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Introduction Accumulation of polyglutamine (polyQ) ataxin-3 (ATXN3) contributes to the pathobiology of spinocerebellar ataxia type 3 (SCA3). Recently, we showed that polyQ ATXN3 is elevated in the plasma and cerebrospinal fluid (CSF) of SCA3 patients, and has the potential to serve as a biological marker for this disease [1]. Based on these findings, we investigated whether polyQ ATXN3 can also be detected in urine samples from SCA3 patients. Methods We analyzed urine samples from 30 SCA3 subjects (including one pre-symptomatic subject), 35 subjects with other forms of ataxia, and 37 healthy controls. To quantify polyQ ATXN3 protein levels, we used our previously developed immunoassay. Results PolyQ ATXN3 can be detected in the urine of SCA3 patients, but not in urine samples from healthy controls or other forms of ataxia. There was a significant statistical association between polyQ ATXN3 levels in urine samples and those in plasma. Further, the levels of polyQ ATXN3 urine associated with an earlier age of SCA3 disease onset. Conclusion As clinical trials for SCA3 advance, urine polyQ ATXN3 protein has potential to be a useful, non-invasive and inexpensive biomarker for SCA3.

Background Many studies have demonstrated that microRNAs, a class of small and non-coding RNA molecules, play an important role in the regulation of glucose and lipid homeostasis. In the present study, we sought to investigate the function of miR-592 in the development of obesity-associated metabolic disorders, including hyperglycemia andinsulin resistance. Methods The expression levels of miR-592 were measured in the liver of obese mice and humans by quantitative reverse transcription PCR. Loss- and gain-of function experiments were employed to explore the metabolic function of miR-592 using locked nucleic acids and adenovirus in lean and obese mice, respectively. The molecular target of miR-592 was determined by western blotting and luciferase reporter assays. Findings We found a significant decreased expression of miR-592 in the liver of obese mice and humans. Inhibition of miR-592 led to elevated blood glucose levels, enhanced gluconeogenesis and reduced insulin sensitivity in lean mice. In contrast, adenovirus-mediated overexpression of hepatic miR-592 improved metabolic disorders in obese mice. Mechanistically, we found that the transcription factor forkhead box O1 (FOXO1) is a direct target gene of miR-592 to mediate its metabolic functions. miR-592 was able to inhibit the mRNA and protein expression of FOXO1 by binding to its 3′-untranslated region. Interpretations Our findings demonstrate that obesity-associated down-regulation of miR-592 plays an important role in the progression of metabolic diseases. Restoration of hepatic miR-592 could improve glucose and lipid metabolism in obese mice. Fund This work is supported by the National Key Research and Development Program of China (No. 2016YFC1304805 to Dr. Chen), Natural Science Foundation of China (No. 81771574 to Dr. Wu), Shanghai Science Foundation (No. 18ZR1437800 to Dr. Li), Science and Technology Commission of Shanghai Municipality (Nos.18dz2304400 and 15,411,970,700 to Dr. Yang).

In this paper, we propose an innovative estimation method for the volatility function in diffusion process and construct the empirical likelihood confidence interval for it. Compared with double smoothing local constant estimator, double smoothing local linear estimator proposed in this paper is an inventive estimation method. Moreover, we find that the empirical likelihood confidence interval constructed with the approximate estimating equation is much better than the one based on the estimating equation, since the latter undermines the predictability of the estimator. Accordingly, new algorithm for simulation is proposed. Through Monte Carlo simulation and empirical analysis, both these approaches are superior to traditional asymptotic normality confidence interval in terms of coverage rate, etc.

Background Atherosclerosis-related cardiovascular diseases are among the leading causes of mortality worldwide. Uptake of modified lipoproteins by monocyte-derived macrophages leads to the formation of foam cells, which by secreting pro-inflammatory cytokines accelerate plaque development. Sorting Nexin 10 (SNX10) plays a critical role in the regulation of macrophage functions as well as in the lipid metabolism. This study aims to explore the precise effects and the underlying molecular mechanisms of SNX10 mediated processes in atherosclerotic diseases. Methods SNX10 knockout mice were generated and bone marrow-derived macrophages (BMDMs) were studied in vitro. Mice were crossed with apolipoprotein E-deficient (ApoE-/-) mice and atherogenesis was monitored for 16 weeks. Results Expression of SNX10 was increased in atherosclerotic plaques from both humans and ApoE-/- mice. SNX10 deficiency decreased foam cell abundance and alleviated atherosclerotic plaque progression in ApoE-/- mice. In addition, high fat, high cholesterol diet fed ApoE-/- mice contained more Ly6ChiCX3CR1lo monocytes than ApoE-/- SNX10-/- (DKO) littermates. ApoE-/- mice showed a higher level of inflammatory macrophages infiltrating into atherosclerotic lesions. SNX10 deficiency reduced the interactions between CD36 and Lyn, thus inhibiting CD36-mediated lipoprotein uptake and foam cell formation. Conclusions Our findings demonstrate CD36-Lyn dependent non-redundant atherogenic role for SNX10 in diet-induced atherogenesis. We propose SNX10 as a potential therapeutic target for the prevention and treatment of atherosclerosis.

SUMMARY Tau accumulation is a major pathological hallmark of Alzheimer’s disease (AD) and other tauopathies, but the mechanism(s) of tau aggregation remains unclear. Taking advantage of the identification of tau filament cores by cryoelectron microscopy, we demonstrate that the AD tau core possesses the intrinsic ability to spontaneously aggregate in the absence of an inducer, with antibodies generated against AD tau core filaments detecting AD tau pathology. The AD tau core also drives aggregation of full-length wild-type tau, increases seeding potential, and templates abnormal forms of tau present in brain homogenates and antemortem cerebrospinal fluid (CSF) from patients with AD in an ultrasensitive real-time quaking-induced conversion (QuIC) assay. Finally, we show that the filament cores in corticobasal degeneration (CBD) and Pick’s disease (PiD) similarly assemble into filaments under physiological conditions. These results document an approach to modeling tau aggregation and have significant implications for in vivo investigation of tau transmission and biomarker development., In brief Carlomagno et al. demonstrate the AD tau filament core is able to spontaneously aggregate and recruit full-length wild-type tau to filaments. They also show that abnormal tau species in brain and CSF from AD patients template the AD core in a real-time QuIC assay., Graphical Abstract

K-nearest neighbor (KNN) is a classic classifier, which is simple and effective. Adaboost is a combination of several weak classifiers as a strong classifier to improve the classification effect. These two classifiers have been widely used in the field of machine learning. In this paper, based on information fuzzy granulation, KNN and Adaboost, we propose two algorithms, a fuzzy granule K-nearest neighbor (FGKNN) and a boosted fuzzy granule K-nearest neighbor (BFGKNN), for classification. By introducing granular computing, we normalize the process of solving problem as a structured and hierarchical process. Structured information processing is focused, so the performance including accuracy and robust can be enhanced to data classification. First, a fuzzy set is introduced, and an atom attribute fuzzy granulation is performed on samples in the classified system to form fuzzy granules. Then, a fuzzy granule vector is created by multiple attribute fuzzy granules. We design the operators and define the measure of fuzzy granule vectors in the fuzzy granule space. And we also prove the monotonic principle of the distance of fuzzy granule vectors. Furthermore, we also give the definition of the concept of K-nearest neighbor fuzzy granule vector and present FGKNN algorithm and BFGKNN algorithm. Finally, we compare the performance among KNN, Back Propagation Neural Network (BPNN), Support Vector Machine (SVM), Logistic Regression (LR), FGKNN and BFGKNN on UCI data sets. Theoretical analysis and experimental results show that FGKNN and BFGKNN have better performance than that of the methods mentioned above if the appropriate parameters are given.

We present an approach for synthesizing Chinese calligraphy with a similar topological style from learning author's written works. Our first contribution is an algorithm to match the trajectory. Second contribution is a method to represent Chinese character topology via WF-histogram. Third contribution is an algorithm to take topological features as features and feed them into the evaluation model-that is Adaboost composed of support vector regressions (SVRs). Fourth contribution is a Genetic Algorithm (GA) introduced in the optimization glyph phase. Moreover, we introduce hypothesis testing and the decay function of transformation amplitude to improve the converge speed. The experiments demonstrate that our approach can obtain a similar topological style Chinese calligraphy with training samples.

Dendritic cells (DCs) are the sentinels of the immune system and play a critical role in initiating adaptive immune responses against pathogens. As the most powerful antigen presenting cells, DCs are also important in maintaining immune homeostasis and participating in the development of autoimmune diseases. How the maturation and function of DCs is regulated in these conditions and what is the function of various transcription factors is still unclear. In this study, we found that the expression of the transcription factor Foxp1 gradually increased during the maturation of DCs. Then, we constructed a recombinant adenovirus carrying Foxp1-interfering RNA (Ad-simFoxp1) and transfected murine bone marrow-derived DCs in vitro. DCs transfected with Ad-simFoxp1 exhibited markedly lower costimulatory molecules, and decreased cytokines. And Ad-simFoxp1 greatly inhibited mature DC-induced T cell responses. Moreover, in vivo infusion with Ad-simFoxp1-modified DCs significantly delayed the onset of experimental autoimmune encephalomyelitis (EAE). Therefore, adoptive transfection of Ad-simFoxp1 in DCs may be a potential treatment strategy against autoimmune diseases.

We propose a re-weighted Nadaraya–Watson estimator for the infinitesimal conditional expectation of the second-order jump-diffusion model. Consistency and asymptotic normality of the estimator require certain regular conditions.

We study the empirical likelihood inference for infinitesimal coefficients in the second-order jump-diffusion model. Under certain regular conditions, we readily verify that an adjusted empirical log-likelihood ratio asymptotically follows 3 2 χ 2 ( 1 ) .

Alkyl methacrylate–maleic anhydride–alkyl methacrylate terpolymers (MR1–MA–MR2) is one of the widely used cold flow improver. In order to develop more efficient MR1–MA–MR2, it is necessary to study the crystallization behavior of n-alkanes when adding MR1–MA–MR2 into diesel fuel. In this paper, MR1–MA–MR2 is prepared by the reaction of long-chain alkyl methacrylate (MR1), maleic anhydride (MA), and short alkyl methacrylate (MR2). The diesel fuel before and after adding MR1–MA–MR2 is in situ filtrated at its cold filter plugging point (CFPP) in a manual CFPP apparatus. Extensive measurements of composition variation of n-alkanes are done by gas chromatograph and the results are compared. The experimental results show that after adding MR1–MA–MR2, the concentration distribution of n-alkanes in the filtrate is wide and arranges from 8 to 26, and mainly centralizes from 10 to 19. For the precipitate, the concentration distribution of n-alkanes gets richer in the lighter n-alkanes and poorer in the heavier n-alkanes. The concentration distribution of n-alkanes in the crystal solid shows a decreasing trend, especially with high carbon number n-alkanes (heavier than C20). About 60–70% of the residual crystal solid is composed of non-paraffins such as isoparaffin, naphthene and other components. Crystallinities of n-alkanes show a slow decrease trend from C8 to C20. When the carbon number n-alkanes are heavier than C20, the crystallinities of n-alkanes begin to sharply reduce with an increase of carbon number. The largest decline of crystallinity is C26 n-alkane from 38.39% to 7.90%.

In order to find efficient cold flow improvers for diesel fuels derived from crude oil, copolymers (R1MC–MA) were prepared making use of the copolymerization of methacrylate (R1MC) of various alkyls with maleic anhydride (MA), and terpolymers (R1MC–MA–R2MC) were prepared by the reaction of long-chain alkyl methacrylate (R1MC), maleic anhydride (MA), and short alkyl methacrylate (R2MC). The additives were purified and characterized by IR, 1H–NMR, and GPC. The activities of the synthetic products as the cold flow improvers in two diesel fuels were investigated. The results indicate that: (1) the alkyl chain length of R1 in R1MC–MA copolymers significantly affects the solid point depressing performance. When the long-chain alkyl R1 is n–C14H29– and the reaction material molar ratio (R1MC/MA) is 1:2, the C14MC–2MA possesses the best ΔSP property; (2) the (C14MC–MA–R2MC) terpolymers all demonstrate excellent solid point depression properties when the short-chain alkyl R2 varies from CH3– to n–C8H17–; (3) however, all of the tested copolymers and terpolymers do not demonstrate necessary cold filter plugging point depression performance.

Three novel ashless triazine–dithiocarbamate derivatives, which are potential environmentally friendly oil additives, were synthesized. Their tribological properties as additives in rapeseed oil (RSO) were evaluated using a four-ball tester. Their anticorrosive properties and thermal stabilities were also investigated. The results indicate that the three novel triazine–dithiocarbamate compounds possess excellent load-carrying capacity, good corrosion inhibiting performance and high thermal stability. Although these additives show friction-reducing property at high additive concentration (5 wt.%), they have friction increase and wear promote natures in most cases. The elemental composition and chemical state of the antiwear films generated on steel counterface were investigated with scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis and X-ray photoelectron spectroscopy (XPS). It was found that the synthetic additives reacted with the counterface metal and generated a surface protective film consisting of sulfate, FeS and absorbed compounds containing organic-N.

The government of the People’s Republic of China (P.R.C.) has announced its intention to make China a global leader in innovation by 2020. Many Chinese business leaders share this goal. The primary focus of this national strategy is to transform China into an exporter of high-technology products based on Chinese designs rather than merely a low cost, high volume manufacturer of products based on technology developed in other countries. This paper will examine the implications for this strategy with regard to the use of computerized management information systems by Chinese businesses, and its relationship to recent law reform efforts intended to promote greater use of electronic commerce among Chinese businesses. This paper considers three case studies of recent reforms of P.R.C. commercial law in light of their contributions to this strategy, and finds that the results so far are quite mixed. The first case study looks at a domestic standard for accounting software issued in 1989 that successfully removed obstacles to the greater use of computerized accounting systems by local businesses and promoted the growth of the domestic accounting software industry. The second and third case studies involve P.R.C. legislation based on model laws developed by United Nations Commission on International Trade Law (UNCITRAL) developed to assist legislators in trading nations to harmonize their national commercial laws in order to eliminate barriers to international trade. The second case study looks at the inclusion of general electronic commerce enabling legislation in the 1999 Contract Law which in theory removed impediments to the use of electronic commerce by Chinese businesses but in reality appears to be too abstract and general to provide much certainty to parties wishing to form contracts using electronic media. The third case study looks at the 2004 Electronic Signature Law which promotes the use of a specific type of technology for authentication. While it is too soon to know whether this law will achieve its intended objectives in China, evidence from other countries with similar laws suggests that it may not., Columbia Journal of Asian Law, Vol. 20 No. 2 (2007)