Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterizing drug interactions in the substrate binding pocket of the P-glycoprotein multidrug efflux pump

CHARACTERIZING DRUG INTERACTIONS IN THE SUBSTRATE BINDING POCKET OF THE P-GLYCOPROTEIN MULTIDRUG EFFLUX PUMP David Ward Advisor: University of Guelph, 2012 Professor F.J. Sharom P-glycoprotein (Pgp, ABCB1) is a polyspecific efflux transporter implicated in multidrug resistance in human cancers. In this study, tetramethylrhodamine-5-carbonyl azide (AzTMR) was covalently crosslinked to the Pgp drug binding pocket with a stoichiometry of 1. The Pgp-AzTMR adduct was functionally equivalent to unlabelled Pgp and retained its ability to transport Hoechst 33342. The binding site of AzTMR in Pgp was nonpolar, with a similar environment to that of propanol. Pgp-AzTMR could bind a second drug molecule, with a higher affinity for H-site drugs and lower affinity for other R-site drugs. Unlabelled Pgp interacted with dimeric versions of known Pgp modulators, binding them with higher affinity than the monomer. These compounds were also found to either stimulate or inhibit Pgp ATPase activity depending on the concentration. Pgp-AzTMR was able to bind dimeric drugs, indicating that 3 substrate moieties can fit into the binding pocket.
Clinico demographic profiling of the Respiratory syncytial virus (RSV) infected children admitted in tertiary care hospital in North India

Background: Acute bronchiolitis is fatal disease involving lower respiratory tract of infants and children of paediatric age group. Respiratory Syncytial Virus (RSV) is responsible for causing more than 70% hospital admissions of children aged less than 2 years thus making a necessity for accurate and timely diagnosis. Aims: The main aim of study was clinicodemographic correlation of RSV positive children presenting to our tertiary care hospital. Setting and Design: It is a retrospective study done between December to January 2018. Materials and Methods: Detection of RSV antigen from nasophyrangeal aspirates using Mouse Monoclonal anti RSV Antibody (by Novatetra) and Goat Anti Mouse Antibody conjugated with FITC as secondary antibody. Results: A total of 147 samples were received in the laboratory and 20 were tested as positive for RSV Antigen. Totally, 19/20 children were aged less than 1 year and with a male predominance. The most common symptom was cough and respiratory distress. Eight percent of the children showed wheezing and 18/20 required assisted ventilation. The clinical course in one child deteriorated leading to death of that patient. Conclusions: The timely diagnosis and management of RSV infected children is utmost needed to prevent morbidity and mortality. The premorbid conditions can assist to differentiate the viral from bacterial pneumonia and thus enable speedy recovery of the child.
Evaluation of levels of oxidative stress as a potential biomarker in patients with rheumatoid arthritis

Objectives: One of the most prevalent autoimmune disease globally, rheumatoid arthritis (RA) is caused by interplay of multiple inflammatory mediators in specific joints. Altered redox balance is one of the key factors in pathophysiology of RA. This study aims to find whether oxidative stress in peripheral blood neutrophil correlates with the disease activity and disability associated with it. Methods: Ten healthy controls and 29 RA patients with moderate to severe disease activity (DAS28 score >3.2) were recruited and reactive oxygen species (ROS) level in peripheral blood neutrophil was measured using flow cytometry at baseline visit and after 6 months follow-up. Functional status of RA patients was measured using Health Assessment Questionnaire Disability Index (HAQ-DI). Results: RA patients showed significantly higher level of ROS in compared to healthy control. DAS28 correlated well with ROS at baseline visit (Pearson's r = +0.63) as well as follow-up visit (Pearson's r = +0.75). HAQ-DI showed weak positive correlation at baseline visit (Pearson's r = 0.1) but it was negative at follow-up visit (Pearson's r = -0.19). Conclusions: Oxidative stress mirrors the disease activity in RA and can be considered as a biomarker, but it is not related with functional ability of the patients.
A review on solubility enhancement methods for poorly water-soluble drugs

One of the most important parameters in pharmacy is drug solubility. Solubility affects the efficacy of a drug. Drug solubility has an important role in determining the concentration of a drug to achieve the necessary pharmacological response, as all drugs absorbed by the body must be in the form of a solution. Drug solubility is quite a common issue and affects the bioavailability of a drug in the body. Drugs with low solubility are poorly absorbed, resulting in poor bioavailability. Many methods have been developed for increasing the solubility of a drug. In this review, we will describe possible efforts for improving the solubility of a drug, e.g., reducing particle size, surfactants, the use of nanosuspension technology, solid dispersion, salt formation, pH adjustment, hydrotropy, cocrystal, amorphous compound formation, and inclusion complexes. The main objective of this review was to focus on efforts that can increase the solubility of a drug to obtain good drug efficacy.
Comprehensive Conservative Care in End-Stage Kidney Disease

In patients with end-stage kidney disease (ESKD), when there maybe situations where dialysis does not offer benefits in terms of survival or health-related quality of life, dialysis should not be viewed as the default therapy. Such patients can be offered comprehensive conservative care as an alternative to dialysis. Conservative (nondialytic) management of ESKD includes careful attention to fluid balance, treatment of anemia, correction of acidosis and hyperkalemia, blood pressure, and calcium/phosphorus metabolism management and dietary modification. Individualized symptom management and supportive care are crucial to maximize the quality of life. We propose that model of comprehensive conservative care in ESKD should manage both diseases as well as provide supportive care. Facilitating implementation of comprehensive conservative care requires coordination between nephrology and palliative care at patient, professional, administrative, and social levels to maximize benefit with the motto to improve the overall quality of life.
A comprehensive overview on sandfly fever

Sandfly fever is a febrile emerging arboviral illness which is a huge threat posed to public health. Sandfly fever viruses (Sicilian, Naples, and Toscana) are endemic to the Mediterranean region. Evidence suggests an increase in the activity of sandfly-borne phleboviruses and their extension to other places. The infection is relatively benign but may cause severe clinical manifestations and complications. Sandfly fever viruses belongs to the genus Phlebovirus (family Bunyaviridae), and the four main serotypes include sandfly fever Sicilian virus, sandfly fever Naples virus, sandfly fever Cyprus virus, and Toscana virus. Sandfly fever has flu-like symptoms such as fever, headache, photophobia, malaise, myalgia, and retro-orbital pain. The incubation period of the disease is 4-8 days, and the patient usually recovers within a week. The first infection provides the host with immunity. Sandfly fever viruses are transmitted through the bites of infected female sandflies, thus, the epidemiology of sandfly fever is closely related to the presence and activity of sandfly species that act as the vectors for transmission. Cases and outbreaks of the disease have been reported worldwide for more than 100 years. All in all, this disease is important for non-endemic countries because it is a travel-related and/or imported illness.
Assessment of Age-Related Changes of Salivary Immunoglobulin A Levels among Healthy Individuals

Background: Secretory immunoglobulin A (IgA) is the first line of defense against pathogens that invade mucosal surfaces. It has been reported that the immune system exhibits profound age-related changes. The aim of this study was to investigate the age-dependent changes of salivary IgA among healthy individuals. Materials and Methods: Saliva samples were collected from 120 healthy individuals (aged 11–70 years). The salivary IgA concentrations were measured by the use of a single radial immunodiffusion technique and analyzed using the Mann–Whitney U, Kruskal–Wallis, and Chi-square tests. Results: The mean salivary IgA levels were 81.11 ± 4.50 mg/dl at age 11–20 years, 92.71 ± 13.76 mg/dl at age 21–30 years, 96.50 ± 4.04 mg/dl at age 31–40 years, 104.96 ± 10.15 mg/dl at age 41–50 years, 113.22 ± 7.85 mg/dl at age 51–60 years, and 91.38 ± 4.77 mg/dl at age 61–70 years. There was a significant difference among the mean salivary IgA levels of different age groups (P < 0.001). Conclusion: These results showed that the salivary IgA levels exhibit age-related changes. Oral immunization may be considered to improve oral immunity when the salivary concentrations of IgA begin to decrease during lifetime.
Effect of malnutrition in infants with cystic fibrosis in India: An underestimated danger

Aims: To assess the clinical profile and nutritional status of infants with cystic fibrosis (CF) and track their nutritional outcomes with treatment. Materials and Methods: This retrospective study was conducted in a tertiary-care institute in South India. Demographic and clinical information were collected. The nutritional status and treatment outcome was assessed by Z-scores for weight-for-age (WAZ), length-for-age (LAZ), and weight-for-length (WLZ) at diagnosis and follow-up. Results: Nineteen infants with CF had mean follow-up duration of 9.7 ± 8.7 months. There was a mean delay of 2.9 ± 2.1 months from symptom onset to diagnosis, by which time infants were severely malnourished (mean WAZ -4.68 ± 1.8). Pneumonia, summer dehydration with electrolyte abnormalities (42.1%), and a combination of anemia, hypoalbuminemia, and malnutrition (42.1%) were the predominant features. Significant weight loss had been recorded in undiagnosed infants by second month of life before symptom onset. At follow-up, there was a remarkable improvement in WAZ (P 0.001), but not LAZ and WLZ. There was a high mortality rate of 37% in these infants. Conclusions: Malnutrition is a significant morbidity in infants with CF in India. There was significant improvement of WAZ with treatment, but it lagged behind the recommended targets. There is an opportunity for identification of CF infants at the time of vaccination at six and ten weeks of age, by the primary care physician and pediatrician. Screening of young infants having failure to thrive in the immunization clinic may be a strategy for early diagnosis of infants with severe CF phenotype.
Novel Zwitterionic Copolymers with Dihydrolipoic Acid: Synthesis and Preparation of Nonfouling Nanorods

We report the synthesis of hydrophilic, zwitterionic copolymers containing pendent disulfide and dithiol groups along a phosphorylcholine methacrylate backbone. These novel copolymers were prepared by controlled free radical copolymerization of methacryloyloxyethyl phosphorylcholine (MPC) and the methacrylate of lipoic acid (LA), using reversible addition–fragmentation chain transfer (RAFT) polymerization, followed by reduction of the disulfides to give dihydrolipoic acid (DHLA) pendent groups. Poly(MPC-co-DHLA) proved useful for surface functionalization of gold nanorods (Au NRs), resulting in removal of the cationic surfactant stabilizing layer present initially on the Au NRs. Au NRs coated with poly(MPC-co-DHLA) proved stable against challenging conditions, and resisted cyanide ion digestion. Au NRs coated with poly(MPC-co-DHLA) also showed nonfouling properties resulting from their surface coating, and the noncytotoxicity of these structures was confirmed in the presence of live cells. The novel polym.
Machine Learning Techniques for Intrusion Detection

This paper aims to equip intrusion analysts with the basic techniques needed to apply machine learning to intrusion detection. It will first review and describe the different approaches to machine learning-based classification (e.g., logistic regression, support vector machines) before explaining the challenges of applying it to network intrusion detection. It will also review methods of data preprocessing, model training, and testing. This paper then describes experiments carried out on a dataset (NSL-KDD) that is widely used to test intrusion detection algorithms. Two sets of experiments demonstrating the application of commonly used machine learning-based classification and methods extensively used to improve model performance (e.g., boosting, bagging, stacking, label smoothing, and embedding) are performed. With a knowledge of the underlying algorithms and the provided source code, network operators can experiment with and eventually apply machine learning-based intrusion detection to their network. © 2 02 1 T he SA NS In sti tut e, Au tho r R eta ins Fu ll R igh ts © 2021 The SANS Institute Author retains full rights. Machine Learning Techniques for Intrusion Detection 2 Yih Han Tan, tanyihhan@gmail.com
Molecular-Biological Properties of the Attenuated Strain of Salmonella Abortus-Equi E-841, used in the Creation of a Vaccine against Abortion of Mares

Salmonella abortion of mares takes a leading place in the in factious pathology of horses and leads to the abortion of pregnant mares and infected stallions become salmonella carriers. The disease with salmonella abortion manifests itself in the last months of pregnancy, maybe-during the mass foal of mares-in the spring. The article results obtained of studies on the biological properties and genetic characteristics of the attenuated strain of Salmonella abortus-equi E-841 compared with the control virulent strain of Salmonella Salmonella abortus-equi 7/1. These strains after inoculation on nutrient media retained their viability and had typical cultural-morphological, tinctorial and serological properties. When determining drug resistance, it showed resistance to rifampicin. As a result of studying the biochemical properties, it was found that the strain does not ferment urea, does not decompose gelatin and does not form indole, does not produce hydrogen sulfide. When determining the antigenic structure, it was shown that the attenuated strain is agglutinated in RA on glass with polyvalent and monoreceptor sera. The presence of mutations was determined by sequencing amplification fragments of the rpoB and rpsL genes. In the attenuated salmonella strain, mutations were found in the nucleotide sequences of fragments of the rpoB and rpsL genomes that cause antibiotic resistance and reduce the virulence of the strain, preventing the transformation of the strain into a virulent prototype of salmonella.
Effects of New Media Use on Health Behaviors: A Case Study in China

Background: Mass communication is one of the most important ways in health communication. The emergence of new media has changed the way people acquire health information and then their health behaviors. However, few studies have been conducted about complicated relations between media use and health behaviors under new media conditions and further systematic explanation is needed. Methods: A hypothesis model for the influence of WeChat use on health behaviors was constructed to explore the internal influencing mechanism of new media use on health behaviors. An empirical analysis on the internal influencing mechanism of WeChat use on health behaviors was carried out with a survey data consist of 463 young active users on famous online social network sites in China from March to June 2019. Results: New media use represented by WeChat has significant positive influence on health behaviors. Individuals who frequently use new media related to health have better health conditions than those who rarely use them. The improvement of health behaviors is mainly attributed to acquisition of health knowledge. Such effect is also mediated by the degree of individuals’ trust in health knowledge. Conclusion: This study not only discloses the influencing mechanism of new media use and health knowledge on health behaviors, but also confirms the value of new media in promoting public health communication and public health behaviors. Conclusions provide significant references in decision-making to develop effective guidance of public health.
A Tailored Regression for Learned Indexes: Logarithmic Error Regression

Although linear regressions are essential for learned index structures, most implementations use Simple Linear Regression, which optimizes the squared error. Since learned indexes use exponential search, regressions that optimize the logarithmic error are much better tailored for the use-case. By using this fitting optimization target, we can significantly improve learned index’s lookup performance with no architectural changes. While the log-error is harder to optimize, our novel algorithms and optimization heuristics can bring a practical performance improvement of the lookup latency. Even in cases where fast build times are paramount, log-error regressions still provide a robust fallback for degenerated leaf models. The resulting regressions are much better suited for learned indexes, and speed up lookups on data sets with outliers by over a factor of 2.
RATE-ADAPTIVE BOOTSTRAP FOR POSSIBLY MISSPECIFIED GMM

We consider inference for possibly misspecified GMM models based on possibly nonsmooth moment conditions. While it is well known that misspecified GMM estimators with smooth moments remain $\sqrt {n}$ consistent and asymptotically normal, globally misspecified nonsmooth GMM estimators are $n^{1/3}$ consistent when either the weighting matrix is fixed or when the weighting matrix is estimated at the $n^{1/3}$ rate or faster. Because the estimator’s nonstandard asymptotic distribution cannot be consistently estimated using the standard bootstrap, we propose an alternative rate-adaptive bootstrap procedure that consistently estimates the asymptotic distribution regardless of whether the GMM estimator is smooth or nonsmooth, correctly or incorrectly specified. Monte Carlo simulations for the smooth and nonsmooth cases confirm that our rate-adaptive bootstrap confidence intervals exhibit empirical coverage close to the nominal level.
Multi-Reconstruction from Points Cloud by Using a Modified Vector-Valued Allen–Cahn Equation

The Poisson surface reconstruction algorithm has become a very popular tool of reconstruction from point clouds. If we reconstruct each region separately in the process of multi-reconstruction, then the reconstructed objects may overlap with each other. In order to reconstruct multicomponent surfaces without self-intersections, we propose an efficient multi-reconstruction algorithm based on a modified vector-valued Allen–Cahn equation. The proposed algorithm produces smooth surfaces and closely preserves the original data without self-intersect. Based on operator splitting techniques, the numerical scheme is divided into one linear equation and two nonlinear equations. The linear equation is discretized using an implicit method, and the resulting discrete system of equation is solved by a fast Fourier transform. The two nonlinear equations are solved analytically due to the availability of a closed-form solution. The numerical scheme has merit in that it can be straightforwardly applied to a graphics processing unit, allowing for accelerated implementation that performs much faster than central processing unit alternatives. Various experimental, numerical results demonstrate the effectiveness and robustness of the proposed method.
Universe Discrete . Granular Reality

Is reality continuous or discrete ? As for the matter and the energy , both are composed of concrete elements : photons , electrons , molecules.Therefore it is pertinent to ask whether spacetime is made of any type of discrete , elementary ingredients . A preliminary approach to this issue is presented . It consists of numerical and geometric equivalences. The introduction of few parameters will help us to analyze some physical and cosmological subjects. © 2016 Elixir All rights reserved. Elixir Space Science 94 (2016) 39945-39949 Space Science Available online at www.elixirpublishers. com (Elixir International Journal) Alberto Coe/ Elixir Space Science 94 (2016) 39945-39949 39946 Once described the two calculation tools will show several results . We have choose only a small set of subjects . An introductory sample wich opens the way to further developments . In order to avoid the dispersal of the references concerning the physical constants , all physical constants used in this article are compiled in the appendix. Results . Surface’s area of a particular sphere Write the formula of the surface’s area of a particular sphere [2] , where (9) Type now the surface’s area of a particular Torus [3] (10) stands for Planck’s length (appendix). Figure 1 shows a view of the topic Divide both equations (11) Figure 1 Now consider a cylinder whose volume is given by (12) stands for Planck’s length (appendix) Suppose that such cylinder follows , while rotating , a circle whose radius is equal to Consequently the length of such circumference is equal to ( figure 2). The resulting toroidal volume reads (13) Once defined and , write the following equivalence (14) Figure 2 . ‘’Planck Torus’’ Electrostatic force and gravitational force under the terms of a spacetime discrete Write Newton’s [4] formula of gravitational force between an electron and a proton (15) Coulomb’s law [5]of the electrostatic force reads (16) The values of the parameters involved in both equations are specified in the appendix. After making the proper calculations , the ratio between gravitational force with respect to the electromagnetic force reads (17) Now consider a basic sphere whose volume is given by Will assign to the radius of such sphere the two values already defined In the case at hand we must set Therefore
The Development of a Physical Theory of Braids An Extension of the Ropelength Model to Braids

Physical knot theory is an area of study in the field of knot theory which seeks to create physical frameworks with which to study knots. One of the most well known models is the ropelength model for knots and links. The ropelength model of a knot or link seeks to model presentations of knots or links that are made of an ideally flexible, thickened rope and to define a tight presentation of a knot or link. It was established by J.W. Alexander in 1923 that every knot or link can be represented as the closure of a braid [1]. With this, we are inspired to extend the ropelength model to braids. In this paper we define a ropelength model for braids and prove the existence of a ropelength minimizing braid presentation within each braid type.