Miracle-dz/UniFAR-FTUs huggingface dataset:
Dengue Virus Inhibition of Autophagic Flux and Dependency of Viral Replication on Proteasomal Degradation of the Autophagy Receptor p62

ABSTRACT Autophagic flux involves formation of autophagosomes and their degradation by lysosomes. Autophagy can either promote or restrict viral replication. In the case of Dengue virus (DENV), several studies report that autophagy supports the viral replication cycle, and describe an increase of autophagic vesicles (AVs) following infection. However, it is unknown how autophagic flux is altered to result in increased AVs. To address this question and gain insight into the role of autophagy during DENV infection, we established an unbiased, image-based flow cytometry approach to quantify autophagic flux under normal growth conditions and in response to activation by nutrient deprivation or the mTOR inhibitor Torin1. We found that DENV induced an initial activation of autophagic flux, followed by inhibition of general and specific autophagy. Early after infection, basal and activated autophagic flux was enhanced. However, during established replication, basal and Torin1-activated autophagic flux was blocked, while autophagic flux activated by nutrient deprivation was reduced, indicating a block to AV formation and reduced AV degradation capacity. During late infection AV levels increased as a result of inefficient fusion of autophagosomes with lysosomes. In addition, endolysosomal trafficking was suppressed, while lysosomal activities were increased. We further determined that DENV infection progressively reduced levels of the autophagy receptor SQSTM1/p62 via proteasomal degradation. Importantly, stable overexpression of p62 significantly suppressed DENV replication, suggesting a novel role for p62 as a viral restriction factor. Overall, our findings indicate that in the course of DENV infection, autophagy shifts from a supporting to an antiviral role, which is countered by DENV. IMPORTANCE Autophagic flux is a dynamic process starting with the formation of autophagosomes and ending with their degradation after fusion with lysosomes. Autophagy impacts the replication cycle of many viruses. However, thus far the dynamics of autophagy in case of Dengue virus (DENV) infections has not been systematically quantified. Therefore, we used high-content, imaging-based flow cytometry to quantify autophagic flux and endolysosomal trafficking in response to DENV infection. We report that DENV induced an initial activation of autophagic flux, followed by inhibition of general and specific autophagy. Further, lysosomal activity was increased, but endolysosomal trafficking was suppressed confirming the block of autophagic flux. Importantly, we provide evidence that p62, an autophagy receptor, restrict DENV replication and was specifically depleted in DENV-infected cells via increased proteasomal degradation. These results suggest that during DENV infection autophagy shifts from a proviral to an antiviral cellular process, which is counteracted by the virus.
Calcium supplementation and risk of dementia in women with cerebrovascular disease

Objective: To determine whether calcium supplementation is associated with the development of dementia in women after a 5-year follow-up. Methods: This was a longitudinal population-based study. The sample was derived from the Prospective Population Study of Women and H70 Birth Cohort Study in Gothenburg, Sweden, and included 700 dementia-free women aged 70–92 years. At baseline in 2000–2001, and at follow-up in 2005–2006, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Dementia was diagnosed according to DSM-III-R criteria. Results: Women treated with calcium supplements (n = 98) were at a higher risk of developing dementia (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.01–4.37, p = 0.046) and the subtype stroke-related dementia (vascular dementia and mixed dementia) (OR 4.40, 95% CI 1.54–12.61, p = 0.006) than women not given supplementation (n = 602). In stratified analyses, calcium supplementation was associated with the development of dementia in groups with a history of stroke (OR 6.77, 95% CI 1.36–33.75, p = 0.020) or presence of white matter lesions (OR 2.99, 95% CI 1.28–6.96, p = 0.011), but not in groups without these conditions. Conclusions: Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease. Because our sample was relatively small and the study was observational, these findings need to be confirmed.
Production and characterization of antibodies to mouse scrapie‐amyloid protein elicited by non‐carrier linked synthetic peptide immunogens

Two polyclonal antibodies were raised by immunizing rabbits with two non carrier‐linked synthetic peptides whose amino acid sequences corresponded to codons 89–107 (peptide P1) and 219–233 (peptide P2) of the translated cDNA sequence of murine PrP protein. These free peptides, whose structural characteristics in solution were studied by circular dichroism, elicited a reasonable immunologic response in animals. Both antibodies still recognized the corresponding immunogens after affinity chromatography purification. However, only antibodies raised to the former sequence reacted by immunobolt with a purified preparation of murine scrapie amyloid protein. These findings are discussed together with their correlation to peptide structure and the effectiveness of this simplified immunization procedure.
Practical dependance of the error of ADC on conversion frequency: Researches with mathematical modeling

Traditionally, the using an analog-to-digital conversion demands agreeing with the requirements of Shannon, Nyquist and Kotel'nikov theorem. According to this theorem, the frequency of the conversion should, at least, twice exceed the upper boundary frequency of the spectrum of the converted signal. It is also traditionally considered that the presence of high-frequency noises of more than one quantization on the higher frequency has an extremely unfavorable effect on the result of the conversion. From this the need follows for pre-filtering of the signal before the conversion begins according to the conditions of this relationship. In this paper, by modeling in the VisSim program, it is shown that the conditions of this theorem are insufficient; the difference is more than an order of magnitude. At the same time, it is shown that the influence of high-frequency noises affects the conversion error much less than the effect of insufficient conversion frequency. In addition, this effect of noise is also greatly weakened by increasing the conversion frequency. The recommendations are based on this recearch are to increase the requirement of this theorem by at least 25 times, that is, requiring a 50 times excess of the conversion frequency over the upper boundary frequency of spectrum of the input signal.
Friction Estimation and Compensation for Steering Angle Control for Highly Automated Driving

This contribution presents a friction estimator for industrial purposes which identifies Coulomb friction in a steering system. The estimator only needs a few, usually known, steering system parameters. Friction occurs on almost every mechanical system and has a negative influence on high-precision position control. This is demonstrated on a steering angle controller for highly automated driving. In this steering system the friction induces limit cycles which cause oscillating vehicle movement when the vehicle follows a given reference trajectory. When compensating the friction with the introduced estimator, limit cycles can be suppressed. This is demonstrated by measurements in a series vehicle. Keywords—Friction estimation, friction compensation, steering system, lateral vehicle guidance.
Underlying liver disease influences volumetric changes in the spared hemiliver after selective internal radiation therapy with 90Y in patients with hepatocellular carcinoma

Hypertrophy of the contralateral liver lobe after treatment with yttrium‐90 (90Y) microspheres has recently been reported. This study aimed to quantify left hepatic lobe hypertrophy after right‐sided radioembolization for hepatocellular carcinoma (HCC) and to identify pretreatment predictive factors of hypertrophy in an Asian population.
Insights into correlation between board-level drop reliability and package-level ball impact test

The ball impact test is developed as a package-level measure for the board-level drop reliability of solder joints in the sense that it leads to fracturing of solder joints around the intermetallics, similar to that from a board-level drop test. In this paper, both board-level drop test and package-level ball impact test are examined numerically for solder joints of different Sn-Ag-Cu compositions. Correlations between the drop reliability and characteristics of the impact force profile are sought
Involvement of phosphatidylcholine‐selective phospholipase C in activation of mitogen‐activated protein kinase pathways in imidazoline receptor antisera‐selected protein

Imidazoline receptor antisera‐selected protein (IRAS) is considered as a candidate for the I1‐imidazoline receptor (I1R), but the signaling pathway mediated by IRAS remains unknown. In our study, the signal transduction pathways of IRAS were investigated in CHO cells stably expressing IRAS (CHO‐IRAS), and compared to the native I1R signaling pathways. Rilmenidine or moxonidine (10 nM–100 µM), I1R agonists, failed to stimulate [35S]‐GTPγS binding in CHO‐IRAS cell membrane preparations, suggesting that G protein may not be involved in IRAS signaling pathway. However, incubation of CHO‐IRAS with rilmenidine or moxonidine for 5 min could induce an upregulation of phosphatidylcholine‐selective phospholipase C (PC‐PLC) activity, and an increase in the accumulation of diacylglycerol (DAG), the hydrolysate of PC‐PLC, in a concentration‐dependent manner. The elevated activation of PC‐PLC by rilmenidine or moxonidine (100 nM) could be blocked by efaroxan, a selective I1R antagonist. Cells treated with rilmenidine or moxonidine showed an increased level of extracellular signal‐regulated kinase (ERK) phosphorylation in a concentration‐dependent manner, which could be reversed by efaroxan or D609, a selective PC‐PLC inhibitor. These results suggest that the signaling pathway of IRAS in response to I1R agonists coupled with the activation of PC‐PLC and its downstream signal transduction molecule, ERK. These findings are similar to those in the signaling pathways of native I1R, providing some new evidence for the relationship between I1R and IRAS. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Mechanism and Experiment of Planar Electrode Sensors in Water Pollutant Measurement

This paper investigates the detecting mechanism of planar electrode sensor in water pollutant detection. A system composed of electrodes, bulk media, and electrode-solution interface is built up, and the corresponding equivalent circuit containing bulk and interfacial impedances is established. The influence of each part is discussed while the impedance at interface is especially focused on. The impedance spectroscopy of the circuit is divided into three parts by the cutoff frequencies caused by interfacial and bulk impedances, and each of the frequency range can be used for the measurement of different physical quantities in water. The effect of electrode, especially the combination of interdigital and coils, is analyzed, and nine different sensors were designed and fabricated. Experiments validate the accuracy and validity of the model, and the sensor with best sensitivity is found. The stability of the planar sensor is proven in the experiment too.
Knee pain, knee osteoarthritis, and the risk of fracture.

OBJECTIVE Patients with osteoarthritis (OA) have increased bone mineral density; however, the association between knee OA and fracture is controversial. Few data exist on the association between knee pain and fracture. We examined the association of knee OA and knee pain with fracture and falls in elderly men and women. METHODS The study group comprised 6,641 men and women ages > or =75 years who participated in a 3-year randomized controlled trial of intramuscular vitamin D therapy. Patients completed a questionnaire about knee pain and OA. Fracture and fall data were collected prospectively every 6 months. RESULTS Knee pain prevalence and a clinician diagnosis of knee OA were 35.2% and 6.8%, respectively. A total of 436 incident nonvertebral fractures were reported, and 3,992 patients sustained a fall. Prevalent knee pain was associated with an increased risk of falls (hazard ratio [HR] 1.26, 95% confidence interval [95% CI] 1.17-1.36) and hip fracture (HR 2.0, 95% CI 1.18-3.37). Increasing severity of knee pain was associated with a greater risk of falls and hip fracture. Clinician diagnosis of knee OA was associated with an increased risk of nonvertebral fractures (HR 1.61, 95% CI 1.09-2.36). The increased risk of fracture was not substantially reduced by adjusting for falls, but was attenuated by adjustment for the use of walking aids. CONCLUSION Patients with a clinical diagnosis of knee OA and with knee pain have an increased risk of nonvertebral and hip fracture. This is not explained by the increased risk of falls, but is more likely to be due to the severity of falls sustained. Knee pain and OA should be regarded as independent risk factors for fracture.
Symbol and Spatial Relation Knowledge Extraction Applied to On-Line Handwritten Scripts. (Extraction de connaissances symboliques et relationnelles appliquée aux tracés manuscrits structurés en-ligne)

Our work concerns knowledge extraction from graphical languages whose symbols are a priori unknown. We are assuming that the observation of a large quantity of documents should allow to discover the symbols of the considered language. The difficulty of the problem is the two-dimensional and handwritten nature of the graphical languages that we are studying. We are considering online handwriting produced by interfaces like touch-screens, interactive whiteboards or electronic pens. The signal is then available as a sampled trajectory of the pen or finger tip, producing a sequence of strokes, themselves composed of a sequence of points. A symbol, the basic element of the alphabet of the language, is composed of a set of strokes with specific structural and relational properties. The extraction of symbols is performed by unveiling the presence of repetitive subgraphs in a global graph modeling the strokes (nodes) and their spatial relationships (arcs) of the entire document set. The principle of minimum description length (MDL) is used to select the best representatives of the symbol set. This work was validated on two experimental datasets. The first one is a dataset of simple mathematical expressions, the second is composed of graphical flowcharts. On these datasets, we can assess the quality of the extracted symbols and compared them to the ground truth. Finally, we were interested in reducing the annotation workload of a database by considering both the problems of segmentation and labeling of the different strokes.
COMPARISON OF THE EFFECTS OF DEPOLARIZING AGENTS AND NEUROTRANSMITTERS ON REGIONAL CNS CYCLIC GMP LEVELS IN VARIOUS'ANIMALS

Abstract— The effects of 121 mm‐K+, 10 mm‐glutamate, 5 mm‐GABA, 1 mm‐glycine, 0.1 mm‐NE, and 1–10 μmACh on cyclic GMP levels in tissue slices prepared from cerebral cortex and cerebellum of mouse, rabbit, guinea‐pig, cat, and rat were studied. Basal levels of cyclic GMP in the cerebella of mice, guinea‐pigs and cats were 4–15 and 70 pmol/mg prot in rat, whereas in the cerebral cortex of the same animals, levels were only 0.6–2 pmol/mg prot. In contrast, basal levels of the cyclic nucleotide were 1–2 pmol/mg prot in both of these regions in rabbit brain. Only 121 mm‐K+ was capable of increasing cyclic GMP levels in all the tissues studied. Elevations ranged from 30% in rat cerebral cortex to 2800% in mouse cerebellum. Glutamate produced a 30–1000% rise of cyclic GMP levels in all tissues except rabbit cerebellum. NE elevated levels of cyclic nucleotide 2‐ to 3‐fold in slices of cerebellum from all species studied but had no effect in cerebral cortex. GABA and glycine had no effect in any tissue except mouse cerebellum. ACh had no consistent effect on levels of cyclic GMP in any brain region investigated. These results suggest that mechanisms regulating cyclic GMP levels in mammalian CNS vary among brain regions and among animal species.
Transformation of human hand positions for robotic hand control

A method for using the human hand as a multidegree-of-freedom teaching device is described. The algorithm is based on a functional analysis of the human hand and results in an algebraic transformation of human hand positions to corresponding positions in a target domain. The target domain should be of lower dimensionality (fewer degrees of freedom) than the human hand but is not constrained in any other way. The target described here is a sixteen-degree-of-freedom robotic hand, with four fingers of four joints each. The target need not, however be a handlike device but, for each use, should have a kinematic structure with poses similar in functionality to natural poses of the human hand. <<ETX>>
Towards a Theory of Dorm Damage

Game theory has been used to analyze the efficiency of alternative institutions for the provision of a variety of public goods, ranging from public transportation to environmental protection (see Prize Committee 2007 for an overview). Game-theoretic models have also been used to analyze the performance of different legal liability regimes in accident and contract law (see Benoı̂t and Kornhauser 2002). In all of these applications, the fundamental problem is generating incentive-compatibility in the presence of externalities. The objective of this paper is to analyze the related issue of designing effective liability rules for damage to common areas of a college dormitory. To take advantage of local knowledge, I will focus on the case of Amherst College. Dorm damage, as the terms is used by the College in its official publications, encompasses a variety of offenses.1 In particular, it includes accidental, negligent and intentional damage done by students and their guests to
The anti-nonGal xenoantibody response to α1,3-galactosyltransferase gene knockout pig xenografts

Purpose of reviewAnti-nonGal xenoantibodies are a major barrier to the survival of genetically modified porcine xenografts. This review summarizes the contribution of anti-nonGal xenoantibodies to the activation of porcine endothelial cells and graft rejection, and further provides an update on recent advancements in defining the unique features of anti-nonGal xenoantibody structure. Recent findingsAnti-nonGal xenoantibodies pre-exist at low levels in humans and nonhuman primates, and are notably absent in neonates. Exposure of nonhuman primates to α1,3-galactosyltransferase gene knockout endothelial cells initiates an induced xenoantibody response that is restricted and encoded by the germline immunoglobulin heavy chain gene IGHV3-21. The target xenoantigen remains undetermined, but several candidate targets have been proposed, including carbohydrate xenoantigens. New advancements in molecular modeling provide insight on the mechanism by which xenoantibodies bind to structurally related carbohydrates. SummaryGenetic manipulation of porcine donors has significantly prolonged the survival of grafts placed into nonhuman primate recipients, but anti-nonGal xenoantibodies and thrombosis limit the ability of these grafts to function on a long-term basis. Recent developments defining pre-existing anti-nonGal xenoantibody levels, the restriction in the anti-nonGal xenoantibody response and the identification of key sites defining xenoantibody–carbohydrate interactions now provide the information necessary to develop new approaches to preventing xenoantibody-mediated rejection.
Tropomodulins: Pointed‐end capping proteins that regulate actin filament architecture in diverse cell types

Tropomodulins are a family of four proteins (Tmods 1–4) that cap the pointed ends of actin filaments in actin cytoskeletal structures in a developmentally regulated and tissue‐specific manner. Unique among capping proteins, Tmods also bind tropomyosins (TMs), which greatly enhance the actin filament pointed‐end capping activity of Tmods. Tmods are defined by a TM‐regulated/Pointed‐End Actin Capping (TM‐Cap) domain in their unstructured N‐terminal portion, followed by a compact, folded Leucine‐Rich Repeat/Pointed‐End Actin Capping (LRR‐Cap) domain. By inhibiting actin monomer association and dissociation from pointed ends, Tmods regulate actin dynamics and turnover, stabilizing actin filament lengths and cytoskeletal architecture. In this review, we summarize the genes, structural features, molecular and biochemical properties, actin regulatory mechanisms, expression patterns, and cell and tissue functions of Tmods. By understanding Tmods' functions in the context of their molecular structure, actin regulation, binding partners, and related variants (leiomodins 1–3), we can draw broad conclusions that can explain the diverse morphological and functional phenotypes that arise from Tmod perturbation experiments in vitro and in vivo. Tmod‐based stabilization and organization of intracellular actin filament networks provide key insights into how the emergent properties of the actin cytoskeleton drive tissue morphogenesis and physiology. © 2012 Wiley Periodicals, Inc
Monocytes from Patients with Type 1 Diabetes Spontaneously Secrete Proinflammatory Cytokines Inducing Th17 Cells1

Autoimmune diseases including type 1 diabetes (T1D) are thought to have a Th1/Th17 bias. The underlying mechanisms driving the activation and differentiation of these proinflammatory T cells are unknown. We examined the monocytes isolated directly from the blood of T1D patients and found they spontaneously secreted the proinflammatory cytokines IL-1β and IL-6, which are known to induce and expand Th17 cells. Moreover, these in vivo-activated monocytes from T1D subjects induced more IL-17-secreting cells from memory T cells compared with monocytes from healthy control subjects. The induction of IL-17-secreting T cells by monocytes from T1D subjects was reduced in vitro with a combination of an IL-6-blocking Ab and IL-1R antagonist. In this study, we report a significant although modest increase in the frequency of IL-17-secreting cells in lymphocytes from long-term patients with T1D compared with healthy controls. These data suggest that the innate immune system in T1D may drive the adaptive immune system by expanding the Th17 population of effector T cells.
Reversal of ABCB1-related Multidrug Resistance of Colonic Adenocarcinoma Cells by Phenothiazines.

BACKGROUND The most common mechanism that reduces the efficacy of anticancer agents is overexpression of ATP-binding cassette (ABC) drug transporters. Phenothiazines and structurally-related compounds can sensitize multidrug-resistant (MDR) cells to chemotherapeutics. MATERIALS AND METHODS Phenothiazine derivatives were investigated regarding their anticancer and MDR-reversing effect on colonic adenocarcinoma cells. The anti-proliferative and cytotoxic effects of the derivatives were assessed by the thiazolyl blue tetrazolium bromide (MTT) method, the modulation of the ABCB1 activity was measured by rhodamine 123 accumulation assay using flow cytometry. RESULTS All phenothiazines exhibited potent cytotoxic effect on the sensitive and MDR colon adenocarcinoma cell lines. The inhibition of the ABCB1 transporter was greater in the presence of the phenothiazine derivatives than for the known ABCB1 inhibitor verapamil. CONCLUSION It can be concluded that these derivatives show synergism in the presence of doxorubicin and could have potential as ABCB1 inhibitors.