Miracle-dz/UniFAR-FTUs huggingface dataset:
Aurintricarboxylic Acid Is a Potent Inhibitor of Influenza A and B Virus Neuraminidases

Background Influenza viruses cause serious infections that can be prevented or treated using vaccines or antiviral agents, respectively. While vaccines are effective, they have a number of limitations, and influenza strains resistant to currently available anti-influenza drugs are increasingly isolated. This necessitates the exploration of novel anti-influenza therapies. Methodology/Principal Findings We investigated the potential of aurintricarboxylic acid (ATA), a potent inhibitor of nucleic acid processing enzymes, to protect Madin-Darby canine kidney cells from influenza infection. We found, by neutral red assay, that ATA was protective, and by RT-PCR and ELISA, respectively, confirmed that ATA reduced viral replication and release. Furthermore, while pre-treating cells with ATA failed to inhibit viral replication, pre-incubation of virus with ATA effectively reduced viral titers, suggesting that ATA may elicit its inhibitory effects by directly interacting with the virus. Electron microscopy revealed that ATA induced viral aggregation at the cell surface, prompting us to determine if ATA could inhibit neuraminidase. ATA was found to compromise the activities of virus-derived and recombinant neuraminidase. Moreover, an oseltamivir-resistant H1N1 strain with H274Y was also found to be sensitive to ATA. Finally, we observed additive protective value when infected cells were simultaneously treated with ATA and amantadine hydrochloride, an anti-influenza drug that inhibits M2-ion channels of influenza A virus. Conclusions/Significance Collectively, these data suggest that ATA is a potent anti-influenza agent by directly inhibiting the neuraminidase and could be a more effective antiviral compound when used in combination with amantadine hydrochloride.
The effects of plasma volume variations on the calcium concentration during epidural anaesthesia

The plasma variations of the ionized and total calcium concentration in relation to protein concentration and plasma volume were studied in 12 patients during epidural anaesthesia for transurethral prostatectomy. The most significant changes were noted during the onset of anaesthesia. From arrival in the operating theatre to start of operation, the plasma concentration of ionized calcium decreased from 1.28 (s.d. = 0.05) mmol/l to 1.22 (s.d. = 0.04) mmol/l and total calcium decreased from 2.39 (s.d. = 0.11) mmol/l to 2.17 is. (s.d. = 0.10) mmol/l. At the same time, however, the decrease in ionized calcium concentration and the increase in plasma volume were associated with a rise of 10.3% in the pool of free calcium ion in plasma. After the start of surgery, the plasma ionized calcium concentration remained almost unaffected throughout the rest of the study period. The total plasma calcium concentration as well as the total protein concentration remained stable during operation, only increasing after the end of surgery. The preoperative changes in the plasma calcium concentration may have been the result of both haemodilution and mobilization of calcium ions from its bone stores. Postoperatively, an increased urinary loss of calcium must have followed the administration of furosemide at the end of surgery.
Matrix Metalloproteinases in Neuropathic Pain and Migraine: Friends, Enemies, and Therapeutic Targets

Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent endopeptidases that mediate extracellular matrix turnover and associated processes, such as cell survival, growth, and differentiation. This paper discusses important functions of MMP in the normal and injured nervous system, focusing on the role played by these proteases in neurological pain syndromes, most prominently in neuropathic pain and migraine headaches. In the past decade, metalloproteinases emerged as key modulators of neuropathic pain, with MMP-9 acting as an initiator of the neuropathic cascade. Increased MMP activity was detected in migraine patients, independent of aura, in tight association with metabolic derangements. The therapeutic implications of MMP inhibition are considered in the context of neurogenic pain regulation.
SPORE: A sequential personalized spatial item recommender system

With the rapid development of location-based social networks (LBSNs), spatial item recommendation has become an important way of helping users discover interesting locations to increase their engagement with location-based services. Although human movement exhibits sequential patterns in LBSNs, most current studies on spatial item recommendations do not consider the sequential influence of locations. Leveraging sequential patterns in spatial item recommendation is, however, very challenging, considering 1) users' check-in data in LBSNs has a low sampling rate in both space and time, which renders existing prediction techniques on GPS trajectories ineffective; 2) the prediction space is extremely large, with millions of distinct locations as the next prediction target, which impedes the application of classical Markov chain models; and 3) there is no existing framework that unifies users' personal interests and the sequential influence in a principled manner. In light of the above challenges, we propose a sequential personalized spatial item recommendation framework (SPORE) which introduces a novel latent variable topic-region to model and fuse sequential influence with personal interests in the latent and exponential space. The advantages of modeling the sequential effect at the topic-region level include a significantly reduced prediction space, an effective alleviation of data sparsity and a direct expression of the semantic meaning of users' spatial activities. Furthermore, we design an asymmetric Locality Sensitive Hashing (ALSH) technique to speed up the online top-k recommendation process by extending the traditional LSH. We evaluate the performance of SPORE on two real datasets and one large-scale synthetic dataset. The results demonstrate a significant improvement in SPORE's ability to recommend spatial items, in terms of both effectiveness and efficiency, compared with the state-of-the-art methods.
Risk factors for Recurrent Anterior Cruciate Ligament Reconstruction: A Population Study in Ontario, Canada with 5-year Follow-up

Objectives: Anterior cruciate ligament reconstruction (ACLR) is routinely performed to treat symptomatic instability. Despite being a common procedure, significant variation persists in technique and graft choice. How patient, provider and surgical factors influence the risk of revision or contralateral primary ACLR has not been investigated using administrative data. The goal of our study was to define the rate and risk factors for ACL re-operation in Ontario. Methods: All primary elective ACLR performed in Ontario, Canada from July 2003 to March 2008 in patients aged 15 to 60 years were identified via billing, diagnosis and procedural databases. The main outcomes were revision and contralateral ACLR, sought until January 2012. Patient factors (age, gender, co-morbidity, income quintile, and length of index hospital admission), provider factors (surgeon volume, academic hospital status) and surgical factors (allograft vs. autograft; fixation: screw, button, staple; concomitant operative procedures) were used as covariates in a Cox Proportional Hazards survivorship model to generate Hazard Ratios (HR) with confidence intervals (alpha 0.05). Kaplan-Meier survivorship curves to revision were generated. Results: A total of 12,967 ACLR with a mean follow-up of 5.2 years were identified. The revision rate was 2.6% [after a median 2.72 years (interquartile range 1.38, 4.11)]. The rate of primary contralateral ACLR was 4.6% [after a median 2.71 years (interquartile range 1.49, 4.22)]. In the Cox model, younger age [15-19 years; HR=2.1 (95% CI: 1.5-2.9), p<0.001], ACLR performed at an academic hospital [HR=1.6 (95% CI: 1.2-2.1), p<0.001] and the use of allograft [HR=1.7 (95% CI: 1.1-2.6), p=0.02] significantly increased the risk of revision ACLR. The K-M curves to revision ACLR for allograft and autograft demonstrated equivalent survivorship for approximately 3 years, after which allograft ACLR were more commonly revised (Figure 1). Only younger age [15-19 years; HR=2.1, (95% CI: 1.6-2.7), p<0.001] was associated with an increased risk of contralateral ACLR. Conclusion: Contralateral ACLR was more frequent than revision ACLR in this population, while both re-operations were significantly more common in patients <20 years old. Academic hospital status but not surgeon volume, and the use of allograft also increased the risk of revision ACLR. Late failure of allograft ACLR is a novel finding.
A Locus on Chromosome 5 Is Associated with Dilated Cardiomyopathy in Doberman Pinschers

Dilated cardiomyopathy (DCM) is a heterogeneous group of heart diseases with a strong genetic background. Currently, many human DCM cases exist where no causative mutation can be identified. DCM also occurs with high prevalence in several large dog breeds. In the Doberman Pinscher a specific DCM form characterized by arrhythmias and/or echocardiographic changes has been intensively studied by veterinary cardiologists. We performed a genome-wide association study in Doberman Pinschers. Using 71 cases and 70 controls collected in Germany we identified a genome-wide significant association to DCM on chromosome 5. We validated the association in an independent cohort collected in the United Kingdom. There is no known DCM candidate gene under the association signal. Therefore, DCM in Doberman Pinschers offers the chance of identifying a novel DCM gene that might also be relevant for human health.
T Cells Line SK-RC-45 Are Involved in Tumor-induced Apoptosis of Gangliosides Expressed by the Renal Cell Carcinoma Cell

It is now understood that the genetic plasticity of cancer cells can lead to alterations that confer selective growth advantages to the tumor, some of which play a role in immune escape. A number of mutations veiling tumor cells from host immune defenses have been well characterized but more recent studies suggest that a variety of tumors can also express products that are actually toxic for the immune effectors. A component of this tumor-induced T-cell death has been attributed to receptor-mediated apoptosis. Some tumors, however, synthesize soluble factors that mediate similar effects. In this regard, we previously showed that supernatants from explanted renal cell carcinoma (RCC) tumors sensitized normal T cells to activation induced cell death, and the responsible products had the features of gangliosides. We have also shown that renal tumor lines, including SK-RC-45, induce apoptosis of both Jurkat cells and normal T lymphocytes. Here, we used the ganglioside synthesis inhibitor PPPP to define the role of gangliosides in RCC cell line (SK-RC-45)-mediated T cell and Jurkat cell apoptosis and to elucidate the proapoptotic molecular events by which the glycosphingolipids produce their effects. The ganglioside-synthesizing SK-RC-45 line stimulated the TUNEL (terminal deoxynucleotidyl transferase-mediated nick end labeling) positivity of cocultured T cells by a mechanism that involved decreasing lymphocyte expression levels of Bcl-2 and Bcl-XL, inducing cytochrome c release from their mitochondria and activating caspases 9 and 3. These proapoptotic events were partially or completely abrogated when tumor cells were pretreated with PPPP for 5 days before the SK-RC-45/T lymphocyte coincubation, a regimen that reduced tumor-associated ganglioside levels by 70–80%. Our results suggest that gangliosides may be key mediators of RCC-induced T-cell apoptosis and imply that they contribute to the T-cell dysfunction in the tumor microenvironment.
Lack of Effect of Ginkgo biloba on Voriconazole Pharmacokinetics in Chinese Volunteers Identified as CYP2C19 Poor and Extensive Metabolizers

Background: Ginkgo biloba is one of the most popular herbal supplements in the world. The supplement has been shown to induce the enzymatic activity of CYP2C19, the main cytochrome P450 isozyme involved in voriconazole metabolism. Because this enzyme exhibits genetic polymorphism, the inductive effect was expected to be modulated by the CYP2C19 metabolizer status. Objective: To examine the possible effects of Ginkgo biloba as an inducer of CYP2C19 on single-dose pharmacokinetics of voriconazole in Chinese volunteers genotyped as either CVP2C19 extensive or poor metabolizers. Methods: Fourteen healthy, nonsmoking volunteers–7 CYP2C19 extensive metabolizers (2C19*1/2C19*1) and 7 poor metabolizers (2C19*2/2C19*2)–were selected to participate in this study. Pharmacokinetics of oral voriconazole 200 mg after administration of Ginkgo biloba 120 mg twice daily for 12 days were determined for up to 24 hours by liquid chromatography–electrospray tandem mass spectrometry in a 2-phase randomized crossover study with 4-week washout between phases. Results: For extensive metabolizers, the median value for voriconazole area under the plasma concentration–time curve from zero to infinity (AUC0-00) was 5.17 μg•h/mL after administration of voriconazole alone and 4.28 μg•/mL after voriconazole with Ginkgo biloba (p > 0.05). The other pharmacokinetic parameters of voriconazole such as AUC0-24, time to reach maximum concentration, half-life, and apparent clearance also did not change significantly for extensive metabolizers in the presence of Ginkgo biloba. Pharmacokinetic parameters followed a similar pattern for poor metabolizers. Conclusions: The results suggest that 12 days of treatment with Ginkgo biloba did not significantly alter the single-dose pharmacokinetics of voriconazole in either CYP2C19 extensive or poor metabolizers. Therefore, the pharmacokinetic interactions between voriconazole and Ginkgo biloba may have limited clinical significance.
Spatio-temporal data clustering based on type-2 fuzzy sets and cloud models

The time series remote sensing data and meteorological satellite data offer new opportunities for understanding the earth system. Spatio-temporal data clustering becomes a kind of idea tool to explore huge data space of spatio-temporal data. Because there are many uncertainties in the huge spatio-temporal data, including fuzziness and randomness, the spatio-temporal clustering methods with uncertainties are needed. Based on type-2 fuzzy sets and cloud models, the paper analyzes the uncertainty of the membership of FCM (fuzzy C-means), and proposes CFFCM (cloud fuzzifier fuzzy C-means) method. Take the time series SST (sea surface temperature) data as examples, the paper applies CFFCM to carry out spatio-temporal clustering analysis, and discovers some interesting patterns.
Molecular analysis of foot-and-mouth disease type O viruses isolated in Saudi Arabia between 1983 and 1995

Partial nucleotide sequence of the capsid polypeptide coding gene 1D (VP1) was determined for 68 serotype O foot-and-mouth disease viruses isolated between 1983 and 1995 from outbreaks occurring in Saudi Arabia. The sequences were compared with previously published sequences: 14 viruses of Middle Eastern origin (isolated between 1987 and 1991); and with four vaccine virus strain sequences, three originating from the Middle East (O1/Turkey/Manisa/69, O1/Sharquia/Egypt/72 and O1/Israel/2/85) and one from Europe (O1/BFS 1860/UK/67). The virus isolates from Saudi Arabia and the Middle East vaccine virus strains formed a related genetic group distinct from the European O1virus. Within this large group 12 distinct genetic sublineages were observed.
Challenge Organisms for Inactivation of Viruses by Ultraviolet Treatment [ Project # 3105 ]

BACKGROUND: Ultraviolet reactors that are used for drinking water disinfection need to be tested to ensure they are delivering the required doses and achieving the desired level of pathogen inactivation to protect public health. Testing methods can use biological, chemical, or particle surrogates, although not all approaches have been approved for reactor validation. The non-pathogenic bacteriophage MS2 and Bacillus subtilis spores are currently recognized as the standard challenge organisms for reactor validation because they are more UV resistant than most waterborne pathogens. However, an important group of potentially waterborne viruses, the adenoviruses, is considerably more UV resistant than other pathogens and the standard MS2 and B. subtilis biodosimeters. Based on the high UV resistance of adenoviruses, the USEPA’s Long Term 2 Enhanced Surface Water Treatment Rule (LT2ESWTR) and Ground Water Rule (GWR) require a UV dose of 186 mJ/cm for 4-log inactivation of viruses. This level of MS2 inactivation is achieved with a dose of approximately 85 mJ/cm, thereby limiting the utility of MS2 for reactor validation at the high doses required for virus inactivation credit, or other high-dose applications. An alternative challenge organism is required that has similar or higher UV resistance compared to adenoviruses. The ideal challenge organism would be non-pathogenic, easily grown to high concentrations, easily enumerated in a growth or infectivity assay, display minimal shoulder (lag) or tailing of the dose response curve, stable for relatively long periods with minimal die-off, robust under typical testing conditions, and effectively model the reactor’s disinfection efficiency toward the target pathogen.
OBFS: A File System for Object-Based Storage Devices

The object-based storage model, in which files are made up of o ne or more data objects stored on self-contained Object-Based Storage Devices (OSDs), is em erging as an architecture for distributed storage systems. The workload presented to the OSDs will be q uite different from that of generalpurpose file systems, yet many distributed file systems employ general-purpose file systems as their underlying file system. We present OBFS, a small and highly ef ficient file system designed for use in OSDs. Our experiments show that our user-level implement ation of OBFS outperforms Linux Ext2 and Ext3 by a factor of two or three, and while OBFS is 1/25 the size of XFS, it provides only slightly lower read performance and 10%‐40% higher write pe rformance.
Estimation and Test of a Simple Model of Intertemporal Capital Asset Pricing

A simple valuation model with time-varying investment opportunities is developed and estimated. The model assumes that the investment opportunity set is completely described by the real interest rate and the maximum Sharpe ratio, which follow correlated Ornstein-Uhlenbeck processes. The model parameters and time series of the state variables are estimated using U.S. Treasury bond yields and expected inflation from January 1952 to December 2000, and as predicted, the estimated maximum Sharpe ratio is related to the equity premium. In cross-sectional asset-pricing tests, both state variables have significant risk premia, which is consistent with Merton's ICAPM. Copyright 2004 by The American Finance Association.
The Influence of the Social Environment Context in Stress and Coping in Sport

Lazarus (1999) model of stress and coping is based on the reciprocal interaction between the person and the environment. The aim of this study therefore was to examine whether the social environment (significant others) are of influence on the stress and coping of team athletes. The study consisted of two separate studies in which a total of 12 team athletes participated. First, six field hockey players (two males, four females) aged 18–29 years (M = 23.0 years) participated in a diary study. Second, six team athletes of different sports (two males, four females) aged 24–29 years (M = 25.8 years) were interviewed. The results showed that in particular teammates are important for the appraisal of stress and coping in team sports. For over half (i.e., 51.5%) of the reported stressors in the diary study the participants felt that others were of influence on their coping. Team athletes experienced the highest stress intensity during competition, or when they appraised the situation as a threat. When others were of influence the team athletes were most likely to appraise the situation as a challenge and use problem- or emotion-focused coping strategies. These finding might provide a new portal for intervention to enhance coping with stress in sport and enhance performance and satisfaction.
A Model for Integrating Elementary Neural Functions into Delayed-Response Behavior

It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning), and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task), or recalling from this image another one that has been associated with it during training (delayed-pair association task). The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.
The role of vitamin D, estrogen, calcium sensing receptor genotypes and serum calcium in the pathogenesis of prostate cancer.

INTRODUCTION Prostate cancer is the second leading cause of cancer death among men in developed countries. Estrogen receptor-alpha (ER-α), vitamin D receptor (VDR), and the calcium-sensing receptor (CaSR), partly through their effects on calcium levels are implicated in the proliferation and carcinogenesis in the prostate gland. VDR, ER-α and CaSR genes show polymorphisms in humans that appear to have clinical significance in many pathological conditions, such as prostate cancer. Our aim was to evaluate the role of ER-α (PvuII, XbaI), VDR (BsmI) and CaSR (A986S) gene polymorphisms and serum calcium levels in the pathogenesis of prostate cancer. MATERIAL AND METHODS Two hundred four patients with prostate cancer and 102 healthy controls were recruited into a hospital-based case control study. After genotyping, the relationship between the individual genotypes and prostate cancer was investigated. RESULTS Both the ER-α XbaI and the VDR BsmI polymorphisms were significantly related to the risk of prostate cancer. An age adjusted logistic regression limited to controls and patients not receiving bisphosphonate therapy showed that higher corrected serum calcium and the VDR Bb/BB genotypes independently increased the risk of prostate cancer. CONCLUSIONS ER-α XbaI and VDR BsmI genetic polymorphisms had a significant association with the risk of prostate cancer. Both VDR BsmI genotypes and serum calcium levels were independently related to the risk of prostate cancer, suggesting an influence of VDR on the development of this malignancy.