A falling-head test is a common method to estimate aquifer properties in which the water level in a well is increased suddenly, which is a key assumption for the data to be analyzed by traditional ...methods such as Cooper et al. and Hvorslev methods. However, there are situations where the water level increases in the well occurs for a relatively long period before it falls. In this case theoretically, there is no existing method to analyze the data. Hydrogeologists or geotechnical engineers still use the traditional methods to analyze the data even the water level increase is not instantaneous. This study derives a semi-analytical solution to describe water level change in this case. The mathematical model consists of the injection stage and water level fall stage. It is found that the water level mound induced by non-instantaneous injection leads to slower decrease of water level in the well comparing to the instantaneous injection. This study further analyses the errors of the estimated hydraulic properties if the data are analyzed by traditional methods. If calculated by Cooper et al. method, the storativity is underestimated but there is no impact on estimated hydraulic conductivity. The hydraulic conductivity calculated by Hvorslev method is underestimated and the error of underestimation increases with injection time and aquifer parameters. The actual hydraulic conductivity can be a few times of the estimated value for typical aquifer parameters in Hong Kong. Furthermore, a field experiment is conducted to compare the instantaneous method, non-instantaneous method and field data. The present solution fits the data well, and the errors of estimated parameters by instantaneous injection method are consistent with the conclusions in the error analysis.
•Analytical solution to the falling-head test with non-instantaneous injection.•Water level mound induced by non-instantaneous injection causes the slower fall.•Storativity and hydraulic conductivity are underestimated by instantaneous method.•The proposed solution matches the field data well.•Errors of parameters estimated by field data are consistent with error analysis.
Brain capillaries are crucial for cognitive functions by supplying oxygen and other nutrients to and removing metabolic wastes from the brain. Recent studies have demonstrated that constriction of ...brain capillaries is triggered by beta-amyloid (Aβ) oligomers via endothelin-1 (ET1)-mediated action on the ET1 receptor A (ETRA), potentially exacerbating Aβ plaque deposition, the primary pathophysiology of Alzheimer’s disease (AD). However, direct evidence is still lacking whether changes in brain capillaries are causally involved in the pathophysiology of AD. Using APP/PS1 mouse model of AD (AD mice) relative to age-matched negative littermates, we identified that reductions of density and diameter of hippocampal capillaries occurred from 4 to 7 months old while Aβ plaque deposition and spatial memory deficit developed at 7 months old. Notably, the injection of ET1 into the hippocampus induced early Aβ plaque deposition at 5 months old in AD mice. Conversely, treatment of ferulic acid against the ETRA to counteract the ET1-mediated vasoconstriction for 30 days prevented reductions of density and diameter of hippocampal capillaries as well as ameliorated Aβ plaque deposition and spatial memory deficit at 7 months old in AD mice. Thus, these data suggest that reductions of density and diameter of hippocampal capillaries are crucial for initiating Aβ plaque deposition and spatial memory deficit at the early stages, implicating the development of new therapies for halting or curing memory decline in AD.
Early detection and accurate monitoring of chronic kidney disease (CKD) could improve care and retard progression to end-stage renal disease. Here, using untargeted metabolomics in 2155 participants ...including patients with stage 1-5 CKD and healthy controls, we identify five metabolites, including 5-methoxytryptophan (5-MTP), whose levels strongly correlate with clinical markers of kidney disease. 5-MTP levels decrease with progression of CKD, and in mouse kidneys after unilateral ureteral obstruction (UUO). Treatment with 5-MTP ameliorates renal interstitial fibrosis, inhibits IκB/NF-κB signaling, and enhances Keap1/Nrf2 signaling in mice with UUO or ischemia/reperfusion injury, as well as in cultured human kidney cells. Overexpression of tryptophan hydroxylase-1 (TPH-1), an enzyme involved in 5-MTP synthesis, reduces renal injury by attenuating renal inflammation and fibrosis, whereas TPH-1 deficiency exacerbates renal injury and fibrosis by activating NF-κB and inhibiting Nrf2 pathways. Together, our results suggest that TPH-1 may serve as a target in the treatment of CKD.
China is planning to introduce emission trading scheme (ETS) to decrease CO2 emission. As low carbon energy (LCE) will play a pivotal role in reducing CO2 emissions, our paper is to assess the extent ...and the conditions under which a carbon ETS can deliver LCE investment in China. We chose wind technology as a case study and a real-option based model was built to explore the impact of a number of variables and design features on investment decisions, e.g. carbon and electricity price, carbon market risk, carbon price floor and ceiling and on-grid ratio. We compute critical values of these variables and features and explore trade-offs among them. According to our work, a carbon ETS has a significant effect on wind power plant investment although it cannot support investment in wind power on its own. Carbon price stabilization mechanisms such as carbon price floor can significantly improve the effect of carbon ETS but the critical floor to support investment is still much higher than the carbon price in China pilot ETSs. Our results show that other policy measures will be needed to promote low-carbon energy development in China.
•The impact of Chinese emission trading scheme on low carbon energy investment is assessed.•A real-option based investment decision model under uncertainty is built and employed.•Key variables and features of ETS influencing wind power investment are explored.•Chinese carbon ETS cannot support low carbon energy investment on its own.•Other policy measures complementing ETS are still needed and should be coordinated.
Lynch syndrome, familial adenomatous polyposis, and Mut Y homolog (MYH)-associated polyposis are three major known types of inherited colorectal cancer, which accounts for up to 5% of all colon ...cancer cases. Lynch syndrome is most frequently caused by mutations in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2 and is inherited in an autosomal dominant manner. Familial adenomatous polyposis is manifested as colonic polyposis caused by mutations in the APC gene and is also inherited in an autosomal dominant manner. Finally, MYH-associated polyposis is caused by mutations in the MUTYH gene and is inherited in an autosomal recessive manner but may or may not be associated with polyps. There are variants of both familial adenomatous polyposis (Gardner syndrome--with extracolonic features--and Turcot syndrome, which features medulloblastoma) and Lynch syndrome (Muir-Torre syndrome features sebaceous skin carcinomas, and Turcot syndrome features glioblastomas). Although a clinical diagnosis of familial adenomatous polyposis can be made using colonoscopy, genetic testing is needed to inform at-risk relatives. Because of the overlapping phenotypes between attenuated familial adenomatous polyposis, MYH-associated polyposis, and Lynch syndrome, genetic testing is needed to distinguish among these conditions. This distinction is important, especially for women with Lynch syndrome, who are at increased risk for gynecological cancers. Clinical testing for these genes has progressed rapidly in the past few years with advances in technologies and the lower cost of reagents, especially for sequencing. To assist clinical laboratories in developing and validating testing for this group of inherited colorectal cancers, the American College of Medical Genetics and Genomics has developed the following technical standards and guidelines. An algorithm for testing is also proposed.
Traditional dance teaching emphasizes the consistency model and lacks the exploration of students’ individual characteristics. However, individualized and diversified dance education is a diversified ...dance talent cultivation oriented to different objects and objectives according to the differences of students’ natural conditions, educational background and development needs. Due to the single and real-time traditional dance teaching mode, there are limitations in the realization of multi-attribute and multi-objective dance talent training. This paper establishes a dance teaching situation with the function of network interaction, and solves the difficulties in individualized and diversified dance teaching. The research shows that the integration of online and offline education mode not only has certain theoretical value in teaching, but also has great practical significance for the cultivation of personalized and diversified dance talents.
Group LASSO for Structural Break Time Series Chan, Ngai Hang; Yau, Chun Yip; Zhang, Rong-Mao
Journal of the American Statistical Association,
06/2014, Volume:
109, Issue:
506
Journal Article
Peer reviewed
Consider a structural break autoregressive (SBAR) process where j = 1, …, m + 1, { t ₁, …, t ₘ} are change-points, 1 = t ₀ < t ₁ < ⋅⋅⋅ < t ₘ ₊ ₁ = n + 1, σ(·) is a measurable function on , and {ϵ ₜ} ...are white noise with unit variance. In practice, the number of change-points m is usually assumed to be known and small, because a large m would involve a huge amount of computational burden for parameters estimation. By reformulating the problem in a variable selection context, the group least absolute shrinkage and selection operator (LASSO) is proposed to estimate an SBAR model when m is unknown. It is shown that both m and the locations of the change-points { t ₁, …, t ₘ} can be consistently estimated from the data, and the computation can be efficiently performed. An improved practical version that incorporates group LASSO and the stepwise regression variable selection technique are discussed. Simulation studies are conducted to assess the finite sample performance. Supplementary materials for this article are available online.
Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis. Furthermore, we now ...appreciate that OA pathogenesis involves not only breakdown of cartilage, but also remodelling of the underlying bone, formation of ectopic bone, hypertrophy of the joint capsule, and inflammation of the synovial lining. That is, OA is a disorder of the joint as a whole, with inflammation driving many pathologic changes. The inflammation in OA is distinct from that in rheumatoid arthritis and other autoimmune diseases: it is chronic, comparatively low-grade, and mediated primarily by the innate immune system. Current treatments for OA only control the symptoms, and none has been FDA-approved for the prevention or slowing of disease progression. However, increasing insight into the inflammatory underpinnings of OA holds promise for the development of new, disease-modifying therapies. Indeed, several anti-inflammatory therapies have shown promise in animal models of OA. Further work is needed to identify effective inhibitors of the low-grade inflammation in OA, and to determine whether therapies that target this inflammation can prevent or slow the development and progression of the disease.
Chronic kidney disease (CKD) has emerged as a major public health problem worldwide. It frequently progresses to end-stage renal disease, which is related to very high cost and mortality. Novel ...biomarkers can provide insight into the novel mechanism, facilitate early detection, and monitor progression of CKD and its response to therapeutic interventions. To identify potential biomarkers, we applied an UPLC-HDMS together with univariate and multivariate statistical analyses using plasma samples from patients with CKD of diverse etiologies (100 sera in discovery set and 120 sera in validation set) and two different rat models of CKD. Using comprehensive screening and validation workflow, we identified a panel of seven metabolites that were shared by all patients and animals regardless of the underlying cause of CKD. These included ricinoleic acid, stearic acid, cytosine, LPA(16:0), LPA(18:2), 3-methylhistidine, and argininic acid. The combination of these seven biomarkers enabled the discrimination of patients with CKD from healthy subjects with a sensitivity of 83.3% and a specificity of 96.7%. In addition, these biomarkers accurately reflected improvements in renal function in response to the therapeutic interventions. Our results indicated that the identified biomarkers may improve the diagnosis of CKD and provide a novel tool for monitoring of the progression of disease and response to treatment in CKD patients.
Dispositional awe refers to the tendency or trait of awe that is a universal and complex human experience. However, the factors influencing this awe have rarely been addressed. For the first time, ...the current study explores the relationship between Honesty-Humility (H-H) and dispositional awe and the mediating role of a Zhong-Yong thinking style (ZY) in Confucian culture. A large sample of 2377 Chinese undergraduates ranging from 18 to 26 years old (mean: 20.7 years, SD = 1.7) was recruited via a cluster sampling. As predicted, H-H was positively correlated with dispositional awe, and this relationship was mediated by ZY. Though H-H was not significantly and directly correlated with dispositional awe in males, multiple-group structural equation modeling supported gender invariance in its direct and mediating effects. The implication of this study has been discussed.
•Honesty-Humility is an important personality trait for awe.•Zhong-Yong thinking style shows a mediating effect in dispositional awe.•Confucian culture and its relating thinking still matter for cultivating awe.
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