Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of an AlphaScreen-Based HIV-1 Integrase Dimerization Assay for Discovery of Novel Allosteric Inhibitors

In recent years, HIV-1 integrase (IN) has become an established target in the field of antiretroviral drug discovery. However, its sole clinically approved inhibitor, the integrase strand transfer inhibitor (INSTI) raltegravir, has a surprisingly low genetic barrier for resistance. Furthermore, the only two other integrase inhibitors currently in advanced clinical trials, elvitegravir and dolutegravir, share its mechanism of action and certain resistance pathways. To maintain a range of treatment options, drug discovery efforts are now turning toward allosteric IN inhibitors, which should be devoid of cross-resistance with INSTIs. As IN requires a precise and dynamic equilibrium between several oligomeric species for its activities, the modulation of this equilibrium presents an interesting allosteric target. We report on the development, characterization, and validation of an AlphaScreen-based assay for high-throughput screening for modulators of HIV-1 IN dimerization. Compounds identified as hits in this assay proved to act as allosteric IN inhibitors. Additionally, the assay offers a flexible platform to study IN dimerization.
Applying the genetic theories of ageing to the cytoplasm: cytoplasmic genetic covariation for fitness and lifespan

Two genetic models exist to explain the evolution of ageing – mutation accumulation (MA) and antagonistic pleiotropy (AP). Under MA, a reduced intensity of selection with age results in accumulation of late‐acting deleterious mutations. Under AP, late‐acting deleterious mutations accumulate because they confer beneficial effects early in life. Recent studies suggest that the mitochondrial genome is a major player in ageing. It therefore seems plausible that the MA and AP models will be relevant to genomes within the cytoplasm. This possibility has not been considered previously. We explore whether patterns of covariation between fitness and ageing across 25 cytoplasmic lines, sampled from a population of Drosophila melanogaster, are consistent with the genetic associations predicted under MA or AP. We find negative covariation for fitness and the rate of ageing, and positive covariation for fitness and lifespan. Notably, the direction of these associations is opposite to that typically predicted under AP.
BUILDING COMPACT N-GRAM LANGUAGE MODELS INCREMENTALLY

In traditional n-gram language modeling, we collect the sta ti tics for all n-grams observed in the training set up to a certain order. The model can then be prune d down to a more compact size with some loss in modeling accuracy. One of the more principl ed methods for pruning the model is the entropy-based pruning proposed by Stolcke (1998). In th is paper, we present an algorithm for incrementally constructing an n-gram model. During the mod el construction, our method uses less memory than the pruning-based algorithms, since we never ha to handle the full unpruned model. When carefully implemented, the algorithm achieves a reaso n ble speed. We compare our models to the entropy-pruned models in both cross-entropy and spee ch r cognition experiments in Finnish. The entropy experiments show that neither of the methods is o pt mal and that the entropy-based pruning is quite sensitive to the choice of the initial model . The proposed method seems better suitable for creating complex models. Nevertheless, even t h small models created by our method perform along with the best of the small entropy-pruned mode ls in speech recognition experiments. The more complex models created by the proposed method outpe rform the corresponding entropypruned models in our experiments.
Induction of Polyploidy in Cultures of Neonatal Rat Aortic Smooth Muscle Cells

Arterial smooth muscle cells become tetraploid with age and hypertension. To further study this phenomenon, neonatal rat aortic smooth muscle cells were placed in cell culture and studied over time. Numerous cells with tetraploid and even octaploid DNA content appeared beginning in primary cultures. These increases in DNA content per cell were determined by quantitative fluorescence microscopy and flow cytometry, and true polyploidy was confirmed by chromosome counts. In contrast, cells from adult rat aortas failed to produce significant polyploid cells over time in culture. In vitro culture of neonatal aortic cells may therefore be a model system for studying the initiation of polyploidy in arterial smooth muscle.
Guggulsterone and bexarotene induce secretion of exosome‐associated breast cancer resistance protein and reduce doxorubicin resistance in MDA‐MB‐231 cells

Many breast cancer cells acquire multidrug resistance (MDR) mediated by ABC transporters such as breast cancer resistance protein (BCRP/ABCG2). Here we show that incubation of human breast cancer MDA‐MB‐231 cells with farnesoid X receptor antagonist guggulsterone (gug) and retinoid X receptor agonist bexarotene (bex) elevated ceramide, a sphingolipid known to induce exosome secretion. The gug+bex combination reduced cellular levels of BCRP to 20% of control cells by inducing its association and secretion with exosomes. Exogenous C6 ceramide also induced secretion of BCRP‐associated exosomes, while siRNA‐mediated knockdown or GW4869‐mediated inhibition of neutral sphingomyelinase 2 (nSMase2), an enzyme generating ceramide, restored cellular BCRP. Immunocytochemistry showed that ceramide elevation and concurrent loss of cellular BCRP was prominent in Aldefluor‐labeled breast cancer stem‐like cells. These cells no longer excluded the BCRP substrate Hoechst 33342 and showed caspase activation and apoptosis induction. Consistent with reduced BCRP, ABC transporter assays showed that gug+bex increased doxorubicin retention and that the combination of gug+bex with doxorubicin enhanced cell death by more than fivefold. Taken together, our results suggest a novel mechanism by which ceramide induces BCRP secretion and reduces MDR, which may be useful as adjuvant drug treatment for sensitizing breast cancer cells and cancer stem cells to chemotherapy.
Foundation and methodologies in computer-aided diagnosis systems for breast cancer detection

Breast cancer is the most prevalent cancer that affects women all over the world. Early detection and treatment of breast cancer could decline the mortality rate. Some issues such as technical reasons, which related to imaging quality and human error, increase misdiagnosis of breast cancer by radiologists. Computer-aided detection systems (CADs) are developed to overcome these restrictions and have been studied in many imaging modalities for breast cancer detection in recent years. The CAD systems improve radiologists' performance in finding and discriminating between the normal and abnormal tissues. These procedures are performed only as a double reader but the absolute decisions are still made by the radiologist. In this study, the recent CAD systems for breast cancer detection on different modalities such as mammography, ultrasound, MRI, and biopsy histopathological images are introduced. The foundation of CAD systems generally consist of four stages: Pre-processing, Segmentation, Feature extraction, and Classification. The approaches which applied to design different stages of CAD system are summarised. Advantages and disadvantages of different segmentation, feature extraction and classification techniques are listed. In addition, the impact of imbalanced datasets in classification outcomes and appropriate methods to solve these issues are discussed. As well as, performance evaluation metrics for various stages of breast cancer detection CAD systems are reviewed.
Surface complex structures modelled with quantum chemical calculations : carbonate , phosphate , sulphate , arsenate and arsenite

Hybrid molecular orbital/density functional theory (MO/DFT) calculations on molecular clusters were used to model infrared (IR) vibrational frequencies and interatomic distances obtained via extended X-ray absorption fine structure (EXAFS) spectroscopy. Molecular clusters were found to provide good agreement with experimental observations for the oxyanions carbonate, phosphate, sulphate, arsenate and arsenite. The results show a consistent tendency to form bidentate bridging surface complexes at low pH, but the protonation and hydration states play a significant role in the results obtained from calculation as various protonation states of monodentate surface complexes are also predicted to be stable as pH increases (i.e. the number of Hþ ions in the model are decreased). A method for estimating the Gibbs free energy of adsorption (DGads) is discussed to complement the comparisons of experimental and theoretical spectroscopic parameters. Calculated DGads values were consistent with the interpretations based on modelling observed spectra.
Toward a Generic Framework for Modeling Human Behaviors in Crowd Simulation

This paper presents our ongoing work on modeling agents with human-like decision making and behavior execution capabilities in crowd simulation. We aim to provide a generic framework that reflects the major cognitive and physical processes as observed from human behaviors in real-life situations. The design of the framework is based on some basic assumptions and related cognitive theories on human behaviors in various real-life situations. In this paper, the cognitive architecture of our framework is presented, which emphasizes the role of experiences in human's decision making. The paper also briefly describes the design of agent's decision making process and presents a case study to show some results in a crowd simulation scenario.
The Criticality of Modeling Formalisms in Software Design Method Comparison

This paper describes experimentation aimed at making the comparison of software design methodologies SDM s more of an exact science Our aim is to lay the foundations for this more exact science by establishing xed methods and conceptual frameworks that are able to assure that comparison e orts will yield predictable reproducible results Earlier papers have proposed the use of a systematic process to compare SDM s This process assumes that the comparison will be done relative to a xed standard SDM feature classi cation schema and with the use of a xed formalism for modeling the SDM s Early experiments with this approach have yielded interesting SDM comparisons but have raised questions about how sensitive these results might be to the choice of modeling formalism In this paper we study this sensitivity by varying the choice of modeling formalism We describe an experiment in which we x a pair of SDM s and then use two di erent formalisms to obtain two di erent comparisons of that pair of SDM s We then compare the comparisons Our results suggest that comparison results may be relatively insensitive to di erences in modeling formalisms This paper also suggests an approach to further experimentation
18F-Labeling Using Click Cycloadditions

Due to expanding applications of positron emission tomography (PET) there is a demand for developing new techniques to introduce fluorine-18 (t 1/2 = 109.8 min). Considering that most novel PET tracers are sensitive biomolecules and that direct introduction of fluorine-18 often needs harsh conditions, the insertion of 18F in those molecules poses an exceeding challenge. Two major challenges during 18F-labeling are a regioselective introduction and a fast and high yielding way under mild conditions. Furthermore, attention has to be paid to functionalities, which are usually present in complex structures of the target molecule. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) and several copper-free click reactions represent such methods for radiolabeling of sensitive molecules under the above-mentioned criteria. This minireview will provide a quick overview about the development of novel 18F-labeled prosthetic groups for click cycloadditions and will summarize recent trends in copper-catalyzed and copper-free click 18F-cycloadditions.
Adherence to a Mediterranean diet and plasma concentrations of lipid peroxidation in premenopausal women 1 – 3

Background: A Mediterranean diet has been associated with a reduced risk of cardiovascular disease and mortality. A possible mechanism is through a decrease in lipid peroxidation (LPO); however, evidence linking the Mediterranean diet with lower LPO in premenopausal women is sparse. Objective: We investigated whether adherence to a Mediterranean diet was associated with lower LPO concentrations in premeno-
When technology is mandatory-factors influencing users satisfaction

One commonly acknowledged factor in the successful implementation of any application or information system is user satisfaction. This paper studied users' judgments on a new technology in an educational context. This study found that, while perceived usefulness and perceived ease of use each had a positive correlation with user satisfaction, there are likely to be additional factors that contribute to user satisfaction.
Defining Escherichia coli as a health-promoting microbe against intestinal Pseudomonas aeruginosa

Gut microbiota acts as a barrier against intestinal pathogens, but species-specific protection of the host from infection remains relatively unexplored. Taking a Koch’s postulates approach in reverse to define health-promoting microbes we find that Escherichia coli naturally colonizes the gut of healthy mice, but it is depleted from the gut of antibiotic-treated mice, which become susceptible to intestinal colonization by Pseudomonas aeruginosa and concomitant mortality. Reintroduction of fecal bacteria and E. coli establishes a high titer of E. coli in the host intestine and increases defence against P. aeruginosa colonization and mortality. Moreover, diet is relevant in this process because high sugars or dietary fat favours E. coli fermentation to lactic acid and P. aeruginosa growth inhibition. To the contrary, low sugars allow P. aeruginosa to produce the oxidative agent pyocyanin that inhibits E. coli growth. Our results provide an explanation as to why P. aeruginosa doesn’t commonly infect the human gut, despite being a formidable microbe in lung and wound infections. Author Summary Here we interrogate the conundrum as to why Pseudomonas aeruginosa is not a clinical problem in the intestine as opposed to other tissues. P. aeruginosa interacts with Neisseria, Streptococcus, Staphylococcus and Actinomyces species found in the human lung. These are predominantly gram-positive bacteria that induce P. aeruginosa virulence. Moreover, peptidoglycan, which is abundant in gram-positive bacteria, can directly trigger the virulence of P. aeriginosa. We reasoned that P. aeruginosa might be benign in the human gut due to the inhibitory action of benign gram-negative intestinal bacteria, such as Escherichia coli. Therefore, we dissected the antagonism between E. coli and P. aeruginosa and the effect of a conventional, a fat-, a carbohydrate-and a protein-based diet in intestinal dysbiosis. Our findings support the notion that an unbalanced diet or antibiotics induces gut dysbiosis by the elimination of commensal E. coli, in addition to lactic acid bacteria, imposing a gut environment conducive to P. aeruginosa infection. Moreover, commensal E. coli provides an explanation as to why P. aeruginosa doesn’t commonly infect the human gut, despite being a formidable microbe in lung and wound infections.
Study on the Residual Current Protection Device Technology

As an important electrical safety protection device in low voltage distribution system, residual current protec- tion device is to protect the insulation line leakage fault; the electric shock of the people plays an important role in fault. From the protection characteristics of residual current protective device to points, those can be divided into, residual cur- rent protection device for residual pulsating direct current and residual dc, according to the residual sinusoidal alternating current.
The Generalization Effect for Multilingual Speech Emotion Recognition across Heterogeneous Languages

Regularization approaches, such as multi-task learning and dropout, prevent overfitting and improve generalization ability. Speech emotion recognition suffers from insufficiently transcribed databases, where labels are subjectively annotated. Because emotions are a more universally recognized language, the paralinguistic feature space of emotional speech can be better generalized, even across substantially heterogeneous languages. We investigate the effect of regularization and normalization frameworks on two emotional speech databases, the IEMOCAP for English and the JTES for Japanese. We obtain absolute gains of unweighted average recall over ten runs (1.48% for the IEMOCAP and 1.03% for the JTES) and achieve a maximum of 59.49% on the IEMOCAP. From comparative experiments, we confirm that dropout and multi-task learning strategies are effective for multilingual speech emotion recognition, and common normalization over two languages leads to further improvement under all conditions, which suggests that better generalization is available even when two highly heterogeneous languages are merged.
Virtualization technologies in web conferencing systems: A performance overview

Virtualization is an important technology in data center environment due to its useful features such as server consolidation, power saving, live migration and faster server provisioning. However, virtualization sometimes incurs some performance loss. There are many virtualization approaches including full virtualization and operating system-level virtualization. Different virtualization platforms differ in terms of features, performance and virtualization overhead. Thus, one platform can be more suitable to certain kind of application than another. Applications being virtualized also differ in resource usage. Web conferencing systems become popular as the clients' bandwidth has increased in last years, in educational, researching and business fields. The BigBlueButton is a web conferencing system that allows multiple users join a conference room, having classes and share their microphone, webcam, desktop and files. In this paper, we use KVM and OpenVZ as virtualization platforms to deploy conference systems using BigBlueButton. We explore its virtual performance under a real-world workload and a set of benchmarks that stress different aspects such as computing power, latency and memory, I/O and network bandwidth. These results can be a valuable information to be taken in account by systems administrators, for capacity planning and systems designing. Which, in turn, lead to cost savings for companies.
Efficient transformation of potato stems segments from cultivar Désirée, using phosphinothricin as selection marker

This work describes the development of a fast and efficient methodology for Agrobacterium tumefaciens-mediated genetic transformation of internodal stem segments from potato (Solanum tuberosum L.), cultivar Desiree, using phosphinothricin (PPT, glufosinate ammonium) as a selection agent. This methodology has a transformation efficiency of 68%, inducing shoots after 4 to 5 weeks in the presence of 2 mg/L of phosphinothricin. The expression of the bar gene in leaf segments from resistant, transformed plants was demonstrated by the chlorophenol red assay, as was its presence in the genome of explants by Polymerase Chain Reaction. An additional observation was the presence of high levels of resistance to phosphinothricin (up to 500 mg/L) in the transgenic clones, with an otherwise normal phenotype. These transgenic plants were transplanted to greenhouses and after aspersion with the herbicide Finale ® (Bayer CropScience) at 2.5 L/ha remained healthy and green, in contrast with the non-transgenic controls which died after 7 days.
Specifying Rhythmic Auditory Stimulation for Robot-assisted Hand Function Training in Stroke Therapy

Following a stroke 90% of all patients suffer from a loss of arm and hand function, whereby 30-40% of them never regain full functionality ever again. Robot-assisted hand function training (RT) intensifies and complements common ergo-therapeutic treatment effectively. Most of robotic rehabilitation devices are connected to multimedia-environments offering playful training to promote motivation. “Rhythmic Acoustic Stimulation” (RAS), an effective therapeutic technique for post-stroketreatment, was never specified, applied nor evaluated for RT. This paper suggests specified sound designs with rhythmic stimuli for RT that aim to enhance function and motivation. Four pilot experiments are described evaluating, if specified rhythmic stimulation designs applied during a fine motor task influence motivation and function in comparison to no stimulation. As results of these experiments indicate that rhythmic stimulation designs may enhance function and motivation, they are discussed for further observations applied in RT with stroke-patients.
Coping with the Rapidity of Information Technology Changes: A Comparison Review on Current Practices

— Information technology managers nowadays are facing with tremendous pressure to plan, implement, and adopt new technology solution due to the rapidity of technology changes. Resulted from a lack of study that have been done in this topic, the aim of this paper is to provide a comparison review on current tools that are currently being used in order to respond to technological changes. The study is based on extensive literature review of published works with majority of them are ranging from 2000 to the first part of 2011. The works were gathered from journals, books, and other information sources available on the Web. Findings show that, each tools has different focus and none of the tools are providing a framework in holistic view, which should include technical, people, process, and business environment aspect. Hence, this result provides potential information about current available tools that IT managers could use to manage changes in technology. Further, the result reveals a research gap in the area where the industries a short of such framework.
Robust Late Fusion on Multi-View Clustering

Multi-view clustering, which seeks a partition of the data in multiple views that often provide complementary information to each other, has received considerable attention in recent years. In real life clustering problems, the data in each view may have considerable noise. However, existing clustering methods blindly combine the information from multi-view data with possibly considerable noise, which often degrades their performance. In this paper, we developed RMC, a method for robust multi-view spectral clustering, which explicitly handles the possible noise in the multi-view input data and recovers a shared similarity matrix via low-rank and sparse decomposition. To solve the optimization problem of RMC, we proposed a procedure based on the ALM scheme. Extensive experiments in real world datasets for multi-view clustering show that RMC has encouraging performance gain over the state-of-the-arts.