing based on the profile of hydrostatic shape of free liquid surface. The dynamic equations of modal coordinates were established through the Galerkin method. The state equations of coupled motion of main rigid platform of the spacecraft were deduced by using the Lagrange's equations in term of general quasi-coordinates. Thruster firing was actuated to the coupled system to analyze the rigid-liquid coupled dynamic behaviors. Computer numerical simulations was carried out to confirm the validity of the method developed in this paper.
This paper focuses on the attitude dynamics and control of liquid filled spacecraft, and the large amplitude fuel slosh dynamics is included by using an improved moving pulsating ball model. The moving pulsating ball model is an equivalent mechanical model that is capable of imitating the whole liquid reorientation process, specifically for the occurrence of large amplitude slosh. This model is improved by incorporating a static capillary force and an effective mass factor. The improvements on this model are validated with previously published experiment results. The spacecraft attitude maneuver is implemented by the momentum transfer technique, and the feedback control strategy is designed based on Lyapunov theory. The effects of liquid viscosity, tank location and desired steady time on sloshing torque and control torque are investigated. The attitude control strategy applied in this paper is proved to be applicable for the coupled liquid filled spacecraft system. The obtained conclusions are useful to aid in liquid filled spacecraft overall design.
Studies of the end-Permian mass extinction have suggested a variety of patterns from a single catastrophic event to multiple phases. But most of these analyses have been based on fossil distributions from single localities. Although single sections may simplify the interpretation of species diversity, they are susceptible to bias from stratigraphic incompleteness and facies control of preservation. Here we use a data set of 1450 species from 18 fossiliferous sections in different paleoenvironmental settings across South China and the northern peri-Gondwanan region, and integrate it with high-precision geochronologic data to evaluate the rapidity of the largest Phanerozoic mass extinction. To reduce the Signor-Lipps effect, we applied constrained optimization (CONOP) to search for an optimal sequence of first and last occurrence datums for all species and generate a composite biodiversity pattern based on multiple sections. This analysis indicates that an abrupt extinction of 62% of species took place within 200 Kyr. The onset of the sudden extinction is around 252.3 Ma, just below Bed 25 at the Meishan section. Taxon turnover and diversification rates suggest a deterioration of the living conditions nearly 1.2 Myr before the sudden extinction. The magnitude of the extinction was such that there was no immediate biotic recovery. Prior suggestions of highly variable, multi-phased extinction patterns reflect the impact of the Signor-Lipps effect and facies-dependent occurrences, and are not supported following appropriate statistical treatment of this larger data set.
The protective effects of dietary pyrroloquinoline quinone disodium (PQQ.Na2) supplementation against oxidized sunflower oil-induced oxidative stress and liver injury in laying hens were examined. Three hundred and sixty 53-week-old Hy-Line Gray laying hens were randomly allocated into one of the five dietary treatments. The treatments included: (1) a diet containing 2% fresh sunflower oil; (2) a diet containing 2% thermally oxidized sunflower oil; (3) an oxidized sunflower oil diet with 100 mg/kg of added vitamin E; (4) an oxidized sunflower oil diet with 0.08 mg/kg of PQQ.Na2; and (5) an oxidized sunflower oil diet with 0.12 mg/kg of PQQ.Na2. Birds fed the oxidized sunflower oil diet showed a lower feed intake compared to birds fed the fresh oil diet or oxidized oil diet supplemented with vitamin E (P=0.009). Exposure to oxidized sunflower oil increased plasma malondialdehyde (P<0.001), hepatic reactive oxygen species (P<0.05) and carbonyl group levels (P<0.001), but decreased plasma glutathione levels (P=0.006) in laying hens. These unfavorable changes induced by the oxidized sunflower oil diet were modulated by dietary vitamin E or PQQ.Na2 supplementation to levels comparable to the fresh oil group. Dietary supplementation with PQQ.Na2 or vitamin E increased the activities of total superoxide dismutase and glutathione peroxidase in plasma and the liver, when compared with the oxidized sunflower oil group (P<0.05). PQQ.Na2 or vitamin E diminished the oxidized sunflower oil diet induced elevation of liver weight (P=0.026), liver to BW ratio (P=0.001) and plasma activities of alanine aminotransferase (P=0.001) and aspartate aminotransferase (P<0.001) and maintained these indices at the similar levels to the fresh oil diet. Furthermore, oxidized sunflower oil increased hepatic DNA tail length (P<0.05) and tail moment (P<0.05) compared with the fresh oil group. Dietary supplementation of PQQ.Na2 or vitamin E decreased the oxidized oil diet induced DNA tail length and tail moment to the basal levels in fresh oil diet. These results indicate that PQQ.Na2 is a potential antioxidant and is as effective against oxidized oil-related liver injury in laying hens as vitamin E. The protective effects of PQQ.Na2 against liver damage induced by oxidized oil may be partially due to its role in the scavenging of free radicals, inhibiting of lipid peroxidation and enhancing of antioxidant defense systems.
Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.
Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine–phosphate–guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine–phosphate–guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.