Miracle-dz/UniFAR-FTUs huggingface dataset:
Alpha-synuclein as a regulator of synaptic signalling

Alpha-synuclein (α-syn) is a protein that becomes aggregated into Lewy bodies and other insoluble inclusions in Parkinson’s disease and some other neurodegenerative diseases. Its expression is increased also in drug addiction. The principal physiological function of the protein appears to be regulation of synaptic dopamine (DA) signaling in the brain, but the protein also seems to regulate other neurotransmitter systems and is expressed throughout the body. The aim of the current work was to examine the neuromodulatory effects by which α-syn influences synaptic signaling in different scenarios. The role of α-syn in development of addiction was studied by comparing α-syn protein expression between two rat lines bred for differential ethanol preference (study I). The ethanol preferring Alko, alcohol rats displayed significantly higher α-syn expression in nucleus accumbens core in comparison to their non-ethanol preferring Alko, non-alcohol counterparts. Constant potential amperometry (CPA) revealed that the increased α-syn expression in the ethanol preferring rats was associated with a decrease in stimulated DA overflow and facilitation of re-uptake. Possible role of α-syn in peripheral cholinergic signaling and motor control was examined with electromyography in wild-type and α-syn knockout mice (study II). Lack of α-syn caused dysregulation in the neuromuscular junction, and the α-syn deficient mice showed signs of deteriorated motor learning, but displayed no significant defects in muscle strength or ambulation. The effect of α-syn on general neuronal excitability and the resulting depolarization was determined by measuring the initiation and propagation of cortical spreading depression in wild-type and α-syn knockout mice using direct current potential recording (study III). However, no differences were revealed between the two lines. α-Syn can be transferred from neuron to neuron via the extracellular space, but it is not known whether exogenous α-syn is able to influence synaptic DA signalling. Therefore αsyn protein was microinjected into the brain of wild-type and α-syn knockout mice, and the effects on DA signaling were measured with CPA (study IV). This revealed that the exogenous protein can affect stimulated DA overflow and that the effects depend on the presence of endogenous α-syn. It can be concluded that α-syn is involved in the fine adjustment of synaptic signalling and its main function under normal conditions is to reduce DA release and facilitate its reuptake, even though α-syn can have also paradoxical effect on these functions under certain conditions. At the behavioral level, this synaptic modulation can affect functions such as preference for substances of abuse and motor learning. National Library of Medicine Classification: QV 126; WK 725; QV 122; WL 102.8; WL 104; WM 270 Medical Subject Headings: alpha-Synuclein; Neurotransmitter Agents; Synaptic Transmission; Neurons; Dopamine; Acetylcholine; Nucleus Accumbens; Neuromuscular Junction; Substance-Related Disorders; Cortical Spreading Depression; Electrochemistry; Electromyography; Rats
Automatic generation of paraphrases to be used as translation references in objective evaluation measures of machine translation

We propose a method that automatically generates paraphrase sets from seed sentences to be used as reference sets in objective machine translation evaluation measures like BLEU and NIST. We measured the quality of the paraphrases produced in an experiment, i.e., (i) their grammaticality: at least 99% correct sentences; (ii) their equivalence in meaning: at least 96% correct paraphrases either by meaning equivalence or entailment; and, (iii) the amount of internal lexical and syntactical variation in a set of paraphrases: slightly superior to that of hand-produced sets. The paraphrase sets produced by this method thus seem adequate as reference sets to be used for MT evaluation.
Plant Extract Mediated Synthesis of Gold Nanoparticles: A Mini-Review

Nanoparticles are an important field of research due to their unique properties as compared to their bulk structures and the diverse applications arising from these properties. The major synthesis methods available involve physical and chemical methods which are expensive and use toxic chemicals. There is hence a need for an eco-friendly synthesis route which is in par with the chemical methods. Green synthesis or biosynthesis is a good alternative where plants or microbes are used to assist nanoparticle synthesis, thereby reducing toxicity. Usually, biosynthesis is done for metallic nanoparticles, especially gold. In this paper, plant extract mediated synthesis of gold nanoparticles and the factors affecting the synthesis are discussed.
Histidine 6.55 Is a Major Determinant of Ligand-Biased Signaling in Dopamine D2L Receptor

In our previous studies, we demonstrated that the mutation of His3936.55 to alanine results in an increased affinity of 1,4-disubstituted phenylpiperazines to the dopamine D2L receptor. This change most likely accounts for the reduced steric hindrance in this part of the binding pocket. In this work, we investigated the role of the steric hindrance imposed by the residue His3936.55 for the receptor activation modulated by 1,4-disubstituted aromatic piperidines/piperazines. Site-directed mutagenesis and ligand modifications were used to probe the structural basis of ligand efficacy. The operational model of agonism was used to quantify the ligand bias between the ability of compounds to inhibit cAMP accumulation and stimulate extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Whereas substantial ligand-biased signaling was observed for the D2L wild-type receptor, an overall increase in agonism was observed for the D2L H3936.55A mutant without noteworthy functional selectivity. Targeted chemical modification of the phenylpiperazine moiety at the site of its interaction with the residue His3936.55 led to the functionally selective ligand {3-[4-(2,3-dihydro-benzofuran-7-yl)-piperazin-1-yl]-propyl}-pyrazol[1,5-a]pyridine-3-carboxamide (FAUC350) that has distinct signaling profiles toward adenylyl cyclase and ERK1/2. FAUC350 behaves as an antagonist in the inhibition of cAMP accumulation and as a partial agonist in the stimulation of ERK1/2 phosphorylation (efficacy = 55%). Overall, the residue His3936.55 and proximate molecular substructures of receptor ligands were identified to be crucial for multidimensional ligand efficacy.
Two distinct proteinase activities required for the processing of a putative nonstructural precursor protein of hepatitis C virus

Gene products of hepatitis C virus (HCV), a possible major causative agent of posttransfusion non-A, non-B hepatitis, are considered to be produced from a precursor polyprotein via proteolytic processing mediated by either host cell or viral proteinases. The presence of HCV serine proteinase has been proposed from analyses of amino acid sequence homology. To examine the processing mechanism of the HCV precursor polyprotein, the amino-terminal region of the putative nonstructural protein region of the HCV genome, containing the serine proteinase motif, was expressed and analyzed by using an in vitro transcription/translation system and a transient expression system in cultured cells. Two distinct proteinase activities which function in the production of a 70-kDa protein (p70) from the precursor polyprotein were detected. One of these proteinase activities, which cleaved the carboxyl (C)-terminal side of p70, required the presence of the serine proteinase motif, which is located in the amino (N)-terminal region of p70. That suggested that the predicted HCV serine proteinase was functional. The other activity, which was responsible for the cleavage of the N-terminal side of p70, required the expression of the region upstream and downstream of that cleavage site, including the p70 serine proteinase domain. From the results of pulse-chase analysis, using proteinase inhibitors coupled with a point mutation analysis, the latter activity was proposed to be a novel zinc-dependent metalloproteinase.
Lossless Frame Memory Compression Using Pixel-Grain Prediction and Dynamic Order Entropy Coding

Power constraints constitute a critical design issue for the portable video codec system, in which the external dynamic random access memory (DRAM) accounts for more than half of the overall system power requirements. With the ultrahigh-definition video specifications, the power consumed by accessing reference frames in the external DRAM has become the bottleneck for the portable video encoding system design. To relieve the dynamic power stresses introduced by the DRAM, a lossless compression algorithm is devised to reduce the external traffic and the memory requirements of reference frames. First, pixel-granularity directional prediction is adopted to decrease the prediction residual energy by 54.1% over the previous horizontal prediction. Second, the dynamic kth-order unary/Exp-Golomb rice coding is applied to accommodate the large-valued prediction residues. With the aforementioned techniques, an average data traffic reduction of 68.5% for the off-chip reference frames is obtained, which consequently reduces the dynamic power requirements of the DRAM by 42.3%. Based on the high data reduction ratio of the proposed compression algorithm, a partition group table-based storage space reduction scheme is provided to improve the utilization of row buffers in the DRAM. Consequently, an additional 14.5% of the DRAM dynamic power can be saved by reducing the number of row buffer activations. In total, a 56.8% decrease in the dynamic power requirements of the external reference frame access can be obtained using our strategies. With TSMC 65-nm CMOS logic technology, our algorithm was implemented in a parallel VLSI architecture based on a compressor and decompressor at the cost of 36.5k and 34.7k, respectively, in terms of gate count. The throughputs of the proposed compressor and decompressor are 1.54 and 0.78 Gpixels/s, which are suitable for quad full high definition (4K) @ 94 frames/s real-time encoding with the level-D reference data reuse scheme.
Several Lipid-Related Gene Polymorphisms Interact with Overweight/Obesity to Modulate Blood Pressure Levels

Little is known about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on blood pressure levels. The present study was undertaken to detect 10 lipid-related gene SNPs and their interactions with overweight/obesity on blood pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII hepatic lipase gene (LIPC) −250G > A, endothelial lipase gene (LIPG) 584C > T, methylenetetrahydrofolate reductase (MTHFR) 677C > T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T > C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed in 978 normal weight and 751 overweight/obese subjects. The interactions were detected by factorial regression analysis. The genotypes of ACAT-1 AC, LIPC GA and AA, and SCARB1 TT; LDL-R A-A- and LIPC GA; and SCARB1 TT were interacted with overweight/obesity to increase systolic, diastolic blood pressure (SBP, DBP) and pulse pressure (PP) levels; respectively. The genotypes of ACAT-1 CC; ACAT-1 AA and CC were interacted with overweight/obesity to decrease SBP, PP levels (p < 0.01–0.001); respectively. The differences in blood pressure levels between normal weight and overweight/obese subjects might partly result from different interactions of several SNPs and overweight/obesity.
Exercise intensity during wheelchair rugby training

Abstract The purpose of this study was to determine the ability of individuals with a cervical spinal cord injury to achieve and sustain a cardiorespiratory training intensity during wheelchair rugby. Nine wheelchair rugby players completed a continuous peak exercise test on a SciFit Pro I arm ergometer with stage increases each minute to determine peak heart rate and power output. Approximately one week after peak exercise testing, heart rate was recorded (every 5 s) during three regularly scheduled rugby training sessions. Data were analysed to determine the number of continuous minutes that participants spent above 70% of heart rate reserve under various rugby training activities. The percent of time spent at or above 70% heart rate reserve varied across participants and conditions. Continuous pushing was the least variable training condition among participants with the sample averaging greater than 73% of time above the target heart rate. Scrimmage training was highly variable across participants with a range of 0% to 98% of time above the criterion. Results of this study indicate that wheelchair rugby training enables some participants to reach a training intensity associated with improved cardiorespiratory fitness, and that the type (or kind) of training activity dictates the extent to which individuals sustain such a threshold.
Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mimics Epstein-Barr Virus EBNA1 Immune Evasion through Central Repeat Domain Effects on Protein Processing

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8 [HHV8]) and Epstein-Barr virus (EBV/HHV4) are distantly related gammaherpesviruses causing tumors in humans. KSHV latency-associated nuclear antigen 1 (LANA1) is functionally similar to the EBV nuclear antigen-1 (EBNA1) protein expressed during viral latency, although they have no amino acid similarities. EBNA1 escapes cytotoxic lymphocyte (CTL) antigen processing by inhibiting its own proteosomal degradation and retarding its own synthesis to reduce defective ribosomal product processing. We show here that the LANA1 QED-rich central repeat (CR) region, particularly the CR2CR3 subdomain, also retards LANA1 synthesis and markedly enhances LANA1 stability in vitro and in vivo. LANA1 isoforms have half-lives greater than 24 h, and fusion of the LANA1 CR2CR3 domain to a destabilized heterologous protein markedly decreases protein turnover. Unlike EBNA1, the LANA1 CR2CR3 subdomain retards translation regardless of whether it is fused to the 5′ or 3′ end of a heterologous gene construct. Manipulation of sequence order, orientation, and composition of the CR2 and CR3 subdomains suggests that specific peptide sequences rather than RNA structures are responsible for synthesis retardation. Although mechanistic differences exist between LANA1 and EBNA1, the primary structures of both proteins have evolved to minimize provoking CTL immune responses. Simple strategies to eliminate these viral inhibitory regions may markedly improve vaccine effectiveness by maximizing CTL responses.
The Clinical Utility and Diagnostic Performance of Magnetic Resonance Imaging for Identification of Early and Advanced Knee Osteoarthritis

Background: Current diagnostic strategies for detection of structural articular cartilage abnormalities, the earliest structural signs of osteoarthritis, often do not capture the condition until it is too far advanced for the most potential benefit of noninvasive interventions. Purpose: To systematically review the literature relative to the following questions: (1) Is magnetic resonance imaging (MRI) a valid, sensitive, specific, accurate, and reliable instrument to identify knee articular cartilage abnormalities compared with arthroscopy? (2) Is MRI a sensitive tool that can be utilized to identify early cartilage degeneration? Study Design: Systematic review. Methods: A systematic search was performed in November 2010 using PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus (from 1985), SCOPUS (from 1996), and EMBASE (from 1974) databases. Results: Fourteen level I and 13 level II studies were identified that met inclusion criteria and provided information related to diagnostic performance of MRI compared with arthroscopic evaluation. The diagnostic performance of MRI demonstrated a large range of sensitivities, specificities, and accuracies. The sensitivity for identifying articular cartilage abnormalities in the knee joint was reported between 26% and 96%. Specificity and accuracy were reported between 50% and 100% and between 49% and 94%, respectively. The sensitivity, specificity, and accuracy for identifying early osteoarthritis were reported between 0% and 86%, 48% and 95%, and 5% and 94%, respectively. As a result of inconsistencies between imaging techniques and methodological shortcomings of many of the studies, a meta-analysis was not performed, and it was difficult to fully synthesize the information to state firm conclusions about the diagnostic performance of MRI. Conclusion: There is evidence in some MRI protocols that MRI is a relatively valid, sensitive, specific, accurate, and reliable clinical tool for identifying articular cartilage degeneration. Because of heterogeneity of MRI sequences, it is not possible to make definitive conclusions regarding its global clinical utility for guiding diagnosis and treatment strategies. Clinical Relevance: Traumatic sports injuries to the knee may be significant precursor events to early onset of posttraumatic osteoarthritis. Magnetic resonance imaging may aid in early identification of structural injuries to articular cartilage as evidenced by articular cartilage degeneration grading.
Amelioration of ultraviolet-induced photokeratitis in mice treated with astaxanthin eye drops

Purpose Ultraviolet (UV) acts as low-dose ionizing radiation. Acute UVB exposure causes photokeratitis and induces apoptosis in corneal cells. Astaxanthin (AST) is a carotenoid, present in seafood, that has potential clinical applications due to its high antioxidant activity. In the present study, we examined whether topical administration of AST has preventive and therapeutic effects on UV-photokeratitis in mice. Methods C57BL/6 mice were administered with AST diluted in polyethylene glycol (PEG) in instillation form (15 μl) to the right eye. Left eyes were given vehicle alone as controls. Immediately after the instillation, the mice, under anesthesia, were irradiated with UVB at a dose of 400 mJ/cm2. Eyeballs were collected 24 h after irradiation and stained with H&E and TUNEL. In an in vitro study, mouse corneal epithelial (TKE2) cells were cultured with AST before UV exposure to quantify the UV-derived cytotoxicity. Results UVB exposure induced cell death and thinning of the corneal epithelium. However, the epithelium was morphologically well preserved after irradiation in AST-treated corneas. Irradiated corneal epithelium was significantly thicker in eyes treated with AST eye drops, compared to those treated with vehicles (p<0.01), in a doses dependent manner. Significantly fewer apoptotic cells were observed in AST-treated eyes than controls after irradiation (p<0.01). AST also reduced oxidative stress in irradiated corneas. The in vitro study showed less cytotoxicity of TKE2 cells in AST-treated cultures after UVB-irradiation (p<0.01). The cytoprotective effect increased with the dose of AST. Conclusions Topical AST administration may be a candidate treatment to limit the damages by UV irradiation with wide clinical applications.
Improving the Recommendation of Collaborative Filtering by Fusing Trust Network

To accurately and actively provide users with their potentially interested information or services is the main task of a recommender system. Collaborative filtering is one of the most widely adopted recommender methods, whereas it is suffering the issue of sparse rating data that will severely degenerate the quality of recommendations. To address this issue, the article proposes a novel method, named the FTRA (Fusing Trust and Ratings), trying to improve the performance of collaborative filtering recommendation by means of elaborately integrating twofold sparse information, i.e., the conventional rating data given by users and the social trust network among the same users. The performance of FTRA is rigorously validated by comparing it with six representative methods on a real-world dataset. The experimental results show that the FTRA outperforms all other competitors in terms of both precision and recall. More importantly, our work suggests that the strategy of augmenting sparse rating data by fusing trust networks does significantly improve the quality of conventional collaborative filtering recommendation, and its quality could be further improved by means of designing more effective integrating schemes.
Continuously Predicting and Processing Barge-in During a Live Spoken Dialogue Task

Barge-in enables the user to provide input during system speech, facilitating a more natural and efficient interaction. Standard methods generally focus on singlestage barge-in detection, applying the dialogue policy irrespective of the barge-in context. Unfortunately, this approach performs poorly when used in challenging environments. We propose and evaluate a barge-in processing method that uses a prediction strategy to continuously decide whether to pause, continue, or resume the prompt. This model has greater task success and efficiency than the standard approach when evaluated in a public spoken dialogue system.
Why do Dominant Personalities Attain Influence in Groups? A Competence-Signaling Account of Trait Dominance

Individuals high in the personality trait dominance consistently attain high levels of influence in groups. Why they do is unclear, because most group theories assert that people cannot attain influence simply by being assertive and forceful; they need to possess superior task abilities and leadership skills. In the current research, we tested the idea that individuals high in trait dominance often attain influence because they behave in ways that make them appear competent (even when they are not). Our two studies examined task groups using a Social Relations analysis (Kenny & LaVoie, 1984). We found that individuals higher in trait dominance were rated as more competent by fellow group members, outside peer observers, and research staff members – even after controlling for their actual abilities. Frequency counts of discrete behaviors confirmed that dominance predicts the display of competence-signaling behaviors, which in turn predicts peer-ratings of competence. These findings extend our understanding of hierarchies in groups and of interpersonal perceptions of competence and abilities.
The effects of model parameter deviations on the variance of a linearly filtered time series

We consider a general linear filtering operation on an autoregressive moving average (ARMA) time series. The variance of the filter output, which is an important quantity in many applications, is not known with certainty because it depends on the true ARMA parameters. We derive an expression for the sensitivity (i.e., the partial derivative) of the output variance with respect to deviations in the model parameters. The results provide insight into the robustness of many common statistical methods that are based on linear filtering and also yield approximate confidence intervals for the output variance. We discuss applications to time series forecasting, statistical process control, and automatic feedback control of industrial processes. © 2010 Wiley Periodicals, Inc. Naval Research Logistics, 2010