Miracle-dz/UniFAR-FTUs huggingface dataset:
Theory of pleiotropic action of biologically active compounds and medicines—Basic principles and practical application

This article represents the main positions of the theory of pleiotropic action of biologically active compounds (BACs) and medicines, which has been designed by the author based on her own experimental researches. The term “pleiotropy” means the ability of the BACs and medicines to implement more than one mechanism of action resulting in the specific biological (pharmacological) effect. The interaction of these mechanisms forms a distinct pattern of biological response (pleiotropic pattern), which reflects the change in his character with the increased dose (concentration)-dependent efficacy of BACs and medicines. The article consists of description of different pleiotropic patterns established in experiments on the model of reactive oxygen species (ROS) generation by macrophages dependent on activity of specialized enzyme called Nox2-NAD(P)H oxidase (Nox2, EC 1.6.3.1). Moreover, it consists of explanation of pharmacodynamic nature of pleiotropic patterns by means of application Chou-Talalay median effect equalization and combination index (CI) theory. The novel theory explains unsolved until now universal aspects of activity BACs and medicines, such as slope angles of “dose-effect” dependences in the conditions relevant in vivo, and it is of fundamental interest. However, it has applications in experimental pharmacology, as it allows defining the choice of the individual compounds and combinations, modulating the trust effect selectively and efficiently. This knowledge opens up new approaches to medicines discovery and evaluation, their rational dosing and combining.
Aspirin for Cardioprotection and Strategies to Improve Patient Adherence

Abstract Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in North America. Aspirin therapy has proven clinical effectiveness in the prevention and treatment of CVD and is one of the most widely used drugs nationwide. However, despite the medication's popularity and utility, adherence to a proper aspirin regimen is suboptimal, resulting in adverse health outcomes and increased health care costs. Our review outlines current knowledge on aspirin therapy adherence, causes of nonadherence, and strategies available to increase adherence to aspirin and medications in general. We demonstrate that, indeed, aspirin adherence rates are suboptimal, ranging from 72% to 92%, and that a combination of patient– and medication–related factors contribute to nonadherence. A multidimensional approach involving patient education and medication innovations to reduce aspirin side effects is imperative to improving rates of aspirin therapy adherence.
Characterization of FAM65B knock-out mice and role of FAM65B in skeletal muscle stem cells differentiation

The family with sequence similarity 65, member B (Fam65b) protein is thought to facilitate fusion of myocytes and formation of myotubes during the differentiation of human myogenic cells. Fam65b and histone deacetylase 6 (HDAC6) coimmunoprecipitate and together regulate the levels of acetylated tubulin, which might control microtubule stability in myogenic cells. In this thesis, to gain further insight on the role of Fam65b in the differentiation pathway and motility of myogenic cells, we characterized a Fam65b knock-out (KO) mouse model. Genotyping and transcriptional analysis revealed that a thirteen exons-long region of the Fam65b gene has been successfully ablated and the mRNA amplicons within the deleted segment are not transcribed. Nevertheless, mRNA products corresponding to genomic regions downstream of the deleted area are still detected. Furthermore, analysis of skeletal muscle lysates via western blot (WB) does not show a complete loss of Fam65b expression, but only reduced translation of some isoforms. Nevertheless, WBs of myogenic cells that have been directly isolated from Fam65b KO mice and expanded in vitro revealed the absence of a 120 Kd band, which putatively corresponds to the long isoform of Fam65b. Finally, our data show that Fam65b KO mice are significantly heavier than wild type (WT) mice, and that this phenotype is consistently observed across both genders during the first seven months of age. While functional and molecular analyses of the KO mouse vi model are still ongoing, future work might include generating a new KO model via the CRISPR-Cas9 technology to ablate all isoforms of Fam65b.
3D Nanoporous Anodic Alumina Structures for Sustained Drug Release

The use of nanoporous anodic alumina (NAA) for the development of drug delivery systems has gained much attention in recent years. The release of drugs loaded inside NAA pores is complex and depends on the morphology of the pores. In this study, NAA, with different three-dimensional (3D) pore structures (cylindrical pores with several pore diameters, multilayered nanofunnels, and multilayered inverted funnels) were fabricated, and their respective drug delivery rates were studied and modeled using doxorubicin as a model drug. The obtained results reveal optimal modeling of all 3D pore structures, differentiating two drug release stages. Thus, an initial short-term and a sustained long-term release were successfully modeled by the Higuchi and the Korsmeyer–Peppas equations, respectively. This study demonstrates the influence of pore geometries on drug release rates, and further presents a sustained long-term drug release that exceeds 60 days without an undesired initial burst.
Decentralized control design using Integrator Backstepping for controlling web winding systems

Many types of materials are manufactured or processed in the form of a sheet or a web (textile, paper, metal, etc.), which then couples the processing rolls and the associated motor drives. In Winding and web transport systems, the main concern is to control independently speed and tension in spite of disturbances such as radius variations and changes of set point, and to the coupling introduced by the elastic web. So the increasing requirement on the control performance led to investigation for sophisticated control strategies. To improve the overall performance of the winding system, we propose to apply decentralized control based an Integrator Backstepping strategy for controlling web winding systems. The advantage of this type of control is to impose stability properties by building recursively a Lyapunov function for the overall cascade system. Our winding system is simulated in Matlab®/Simulink™ environment, the results obtained illustrate the efficiency of the proposed control, with no overshoot, and the rising time is improved with good disturbance rejection comparing with the classical control law (PI controller).
Effect of dietary Rhodobacter capsulatus on lipid fractions and egg-yolk fatty acid composition in laying hens.

The present study was conducted to investigate the effect of dietary Rhodobacter capsulatus on lipid fractions and egg-yolk fatty acid composition in laying hens. Thirty-six laying hens (30 weeks old) were randomly assigned into two dietary groups fed diets with (0.04%) or without (control) R. capsulatus for a 60-day feeding trial. Dietary R. capsulatus decreased (p < 0.05) serum and hepatic cholesterol and increased (p < 0.05) the excreta cholesterol, and resultant lower (p < 0.05) cholesterol contents in egg yolk. The concentration of polyunsaturated fatty acids (PUFA) and ratio to saturated fatty acids in egg yolk was improved (p < 0.05) by dietary R. capsulatus. The concentration of hepatic bile acid was increased (p < 0.05) and excreta bile acid was decreased (p < 0.01) in the laying hens fed R. capsulatus diet. The incorporation of 1-(14) C-palmitic acid into hepatic lipids and lipid fractions was increased (p < 0.05) in laying hens fed R. capsulatus diet. Moreover, dietary R. capsulatus did not appear to cause any adverse effects on laying hen performances. Therefore, dietary supplementation of R. capsulatus in layer diets may be a feasible means of producing eggs with lower cholesterol and higher PUFA contents for health conscious consumers.
Protease‐catalyzed incorporation of 18O into peptide fragments and its application for protein sequencing by electrospray and matrix‐assisted laser desorption/ionization mass spectrometry

Proteins were digested in normal and highly 18O‐enriched water using proteases commonly employed for protein sequencing. The extent of 18O incorporation into the resulting peptide fragments was characterized by electrospray ionization (ESI) and matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry (MS). The endoproteinases trypsin, Lys‐C and Glu‐C incorporate two atoms of 18O, resulting in a mass shift of +4 D for the peptide fragments. This indicates that, following proteolytic cleavage, peptide products continue to interact with these proteases and undergo repeated binding/hydrolysis cycles, resulting in complete equilibration of both oxygens in the carboxy terminus of the fragments with oxygen from solvent water. In contrast, chymotrypsin and Asp‐N incorporate only one atom of 18O, resulting in a mass shift of +2 D, indicating that after the cleavage step these proteases do not accept the peptides as substrates. In addition, it was found that the proteases trypsin, Glu‐C, and Lys‐C exhibit minor or nontypical sequence specificities, resulting in unexpected peptide fragments. These fragments incorporate only one 18O atom, indicating that they do not undergo further binding/hydrolysis cycles with the enzyme. Thus, it is possible to discriminate between enzyme‐typical peptide fragments with mass shifts of +4 D and nontypical fragments with mass shifts of only +2 D. Based on these observations, protein digest strategies are described for the generation of 1:1 ion doublets spaced either by 2 or 4 D. In addition, the C‐terminus of a protein can be identified by the absence of an ion doublet in the corresponding peptide fragment. In protein sequencing by mass spectrometry, digest protocols generating ion doublets provide the most clear‐cut analytical results for the recognition of ion series in ESI‐MS/MS and MALDI post‐source decay (PSD) product ion specta. Only the mass spectrometric fragment ions of a C‐terminal series show ion doublets spaced either by 2 or 4 D, whereas the fragment ions belonging to an N‐terminal series remain unshifted. This assignment unequivocally reveals the direction of the identified sequence.
Antibody‐mediated enhancement of the rate, magnitude, and responsiveness of vesicular stomatitis virus induced alpha interferon production

A majority of adults without evidence of exposure to vesicular stomatitis virus (VSV) have serum IgG antibodies that interact with pro‐inflammatory TLR7 in the presence of VSV, and enhance several aspects of VSV‐induced IFN‐α production. Enhancing IgG antibody enables human PBMC to make IFN‐α more rapidly and in higher titers in response to a broad range of VSV‐concentrations that include those too low to independently stimulate IFN‐α production. These antibody‐mediated functions compensate for the inherent delay in virus‐induced IFN‐α production in vitro, and have the potential to improve the in vivo IFN‐α response and effectively terminate infection before the occurence of clinically apparent disease. The frequent presence of enhancing antibody in persons without predictable VSV exposure has implications for naturally occurring infections with this and other viruses, and for the use of viruses as vaccine vectors and oncolytic agents. J. Med. Virol. 80:1675–1683, 2008. © 2008 Wiley‐Liss, Inc.
Cytoplasmic Domain of Rhodopsin Is Essential for Post-Golgi Vesicle Formation in a Retinal Cell-free System (*)

In retinal photoreceptors, highly polarized organization of the light-sensitive organelle, the rod outer segment, is maintained by the sorting of rhodopsin and its associated proteins into distinct post-Golgi vesicles that bud from the trans-Golgi network (TGN) and by their vectorial transport toward the rod outer segment. We have developed an assay that reconstitutes the formation of these vesicles in a retinal cell-free system. Vesicle formation in this cell-free assay is ATP-, GTP-, and cytosol-dependent. In frog retinas vesicle budding also proceeds at 0°C, both in vivo and in vitro. Vesicles formed in vitro are indistinguishable from the vesicles formed in vivo by their buoyant density, protein composition, topology, and morphology. In addition to the previously identified G-proteins, these vesicles also contain rab11. Concurrently with vesicle budding, resident proteins are retained in the TGN. Collectively these data suggest that rhodopsin and its associated proteins are sorted upon exit from the TGN in this cell-free system. Removal of membrane-bound GTP-binding proteins of the rab family by rab GDP dissociation inhibitor completely abolishes formation of these vesicles and results in the retention of rhodopsin in the Golgi. A monoclonal antibody to the cytoplasmic (carboxyl-terminal) domain of rhodopsin and its Fab fragments strongly inhibit vesicle formation and arrest newly synthesized rhodopsin in the TGN rather than the Golgi. Therefore rhodopsin sorting at the exit from the TGN is mediated by the interaction of its cytoplasmic domain with the intracellular sorting machinery.
A Tensor Based Deep Learning Technique for Intelligent Packet Routing

Recently, network operators are confronting the challenge of exploding traffic and more complex network environments due to the increasing number of access terminals having various requirements for delay and package loss rate. However, traditional routing methods based on the maximum or minimum single metric value aim at improving the network quality of only one aspect, which makes them become incapable to deal with the increasingly complicated network traffic. Considering the improvement of deep learning techniques in recent years, in this paper, we propose a smart packet routing strategy with Tensor-based Deep Belief Architectures (TDBAs) that considers multiple parameters of network traffic. For better modeling the data in TDBAs, we use the tensors to represent the units in every layer as well as the weights and biases. The proposed TDBAs can be trained to predict the whole paths for every edge router. Simulation results demonstrate that our proposal outperforms the conventional Open Shortest Path First (OSPF) protocol in terms of overall packet loss rate and average delay per hop.
A proportional integral extremum-seeking control approach

Abstract This paper proposes an alternative extremum seeking control design technique for the solution of real-time optimization control problems. The technique considers a proportional-integral approach that avoids the need for a time-scale separation in the formulation of the ESC. It is assumed that the equations describing the dynamics of the nonlinear system and the cost function to be minimized are unknown and that the objective function is measured. The dynamics are assumed to be asymptotically stable and relative order one with respect to the objective function. The extremum-seeking problem is solved using a time-varying parameter estimation technique.
Skill learning from observations

This paper presents a new approach for representing and registering skills based on state transition graphs. First, we generate clusters of feasible state transitions from the experimental data such that the union of these clusters represents the feasible state transition region of the system. Globally competitive and locally cooperative (GCLC) algorithm is formulated for self-organizing clusters and state transitions accurately through interpolation. A state transition graph is then constructed by representing possible transitions between clusters. Skills are considered embedded in this state transition graph and can be extracted by searching for an optimal path from the current to the goal states. The reactive nature of skills can be implemented by forming priority indices for sibling branches for local decision with possible merging and splitting of clusters to ensure consistency in prioritization. Experimental results are shown. <<ETX>>
Why does fertilization reduce plant species diversity? Testing three competition‐based hypotheses

1 Plant species diversity drops when fertilizer is added or productivity increases. To explain this, the total competition hypothesis predicts that competition above ground and below ground both become more important, leading to more competitive exclusion, whereas the light competition hypothesis predicts that a shift from below‐ground to above‐ground competition has a similar effect. The density hypothesis predicts that more above‐ground competition leads to mortality of small individuals of all species, and thus a random loss of species from plots.
The BRCT Domain Is a Phospho-Protein Binding Domain

The carboxyl-terminal domain (BRCT) of the Breast Cancer Gene 1 (BRCA1) protein is an evolutionarily conserved module that exists in a large number of proteins from prokaryotes to eukaryotes. Although most BRCT domain–containing proteins participate in DNA-damage checkpoint or DNA-repair pathways, or both, the function of the BRCT domain is not fully understood. We show that the BRCA1 BRCT domain directly interacts with phosphorylated BRCA1-Associated Carboxyl-terminal Helicase (BACH1). This specific interaction between BRCA1 and phosphorylated BACH1 is cell cycle regulated and is required for DNA damage–induced checkpoint control during the transition from G2 to M phase of the cell cycle. Further, we show that two other BRCT domains interact with their respective physiological partners in a phosphorylation-dependent manner. Thirteen additional BRCT domains also preferentially bind phospho-peptides rather than nonphosphorylated control peptides. These data imply that the BRCT domain is a phospho-protein binding domain involved in cell cycle control.
Financial early-warning models on cross-holding groups

Purpose – This paper primarily uses statistical methods to establish financial early‐warning models that make it possible to predict, in advance, the probability of a company experiencing financial distress.Design/methodology/approach – In its empirical analysis, this is the first study that attempts to use financial ratios and non‐financial ratios as variables to analyze business groups, and the present study uses the (K‐S tests), and (M‐U tests) and logit regressions model.Findings – Financial ratio variables remain the primary variables for predicting corporate financial distress. Upon examining the predictor variables for corporate financial distress at one, two, and three years prior to distress, it was found that financial ratio variables were the main ones at one and two years prior to distress, while at three years prior to distress there was one financial ratio variable and two ownership structure variables that showed significant differences. Financial structure, solvency, profitability, and cas.
The bootstrap: To smooth or not to smooth?

SUMMARY The bootstrap and smoothed bootstrap are considered as alternative methods of estimating properties of unknown distributions such as the sampling error of parameter estimates. Criteria are developed for determining whether it is advantageous to use the smoothed bootstrap rather than the standard bootstrap. Key steps in the argument leading to these criteria include the study of the estimation of linear functionals of distributions and the approximation of general functionals by linear functionals. Consideration of an example, the estimation of the standard error in the variance-stabilized sample correlation coefficient, elucidates previously-published simulation results and also illustrates the use of computer algebraic manipulation as a useful technique in asymptotic statistics. Finally, the various approximations used are vindicated by a simulation study.
Towards an automated tool for software certification

The theoretical foundation and the main functionalities of the ATHENA software quality and certification tool are outlined. ATHENA supports the measurement of software quality factors, calculates a wide range of software quality metrics, and reports on the quality of software packages, using a software certification expert subsystem. The measurement kernel and the expert subsystem are described. <<ETX>>
Performance Analysis of VoIP Services in the IEEE 802.16e OFDMA System With Inband Signaling

Although the voice over Internet protocol (VoIP) service is expected to be widely supported in wireless mobile networks, the feasibility and capacity of the protocol have not previously been studied in relation to the emerging IEEE 802.16e orthogonal frequency-division multiple access (OFDMA) system. Informing subscriber stations about new downlink or uplink resource assignments creates a signaling overhead that influences the system throughput. In particular, the performance of VoIP services is seriously affected by the signaling overhead because the symmetry between the downlink and uplink causes immense downlink overheads. However, previous research on the IEEE 802.16e OFDMA system has not taken the signaling overhead into consideration. In the analytical model presented here, the signaling overhead is considered in the evaluation of the uplink and downlink performance of VoIP services in the IEEE 802.16e OFDMA system.
Appreciative inquiry into lifeskills-based HIV/AIDS education in South African schools

With a steady rise in the prevalence of HIV and AIDS throughout the world it has become vital for programme implementers at all levels to ensure that all HIV intervention programmes are effectively put into practice. The present research used qualitative and quantitative data to evaluate the lifeskills-based HIV/AIDS education programme being implemented in primary and secondary schools in South Africa, with special reference to KwaZulu-Natal. A qualitative questionnaire gathered information from nine respondents at three levels: Department of Education district officials, educators and learners. Six key themes were consequently identified to guide the evaluation: communication, empowerment, resources, networking, motivation, and evaluation and feedback. A quantitative questionnaire completed by 30 educators revealed an overall positive attitude towards the programme, regardless of the educator's gender, age or level of formal education. The results are discussed with special reference to continuation and improvement of the lifeskills-based HIV/AIDS education programme.
Celiac, fatty liver, and pancreatic insufficiency.

Exocrine pancreatic insufficiency is common in patients with celiac disease (1,2), is thought to be related to the intestinal mucosal damage (3,4), and is usually reversible when the patient is placed on a gluten-free diet (1,5,6). Irreversible pancreatic insufficiency is rare and has been reported in elderly patients with celiac disease (7) and post mortem studies of patients with celiac disease (8). It is believed to be caused by prolonged lack of pancreatic stimulation and malnutrition (9,10). It is well known that prevalence of celiac disease is increased in the patients with insulin-dependent diabetes mellitus (IDDM), ranging from 3% to 7% (11–13). Adults with celiac disease commonly have liver enzyme abnormalities (14,15), and celiac disease is common among patients with idiopathic hypertransaminasemia (16,17). It is believed that the liver enzyme abnormalities are caused by hepatic steatosis (15,18). This case report describes a 17-year-old girl with the unusual combination of celiac disease, permanent pancreatic insufficiency, diabetes mellitus, and hepatic and pancreatic steatosis.