Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling the Binding Affinity of p38α MAP Kinase Inhibitors by Partial Least Squares Regression

The p38 mitogen‐activated protein kinase is activated by environmental stress and cytokines and plays a role in transcriptional regulation and inflammatory responses. Factors influencing the activity and selectivity of the p38α mitogen‐activated protein kinase inhibitors have been investigated in this paper by inspecting the binding orientation and the possible residue‐inhibitor interactions in the binding site. The binding pattern of a set of 45 different inhibitors against p38α mitogen‐activated protein kinase was studied through Molecular Dynamic Simulations of the protein‐inhibitor complexes. Further, Partial Least Squares regression was used to develop a Quantitative Structure Activity Relationship model to predict the binding affinities of ligands. The selected model successfully predicted the test set with a Root Mean Square Error of Prediction of 1.36. The regression coefficients and the Variable Importance in Projection plots highlighted the residue‐inhibitor interactions which exhibited the largest absolute effect on the ligand binding, such as the van der Waals interaction with LYS50, ILE81, ASP165; electrostatic interactions with SER29, LEU164; hydrogen bonds with MET106; and total energy interaction with SER29 and LEU83.
Nitric Oxide-dependent Parasympathetic Signaling Is Due to Activation of Constitutive Endothelial (Type III) Nitric Oxide Synthase in Cardiac Myocytes (*)

Nitric oxide synthase (NOS) isoforms are discovered in an increasing variety of cell types with different roles in signaling. The inducible NOS (i.e. iNOS or NOS II) is expressed in cardiac myocytes in response to specific cytokines. Independent of iNOS induction, however, receptor-dependent signaling is modulated by a constitutive nitric oxide (NO) synthase isoform in these cells (Balligand, J. L., Kelly, R. A., Marsden, P. A., Smith, T. W., and Michel, T.(1993) Proc. Natl. Acad. Sci. U. S. A. 90, 347-351). We now show that cardiac myocytes constitutively express the endothelial isoform of NO synthase (ecNOS or NOS III). Transcripts for NOS III were detected by Northern blot in myocyte extracts using as a probe a polymerase chain reaction-generated cDNA amplified with isoform and species-specific primers. In subcellular fractionation experiments, a calcium-sensitive NO synthase activity was present primarily in the particulate fraction, coinciding with the distribution of NOS III analyzed by protein immunoblotting. The localization of NOS III within cardiac myocytes was further demonstrated by immunohistochemistry. The functional role of NOS III was explored by analyzing the effects of NOS inhibitors on single myocyte L-type calcium current and contractility. Inhibition of NOS blocked the attenuation by carbamylcholine of the increases in both parameters induced by β-adrenergic stimulation. We conclude that NO-dependent parasympathetic signaling is mediated by NOS III in cardiac myocytes.
Construction of the Chimeric Reverse Transcriptase of Simian Immunodeficiency Virus Sensitive to Nonnucleoside Reverse Transcriptase Inhibitor

A number of structurally diverse compounds have been shown to be potent inhibitors of the DNA polymerase activity of human immunodeficiency virus type 1 (HIV‐1) reverse transcriptase (RT). The compounds can be grouped into two broad classes; nucleoside analogs and nonnucleoside RT inhibitors. The nonnucleoside RT inhibitors are quite specific for HIV‐1 RT but not human immunodeficiency virus type 2 (HIV‐2) and simian immunodeficiency virus (SIV) RT. We have investigated the property of SIV/HIV‐1 chimeric viruses in which portions of SIVMAC RT were exchanged with the corresponding domain of HIV‐1 RT; amino acids 176‐190, 176‐383 and 176‐495 of HIV‐1 RT. The chimeric virus, which was substituted amino acids 176‐190 of RT, had detectable RT activity, and this chimeric RT was sensitive to three nonnucleoside RT inhibitors [nevirapine, HEPT derivative (E‐EBU‐dM) and TIBO derivative (R82913)]. To further study this chimeric virus, we purified the chimeric RT enzyme expressed in Escherichia coli and determined its kinetic properties; the Km and Vmax values, and the Ki value of HEPT derivative calculated for the DNA polymerase activity. This study reveals that amino acids 176‐190 of SIVMAC RT were important for the enzymatic activity and the SIV/HIV‐1 chimeric RT, which had amino acids 176‐190 of HIV‐1, was sensitive to the nonnucleoside RT inhibitor.
Cloning and characterization of an aminoglycoside 6'-N-acetyltransferase gene from Citrobacter freundii which confers an altered resistance profile

A novel gene encoding a 6'-N-aminoglycoside acetyltransferase, aac(6')-In, has been cloned and sequenced from Citrobacter freundii 13996-19, a clinical isolate from Venezuela. This gene mediates resistance to amikacin, 2'-N-ethylnetilmicin, isepamicin, kanamycin, netilmicin, and tobramycin. The aac(6')-In gene is 573 nucleotides in length and encodes a putative protein of 190 amino acids. AAC(6')-In is most closely related to AAC(6')-Im and AAC(6')-Ie, demonstrating 64.4% and 62.3% similarity, respectively, at the protein level, suggesting these proteins share a common ancestor. The aac(6')-In flanking sequences demonstrated homology to integron- and transposon-related elements which are often found associated with resistance determinants. Hybridization studies performed with an intragenic probe specific for aac(6')-In indicate that this gene is prevalent within Venezuela but has not been observed outside of the country. Furthermore, the aac(6)-In gene was found in 10 different species of gram-negative bacteria.
Value of Improved Information About Forest Protection Values, with Application to Rainforest Valuation

What is the utility from obtaining more precise values of natural resource objects (rainforests), through surveys or other similar information gathering? In the value of information problems studied here, a principal who wishes to preserve a resource sets a price to offer to a seller without knowing precisely the protection value or opportunity value, to the seller. The value of information related to more precise information about the protection value for the principal is a key issue in environmental and natural resource valuation, but it is in most cases implicit and not analyzed. More precise resource values reduce the frequency of two types of mistakes (saving the resource when it should not be saved, and not saving the resource when it should be saved), and increases the principal’s ex ante expected utility value. This paper applies the model to Amazon rainforest protection and considers the hypothetical value of perfect information. The analysis finds that the value of perfect information can easily exceed realistic information costs, thus perhaps justifying significant expenditures for valuation studies, given that all available information is used efficiently for conservation decision purposes. The value of perfect information also depends on the nature of buyer-seller interactions, and is higher in the altruistic case, where the principal has full concern for the outcome for the seller.
Leveraging IT Capabilities and Competitive Process Capabilities for the Management of Interorganizational Relationship Portfolios

Firms are increasingly dependent on external resources and are establishing portfolios of interorganizational relationships (IRs) to leverage external resources for competitive advantage. However, the systems of information technology (IT) and process capabilities that firms should develop to manage IR portfolios dynamically are not well-understood. In order to theorize how key structural IT capabilities (IT integration and IT reconfiguration) and competitive process capabilities (process alignment, partnering flexibility, and offering flexibility) operate as systems of complements, we draw on the competitive dynamics perspective and resource dependency theory and on the literature for IT business value, interorganizational systems, and interorganizational relationship management. We also theorize how a firm's IR portfolio moderates the effects of structural IT capabilities on competitive process capabilities and why a firm's environmental turbulence moderates the effects of complementary process capabilities on competitive performance. We test our model using survey data from 318 firms in 4 industries. Our results provide broad support for the following: (1) structural IT capabilities and process capabilities operating as a system of complements, (2) the effects of structural IT capabilities on competitive process capabilities being contingent on IR portfolio concentration, and (3) the effects of complementary process capabilities on competitive performance being contingent on environmental turbulence. We discuss the theoretical and practical implications of how firms should develop complementary systems of structural IT capabilities and competitive process capabilities to manage IR portfolios dynamically and leverage external resources.
Comparative molecular characterization of bovine herpesvirus-1 strains from Egypt and the United States

Bovine herpesvirus 1 (BoHV-1) is an important contagious viral pathogen negatively affecting the livestock industry because of respiratory illness and /or abortion. Most of the disease protection programmes in Egypt depend on imported vaccines and unfortunately molecular studies on molecular and phylogenic analysis of viral strains are rare. Such studies are needed to determine which viral strains should be used in vaccine manufacture so as to provide proper protection to susceptible animals in Egypt. The gB, gC, gD and gE glycoproteins of BoHV-1 are the most important because of their functional properties including virus entry into target cells, viral gene expression, DNA replication, and phylogenetic relationships. This is the first report in which glycoproteins of Egyptian BoHV-1.1 virulent strains have been sequenced and compared with U.S. strains, thus increasing our understanding about the genetic relatedness of various strains of BoHV-1 and between bovine alphaherpesviruses (BoHV-1 and BoHV-5). Our results indicate that the Egyptian Abu-Hammad strains are 100% similar to each other and with U.S. Cooper reference strain suggesting that vaccines based on the latter strain are adequate in providing protection to susceptible animals in Egypt. (Sobhy NM, Mor SK, Mohammed MEM, Bastawecy IM, Fakhry HM, Youssef CRB, Goyal SM. Comparative molecular characterization of bovine herpesvirus-1 strains from Egypt and the United States. Life Sci J 2014;11(9):493-499). (ISSN:1097-8135). http://www.lifesciencesite. com. 82
Choosing Optimal Seller Based on off-line Learning Negotiation History and K-armed Bandit Problem

When a buying agent carries user’s requirements to look for a selling agent for negotiation, there may be some sellers to meet user’s requirement, but the buyer must choose a seller who can not only meet user’s requirements, but also make the buyer’s negotiation outcome gain maximal utility before negotiation. This paper solves problem of choosing seller before negotiation in order to improve accuracy of the multi-issue negotiation and buyer’s utility. In order to fully utilize negotiation history, this paper transforms the problem of choosing seller into K-armed bandit problem to solve. Several improved algorithms, which are used to learn reward distribution by off-line learning, and combine technologies for K-armed bandit problem and learning by neural network, are presented. Finally, combining the improved algorithms with trust vectors improves accuracy and practicability of choosing a seller. The experiment proves validity of the work in application.
A southeastern Mediterranean PV streamer and its role in December 2001 case with torrential rains in Israel

Abstract. A precipitation event of unprecedented intensity took place over northern part of Israel during 4 December 2001–5 December 2001. The case was associated with formation of a Cyprus Low cyclone over the Asia Minor. In the current study the synoptic developments over the eastern part of the Mediterranean region are simulated with the MM5 nonhydrostatic model and analyzed based on dynamic tropopause patterns calculated from the simulation results. According to the results, a powerful potential vorticity (PV) streamer system played a major role in the process over the southeastern Mediterranean region. The PV streamer created conditions for seclusion of moist air masses from the equatorial East Africa and Atlantics during the cyclone development. Condensation of the moisture, associated with the latent heat release processes have contributed to the intense thunderstorm activity and heavy precipitation of the event.
Kinetic Characterization of VIM-7, a Divergent Member of the VIM Metallo-β-Lactamase Family

ABSTRACT Purified recombinant VIM-7 possesses efficient penicillinase and carbapenemase activities comparable to those of VIM-2. Cephalosporinase activity was variable and generally lower than those of VIM-1 and VIM-2. A homology model suggests that the VIM-7 Tyr-218 Phe substitution may be responsible for the reduced catalytic efficiency against certain cephalosporins, including ceftazidime and cefepime.
Nutrient Intake and Adherence to Dietary Recommendations Among US Workers

Objective: To assess nutrient intake according to dietary guidelines among US worker groups. Methods: Participants of 1999 to 2004 National Health and Nutrition Examination Survey completed two 24-hour recall dietary interviews to assess daily intake of protein, carbohydrate, fat, cholesterol, calcium, sodium, and fiber. Employed participants (n = 8987) were classified as (1) white collar, (2) service worker, (3) farmer, and (4) blue collar. Results: Nutrient intake varied by occupational group, particularly for fiber, sodium, calories, and percentage of calories from protein, saturated fat, and carbohydrate. Adherence to recommendations was noted for saturated fat and cholesterol, but workers were poorly adherent to recommendations for all other nutrients, particularly fiber. Conclusions: Workers display differences in nutrient intake across occupational groups with poor eating behaviors evident across all groups. Fiber is particularly poorly consumed, with less than 5% of all US workers meeting the recommendations.
Myosin-1A Targets to Microvilli Using Multiple Membrane Binding Motifs in the Tail Homology 1 (TH1) Domain*

Background: Myo1a is an abundant membrane binding motor that targets to microvilli in intestinal epithelial cells. Results: Myo1a interacts with acidic phospholipids using distinct motifs at the N and C terminus of the TH1 domain. Conclusion: Membrane binding potential of Myo1a is distributed throughout TH1 rather than localized to a single motif. Significance: Different class I myosins rely on different strategies for targeting to cellular membranes. One of the most abundant components of the enterocyte brush border is the actin-based monomeric motor, myosin-1a (Myo1a). Within brush border microvilli, Myo1a carries out a number of critical functions at the interface between membrane and actin cytoskeleton. Proper physiological function of Myo1a depends on its ability to bind to microvillar membrane, an interaction mediated by a C-terminal tail homology 1 (TH1) domain. However, little is known about the mechanistic details of the Myo1a-TH1/membrane interaction. Structure-function analysis of Myo1a-TH1 targeting in epithelial cells revealed that an N-terminal motif conserved among class I myosins and a C-terminal motif unique to Myo1a-TH1 are both required for steady state microvillar enrichment. Purified Myo1a bound to liposomes composed of phosphatidylserine and phosphoinositol 4,5-bisphosphate, with moderate affinity in a charge-dependent manner. Additionally, peptides of the N- and C-terminal regions required for targeting were able to compete with Myo1a for binding to highly charged liposomes in vitro. Single molecule total internal reflection fluorescence microscopy showed that these motifs are also necessary for slowing the membrane detachment rate in cells. Finally, Myo1a-TH1 co-localized with both lactadherin-C2 (a phosphatidylserine-binding protein) and PLCδ1-PH (a phosphoinositol 4,5-bisphosphate-binding protein) in microvilli, but only lactaderin-C2 expression reduced brush border targeting of Myo1a-TH1. Together, our results suggest that Myo1a targeting to microvilli is driven by membrane binding potential that is distributed throughout TH1 rather than localized to a single motif. These data highlight the diversity of mechanisms that enable different class I myosins to target membranes in distinct biological contexts.
Validation and extension of the endophenotype model in ADHD patterns of inheritance in a family study of inhibitory control.

OBJECTIVE Endophenotypes, markers of underlying liability to psychiatric disorders, can improve the power to detect genetic risks relative to a complex clinical endpoint. Motor response inhibition is a prime candidate endophenotype in ADHD. In this study, the authors sought to extend the endophenotype model and further demonstrate its utility by investigating the parental origin of shared genetic risk in ADHD. METHOD Inhibitory control was studied in children with ADHD, unaffected siblings, and their biological parents. Covariation in inhibitory control within families was investigated. Differential covariation as a function of parental sex was also studied. A number of validity criteria for inhibitory control as an endophenotype were assessed, including sensitivity to the disorder and presence in unaffected relatives. RESULTS The results confirmed an inhibitory control deficit in children with ADHD as well as in their parents, independent of symptom severity in both generations. Inhibitory control ability in children was significantly predicted by the ability of their parents, particularly their fathers. CONCLUSIONS These findings indicate that an inhibitory control deficit is a cognitive marker of genetic risk shared by parents and offspring. The endophenotype model is also extended by evidence of differential parental contributions to this risk, consistent with findings of parent-of-origin effects in the transmission of certain risk alleles observed in molecular analyses. The identification of these effects at the endophenotype level and their incorporation in genetic modeling can improve both linkage detection and localization of quantitative trait loci.
Nearly Zero Inclination Geosynchronous SAR Mission Analysis With Long Integration Time for Earth Observation

In this paper, the performance of a nearly zero inclination and low eccentricity geosynchronous synthetic aperture radar (GEOSAR) mission for midlatitude (30°-60°) Earth observation is analyzed. The slow motion of such satellites with respect to the Earth's surface makes it necessary to consider long coherent combination of pulses during hours to reach the desired along-track resolution. A system based on moderate transmitted powers and antenna sizes is considered. The necessary sensitivity in such GEOSAR system is obtained from the accumulated energy of the raw data using a pulse repetition frequency above the Doppler bandwidth and a long integration time. Several issues as a result of the long acquisition, such as target and atmospheric phase screen decorrelation, speckle noise impact on the received signal, and satellite station-keeping requirements, are analyzed. The feasibility of such systems to be placed on a broadcasting communication satellite makes nearly zero inclination GEOSAR a low-cost alternative of current SAR missions.
Research on fire algorithm of pulse thrusters for interceptor missile

In order to ensure the control precision of lateral thrust for interceptor missile, a new fire algorithm of pulse thrusters is presented. With a view to defect of lateral thrust from spinning interceptor missile, a method to search fire direction and fire quantity of pulse thrusters is presented. And improved genetic algorithm is given. In this improved genetic algorithm, the genetic operation is amended to overcome the local optimization in simple genetic algorithm. According to an improved genetic algorithm, the fire quantity of pulse thrusters is optimized, and the track error of fire command is compensated to ensure the control precision of lateral thrust. Simulation results show that this fire algorithm can implement efficiently control mission of lateral thrust for interceptor missile as well as preferable performance.
Tense Interpretation in the Context of Narrative

This paper presents an algorithm which makes use of tense interpretation to determine the intended temporal ordering between the states and events mentioned in a narrative. This is done by maintaining a temporal focus and interpreting the tense of each new statement of the narrative with respect to this focus. In particular, we propose heuristics for determining the temporal ordering and constraints for characterizing coherent tense sequences. The algorithm is further defended through experiments with naturally occurring examples.
A comparison of walk-in counselling and the wait list model for delivering counselling services*

Abstract Background: Walk-in counselling has been used to reduce wait times but there are few controlled studies to compare outcomes between walk-in and the traditional model of service delivery. Aims: To compare change in psychological distress by clients receiving services from two models of service delivery, a walk-in counselling model and a traditional counselling model involving a wait list. Method: Mixed-methods sequential explanatory design including quantitative comparison of groups with one pre-test and two follow-ups, and qualitative analysis of interviews with a sub-sample. Five-hundred and twenty-four participants ≥16 years were recruited from two Family Counselling Agencies; the General Health Questionnaire-12 assessed change in psychological distress. Results: Hierarchical linear modelling revealed clients of the walk-in model improved faster and were less distressed at the four-week follow-up compared to the traditional service delivery model. Ten weeks later, both groups had improved and were similar. Participants receiving instrumental services prior to baseline improved more slowly. The qualitative data confirmed participants highly valued the accessibility of the walk-in model, and were frustrated by the lengthy waits associated with the traditional model. Conclusions: This study improves methodologically on previous studies of walk-in counselling, an approach to service delivery not conducive to randomized controlled trials.
Estimating and Reducing Uncertainty in Reverberation-Chamber Characterization at Millimeter-Wave Frequencies

This contribution provides techniques for accurately characterizing uncertainty when measuring total radiated power (TRP) at millimeter-wave frequencies. The setup is based on the reverberation chamber as a well-known measurement environment capable of performing TRP measurements of wireless devices. We show that by applying various stirring techniques, we can reduce the random component of measurement uncertainty to around 2%. We use a model for estimating the uncertainty for TRP measurements based on the K factor, which is compared with uncertainties calculated from relative power measurements and we show excellent agreement. We perform a significance test to confirm that the uncertainty due to the limited number of mode-stirred samples dominates over the uncertainty due to the lack of spatial uniformity. The observed uncertainty is also compared with an ideal chamber situation and shows good agreement.