Miracle-dz/UniFAR-FTUs huggingface dataset:
The Predominant Mechanism by Which Ribavirin Exerts Its Antiviral Activity In Vitro against Flaviviruses and Paramyxoviruses Is Mediated by Inhibition of IMP Dehydrogenase

ABSTRACT It is not yet clear to what extent depletion of intracellular GTP pools contributes to the antiviral activity of ribavirin. Therefore, the antiviral activities of (i) ribavirin, (ii) its 5-ethynyl analogue, 5-ethynyl-1-β-d-ribofuranosylimidazole-4-carboxamide (EICAR), and (iii) mycophenolic acid (MPA) (a compound that inhibits only cellular IMP dehydrogenase activity) were studied on the replication of flaviviruses and paramyxoviruses. In addition, the effects of these three compounds on intracellular GTP pools were assessed. A linear correlation was observed over a broad concentration range between the antiviral activities of ribavirin, EICAR, and MPA and the effects of these compounds on GTP pool depletion. When the 50% effective concentrations (EC50s) for the antiviral activities of ribavirin, EICAR, and MPA were plotted against the respective EC50 values for GTP pool depletion, a linear correlation was calculated. These data provide compelling evidence that the predominant mechanism of action of ribavirin in vitro against flavi- and paramyxoviruses is based on inhibition of cellular IMP dehydrogenase activity.
Brain Tumor Detection Using Image Segmentation

-In medical image processing brain tumor detection is a challenging task. Image of brain is difficult to understand. Noise and delay affects the image accuracy. In thistechniqueMRI (magnetic resonance imaging) has became a useful medical diagnostic tool for diagnosis of brain and other medical images. Image segmentation is a major area of medical image processing. The main objective of this paper is to delay using watershed and contrast technique.
Efficacy and safety of early parenteral anticoagulation as a bridge to warfarin after mechanical valve replacement

Summary Limited evidence exists to guide the use of early parenteral anticoagulation following mechanical heart valve replacement (MVR). The purpose of this study was to compare the 30-day rates of thrombotic and bleeding complications for MVR patients receiving therapeutic versus prophylactic dose bridging regimens. In this retrospective cohort study we reviewed anticoagulation management and outcomes of all patients undergoing MVR at five Canadian hospitals between 2003 and 2010. The primary efficacy outcome was thromboembolism (stroke, transient ischaemic attack, systemic embolism or valve thrombosis) and the primary safety outcome was major bleeding at 30-days. Outcomes were compared using a logistic regression model adjusting for propensity score and in a 1:1 propensity matched sample. A total of 1777 patients underwent mechanical valve replacement, of whom 923 received therapeutic dose bridging anticoagulation and 764 received prophylactic dose bridging postoperatively. Sixteen patients (1.8 %) who received therapeutic dose bridging and fifteen patients (2.1 %) who received prophylactic dose bridging experienced the primary efficacy outcome (odds ratio [OR] 0.90; 95 % confidence interval [CI], 0.37 to 2.18, p=0.81). Forty-eight patients (5.4 %) in the therapeutic dosing group and 14 patients (1.9 %) in the prophylactic dosing group experienced the primary safety outcome of major bleeding (OR 3.23; 95 % CI, 1.58 to 6.62; p=0.001). The direction of the effects, their magnitude and significance were maintained in the propensity matched analysis. In conclusion, we found that early after mechanical valve replacement, therapeutic dose bridging was associated with a similar risk of thromboembolic complications, but a 2.5 to 3-fold increased risk of major bleeding compared with prophylactic dose bridging.
Genomic Changes of Chagas Disease Vector, South America

We analyzed the main karyologic changes that have occurred during the dispersion of Triatoma infestans, the main vector of Chagas disease. We identified two allopatric groups, named Andean and non-Andean. The Andean specimens present C-heterochromatic blocks in most of their 22 chromosomes, whereas non-Andean specimens have only 4–7 autosomes with C-banding. These heterochromatin differences are the likely cause of a striking DNA content variation (approximately 30%) between Andean and non-Andean insects. Our study, together with previous historical and genetic data, suggests that T. infestans was originally a sylvatic species, with large quantities of DNA and heterochromatin, inhabiting the Andean region of Bolivia. However, the spread of domestic T. infestans throughout the non-Andean regions only involved insects with an important reduction of heterochromatin and DNA amounts. We propose that heterochromatin and DNA variation mainly reflected adaptive genomic changes that contribute to the ability of T. infestans to survive, reproduce, and disperse in different environments.
Potentially functional polymorphisms in DNA repair genes and non‐small‐cell lung cancer survival: A pathway‐based analysis

To assess systematically whether potentially functional polymorphisms in DNA repair genes influence the clinical behavior of non‐small‐cell lung cancer (NSCLC), we examined the impact of a comprehensive panel of 218 signal nucleotide polymorphisms (SNP) in 50 candidate DNA repair genes on overall survival of NSCLC in a case‐cohort of 568 lung cancer patients. SNPs associated with lung cancer prognosis primarily mapped to 14 genes in different repair pathways, and 6 SNPs were remained in the final model after multivariate stepwise Cox regression analysis: ATM rs189037; MRE11A rs11020802; ERCC2 rs1799793; MBD4 rs140693; XRCC1 rs25487, and PMS1 rs5742933. In the combined analysis of these 6 SNPs, an increasing number of unfavorable loci was associated with a poorer prognosis (P for trend: <0.0001) and patients having 2–4 unfavorable loci had a 1.99‐fold elevated risk of death 95% confidence interval (CI) = 1.58–2.50, compared with those carrying 0–1 unfavorable loci, and this elevated risk was more evident among stages I–II patients (hazard ratio = 3.04, 95% CI = 1.86–4.98, P for heterogeneity: 0.07). Furthermore, a significant effect of SNPs in nucleotide excision repair pathway on lung cancer survival was observed among 185 stages III–IV patients treated with platinum‐based chemotherapy without surgical operation: XPC rs2228000 (Ala499Val; P = 0.002) and ERCC1 rs11615 (Asn118Asn; P = 0.012). Our data indicate that potentially functional polymorphisms in DNA repair genes may serve as candidate prognostic markers of clinical outcome of NSCLC. © 2011 Wiley Periodicals, Inc.
Influence in Classification via Cooperative Game Theory

A dataset has been classified by some unknown classifier into two types of points. What were the most important factors in determining the classification outcome? In this work, we employ an axiomatic approach in order to uniquely characterize an influence measure: a function that, given a set of classified points, outputs a value for each feature corresponding to its influence in determining the classification outcome. We show that our influence measure takes on an intuitive form when the unknown classifier is linear. Finally, we employ our influence measure in order to analyze the effects of user profiling on Google's online display advertising.
The ica Locus of Staphylococcus epidermidis Encodes Production of the Capsular Polysaccharide/Adhesin

ABSTRACT Clinical isolates of coagulase-negative staphylococci often elaborate a biofilm involved in adherence to medical devices and resistance to host defenses. The biofilm contains the capsular polysaccharide/adhesin (PS/A), which mediates cell adherence to biomaterials, and another antigen, termed polysaccharide intercellular adhesin (PIA), which is thought to mediate bacterial accumulation into cellular aggregates. PIA is a polymer of β-1,6-linkedN-acetyl glucosamine residues with a molecular mass of <30,000 kDa. We found that recombinant Staphylococcus carnosus and Staphylococcus aureus carrying a plasmid with genes of the ica locus, which was reported to encode the biosynthetic proteins for production of PIA, were also able to synthesize PS/A. PS/A and a chemically and immunologically identical polysaccharide isolated from S. carnosus carrying theica genes on plasmid pCN27 were found to be high-molecular-mass (>250,000 kDa), acid-stable polymers of β-1,6-linked glucosamine substituted on the amino group primarily with succinate, although some preparations also contained acetate. Moreover, all recombinant staphylococcal strains with theica genes had the biologic properties previously attributed to PS/A. ica-positive strains readily formed an in vitro biofilm on plastic, adhered 3- to 10-fold more to catheters during a 30-min assay compared with control strains carrying only the cloning vector, adsorbed out antibodies to PS/A from immune serum, and elaborated a capsule visualized by immunoelectron microscopy with antisera to PS/A. These properties were also seen with PS/A-producing strains of Staphylococcus epidermidis, but not with transposon mutants lacking PS/A. An antiserum raised to PIA contained high-titer antibody to PS/A that was readily adsorbed out by PS/A-positive strains of S. epidermidis and recombinant strains of staphylococci carrying the ica genes. We conclude that the ica locus encodes production of PS/A and that the properties of S. epidermidis associated with initial bacterial adherence, biofilm formation, and intercellular adhesion can be correlated with elaboration of PS/A.
What is left to be understood in ATIS?

One of the main data resources used in many studies over the past two decades for spoken language understanding (SLU) research in spoken dialog systems is the airline travel information system (ATIS) corpus. Two primary tasks in SLU are intent determination (ID) and slot filling (SF). Recent studies reported error rates below 5% for both of these tasks employing discriminative machine learning techniques with the ATIS test set. While these low error rates may suggest that this task is close to being solved, further analysis reveals the continued utility of ATIS as a research corpus. In this paper, our goal is not experimenting with domain specific techniques or features which can help with the remaining SLU errors, but instead exploring methods to realize this utility via extensive error analysis. We conclude that even with such low error rates, ATIS test set still includes many unseen example categories and sequences, hence requires more data. Better yet, new annotated larger data sets from more complex tasks with realistic utterances can avoid over-tuning in terms of modeling and feature design. We believe that advancements in SLU can be achieved by having more naturally spoken data sets and employing more linguistically motivated features while preserving robustness due to speech recognition noise and variance due to natural language.
Revisiting the cognitive buffer hypothesis for the evolution of large brains

Why have some animals evolved large brains despite substantial energetic and developmental costs? A classic answer is that a large brain facilitates the construction of behavioural responses to unusual, novel or complex socioecological challenges. This buffer effect should increase survival rates and favour a longer reproductive life, thereby compensating for the costs of delayed reproduction. Although still limited, evidence in birds and mammals is accumulating that a large brain facilitates the construction of novel and altered behavioural patterns and that this ability helps dealing with new ecological challenges more successfully, supporting the cognitive-buffer interpretation of the evolution of large brains.
A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC) associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd) carrying sequences of amastigote surface protein-2 (rAdASP2) and trans-sialidase (rAdTS) T. cruzi antigens. For prophylactic vaccination, naïve C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax) using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi), when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFN)γ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi) and the boost (analysis at 180 and 230 dpi). Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28), CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO) levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells, preserved the number of IFNγ+ cells, increased the expression of IFNγ mRNA but reduced inducible NO synthase mRNA. Vaccine-based immunostimulation with rAd might offer a rational alternative for re-programming the immune response to preserve and, moreover, recover tissue injury in Chagas’ heart disease.
Influence of a Cardiac Rehabilitation Program on Renal Function in Patients With Cardiovascular Disease in a One-Year Follow-Up

Background Exercise training may improve renal function in patients with chronic kidney disease (CKD). The effect of cardiac rehabilitation (CR) with exercise training on renal function has not yet been established. We evaluated the effects of CR on renal function in patients with cardiovascular disease (CVD). Methods Twenty-three CVD patients in a 1-year CR program (CR group) who had ischemic heart disease (IHD) and/or heart failure were compared with 26 age- and gender-matched CVD patients without CR (non-CR group, standard pharmacological care alone). At baseline and after 1 year, urea nitrogen (UN), creatinine (Cr), potassium (K), estimated glomerular filtration rate (eGFR) and hematocrit (Hct) in blood were assessed. Results There were no differences in the patient characteristics at baseline between the CR and non-CR groups except for the percentages of heart failure and the use of calcium channel blocker. After 1 year, there were no significant changes in UN, Cr, K, eGFR or Hct in either the CR or non-CR groups. The patients in the CR group were divided into two groups according to the eGFR level at baseline: low (n = 12, eGFR < 51 mL/minute/1.73 m2, indicating mild-to-moderate CKD) and high (n = 11, eGFR ≥ 51 mL/minute/1.73 m2) eGFR groups. Although there were no differences in the patient characteristics at baseline between the low and high eGFR groups, the low eGFR group showed a significant increase in eGFR after the 1-year CR program. Conclusions CR may improve renal function in patients with mild-to-moderate CKD.
Long term outcome of trapeziectomy with ligament reconstruction/tendon interposition versus thumb basal joint prosthesis

Several surgical techniques to treat thumb basal joint arthritis have been described. In this study we compared the results of a cemented thumb basal joint with trapeziectomy with a ligament reconstruction and tendon interposition. A questionnaire was sent to all 519 patients, 322 (with 382 procedures) responded. No significant differences were found when comparing impairment, pain, patient satisfaction and disability. Given the fact that the superiority of a prosthesis cannot be proven and the cost of the implant is greater, we recommend the trapeziectomy with ligament reconstruction and tendon interposition as opposed to arthroplasty as the first choice in the treatment of basal joint osteoarthritis of the thumb.
MULTI-SENSORY DISPLAYS AND VISUALIZATION TECHNIQUES SUPPORTING THE CONTROL OF UNMANNED AIR VEHICLES

Unmanned Air Vehicles (UAVs) have many potential benefits compared to manned systems. These advantages include increased loiter capability, less expensive airframes, and expendability without loss of human life. An example of this is the US Air Force Predator UAV. Although relatively new to the US Air Force inventory, the Predator has demonstrated its worth in performing various intelligence, surveillance, and reconnaissance (ISR) missions around the world. Although their potential benefits are many, current UAV control stations have several human factors deficiencies including issues of crew coordination, control/display design, and system time delays (Gawron, 1998). A research program is underway to explore how advanced multi-sensory interface technologies and visualization techniques might improve UAV operator performance and situation awareness while reducing workload. Advanced technologies under consideration include haptic feedback, head-mounted displays, spatialized audio, and virtual environments. The results of two studies are summarized and future research plans are described.
Biochemical Mapping of Interactions within the Intraflagellar Transport (IFT) B Core Complex

Cilia and flagella are complex structures emanating from the surface of most eukaroytic cells and serve important functions including motility, signaling, and sensory reception. A process called intraflagellar transport (IFT) is of central importance to ciliary assembly and maintenance. The IFT complex is required for this transport and consists of two distinct multisubunit subcomplexes, IFT-A and IFT-B. Despite the importance of the IFT complex, little is known about its overall architecture. This paper presents a biochemical dissection of the molecular interactions within the IFT-B core complex. Two stable subcomplexes consisting of IFT88/70/52/46 and IFT81/74/27/25 were recombinantly co-expressed and purified. We identify a novel interaction between IFT70/52 and map the interaction domains between IFT52 and the other subunits within the IFT88/70/52/46 complex. Additionally, we show that IFT52 binds directly to the IFT81/74/27/25 complex, indicating that it could mediate the interaction between the two subcomplexes. Our data lead to an improved architectural map for the IFT-B core complex with new interactions as well as domain resolution mapping for several subunits.
Phylogenetic Diversity of Peltigera Cyanolichens and Their Photobionts in Southern Chile and Antarctica

The lichen genus Peltigera has been mainly revised in the Northern Hemisphere, with most species being recorded in Europe and North America. This study assessed the phylogenetic diversity of the mycobionts and cyanobionts of Peltigera cyanolichens collected in Southern Chile and Antarctica, areas in which lichens are extremely diverse but poorly studied. The operational taxonomic units (OTUs) of each symbiont were defined by analyzing the genetic diversity of the LSU and SSU rDNA of the mycobionts and cyanobionts, respectively, and a phylogenetic approach was used to relate these OTUs with sequences previously reported for Peltigera and Nostoc. Among the 186 samples collected, 8 Peltigera and 15 Nostoc OTUs were recognized, corresponding to sections Peltigera, Horizontales, and Polydactylon, in the case of the mycobionts, and to the Nostoc clade II, in the case of the cyanobionts. Since some of the OTUs recognized in this study had not previously been described in these areas, our results suggest that the diversity of Peltigera reported to date in the regions studied using traditional morphological surveys has underestimated the true diversity present; therefore, further explorations of these areas are recommended.
A Situational Perspective on Workarounds in IT-Enabled Business Processes: a Multiple Case Study

Workarounds are still one of the most puzzling phenomena in business process management research and practice. From a compliance perspective, workarounds are studied as control failure and the cause for inferior process quality. From a process reengineering perspective, however, workarounds are studied as an important source of process improvement. In this paper, we advance recent theory on the emergence of workarounds to resolve this puzzle by analyzing empirical evidence from a multiple case study. Our analysis reveals that employees utilize workarounds based on a risk-benefit analysis of the situational context. If the realized benefits (efficiency gains) outweigh the situational risks (exposure of process violations), workarounds will be perceived as process improvement. Erroneous risk-benefit analysis, however, leads to exposure of the same workaround as control failure. Quite unexpectedly, we found that information systems serve as critical cues for the situational balance of benefits and risks. Our result suggests that process-instance-level workarounds are treated as options that are engaged if the situation permits, in contrast to process-level workarounds that manifest as unofficial routines. We also contribute the notion of situational risk-benefits analysis to the theory on workarounds.
Development and Specification of Virtual Environments

This thesis concerns the issues involved in the development of virtual environments (VEs). VEs are more than virtual reality. We identify four main characteristics of them: graphical interaction, multimodality, interface agents, and multi-user. These characteristics are illustrated with an overview of different classes of VE-like applications, and a number of state-of-the-art VEs. To further define the topic of research, we propose a general framework for VE systems development, in which we identify five major classes of development tools: methodology, guidelines, design specification, analysis, and development environments. Of each, we give an overview of existing best practices.
Leveraging Large Amounts of Weakly Supervised Data for Multi-Language Sentiment Classification

This paper presents a novel approach for multi-lingual sentiment classification in short texts. This is a challenging task as the amount of training data in languages other than English is very limited. Previously proposed multi-lingual approaches typically require to establish a correspondence to English for which powerful classifiers are already available. In contrast, our method does not require such supervision. We leverage large amounts of weakly-supervised data in various languages to train a multi-layer convolutional network and demonstrate the importance of using pre-training of such networks. We thoroughly evaluate our approach on various multi-lingual datasets, including the recent SemEval-2016 sentiment prediction benchmark (Task 4), where we achieved state-of-the-art performance. We also compare the performance of our model trained individually for each language to a variant trained for all languages at once. We show that the latter model reaches slightly worse - but still acceptable - performance when compared to the single language model, while benefiting from better generalization properties across languages.