Miracle-dz/UniFAR-FTUs huggingface dataset:
Deletion of C9ORF72 Results in Motor Neuron Degeneration and Stress Sensitivity in C. elegans

An expansion of the hexanucleotide GGGGCC repeat in the first intron of C9ORF72 gene was recently linked to amyotrophic lateral sclerosis. It is not known if the mutation results in a gain of function, a loss of function or if, perhaps both mechanisms are linked to pathogenesis. We generated a genetic model of ALS to explore the biological consequences of a null mutation of the Caenorhabditis elegans C9ORF72 orthologue, F18A1.6, also called alfa-1. alfa-1 mutants displayed age-dependent motility defects leading to paralysis and the specific degeneration of GABAergic motor neurons. alfa-1 mutants showed differential susceptibility to environmental stress where osmotic stress provoked neurodegeneration. Finally, we observed that the motor defects caused by loss of alfa-1 were additive with the toxicity caused by mutant TDP-43 proteins, but not by the mutant FUS proteins. These data suggest that a loss of alfa-1/C9ORF72 expression may contribute to motor neuron degeneration in a pathway associated with other known ALS genes.
Methylene chloride induced mouse liver and lung tumours: An overview of the role of mechanistic studies in human safety assessment

B6C3F1 mice exposed to high dose levels of methylene chloride by inhalation for 2 years had an elevated incidence of liver and lung tumours. These tumours were not increased in rats or hamsters exposed under the same or similar conditions. This paper gives an overview of research conducted over the last 10 years into the mechanism of action of methylene chloride as a mouse carcinogen and into the relevance of the mouse data to humans exposed to this chemical. Data are presented on the comparative metabolism and pharmacokinetics of methylene chloride in mice, rats, hamsters and humans, on the toxicity of methylene chloride to the target organs in the mouse, and on the genotoxicity of methylene chloride in vitro and in vivo. The enzyme which activates methylene chloride to its carcinogenic form has been isolated, sequenced, and cloned, and its distribution studied within cells, organs and between species. Evidence has been obtained to show that methylene chloride caused cancer in mice as a result of interactions between metabolites of the glutathione S-transferase pathway and DNA. Damage to mouse lung Clara cells and increased cell division are believed to have influenced the development of the lung tumours. The species specificity was a direct consequence of the very high activity and specific cellular and nuclear localisation of a theta class glutathione S-transferase enzyme which was unique to the mouse. Consequently, DNA damage was not detectable in rats in vivo, or in hamster and human hepatocytes exposed to cytotoxic dose levels of methylene chloride in vitro. These results provide evidence that the mouse is unique in its response to methylene chloride and that it is an inappropriate model for human health assessment.
Can Fixed Time Delay Signature be Concealed in Chaotic Semiconductor Laser With Optical Feedback?

External-cavity lasers are usually used for chaos encryption in optical chaos-based communication systems. The external-cavity round-trip time (the time delay in the laser dynamics) is often regarded as an additional key to encode messages, which is a critical security parameter. The feasibility of identifying the time delay has been a crucial issue in chaotic optical communication. Some researchers propose that the time delay can be hidden by modulating the value of feedback strength or increasing the number of feedback cavities. In this paper, we experimentally and numerically demonstrate that the time delay signatures cannot be concealed in optical feedback semiconductor lasers. Whether single or double optical feedback, the time delay signatures can all be identified by the power spectrum analysis method. Furthermore, adjusting the feedback strength, the pumping current and the time-delay value, we find that the extraction of the time delay signatures still cannot be influenced.
Polymorphic Epithelial Mucin (PEM) Epitopes in the Estimation of the Sequence of Neoplastic Changes in Colon Adenocarcinoma

Aims The relation between the expression of PEM epitopes and the sequence of neoplastic changes in individual patients with colon adenocarcinoma was investigated. Methode Immunohistochemical staining was performed using four monoclonal antibodies to PEM epitopes (139H2, 140C1, 115D8, 115F5) on tissue sections from frankly malignant lesions, adjacent mucosa, colonic mucosa taken 1 cm and 5 cm from the lesion and normal control mucosa. Results A clear correlation between PEM expression and the site of mucosa sampling was demonstrated. The expression of PEM molecules defined by all studied monoclonal antibodies was highest in colon adenocarcinoma, similar but slightly weaker in adjacent mucosa and colon mucosa taken 1 cm from the frankly malignant lesion, lowest in mucosa 5 cm from the lesion, and virtually absent in control normal colonic mucosa. Conclusions The immunological changes could be one of the first signs of a premalignant process and the estimation of PEM epitopes could show some cellular abnormalities not detectable by standard pathomorphological criteria.
Conditional diagnosability and strong diagnosability of shuffle-cubes under the comparison model

The growing size of multiprocessor systems increases the vulnerability to component failures. It is crucial to locate and replace faulty processors to maintain the system's high reliability. Processor fault diagnosis is essential to the reliability of a multiprocessor system and the diagnosabilities of many well-known networks (such as hierarchical hypercubes and crossed cubes [S. Zhou, L. Lin and J.-M. Xu, Conditional fault diagnosis of hierarchical hypercubes, Int. J. Comput. Math. 89(16) (2012), pp. 2152–2164 and S. Zhou, The conditional diagnosability of crossed cubes under the comparison model, Int. J. Comput. Math. 87(15) (2010), pp. 3387–3396]) have been investigated in the literature. A system is t-diagnosable if all faulty nodes can be identified without replacement when the number of faults does not exceed t, where t is some positive integer. Furthermore, a system is strongly t-diagnosable if it is t-diagnosable and can achieve (t+1)-diagnosability except for the case where a node's neighbours are all faulty. In addition, conditional diagnosability has been widely accepted as a new measure of diagnosability by assuming that any fault-set cannot contain all neighbours of any node in a multiprocessor system. In this paper, we determine the conditional diagnosability and strong diagnosability of an n-dimensional shuffle-cube SQn, a variant of hypercube for multiprocessor systems, under the comparison model. We show that the conditional diagnosability of shuffle-cube SQn (n=4k+2 and k≥2) is 3n−9, and SQn is strongly n-diagnosable under the comparison model.
Reduced order observers for the sliding mode control of mechanical systems with elastic joints

In this article the control of mechanical systems with elastic joints is addressed. This kind of system is characterised by a high relative degree. The mechanical control input must be designed to be continuous. Different reduced order observers are introduced and conditions are found to guarantee the exponential convergence of the observation errors. The error stability is ensured provided a certain matrix inequality has a solution. The proposed second-order sliding mode point-to-point controller based on the observed state is proven to stabilise the mechanical system with elastic joints about the desired reference position.
The extent and pattern of organ damage in small vessel vasculitis measured by the Vasculitis Damage Index (VDI)

Objectives: To assess the extent and pattern of irreversible organ damage in patients with Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), polyarteritis nodosa (PAN), and Churg–Strauss syndrome (CSS) by a cross‐sectional point prevalence study within a defined geographical area. Methods: The Vasculitis Damage Index (VDI) was recorded for 86 prevalent cases, classified as 46 patients with WG, 27 with MPA, nine with PAN, and four with CSS from a defined population in southern Sweden, with a median age of 64.8 years and a median disease duration of 9 years. The VDI was determined for all patients at the day of point prevalence (pp), 1 January 2003. Results: The median VDI score was 3 [interquartile range (IQR) 2–5] for all patients: 3 (2–4) for WG, 3 (1.5–4.5) for MPA, 5 (2–6) for PAN, and 1.5 (0.75–2.75) for CSS. Only 9% of patients had not been assigned a single item of damage. The most common damage was cardiovascular, followed by renal, neuropsychiatric, ear nose and throat (ENT), and musculoskeletal. Major vascular and treatment‐related damage was associated with advanced age whereas ENT damage was more prevalent in younger patients. There was an almost complete separation between ENT damage and cardiac and renal damage with only two out of the 22 patients assigned ENT damage having experienced renal damage; none had been assigned cardiac damage. Patients with cardiac damage had significantly higher damage rates. Conclusions: Damage remains an important problem for patients with systemic vasculitis despite effective remission‐inducing drugs. Only a small fraction of patients are unmarked by their disease.
Resistin involved in endothelial dysfunction among preclinical Tibetan male young adults

Introduction: Resistin, an adipocyte-derived hormone, was found to be linked to metabolic syndrome and insulin resistance over the past decade. There is growing evidence that resistin plays a potential role in endothelial dysfunction. To the best of our knowledge, few studies have been concerned with the effect of resistin on endothelial function in a Tibetan population. Aims: To investigate the correlation of resistin and endothelial function among preclinical Tibetan male young adults. Materials and methods: All participants recruited were young adults between 30 and 40 years old of male gender in Lhasa city. All subjects were native Tibetan. A total of 90 healthy subjects were accepted after excluding hypertension, diabetes, hyperlipidemia or coronary artery disease. The subjects were divided into three groups according to flow-mediated dilation (FMD): lower FMD (group A), intermediate FMD (group B) and higher FMD (group C). Body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP) and cigarette smoking were evaluated. Venous blood was sampled for the measurement of lipid profile, fasting blood glucose (FBG), fasting insulin (FINS), endothelin-1 (ET-1) and plasma resistin quantitation. The non-invasive vascular endothelial function was evaluated through the measurement of FMD with B-mode ultrasound. The insulin resistance was estimated as homeostatic model assessment of insulin resistance (HOMA-IR) = FINS(mu/L)*FBG(mmol/L)/22.5. Results: No statistical significance was found between groups in age, smoking, SBP, DBP, fasting insulin, total cholesterol and HOMA-IR (p>0.05). In the lipid profile, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in group C were better than in groups A and B (p<0.01). Body mass index, which is an indicator for obesity, was much lower in group C than in group A and B (p<0.05 and 0.01 respectively). Comparison of plasma resistin concentrations: group A > group B > group C (p<0.01). Comparison of plasma ET-1 concentrations had a similar result: group A > group B > group C (p<0.05). The multivariate regression analysis showed that total cholesterol (p<0.05), LDL cholesterol (p<0.01), plasma resistin (p<0.01) and plasma ET-1 (p<0.01) were correlated with FMD. Conclusions: Resistin is involved in endothelial dysfunction in preclinical male young Tibetan adults.
Seasonal changes in fine structure of the ductuli efferentes of the ground squirrel, Citellus lateralis (say)

The morphoogical changes that the ductuli efferentes undergo during the seasonal breeding cycle of the ground squirrel Citellus lateralis were examined by means of electron microscopy. At the time of spermatogeneetic activity the epithelium of the ductuli was composed of highly differntiated principal and ciliated cells. Distinctive cytological features of these cells during this period were the presence of a heterogeneous collection of numerous membrane‐bound granules in principal cells and large accumulation of glygen in ciliated cells. Structurally these cells were specialized for movement of luminal contents and its modification by absorption and possible secretion. With the onset of testicular regression, profound changes occurred in both cell types. Initially the lumen of the ductuli became occluded by masses of apical cytoplasm protruded from principal and ciliated cells as well as by degenerating cells which had been sloughed from the epithelium. This leads eventually, by the time of complete testicular regression, to reduced ductuli containing cells smaller in size with fewer organelles than those present during the period of spermatogenesis. The membrane‐bound granules in principal cells and the accretions of glycogen in ciliated cells had now virtually disappeared. There was, however, a dramatic increase in dense inclusions representing deposits of lipofuchsin. As yet the cellular mechanisms controlling and effecting these dramatic changes in morphological appearance are unknwon.
Big data analysis of public library operations and services by using the Chernoff face method

The purpose of this paper is to conduct a big data analysis of public library operations and services of two cities in two countries by using the Chernoff face method. ,The study is designed to evaluate library services by analyzing the Chernoff face. Big data on public libraries in London and Seoul were collected, respectively, from Chartered Institute of Public Finance and Accountancy and the Korean government’s website for drawing a Chernoff face. The association of variables and human facial features was decided by survey. Although limited in its capacity to handle a large number of variables (eight were analyzed in this study) the Chernoff face method does readily allow for the comparison of a large number of instances of analysis. A total of 58 Chernoff faces were drawn from the formatted data by using the R programming language. ,The study reveals that most of the local governments in London perform better than those of Seoul. This consequence is due to the fact that local governments in London operate more libraries, invest more budgets, allocate more staff and hold more collections than local governments in Seoul. This administration resulted in more use of libraries in London than Seoul. The study validates the benefit of using the Chernoff face method for big data analysis of library services. ,The Chernoff face method for big data analysis offers a new evaluation technique for library services and provides insights that may not be as readily apparent and discernible using more traditional analytical methods. ,This study is the first to use the Chernoff face method for big data analysis of library services in library and information research.
Binding Energetics of Ferredoxin‐NADP+ Reductase with Ferredoxin and Its Relation to Function

To obtain insight into the motional features of proteins for enzymatic function, we studied binding reactions between ferredoxin‐NADP+ reductase (FNR) and ferredoxin (Fd) using isothermal titration calorimetry and NMR‐based magnetic relaxation and hydrogen/deuterium exchange (HDex). Fd–FNR binding was accompanied by endothermic reactions and driven by the entropy gain. Component‐wise analysis of the net entropy change revealed that increases in the conformational entropy of the Fd–FNR complex contributed largely to stabilizing the complex. Intriguingly, analyses of magnetic relaxation and HDex rates with X‐ray B factor implied that Fd binding led to both structural stiffening and softening of FNR. Enhanced FNR backbone fluctuations suggest favorable contributions to the net conformational entropy. Fd‐bound FNR further showed that relatively large‐scale motions of the C terminus, a gatekeeper for interactions of NADP+(H), were quenched in the closed form, thereby facilitating exit of NADP+(H). This can provide a first dynamic structure‐based explanation for the negative cooperativity between Fd and NADP+(H) via FNR.
A monovision-based 3D pose estimation system for vehicle behavior prediction

Collision accidents have become a crucial and urgent problem. Advanced Driver Assistance Systems (ADAS) can enhance traffic safety and improve efficiency. Toward this direction, we propose a robust low-cost system based on monovision to estimate the accurate 3D pose information of the target vehicles for further behavior prediction. Firstly, we combine the Haar features with AdaBoost classification for vehicle detection, and then use the Hypothesis Verification to remove the false detection; Then, the system keeps tracking and locates the license plate(LP); Finally, the typical PnP problem is applied to estimate the 3D pose information including the rotation matrix and translation matrix relative to the target vehicles. Compared to stereovision systems, the monovision-based system significantly reduces the computational cost and has a lower requirement for equipment. Moreover, it can work on slope road and is easily applied to different countries due to the standardized LP in each country. The experiments in the real-world have been tested, showing excellent performance in vehicle detection, LP location and 3D pose estimation.
Effectiveness of introducing Human-Centered Design process

This paper analyzes the effectiveness of introducing Human-Centered Design (HCD) into the development site of a company. In general, the effectiveness of HCD has been discussed over reductions of the total cost accrued during the development life cycle. However, reductions in cost do not always lead to a motivation for the development personnel on site. In order to analyze the effectiveness of introducing HCD at the “on-site level”, an experiment is implemented to have user interfaces (UIs) be designed though two different processes: HCD processes and existing processes. The results reveal that it is difficult to show the development personnel the effectiveness obtained from the introduction of HCD. However, the results also suggest that in an effort of spreading HCD throughout the organization under such circumstances, the key to understanding the effectiveness of HCD lies in identifying the issues in such activities as requirements analysis, UI design, and validation.
Dibasic protein kinase A sites regulate bursting rate and nucleotide sensitivity of the cystic fibrosis transmembrane conductance regulator chloride channel

1 The relationship between phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and its gating by nucleotides was examined using the patch clamp technique by comparing strongly phosphorylated wild‐type (WT) channels with weakly phosphorylated mutant channels lacking four (4SA) or all ten (10SA) dibasic consensus sequences for phosphorylation by protein kinase A (PKA). 2 The open probability (Po) of strongly phosphorylated WT channels in excised patches was about twice that of 4SA and 10SA channels, after correcting for the number of functional channels per patch by addition of adenylylimidodiphosphate (AMP‐PNP). The mean burst durations of WT and mutant channels were similar, and therefore the elevated Po of WT was due to its higher bursting rate. 3 The ATP dependence of the 10SA mutant was shifted to higher nucleotide concentrations compared with WT channels. The relationship between Po and [ATP] was noticeably sigmoid for 10SA channels (Hill coefficient, 1.8), consistent with positive co‐operativity between two sites. Increasing ATP concentration to 10 mM caused the Po of both WT and 10SA channels to decline. 4 Wild‐type and mutant CFTR channels became locked in open bursts when exposed to mixtures of ATP and the non‐hydrolysable analogue AMP‐PNP. The rate at which the low phosphorylation mutants became locked open was about half that of WT channels, consistent with Po being the principal determinant of locking rate in WT and mutant channels. 5 We conclude that phosphorylation at ‘weak’ PKA sites is sufficient to sustain the interactions between the ATP binding domains that mediate locking by AMP‐PNP. Phosphorylation of the strong dibasic PKA sites controls the bursting rate and Po of WT channels by increasing the apparent affinity of CFTR for ATP.
Structural basis for isotype selectivity of the human retinoic acid nuclear receptor.

The human retinoic acid receptor (hRAR) belongs to the family of nuclear receptors that regulate transcription in a ligand-dependent way. The isotypes RARalpha,beta and gamma are distinct pharmacological targets for retinoids that are involved in the treatment of various skin diseases and cancers, in particular breast cancer and acute promyelocytic leukemia. Therefore, synthetic retinoids have been developed aiming at isotype selectivity and reduced side-effects. We report the crystal structures of three complexes of the hRARgamma ligand-binding domain (LBD) bound to agonist retinoids that possess selectivity either for RARgamma (BMS184394) or for RARbeta/gamma (CD564), or that are potent for all RAR-isotypes (panagonist BMS181156). The high resolution data (1.3-1. 5 A) provide a description at the atomic level of the ligand pocket revealing the molecular determinants for the different degrees of ligand selectivity. The comparison of the complexes of the chemically closely related retinoids BMS184394 and CD564 shows that the side-chain of Met272 adopts different conformations depending on the presence of a hydrogen bond between its sulfur atom and the ligand. This accounts for their different isotype selectivity. On the other hand, the difference between the pan- and the RARbeta, gamma-selective agonist is probably due to a steric discrimination at the level of the 2-naphthoic acid moiety of CD564. Based on this study, we propose a model for a complex with the RARgamma-specific agonist CD666 that shows the possible applications for structure-based drug design of RAR isotype-selective retinoids.
Modulating Effects of Arabinogalactans from Plant Gum Exudates on Human Complement System

Gum arabic and cashew nut tree gum exudate polysaccharide (CNTG) are plant polysaccharides composed of galactose and arabinose known as arabinogalactans (AGs). Although these fractions are used in food and pharmaceutical industry, cases of allergic reactions were described in clinical reports. As AGs were reported as modulators of the classical (CP) and alternative pathways (AP) of complement system (CS), in the present work, we investigate whether gum arabic and CNTG have an effect on both CS pathways. The complement fixation tests were performed with (CP‐30 and AP‐30) and without pre‐incubation (CP‐0 and AP‐0). For CP‐30, CNTG and gum arabic (833 μg/ml) showed a reduction of 28.0% (P = 0.000174) and 48.5% (P = 0.000143), respectively, on CP‐induced haemolysis. However, no effect was observed for CP‐0 in the CP‐induced haemolysis. For AP‐30, both CNTG and gum arabic (833 μg/ml) showed 87% reduction on the CP‐induced haemolysis, with IC50 values of 100 and 7 μg/ml, respectively. For AP‐0, a reduction of 11.3% for gum arabic and no effect for the CNTG on the CP‐induced haemolysis were observed. These results suggested that gum arabic and CNTG could be acting as activators of the CS. Thus, this effect on the CS, especially on the AP, which accounts for up to 80–90% of total CS activation, indicates that both fractions may be harmful because of their potential pro‐inflammatory action. Considering that CS activation induces inflammatory response, further studies confirming this immunomodulatory effect of these fractions are required to insure their safe use.