Miracle-dz/UniFAR-FTUs huggingface dataset:
Fragment-based approaches to anti-HIV drug discovery: state of the art and future opportunities

Introduction: The search for additional drugs to treat HIV infection is a continuing effort due to the emergence and spread of HIV strains resistant to nearly all current drugs. The recent literature reveals that fragment-based drug design/discovery (FBDD) has become an effective alternative to conventional high-throughput screening strategies for drug discovery. Areas covered: In this critical review, the authors describe the state of the art in FBDD strategies for the discovery of anti-HIV drug-like compounds. The article focuses on fragment screening techniques, direct fragment-based design and early hit-to-lead progress. Expert opinion: Rapid progress in biophysical detection and in silico techniques has greatly aided the application of FBDD to discover candidate agents directed at a variety of anti-HIV targets. Growing evidence suggests that structural insights on key proteins in the HIV life cycle can be applied in the early phase of drug discovery campaigns, providing valuable information on the binding modes and efficiently prompting fragment hit-to-lead progression. The combination of structural insights with improved methodologies for FBDD, including the privileged fragment-based reconstruction approach, fragment hybridization based on crystallographic overlays, fragment growth exploiting dynamic combinatorial chemistry, and high-speed fragment assembly via diversity-oriented synthesis followed by in situ screening, offers the possibility of more efficient and rapid discovery of novel drugs for HIV-1 prevention or treatment. Though the use of FBDD in anti-HIV drug discovery is still in its infancy, it is anticipated that anti-HIV agents developed via fragment-based strategies will be introduced into the clinic in the future.
A Keyword Extraction Approach for Single Document Extractive Summarization Based on Topic Centrality

Graph based keyword extraction approaches represent the text document as a graph with the words as vertices. An edge between two vertices exists only if the corresponding words are related. The effectiveness of the graph representation is dependent on how the relationship is defined between two words. Early approaches used word order, word co-occurrence and syntactic relationships. Recent graph representation approaches are using lexical association measures for defining relationship between two words. The existing relationships can only help in identifying the words which form the topics in a document. But the topics in a document essentially form a theme in the document. Theme is the central idea conveyed though the topics in a document. In this paper a new relationship is defined between the words to capture the words which convey the theme of the document. This relationship is defined using lexical association among the words in the document. Based on the relationship a graph representation of text is defined and used for extracting the words that build the theme of the document. These words are used for selecting important sentences in the document. Experiments on DUC 2002 data set indicated that the proposed keyword extraction approach improves the quality of Extractive summarization.
Detecting and Identifying Bias-Heavy Sentences in News Articles

This project investigates the advantages of using neural networks to approach the task of identifying biased sentences in news articles. In particular, convolutional neural nets (CNN) were used to classify articles by the news provider that published them and a bidirectional RNN was used to extract the sentences that the classifier found important for this prediction. Overall the system showed promise, with the CNN classifier outperforming a baseline bag-of-vectors model to achieve 84% accuracy and the bidirectional RNN achieving 99.6% consistency with the classifier prediction.
In Vivo Selection of Fluoroquinolone-Resistant Escherichia coli Isolates Expressing Plasmid-Mediated Quinolone Resistance and Expanded-Spectrum β-Lactamase

ABSTRACT A ciprofloxacin-resistant Escherichia coli isolate, isolate 1B, was obtained from a urinary specimen of a Canadian patient treated with norfloxacin for infection due to a ciprofloxacin-susceptible isolate, isolate 1A. Both isolates harbored a plasmid-encoded sul1-type integron with qnrA1 and blaVEB-1 genes. Isolate 1B had amino acid substitutions in gyrase and topoisomerase.
Incorporation of dITP or 7-deaza dGTP during PCR improves sequencing of the product.

Premature enzyme pausing due to regions of complex secondary structure is a common problem in sequencing reactions. This not only makes the sequence impossible to interpret at this particular region, but often decreases the signal intensity of the rest of the sequence as well. Different methods have been proposed to diminish secondary structure formation (1 -4). We tested some of these methods in the sequencing of PCR products of several 'problem-fragments' of the p53 gene without success, suggesting that the in
Effects of physical inactivity and obesity on morbidity and mortality: current evidence and research issues.

PURPOSE The purpose of this review was to address three specific questions. 1) Do higher levels of physical activity attenuate the increased health risk normally observed in overweight or obese individuals? 2) Do obese but active individuals actually have a lower morbidity and mortality risk than normal weight persons who are sedentary? 3) Which is a more important predictor of mortality, overweight or inactivity? METHODS We initially identified more than 700 articles that included information on the exposure variables of body habitus (body mass index, body composition, or body fat pattern) and physical activity habits, and on outcomes such as morbidity or mortality. To be included in the review, we required that an article include an analysis of one of our outcomes by strata of the two exposure variables. We excluded review articles and reports of cross-sectional analyses. We used an evidence-based approach to evaluate the quality of the published data. RESULTS We summarized results from 24 articles that met all inclusion criteria. Data were available for the outcomes of all-cause mortality, cardiovascular disease mortality, coronary heart disease (CHD), hypertension, type 2 diabetes mellitus, and cancer. Summary results for all outcomes except cancer were generally consistent in showing that active or fit women and men appeared to be protected against the hazards of overweight or obesity. This apparent protective effect was often stronger in obese individuals than in those of normal weight or who were overweight. There were too few data on cancer to permit any conclusions. CONCLUSIONS There are no randomized clinical trials on the topics addressed in this review. All studies reviewed were prospective observational studies, so all conclusions are based on Evidence Category, C. The conclusions for the three questions addressed in the review are: 1) regular physical activity clearly attenuates many of the health risks associated with overweight or obesity; 2) physical activity appears to not only attenuate the health risks of overweight and obesity, but active obese individuals actually have lower morbidity and mortality than normal weight individuals who are sedentary, and 3) inactivity and low cardiorespiratory fitness are as important as overweight and obesity as mortality predictors. Research needs include extending current observations to more diverse populations, including more studies in women, the elderly, and minority groups, assessment methods need to be improved, and randomized clinical trials addressing the questions discussed in this review should be undertaken. Owing to size, complexity, and cost, these trials will need to be designed with valid noninvasive measures of subclinical disease processes as outcomes.
Beamforming and imageforming for 3D ultrasound imaging system using 2-D CMUT-on-ASIC arrays

For real-time volumetric imaging system using 2-D arrays, control of massive ultrasound data acquired from a large number of system channels is challenging. Given a system with manageable number of channels, new methods of array configuration and beamforming are necessary to achieve the performance of utilizing the full array elements and channels. In this paper, Electric Wobbling (EW) and Elevational Synthetic Focusing (ESF) methods are proposed. Theoretical studies and simulation were performed to evaluate the quality of 3-D volume imaging methods.
Context-based semantic matchmaking to enhance tourists ’ experiences

Tourists, preparing for a journey, suffer from information overload when they use the Internet to look for information about their next potential destination. Although approaches to support tourists in decision making exist (e.g., in form of recommendation systems), providing the right information for each type of tourist is still a challenging task. This is especially a major issue when tourists are already at a particular destination and desire to use their mobile devices to consume up-to-date travel-related information tailored to their current situation, i.e. context. This paper presents a context-based matchmaking approach that addresses the needs of tourists during their trip and aims to provide a more satisfying visit experience. In order to identify a set of tourism objects (e.g., attractions) that are most attractive for tourists, the CONCERT framework is presented exploits contextual information such as location and time as a filter to select relevant tourism objects. Within a second step, the matchmaking framework VMTO is introduced that acts on top of CONCERT and ranks the selected tourism objects according to personal tourist preferences.
Abnormal reinnervation of skeletal muscle in a tenascin‐C‐deficient mouse

The possible involvement of tenascin‐C in the reinnervation of a skeletal muscle was investigated in the tenascin‐C‐deficient mouse (T–/–) produced by Saga et al. (1992; Genes Dev 6:1821–1831). The pattern of reinnervation, observed after denervation of the triangularis sterni muscle, differs in T–/– and wild‐type muscles in several traits. Axonal growth and stability of terminal arbors are impaired in the T–/– muscle: Some axons in mutant muscles grow beyond their original targets and reinnervate other synaptic sites, which may become dually innervated. In contrast to wild type, polyinnervation increases with time after denervation in T–/– muscles and is still present 7 months after nerve crush. The expression of a tenascin‐C mRNA product disappears between 1 and 2 months after nerve crush. Of interest is that this transcriptional regulation in T–/– muscles occurs when major alterations in the morphology of regenerating endings become obvious. These observations strongly implicate tenascin‐C in the formation, maturation, and stabilization of the neuromuscular junction. © 2002 Wiley‐Liss, Inc.
Landscape Use and Movements of Wolves in Relation to Livestock in a Wildland–Agriculture Matrix

Abstract Wolves (Canis lupus) have expanded their distribution into areas of the midwest United States that have not had wolves for several decades. With recolonization of wolves into agricultural areas, there is increasing concern of wolf–livestock conflicts. To assess the risk wolves may pose to livestock, we initiated a 3-year study investigating the activity patterns, movements, habitat use, visitation to livestock pastures by wolves, and the occurrence of depredation events in an agricultural–wildland matrix in northwestern Minnesota, USA. From June 1997 to November 1999, we captured 23 wolves, including pups, from 3 packs; we radiocollared 16 of these wolves. We tracked radioed wolves intensively on a 24-hour basis during the spring, summer, and autumn of 1998 and 1999. We found wolves passed directly through a pasture containing cattle on 28% of the nights of tracking; 58% and 95% of the wolf locations were ≤1 km and ≤5 km from a pasture, respectively. Space use of wolves showed that while they visited livestock pastures during the 24-hour tracking sessions, they apparently were passing through these pastures with cattle and not preying on livestock. When compared to random simulations of movements, wolves appeared to encounter livestock pastures randomly. Thirty percent of random movements passed directly through a pasture; 65% and 95% of random movements were within ≤1 km and ≤5 km of a pasture, respectively. Wolves were more active at night than during the day. Wolves avoided pastures during the day and visited pastures at night when depredations were most likely (i.e., human presence was low). Visitation of livestock pastures was not related to any discernible characteristics of the pastures (i.e., pasture size, cattle density, distance to human habitation, percent forest cover, index of deer abundance). However, pastures in which livestock were killed by wolves contained more cattle than pastures without depredations, but in 1998 only. While the risk of wolf predation on livestock was potentially high (wolves were within ≤1 km of a pasture on 58% of nights), few livestock were actually killed. During the 3-year study, only 8 animals (all young or vulnerable livestock) were depredated by wolves. Maintaining healthy wild prey populations, removing offending wolves that kill livestock, and encouraging effective and proper husbandry practices (e.g., disposal of carcasses) among livestock producers, should allow for the persistence of wolves in northwestern Minnesota, USA, while minimizing their impact to farmers in this agriculture–wildland matrix.
The Effect of Caffeine Ingestion on Field Hockey Skill Performance Following Physical Fatigue

This study examined the impact of caffeine ingestion on field hockey skill performance following high-intensity fatigue. Thirteen male hockey players (mean age = 21.1 ± 1.2 years) performed hockey sprint dribble and ball handling tests at rest and after a bout of total body fatigue (90% maximal capacity) following caffeine (5mg kg−1) or placebo ingestion. Sprint dribble times were slower postfatigue compared with rest but were significantly faster postfatigue with caffeine compared with postfatigue with placebo ingestion (P < 0.01). Ball handling scores were higher at rest compared with postfatigue, but scores postfatigue were higher following caffeine than placebo ingestion (P < 0.01). Rating of perceived exhaustion (RPE) was lower (P < 0.01) and readiness to invest physical (P < 0.01) and mental effort (P = 0.01) were significantly higher in the caffeine condition. Caffeine ingestion may therefore be effective in offsetting decrements in skilled performance associated with fatigue.
Do we think about time in terms of space

The human capacity for abstract thought poses an unsolved problem for the neural and cognitive sciences. How are people able to think about things that they can never see or touch, like ideas, mathematics, or time? A potential solution has emerged independently from such diverse fields as evolutionary biology and cognitive linguistics: the mind recruits old structures for new uses. It has been proposed, for example, that sensory and motor processes underlying spatial cognition are co-opted to support our thinking about phenomena such as mathematics and time. Empirical support for this proposal has been elusive. Until recently, arguments have rested largely on patterns observed in human language. Here we present a series of psychophysical experiments that investigate mental representations in the abstract domain of time and in the perceptually richer domain of space. Results show that people rely on spatial information to estimate time, but not the other way around. These studies provide some of the first entirely nonlinguistic evidence that spatial representations subserve temporal representations, and suggest a new way to explore the perceptual foundations of abstract thought.
umuDC-dnaQ Interaction and Its Implications for Cell Cycle Regulation and SOS Mutagenesis inEscherichia coli

ABSTRACT The Escherichia coli SOS-regulated umuDCgene products participate in a DNA damage checkpoint control and in translesion DNA synthesis. Specific interactions involving the UmuD and UmuD′ proteins, both encoded by the umuD gene, and components of the replicative DNA polymerase, Pol III, appear to be important for regulating these two biological activities of theumuDC gene products. Here we show that overproduction of the ɛ proofreading subunit of Pol III suppresses the cold sensitivity normally associated with overexpression of the umuDC gene products. Our results suggest that this suppression is attributable to specific interactions between UmuD or UmuD′ and the C-terminal domain of ɛ.
Mouse T cell clones against Mycobacterium avium: identification of clones that modify resistance against atypical mycobacteria infection

Mouse T cell clones against live Mycobacterium avium were generated from the spleens of BALB/c mice infected with M. avium TMC 702. Eighth clones were of the L3T4+ subset, whereas two were of Lyt2+ subset. Six of the L3T4+ T cell clones were of the TH1 subset whereas two were of the TH2 subset, judged on the profile of cytokine release. One of the Lyt2+ clones exhibited significant cytotoxicity against M. avium‐infected mouse macrophages. Transfer of clones to nude BALB/c mice infected with M. avium was associated with insignificant changes in resistance for seven clones. One clone, of the L3T4+/TH2 subset, transferred significant resistance to the infection, also associated with infusion of supernatants from the clone, which was fully inhibited by neutralizing with anti–interleukin 4. By contrast, infusion of one TH1 clone and the cytolytic Lyt2+ led to increased microbial growth in the spleens and livers of infected mice, which was not apparent on infusion with supernatants. Application of clones' supernatants on infected macrophages had marginal effects on M. avium growth and was not correlated with protective or suppressive activity. Overall, these results suggest that T cells may influence M. avium growth in vivo in a bidirectional manner and also suggest that interleukin 4 may be an important factor in host resistance to M. avium.
Folate-modified, cisplatin-loaded lipid carriers for cervical cancer chemotherapy

Abstract Background: Cervical cancer chemotherapy calls for the efficiently delivery of anticancer drug into cancer cells by nanoparticles. In this study, folate (FA) modified, cisplatin (CIS)-loaded nanostructured lipid carriers (NLCs) were constructed and evaluated. Methods: FA containing polyethylene glycol (PEG)-distearoylphosphatidylethanolamine (DSPE) (FA-PEG-DSPE) was synthesized. FA-PEG-DSPE modified, CIS-loaded NLCs (FA-CIS-NLCs) were prepared. Their particle size, zeta potential, drug encapsulation efficiency (EE) and in vitro delivery behavior were evaluated. In vitro cytotoxicity study of FA-CIS-NLCs was tested in human cervix adenocarcinoma cell line (HeLa cells). In vivo anti-tumor efficacies of the carriers were evaluated on a mice-bearing cervical cancer model. Results: The optimum FA-CIS-NLCs formulations have a particle size of 143.2 nm and a +25.7 mV surface charge. FA-CIS-NLCs displayed the best anti-tumor activity than other formulations in vitro and in vivo. Conclusions: The results demonstrated that FA-CIS-NLCs were efficient in selective delivery to cancer cells over-expressing FA receptors (FRs). FA-CIS-NLCs targeted transfer CIS to the cervical cancer cells, enhance the anti-tumor capacity. The novel constructed NLCs could function as outstanding nanocarriers for the delivery of drugs for the targeted treatment of cervical cancers.
An Antibody Reactivity-Based Assay for Diagnosis of Invasive Candidiasis Using Protein Array

The increased incidence of invasive candidiasis and of patients at risk requires early diagnosis and treatment to improve prognosis and survival. The aim of this study was to set up a ten-protein array-based immunoassay to assess the IgG antibody responses against ten well-known immunogenic C. albicans proteins (Bgl2, Eno1, Pgk1, Pdc11, Fba1, Adh1, Als3, Hwp1, Hsp90 and Grp2) in 51 patients with invasive candidiasis (IC) and in 38 culture-negative controls (non-IC). Antibody levels were higher against Bgl2, Eno1, Pgk1, Als3, Hwp1 and Grp2, than against Adh1, Pdc11, Fba1 and Hsp90, irrespectively of the patient group considered. Moreover, the IgG levels against Bgl2, Eno1, Pgk1 and Grp2 were significantly higher in IC than in non-IC patients. Furthermore, the ROC curves generated by the analysis of the antibody responses against Bgl2, Grp2 and Pgk1 displayed AUC values above 0.7, thus discriminating IC and non-IC patients. According to these results, the employment of the microarray immunoassay (a rapid, sensitive and multiparametric system), in parallel with conventional diagnostics, can help to spot IC patients. This ultimately will allow to initiate an early, focused and optimized antifungal therapy.
Modelling and dynamic performance of a direct-drive direct-grid slip permanent magnet wind generator

In this paper a transfer function model is developed to evaluate the dynamic performance of the direct-drive direct-grid connected slip permanent magnet wind generator system. The modelling of the generator is done in the dq reference frame fixed to the PM-rotor, for both the grid frequency and slip-frequency generator components. The transient response of a single, 15 kW grid-connected system to changes in turbine torque and grid voltage and frequency is evaluated. It is shown that the generator is very stable under transient turbine-torque conditions and that it acts as a filter to prevent voltage flickering. The dynamic performance is confirmed by laboratory measurements on a 15 kW direct drive slip permanent magnet generator.
A Comprehensive Review on Capital Structure Theories

This studyreviews different theories andhypothesisin regard with obtaningan optimal capital structure. Many researchers believe that capital structure includes share issuance, private investment, bank debt, business debts, leasing contracts, tax debt, retirement debt, deferred compensation for executives and employees, deposits, product related-debt and other probable debt. These theories and hypothesis include: Net income,net operational income, traditional approach theory, Miller andModigliani theory, static trade–off theory, asymmetric of the information hypothesis, pecking order theory, signaling theory, agency cost theory,free cash flow hypothesis, dynamic trade-off theory and market timing theory. By applying these theories, we will be able to reach a maximum return with minimum risk and also increase the value of corporation. Because of the close relationship between profitability and capital structure in this paper is going to apply genetic algorithmmodel, support vector regression and profitability factor to reach an international range of optimal capital structure hoping to find an international point of capital structure in the future. Key words: Profit Margin, Support Vector Regression, International Optimal Capital Structure, Leverage, Genetic Algorithm.