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To investigate the influences of cobalt (Co) and folic acid (FA) on growth performance and rumen fermentation, Holstein male calves (n 40) were randomly assigned to four groups according to their body weights. Cobalt sulphate at 0 or 0·11 mg Co/kg DM and FA at 0 or 7·2 mg/kg DM were used in a 2 × 2 factorial design. Average daily gain was elevated with FA or Co supplementation, but the elevation was greater for supplementing Co in diets without FA than with FA. Supplementing FA or Co increased DM intake and total-tract nutrient digestibility. Rumen pH was unaltered with FA but reduced with Co supplementation. Concentration of rumen total volatile fatty acids was elevated with FA or Co inclusion. Acetate percentage and acetate to propionate ratio were elevated with FA inclusion. Supplementing Co decreased acetate percentage and increased propionate percentage. Activities of xylanase and α-amylase and populations of total bacteria, fungi, protozoa, Ruminococcus albus, Fibrobacter succinogenes and Prevotella ruminicola increased with FA or Co inclusion. Activities of carboxymethyl-cellulase and pectinase increased with FA inclusion and population of methanogens decreased with Co addition. Blood folates increased and homocysteine decreased with FA inclusion. Blood glucose and vitamin B12 increased with Co addition. The data suggested that supplementing 0·11 mg Co/kg DM in diets containing 0·09 mg Co/kg DM increased growth performance and nutrient digestibility but had no improvement on the effects of FA addition in calves.
The Upper Triassic Xujiahe Formation is a typical tight gas reservoir in which natural fractures determine the migration, accumulation and production capacity of tight gas. In this study, we focused on the influences of natural fractures on the tight gas migration and production. We clarified characteristics and attributes (i.e. dips, apertures, filling degree and cross-cutting relationships) of the fractures based on image logging interpretations and core descriptions. Previous studies of electron spin resonance, carbon and oxygen isotopes, homogenization temperature of fluid inclusions analysis and basin simulation were considered. This study also analysed the fracture sequences, source of fracture fillings, diagenetic sequences and tight gas enrichment stages. We obtained insight into the relationship between fracture evolution and hydrocarbon charging, particularly the effect of the apertures and intensity of natural fractures on tight gas production. We reveal that the bedding fractures are short horizontal migration channels of tight gas. The tectonic fractures with middle, high and nearly vertical angles are beneficial to tight gas vertical migration. The apertures of fractures are controlled by the direction of maximum principal stress and fracture angle. The initial gas production of the vertical wells presents a positive correlation with the fracture abundance, and the intensity and aperture of fractures are the fundamental factors that determine the tight gas production. With these findings, this study is expected to guide the future exploration and development of tight gas with similar geological backgrounds.
Extreme wave runup around a simplified representative floating production, storage and offloading vessel hull with a vertical bow is studied using computational fluid dynamics, complemented by experimental and diffraction analysis. This is a highly nonlinear system involving large vessel motions and extreme surface waves, and the behaviour is important for offshore design and operations. A separation method based on phase manipulation is carried out to facilitate the extraction of harmonics associated with the Stokes expansion of nonlinear waves. The separation method is applied to numerical and experimental data, and found to work well even for a highly nonlinear wave field scattered from a freely floating ship-shaped body. It is found that both low- and high-frequency second harmonic components can lead to wave runup at significantly higher levels than predicted by a linear analysis, while the vessel motions are very close to linear. The nonlinearity in the local wave field rather than vessel motion is key for the excitation of nonlinear extreme runup.
Hypertension represents one of the most common pre-existing conditions and comorbidities in Coronavirus disease 2019 (COVID-19) patients. To explore whether hypertension serves as a risk factor for disease severity, a multi-centre, retrospective study was conducted in COVID-19 patients. A total of 498 consecutively hospitalised patients with lab-confirmed COVID-19 in China were enrolled in this cohort. Using logistic regression, we assessed the association between hypertension and the likelihood of severe illness with adjustment for confounders. We observed that more than 16% of the enrolled patients exhibited pre-existing hypertension on admission. More severe COVID-19 cases occurred in individuals with hypertension than those without hypertension (21% vs. 10%, P = 0.007). Hypertension associated with the increased risk of severe illness, which was not modified by other demographic factors, such as age, sex, hospital geological location and blood pressure levels on admission. More attention and treatment should be offered to patients with underlying hypertension, who usually are older, have more comorbidities and more susceptible to cardiac complications.
We investigated motor cortical excitability (CE) in unilateral temporal lobe epilepsy (TLE) and its relationship to bilateral tonic-clonic seizure (BTCS) using paired-pulse transcranial magnetic stimulation (TMS).
In this cross-sectional study, we enrolled 46 unilateral TLE patients and 16 age-and sex-matched healthy controls. Resting motor thresholds (RMT); short-interval intracortical inhibition (SICI, GABAA receptor-mediated); facilitation (ICF, glutamatergic-mediated) with interstimulus intervals (ISIs) of 2, 5, 10, and 15 ms; and long-interval intracortical inhibition (LICI, GABAB receptor-mediated) with ISIs of 200–400 ms were measured via paired-pulse TMS. Comparisons were made between controls and patients with TLE, and then among the TLE subgroups (no BTCS, infrequent BTCS and frequent BTCS subgroup).
Compared with controls, TLE patients had higher RMT, lower SICI and higher LICI in both hemispheres, and higher ICF in the ipsilateral hemisphere. In patients with frequent BTCS, cortical hyperexcitability in the ipsilateral hemisphere was found in a parameter-dependent manner (SICI decreased at a stimulation interval of 5 ms, and ICF increased at a stimulation interval of 15 ms) compared with patients with infrequent or no BTCS.
Our results demonstrate that motor cortical hyper-excitability in the ipsilateral hemisphere underlies the epileptogenic network of patients with active BTCS, which is more extensive than those with infrequent or no BTCS.
Findings for the roles of dairy products, Ca and vitamin D on ovarian cancer risk remain controversial. We aimed to assess these associations by using an updated meta-analysis. Five electronic databases (e.g. PubMed and Embase) were searched from inception to 24 December 2019. Pooled relative risks (RR) with 95 % CI were calculated. A total of twenty-nine case–control or cohort studies were included. For comparisons of the highest v. lowest intakes, higher whole milk intake was associated with increased ovarian cancer risk (RR 1·35; 95 % CI 1·15, 1·59), whereas decreased risks were observed for higher intakes of low-fat milk (RR 0·84; 95 % CI 0·73, 0·96), dietary Ca (RR 0·71; 95 % CI 0·60, 0·84) and dietary vitamin D (RR 0·80; 95 % CI 0·67, 0·95). Additionally, for every 100 g/d increment, increased ovarian cancer risks were found for total dairy products (RR 1·03; 95 % CI 1·01, 1·04) and for whole milk (RR 1·07; 95 % CI 1·03, 1·11); however, decreased risks were found for 100 g/d increased intakes of low-fat milk (RR 0·95; 95 % CI 0·91, 0·99), cheese (RR 0·87; 95 % CI 0·76, 0·98), dietary Ca (RR 0·96; 95 % CI 0·95, 0·98), total Ca (RR 0·98; 95 % CI 0·97, 0·99), dietary vitamin D (RR 0·92; 95 % CI 0·87, 0·97) and increased levels of circulating vitamin D (RR 0·84; 95 % CI 0·72, 0·97). These results show that whole milk intake might contribute to a higher ovarian cancer risk, whereas low-fat milk, dietary Ca and dietary vitamin D might reduce the risk.
The aim of this study was to evaluate long-term survival and risk factors associated with multidrug-resistant tuberculosis (MDR-TB) patient survival in Central China. Between December 2006 and June 2011, incident and retreatment adult MDR-TB patients were enrolled in the present study. Cox proportional hazard regression analysis was used to evaluate the risk factors affecting survival. The total follow-up period was 270 person-years (PY) for 356 MDR-TB cases in Wuhan. Of the 356 cases, 103 patients died, yielding an average case fatality rate of 381.2 per 1000 TB patients per year. Using adjusted Cox regression analysis, older age (adjusted hazard ratio (aHR) >3.0 starting from 30 years) and low education level (primary and middle school; aHR 1.67 (95% CI 1.01–2.77)) were independently associated with lower survival. Diabetes mellitus profoundly affected the survival of MDR-TB patients (aHR 1.95 (95% CI 1.30–2.93)). Our data demonstrate that coexistent diabetes significantly and negatively impacted MDR-TB patient survival. In addition, MDR-TB patients aged 60 years or older exhibited a greater risk of mortality during follow-up. Our findings emphasise that MDR-TB patients with comorbidities that increase their risk of death require additional medical interventions to reduce mortality.
Cognitive impairment in late-life depression is common and associated with a higher risk of all-cause dementia. Late-life depression patients with comorbid cardiovascular diseases (CVDs) or related risk factors may experience higher risks of cognitive deterioration in the short term. We aim to investigate the effect of CVDs and their related risk factors on the cognitive function of patients with late-life depression.
A total of 148 participants were recruited (67 individuals with late-life depression and 81 normal controls). The presence of hypertension, coronary heart disease, diabetes mellitus, or hyperlipidemia was defined as the presence of comorbid CVDs or related risk factors. Global cognitive functions were assessed at baseline and after a one-year follow-up by the Mini-Mental State Examination (MMSE). Global cognitive deterioration was defined by the reliable change index (RCI) of the MMSE.
Late-life depression patients with CVDs or related risk factors were associated with 6.8 times higher risk of global cognitive deterioration than those without any of these comorbidities at a one-year follow-up. This result remained robust after adjusting for age, gender, and changes in the Hamilton Depression Rating Scale (HAMD) scores.
This study suggests that late-life depression patients with comorbid CVDs or their related risk factors showed a higher risk of cognitive deterioration in the short-term (one-year follow up). Given that CVDs and their related risk factors are currently modifiable, active treatment of these comorbidities may delay rapid cognitive deterioration in patients with late-life depression.
Vetulicolians are a group of exclusively Cambrian animals characterized by an anterior section with lateral pouches and a posterior section that appears segmented. The precise phylogenetic affinity of vetulicolians is debated because there is a lack of consensus regarding the interpretation of their anatomical features. Their disparate morphology might even cause one to question whether this is a monophyletic taxon. In total, there are 15 species grouped into three families included in vetulicolians. Here we focus on new specimens of Yuyuanozoon magnificissimi Chen, Feng, and Zhu in Chen et al., 2003, a species that was first described from only a single specimen from the Chengjiang Biota (Cambrian Series 2, Stage 3, Eoredlichia-Wutingaspis trilobite Biozone), Yunnan Province, China. The species is notable in being exceptionally large (up to 20 cm long). Morphological observations on the new specimens clarify the nature of the wide circular opening at the presumed anterior end of the animal and the cowl-shaped lateral openings within this anterior section. Taphonomic observations identify wrinkles in the anterior section and twists in the posterior segmented section. In particular, the shape of the anterior opening of Yuyuanozoon magnificissimi suggests significant differences from other vetulicolians. Taxonomic reappraisal of Y. magnificissimi indicates that it belongs within the family Didazoonidae, as that is presently defined.
Neoseiulus barkeri (HUGHES) is the natural enemy of spider mites, whiteflies and thrips. Screening for chemically-resistant predatory mites is a practical way to balance the contradiction between the pesticide using and biological control. In this study, the number of eggs laid by fenpropathrin-susceptible and resistant strains of N. barkeri was compared. Additionally, we cloned three N. barkeri vitellogenin (Vg) genes and used quantitative real-time polymerase chain reaction to quantify Vg expression in susceptible and resistant strains. The total number of eggs significantly increased in the fenpropathrin-resistant strain. The full-length cDNA cloning of three N. barkeri Vg genes (NbVg1, NbVg2 and NbVg3) revealed that the open reading frames of NbVg1, NbVg2 and NbVg3 were 5571, 5532 and 4728 bp, encoding 1856, 1843 and 1575 amino acids, respectively. The three N. barkeri Vg possessed the Vitellogenin-N domain (or lipoprotein N-terminal domain (LPD_N)), von Willebrand factor type D domain (VWD) and the domain with unknown function 1943 (DUF1943). The NbVg1 and NbVg2 expression levels were significantly higher in the resistant strain than in the susceptible strain, while the NbVg3 expression level was lower in the resistant strain. Thus, we speculate that the increased number of eggs laid by the fenpropathrin-resistant strain of N. barkeri may be a consequence of changes in Vg gene expression.
We investigate a degenerate parabolic variational inequality arising from optimal continuous exercise perpetual executive stock options. It is also shown in Qin et al. (Continuous-Exercise Model for American Call Options with Hedging Constraints, working paper, available at SSRN: http://dx.doi.org/10.2139/ssrn.2757541) that to make this problem non-trivial the stock's growth rate must be no smaller than the discount rate. Well-posedness of the problem is established in Lai et al. (2015, Mathematical analysis of a variational inequality modeling perpetual executive stock options, Euro. J. Appl. Math., 26 (2015), 193–213), Qin et al. (2015, Regularity free boundary arising from optimal continuous exercise perpetual executive stock options, Interfaces and Free Boundaries, 17 (2015), 69–92), Song & Yu (2011, A parabolic variational inequality related to the perpetual American executive stock options, Nonlinear Analysis, 74 (2011), 6583-6600) for the case when the underlying stock's expected return rate is smaller than the discount rate. In this paper, we consider the remaining case: the discount rate is bigger than the growth rate but no bigger than the return rate. The existence of a unique classical solution as well as a continuous and strictly decreasing free boundary is proved.
The recently described radiodontan Lyrarapax unguispinus Cong et al., 2014 from the Chengjiang biota (Cambrian Series 2, Stage 3) highlighted a new morphological type of frontal appendage and unique mouth structures, a functional combination reinforcing the diversification of feeding strategies of radiodontans during the early Cambrian. Here we describe Lyrarapax trilobus n. sp. from the same fossil Konservat-Lagerstätte. The new species differs from L. unguispinus in the morphology and distribution of endites on the frontal appendage and the strengthening structure of the body flaps. The two species resemble each other in body shape (pattern of flap size), neck segment number, cephalic plates, and most importantly a mouth characterized by concentric wrinkled furrows. The latter confirms that a soft mouth without sclerotized plates is a real feature of Lyrarapax and supports the idea that oral structures provide valid diagnostic characters within Radiodonta.
High-resolution δ18O records from a Geladaindong mountain ice core spanning the period 1477-1982 were used to investigate past temperature variations in the Yangtze River source region of the central Tibetan Plateau (TP). Annual ice-core δ18O records were positively correlated with temperature data from nearby meteorological stations, suggesting that the δ18O record represented the air temperature in the region. A generally increasing temperature trend over the past 500 years was identified, with amplified warming during the 20th century. A colder stage, spanning before the 1850s, was found to represent the Little Ice Age with colder periods occurring during the 1470s–1500s, 1580s–1660s, 1700s–20s and 1770s–1840s. Compared with other temperature records from the TP and the Northern Hemisphere, the Geladaindong ice-core record suggested that the regional climate of the central TP experienced a stronger warming trend during the 20th century than other regions. In addition, a positive relationship between the Geladaindong δ18 O values and the North Atlantic Oscillation index, combined with a wavelet analysis of δ18 O records, indicated that there was a potential atmospheric teleconnection between the North Atlantic and the central TP.
After the completion of the Human Genome Project (Lander et al., 2001; Venter et al., 2001) and initiation of the International HapMap Project (Sachidanandam et al., 2001), genome-wide association studies (GWAS) were designed to survey the role of common genetic variations in complex human diseases. It was expected that GWAS would have the advantage of not relying on prior knowledge of biological pathways compared with “candidate gene” studies (Tabor et al., 2002; Wang et al., 2005), because it assays a dense set of single-nucleotide polymorphisms (SNPs) across the whole genome. This advantage allows GWAS to overcome the bias of “candidate gene” studies due to incomplete prior knowledge. It was also expected that GWAS would have higher power and finer resolution to identify genetic variants of modest effects compared to family-based linkage studies (Risch & Merikangas, 1996).
The success of identifying genes for age-related macular degeneration (AMD) under the GWAS paradigm (Klein et al., 2005) convinced the genetics community on the efficiency and feasibility of the GWAS approach to identify unknown disease-associated variants. This study used a commercial genotyping array and assayed about 100,000 SNPs throughout the human genome. It identified the association of complement factor H (CFH) with AMD. The success of finding a common risk allele with an odds ratio (OR) of 4.6 in a small sample set of 96 cases and 50 controls has generated considerable excitement in the genetics community. The p-value of the strongest SNP association surpassed the genome-wide significance threshold after the Bonferroni correction. More importantly, this finding was replicated in the following-up studies (Donoso et al., 2010). Undoubtedly, this encouraging finding raised the confidence among researchers to detect genetic variants that underlie various complex diseases through GWAS. In 2007, the Wellcome Trust Case Control Consortium (WTCCC) published the results of seven GWAS, including Bipolar Disorder, Coronary Artery Disease, Crohn's Disease, Hypertension, Rheumatoid Arthritis, Type 1 Diabetes, and Type 2 Diabetes (The Wellcome Trust Case Control Consortium, 2007). The WTCCC study is considered the starting point of large-scale GWAS (Visscher et al., 2012). Since then, an increasing number of GWAS have been conducted and over 10,000 loci have been reported to be significantly associated with at least one complex trait (see the web resource of GWAS catalog (Hindorff et al., 2009), http://www.genome.gov/gwastudies/).
With an influx of successful genome-wide association studies to identify genetic variations associated with complex diseases, an unprecedented wealth of knowledge has been accumulated for SNP–phenotype associations (McCarthy et al., 2008; Witte 2010; Manolio 2013). However, many SNP–disease associations do not lend themselves to molecular interpretations, because many of the identified loci are located outside of the coding regions. Even when a gene can be inferred to be causal, there is often a significant gap towards the understanding of the underlying molecular mechanisms (Schadt et al., 2005; McCarthy et al., 2008). Genome-wide eQTL mapping has been one effective approach to bridge this gap (Mackay et al., 2009). In eQTL studies, gene expression levels measured by high-throughput technologies, such as microarrays and RNA-Seq, are treated as quantitative traits. Marker genotypes are also collected from the same set of individuals, and statistical analyses are performed to detect associations between markers and expression traits. By simultaneously capturing many regulatory interactions, eQTLs offer valuable insights on the genetic architecture of expression regulation (Rockman and Kruglyak 2006). The ultimate goal of eQTL studies is to elucidate how genetic variations affect phenotypes by using gene expression levels as intermediate molecular phenotypes (Nica and Dermitzakis 2008). In this chapter, we provide an overview of the eQTL analysis workflow (Figure 14.1), introduce publicly available tools for analysis, and further discuss challenges and issues.
Genome-wide eQTL mapping considers high-density SNP genotype data and gene expression data from the same individuals in a segregating population. Both require appropriate pre-processing as described below for subsequent analysis.
Three quality control (QC) criteria are often used in the pre-processing of the genotype data. (1) Missing rate: individuals with a large proportion of missing SNP genotypes (e.g., 10%) should be excluded because the DNA samples of those individuals may be of poor quality. SNPs with a large missing rate (e.g., 5%) should also be filtered out. (2) Hardy–Weinberg Equilibrium (HWE): statistically significant deviations from HWE often result from genotyping errors. Therefore, SNPs that fail an exact HWE test (e.g., a P-value less than 0.001) should be filtered out. The criterion does not apply to haploid organisms, such as yeast. (3) Minor allele frequency (MAF): SNPs with low MAF (e.g., 0.05) are sometimes filtered out because of the insufficient statistical power for studies with a relatively small sample size and potentially higher genotype calling error.
Alpha-lipoic acid (ALA) is known to be a natural antioxidant. The aim of the present study was to evaluate the cryoprotective effect of ALA on the motility of boar spermatozoa and its antioxidant effect on boar spermatozoa during freezing–thawing. Different concentrations (2.0, 4.0, 6.0, 8.0 or 10.0 mg/ml) of ALA were added to the extender used to freeze boar semen, and the effects on the quality and endogenous antioxidant enzyme activities of frozen–thawed spermatozoa were assessed. The results indicated that the addition of ALA to the extender resulted in a higher percentage of motile spermatozoa post-thaw (P < 0.05). The activities of superoxide dismutase, lactate dehydrogenase, glutamic-oxaloacetic transaminase and catalase improved after adding ALA to the extender (P < 0.05). Artificial insemination results showed that pregnancy rate and litter size were significantly higher at 6.0 mg/ml in the ALA group than in the control group (P < 0.05). In conclusion, ALA conferred a cryoprotective capacity to the extender used for boar semen during the process of freezing–thawing, and the optimal concentration of ALA for the frozen extender was 6.0 mg/ml.
In this study, a novel hybrid block copolymer containing POSS (BCP), poly(methacrylisobutyl-POSS)-b-poly(methylmethacrylate) (PMAiBuPOSS-b-PMMA) was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The structure and molecular weight were characterized via 1H NMR and GPC. BCP was creatively used as the compatibilizer to overcome the bad compatibility of epoxy and POSS in their blend system. SEM and dynamic mechanical thermal analyses (DMTA) were used to observe the surface morphology and thermal–mechanical behaviors of the resultant products. We found that the amount of microaggregation domains of POSS decreased, while the nano ones increased, when BCP content increased. All the aggregation domains were distributed in epoxy matrix uniformly at nanoscale with the addition of 10 phr BCP and 5 phr POSS monomers. The results indicated that BCP could effectively improve the compatibility between epoxy resin and POSS owing to its amphiphilicity in DGEBA. The fracture behavior of products transformed from brittle fracture to ductile fracture gradually with the increase of BCP, whereas the Tg and E′ decreased.
In this paper, we establish the existence and uniqueness of a classical solution of a degenerate parabolic variational inequality of which a strong solution was shown to exist by Song and Yu . The problem arises from optimal stochastic control of exercising continuously perpetual executive stock options (ESOs). We also characterize the basic graph, continuity, and monotonicity properties of the free boundary from which the optimal control strategy can be described precisely.
We prove that for a finitely generated infinite nilpotent group G with structure (G, ·, …), the connected component G*0 of a sufficiently saturated extension G* of G exists and equals
We construct an expansion of ℤ by a predicate (ℤ, +, P) such that the type-connected component is strictly smaller than ℤ*0. We generalize this to finitely generated virtually solvable groups. As a corollary of our construction we obtain an optimality result for the van der Waerden theorem for finite partitions of groups.
We performed polarization sensitive VLBI observations of 6.7 GHz methanol masers toward high-mass young stellar objects with clear outflow seen from Spitzer IRAC images in the 4.5 μm band (i.e. EGOs, see Cyganowski et al. 2008) with the EVN to investigate the birthplace of the masers. By comparing direction of the major axis of methanol maser distributions with directions of higher resolution outflow and magnetic field vector, we suggest that the methanol masers toward source G28.83-0.25 may arise from surrounding disk.