Miracle-dz/UniFAR-FTUs huggingface dataset:
Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures

Monoamine oxidase B (MAO-B) is an outer mitochondrial membrane-bound enzyme that catalyzes the oxidative deamination of arylalkylamine neurotransmitters and has been a target for a number of clinically used drug inhibitors. The 1.7-Å structure of the reversible isatin–MAO-B complex has been determined; it forms a basis for the interpretation of the enzyme's structure when bound to either reversible or irreversible inhibitors. 1,4-Diphenyl-2-butene is found to be a reversible MAO-B inhibitor, which occupies both the entrance and substrate cavity space in the enzyme. Comparison of these two structures identifies Ile-199 as a “gate” between the two cavities. Rotation of the side chain allows for either separation or fusion of the two cavities. Inhibition of the enzyme with N-(2-aminoethyl)-p-chlorobenzamide results in the formation of a covalent N(5) flavin adduct with the phenyl ring of the inhibitor occupying a position in the catalytic site overlapping that of isatin. Inhibition of MAO-B with the clinically used trans-2-phenylcyclopropylamine results in the formation of a covalent C(4a) flavin adduct with an opened cyclopropyl ring and the phenyl ring in a parallel orientation to the flavin. The peptide bond between the flavin-substituted Cys-397 and Tyr-398 is in a cis conformation, which allows the proper orientation of the phenolic ring of Tyr-398 in the active site. The flavin ring exists in a twisted nonplanar conformation, which is observed in the oxidized form as well as in both the N(5) and the C(4a) adducts. An immobile water molecule is H-bonded to Lys-296 and to the N(5) of the flavin as observed in other flavin-dependent amine oxidases. The active site cavities are highly apolar; however, hydrophilic areas exist near the flavin and direct the amine moiety of the substrate for binding and catalysis. Small conformational changes are observed on comparison of the different inhibitor–enzyme complexes. Future MAO-B drug design will need to consider “induced fit” contributions as an element in ligand–enzyme interactions.
Protective Efficacy of a Sulfated Sialyl Lipid (NMSO3) against Human Rotavirus-Induced Diarrhea in a Mouse Model

ABSTRACT Antiviral activity of sulfated sialyl lipid (NMSO3) against human rotavirus (RV) was examined in vitro and in vivo. NMSO3 inhibited the replication of four major serotypes (G1 to G4) of human rotavirus with a low 50% effective concentration of 1 to 5 μg/ml and 50% cytotoxic concentration of 153 μg/ml when determined by plaque assays with MA104 cells. Exposure of NMSO3 to HCl (pH 2.0) for 30 min exhibited no loss of anti-RV activity. Time-of-addition experiments revealed that NMSO3 inhibited the adsorption of four serotypes of RV to MA104 cells. Furthermore, an assay of virus binding with radiolabeled RVs revealed that NMSO3 inhibited the binding of virus to MA104 cells, suggesting that NMSO3 may bind to VP4 and/or VP7. Prophylactic oral administration of NMSO3 (10 μg three times per day, 4 days) to five suckling mice starting 30 min before inoculation of MO strain (3 × 106 PFU/mouse) prevented the development of diarrhea. Four of five mice showed no stool or brown formed stool, and only one mouse showed brown soft stool, while water treatment caused watery diarrhea in all five mice. The mean titer of antibody to RV in mice which received NMSO3 at 10 μg three times per day for 4 days was significantly lower than that of untreated, infected mice. NMSO3 is a promising candidate for the prophylactic treatment of human RVs.
Reducing magneto-inductive positioning errors in a metal-rich indoor environment

Ferrous objects distort magnetic fields and can significantly increase magneto-inductive positioning errors in indoor environments. In this work, we use image theory in order to formulate an analytical channel model for the magnetic field of a quasi-static magnetic dipole positioned above a perfectly conducting half-space. The proposed model can be used to compensate for the distorting effects that metallic reinforcement bars (rebars) impose on the magnetic field of a magneto-inductive transmitter node in an indoor environment. Good agreement is observed between the analytical solution and numerical solutions obtained from 2-D finite element simulations when the transmitter node is located more than 0.4 m above the distorters. Experimental results indicate that the image theory model shows significant improvement over the free space dipole model in estimating position along the normal to the plane of the rebars, typically reducing positioning errors by 36% in 90% of the cases.
Engineering of a novel thioether bridge and role of modified residues in the lantibiotic Pep5

Pep5 is a 34-amino-acid antimicrobial peptide, produced by Staphylococcus epidermidis 5, that contains the thioether amino acids lanthionine and methyllanthionine, which form three intramolecular ring structures. In addition, two didehydrobutyrines are present in the central part of the lantibiotic and an oxobutyryl residue is located at the N terminus. All rare amino acids are introduced by posttranslational modifications of a ribosomally made precursor peptide. To elucidate the function of the modified residues for the antimicrobial action of Pep5, mutant peptides, in which single modified residues had been eliminated, were produced by site-directed mutagenesis. All of these peptides showed a reduced antimicrobial activity. In addition, those peptides from which the ring structures had been deleted became susceptible to proteolytic digest. This demonstrates that the ring structures serve as stabilizers of conformations essential for activity, e.g., amphiphilicity, as well as for protecting Pep5 against proteases of the producing strains. In addition, residues that could serve as precursors of new modified amino acids in lantibiotics were introduced into the Pep5 precursor peptide. This way, a novel methyllanthionine and a didehydroalanine were inserted into the flexible central part of Pep5, demonstrating that biosynthesis of modified amino acids is feasible by protein engineering and use of the lantibiotic modification system.
M2M-REP: Reputation of Machines in the Internet of Things

The Internet of Things (IoT) is the integration of a large number of autonomous heterogeneous devices that report information from the physical environment to the monitoring system for analytics and meaningful decisions. The compromised machines in the IoT network may not only be used for spreading unwanted content such as spam, malware, viruses etc, but can also report incorrect information about the physical world that might have a disastrous consequence. The challenge is to design a collaborative reputation system that calculates trustworthiness of machines in the IoT-based machine-to-machine network without consuming high system resources and breaching the privacy of participants. To address the challenge of privacy preserving reputation system for the decentralized IoT environment, this paper presents a novel M2M-REP (Machine to Machine Reputation) system that computes global reputation of the machine by aggregating the encrypted local feedback provided by machines in a fully decentralized and secure way. The privacy of participating machines is well protected such that machines or analyst would not learn any information about the feedback score provided by the participating machines other than the final aggregated statistical score. We present a decentralized reputation aggregation system for two scenarios: a semi-honest (honest-but-curious) setup where machines are trustworthy in providing feedback but are curious to learn sensitive information about the collaborating machines, and the malicious model where machines not only try to learn the sensitive information of participants but also do not follow the protocol specification in providing feedback. We analyzed the security and privacy properties of the M2M-REP system for different adversarial models.
Intermittent “Real‐time” fMRI Feedback Is Superior to Continuous Presentation for a Motor Imagery Task: A Pilot Study

Real‐time functional MRI feedback (RTfMRIf) is a developing technique, with unanswered methodological questions. Given a delay of seconds between neural activity and the measurable hemodynamic response, one issue is the optimal method for presentation of neurofeedback to subjects. The primary objective of this preliminary study was to compare the methods of continuous and intermittent presentation of neural feedback on targeted brain activity.
Glucose transporter expression is developmentally regulated in in vitro derived bovine preimplantation embryos

Glucose is readily been taken up and utilized by preimplantation embryos from different species. However, a comprehensive analysis of the glucose transporter expression throughout preimplantation development is still missing. Here, we have investigated the expression of facilitative glucose transporters (Glut1–5 and 8) and sodium‐dependent‐glucose transporter (SGLT‐I) in bovine oocytes and preimplantation embryos up to d16 of development, using RT‐PCR and immunohistochemistry. The embryos were produced in vitro by IVM–IVF. Glut1, Glut3, Glut8, and SGLT‐I were expressed in all stages studied. Glut4 transcripts were first detected at the blastocyst stage. Glut2 expression was restricted to the period of blastocyst elongation at d14 and d16. Transcription of the fructose transporter Glut5 started at the 8‐/16‐cell stage. Our results show a distinct expression pattern for glucose transporters during bovine embryo development in vitro indicating specialized functions for these isoforms at different developmental stages in bovine embryos. Mol. Reprod. Dev. 60:370‐376, © 2001 Wiley‐Liss, Inc.
RNAse A‐like enzymes in serum inhibit the anti‐neoplastic activity of siRNA targeting polo‐like kinase 1

Down‐modulation of target molecules in tumor cells by small interfering (si) RNAs is a promising anti‐cancer strategy. A major challenge of this approach is the loss of silencing activity of the siRNAs in vivo. Our study aimed at investigating the influence of the serum compartment on the anti‐tumor activity of siRNA directed against Polo‐like kinase 1 (Plk1), a mitosis‐associated serine/threonine kinase. The data showed that siRNA‐induced suppression of Plk1 expression effectively reduced the viable cell mass and increased apoptosis in several cancer cell lines. Preincubation of the siRNA in human serum led to shortening of the siRNA as well as loss of its Plk1 silencing and anti‐tumor activity. This loss of activity was prevented by inhibition of RNAse A‐like enzymes. These data indicate that the anti‐neoplastic effect of siRNAs declines upon incubation in human serum. This loss of anti‐neoplastic activity can be prevented by inhibition of their degradation by RNAse A‐like enzymes. This may have important implications for the development of a human therapeutic application of siRNAs. © 2007 Wiley‐Liss, Inc.
Method of separation and concentration of fetal nucleated red blood cells in maternal blood and its application to fetal diagnosis

ABSTRACT A fetal diagnostic method that is without risk to the embryo has been long awaited in the field of gene diagnosis. Establishment of non‐invasive fetal diagnosis using maternal peripheral blood will greatly contribute to perinatal medical care. The lectin method that we have studied and developed selectively recovers nucleated red blood cells (NRBC) among fetal cells mixed in maternal peripheral blood.
Structural basis of a protein partner switch that regulates the general stress response of α-proteobacteria

α-Proteobacteria uniquely integrate features of two-component signal transduction (TCS) and alternative sigma factor (σ) regulation to control transcription in response to general stress. The core of this regulatory system is the PhyR protein, which contains a σ-like (SL) domain and a TCS receiver domain. Aspartyl phosphorylation of the PhyR receiver in response to stress signals promotes binding of the anti-σ factor, NepR, to PhyR-SL. This mechanism, whereby NepR switches binding between its cognate σ factor and phospho-PhyR (PhyR∼P), controls transcription of the general stress regulon. We have defined the structural basis of the PhyR∼P/NepR interaction in Caulobacter crescentus and characterized the effect of aspartyl phosphorylation on PhyR structure by molecular dynamics simulations. Our data support a model in which phosphorylation of the PhyR receiver domain promotes its dissociation from the PhyR-SL domain, which exposes the NepR binding site. A highly dynamic loop–helix region (α3-α4) of the PhyR-SL domain plays an important role in PhyR∼P binding to NepR in vitro, and in stress-dependent activation of transcription in vivo. This study provides a foundation for understanding the protein-protein interactions and protein structural dynamics that underpin general stress adaptation in a large and metabolically diverse clade of the bacterial kingdom.
An EPEC Analysis for Power Allocation in LTE-V Networks

With large coverage area, high data rate, low latency and high spectral efficiency, LTE-V has been considered as a promising communication technology in the vehicular networks. However, as all vehicles share the same wireless resource, in LTE-V, how to design power allocation strategy for each vehicle while motivating other vehicles to forward the data remains challenging. In this paper, we model the data transmission in the uplink scenario of the vehicular network as an equilibrium program with equilibrium constraints (EPEC), where the upper-layer vehicles as receivers (VaRs) provide priced relaying service to vehicle as a transmitter (VaT) in the bottom layer. Observing the prices set by serving VaRs in allocated channels, we adopt multi-level water- filling algorithm at the VaT for power allocation. With joint consideration on the optimal reaction of the VaT and the pricing strategy of other VaRs, each VaR optimizes its setting price by adopting the sub-gradient algorithm such that the equilibrium of the formulated EPEC is finally achieved. Simulation results corroborate our theoretical analysis and demonstrate the performance superiority of our proposal as compared with classic pricing strategies of VaRs.
Thiazolidinedione therapy and breast cancer risk in diabetic women: A systematic review and meta‐analysis

Rising experimental evidence suggests that thiazolidinediones (TZDs) exert a protective effect on breast cancer. However, studies concerning this issue were inconsistent and limited. Hence, we performed a meta‐analysis with data from currently available studies to evaluate the effect of TZDs on breast cancer risk among diabetic women. We comprehensively searched for all pertinent studies addressing TZDs use and breast cancer risk published before January 1, 2016, in PubMed, Clinical Trials, and Cochrane Library. Data synthesis was performed in a random‐effects model using Stata version 12.0 (Stata Corp, College Station, Texas). Fourteen independent studies were eventually selected in this meta‐analysis, including 5 randomized controlled clinical trials (RCTs), 7 cohort studies, and 2 case‐control studies. No significant associations of TZD use and risk of breast cancer were observed in the RCTs (pooled risk ratio [RR]: 0.77, 95% confidence interval (CI), 0.39‐1.53, I2 = 26%) or case‐control studies (pooled odds ratio, 0.99, 95% CI, 0.76‐1.28, I2 = 31%). A 19% reduction in breast cancer risk (pooled RR: 0.81, 95% CI, 0.66‐0.99, I2 = 72%) was found in the cohort studies. However, after removing the study with the smallest event number and the greatest effect size, the association became nonsignificant with greatly decreased heterogeneity (pooled RR: 0.94, 95% CI, 0.86‐1.03, I2 = 16%). This meta‐analysis did not find any significant association between TZDs use and risk of breast cancer among diabetic women.
Oxazepam is mutagenic in vivo in Big Blue transgenic mice.

Although oxazepam (Serax), a widely used benzodiazepine anxiolytic, does not induce gene mutations in vitro or chromosomal aberrations in vivo, it was found to be a hepatocarcinogen in a 2 year bioassay in B6C3F1 mice. Thus, it was of interest to determine whether this carcinogen is mutagenic in vivo. Male B6C3F1 Big Blue transgenic mice were fed 2500 p.p.m. oxazepam or control diet alone for 180 days and killed on the next day. The mutant frequency (MF) of lacI in control mice was 5.02 +/- 2.4x10(5), whereas the MF in the oxazepam-treated mice was 9.17 +/- 4.82x10(-5), a significant increase (P < 0.05). Correction of the mutant frequency of lacI from the oxazepam-treated mice for clonality resulted in a decrease in the mean mutant frequency to 8.15 +/- 2. 54x10(-5). Although the mutant frequency difference was small, sequencing of a random collection of the mutants from each oxazepam-exposed mouse showed a significant difference (P < 0.015) in the mutation spectrum compared with that from control mice. In the oxazepam-exposed mice, an increase in G:C-->T:A and G:C-->C:G transversions and a concomitant decrease in G:C-->A:T transitions were observed. Clonal expansion of mutations at guanines in 5'-CpG-3' sequencing contexts at three sites was noted. It is postulated that some of the mutations found in the oxazepam-derived spectrum were due to oxidative damage elicited by induction of CYP2B isozymes as the result of chronic oxazepam administration. This study demonstrates that the in vivo Big Blue transgenic rodent mutation assay can detect mutations derived from a carcinogen that did not induce gene mutations in vitro or micronuclei in mouse bone marrow. Moreover, the sequencing of the recovered mutants can distinguish between the mutation spectrum from treated mice compared with that from control mice, thereby confirming the genotoxic consequences.
Traditional and Nonlinear Heart Rate Variability Are Each Independently Associated with Mortality after Myocardial Infarction

Introduction: Decreased heart rate variability (HRV) and abnormal nonlinear HRV shortly after myocardial infarction (MI) are risk factors for mortality. Traditional HRV predicts mortality in patients with a range of times post‐MI, but the association of nonlinear HRV and outcome in this population is unknown.
Cascade PI-continuous second-order sliding mode control for induction motor

This paper presents the cascaded PI-continuous second order sliding mode control for induction motor in the presence of operational constraints. The inner-loop Sliding Mode Control (SMC) is designed to control the current dynamics of the motor while the outer-loop control is the PI control of speed. The main advantages of the proposed method are that the PI control provides reference to inner-loop SMC with constraints according to the system requirements in terms of maximum current and speed limits. Moreover the inner-loop dynamics of the motor being more non-linear, SMC design has more importance in terms of robustness and disturbance rejection capability. The proposed cascade PI with SMC is chattering-free control action with fixed-time convergence. The performance of the developed controller is validated and compared by carrying out real-time experimental studies. Experimental results demonstrate remarkable robust tracking performance of the controller in terms of transient response speed and steady-state accuracy.
Genome-wide Protein-chemical Interaction Prediction

The analysis of protein-chemical reactions on a large scale is critical to understanding the complex interrelated mechanisms that govern biological life at the cellular level. Chemical proteomics is a new research area aimed at genome-wide screening of such chemical-protein interactions. Traditional approaches to such screening involve in vivo or in vitro experimentation, which while becoming faster with the application of high-throughput screening technologies, remains costly and time-consuming compared to in silico methods. Early in silico methods are dependant on knowing 3D protein structures (docking) or knowing binding information for many chemicals (ligand-based approaches). Typical machine learning approaches follow a global classification approach where a single predictive model is trained for an entire data set, but such an approach is unlikely to generalize well to the protein-chemical interaction space considering its diversity and heterogeneous distribution. In response to the global approach, work on local models has recently emerged to improve generalization across the interaction space by training a series of independant models localized to each predict a single interaction. This work examines current approaches to genome-wide protein-chemical interaction prediction and explores new computational methods based on modifications to the boosting framework for ensemble learning. The methods are described and compared to several competing classification methods. Genome-wide chemicalprotein interaction data sets are acquired from publicly available resources, and a series of experimental studies are performed in order to compare the the performance of each method under a variety of conditions.
Hexagonal undersampling for faster MRI near metallic implants

Slice encoding for metal artifact correction acquires a three‐dimensional image of each excited slice with view‐angle tilting to reduce slice and readout direction artifacts respectively, but requires additional imaging time. The purpose of this study was to provide a technique for faster imaging around metallic implants by undersampling k‐space.
Accuracy of 18F-FDG PET/CT for Diagnosing Inguinal Lymph Node Involvement in Penile Squamous Cell Carcinoma: Systematic Review and Meta-Analysis of the Literature

Purpose: Metastatic involvement of the inguinal lymph nodes is associated with decreased survival and is a strong prognostic factor in penile squamous cell carcinoma. The aim of the current systematic review was to evaluate the accuracy of 18F-FDG PET/CT for inguinal lymph node staging in penile squamous cell carcinoma and possible influential factors. Materials and Methods: Medline, SCOPUS, Springer, Science Direct, and Google Scholar were searched using the key words “(penile or penis) and PET,” with no date or language limitation. The meeting abstracts were not excluded either. Statistical pooling was performed using the random-effects model. Results: Seven studies were included in the meta-analysis. One article had 2 different subgroups of patients, and each subgroup was considered as a separate study. Pooled sensitivity and specificity were 80.9% (95% confidence interval [CI]: 69.5%–89.4%) and 92.4% (95% CI: 86.8%–96.2%), respectively. Pooled sensitivity was 96.4% (95% CI: 81.7%–99.9%) for cN+ and 56.5% (95% CI: 34.5%–76.8%) for cN0 patients. Conclusions: 18F-FDG PET/CT imaging has relatively low sensitivity (especially in cN0 patients) for detection of inguinal lymph node involvement in penile cancer patients, which does not justify its routine use. However, patients with clinically palpable lymph nodes may benefit from 18F-FDG PET/CT because the sensitivity in this subgroup of patients is high.