Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutrophils Activate Macrophages for Intracellular Killing of Leishmania major through Recruitment of TLR4 by Neutrophil Elastase1

We investigated the role of neutrophil elastase (NE) in interactions between murine inflammatory neutrophils and macrophages infected with the parasite Leishmania major. A blocker peptide specific for NE prevented the neutrophils from inducing microbicidal activity in macrophages. Inflammatory neutrophils from mutant pallid mice were defective in the spontaneous release of NE, failed to induce microbicidal activity in wild-type macrophages, and failed to reduce parasite loads upon transfer in vivo. Conversely, purified NE activated macrophages and induced microbicidal activity dependent on secretion of TNF-α. Induction of macrophage microbicidal activity by either neutrophils or purified NE required TLR4 expression by macrophages. Injection of purified NE shortly after infection in vivo reduced the burden of L. major in draining lymph nodes of TLR4-sufficient, but not TLR4-deficient mice. These results indicate that NE plays a previously unrecognized protective role in host responses to L. major infection.
Investigating implantable glucose biosensors pitfalls: a fault tree analysis approach

Implantable sensors for glucose monitoring are the first step towards the development of an implantable closed-loop diabetes control system. Although significant advances in the designs and chemistries employed to prepare intravascular and subcutaneous devices have been achieved, the biological responses can have a dramatic impact on the analytical accuracy of such probes. With a view to assisting the effective design of such devices for assuring clinical performance, the causes of implantable glucose sensor failure have been investigated by means of Fault Tree Analysis (FTA) relying on fuzzy reasoning to account for uncertainty. The approach suggested may contribute significantly to the self-optimisation of the measuring equipment from one generation to the next as it supports the flexible, ad hoc, and tailor made sensor development, thus potentiating the progress of epidemics from statistics to individualisation.
The MicroRNA-17–92 Cluster Enhances Axonal Outgrowth in Embryonic Cortical Neurons

MicroRNAs (miRNAs) regulate dendritogenesis and plasticity. However, the biological function of miRNAs in axons has not been extensively investigated. Here, using rat primary cortical neurons cultured in a microfluidic chamber, we found that the distal axons of the neurons expressed the miR-17–92 cluster, and proteins that regulate production and activity of mature miRNAs, Dicer and Argonaute 2, respectively, were present in the distal axons. Overexpression of the miR-17–92 cluster in cortical neurons substantially increased axonal outgrowth, whereas distal axonal attenuation of endogenous miR-19a, a key miRNA of the miR-17–92 cluster, with the miRNA hairpin inhibitor suppressed axonal outgrowth. Moreover, overexpression of the miR-17–92 cluster reduced phosphatase and tensin homolog (PTEN) proteins and elevated phosphorylated mammalian target of rapamycin (mTOR) in the distal axons. In contrast, distal axonal attenuation of miR-19a increased PTEN proteins and inactivated mTOR in the axons, but did not affect these protein levels in the cell bodies. Overexpression of PTEN and attenuation of endogenous PTEN prevailed over the enhancement and inhibitory effects of the miR-19a on axonal outgrowth, respectively. Axonal application of LY294002, a phosphoinositide3-kinase inhibitor, or rapamycin, an mTOR inhibitor, abolished axonal outgrowth enhanced by overexpression of the miR-17–92 cluster. Collectively, these findings demonstrate that axonal alteration of miR-17–92 cluster expression regulates axonal outgrowth and that local modulation of PTEN protein levels by miR-19a likely contributes to the axonal outgrowth.
Clustering of metabolic syndrome factors in Malaysian population: Asian Criteria revisited

Introduction: Metabolic syndrome (MetS) had been known as clustering of risk factors for cardiovascular disease and diabetes. Over the years, clinical criteria had been revised to highlight importance of various risk factors in defining MetS. Studies had reported different clustering of factors based on different population characteristics. Objective: Our study aimed to identify the clustering factors among our Malaysian population based on sexes and 4 major ethnic groups namely Malay, Chinese, Indian and other minor ethnic Methods: A national cross sectional study was done covering both Peninsular and East Malaysia. Subjects’ sociodemographic, body mass index (BMI), waist, hip and neck circumference, blood pressure, fasting triglycerides (TG) and HDL-cholesterol and glucose, urine microalbumin and serum insulin were taken. Principal component factor analysis with Varimax rotation was done to identify the clustering based on sex and ethnic groups. Results: One thousand two hundred and sixty eight male and 2355 female subjects were recruited. Majority of subjects were Malays (63.0%) followed by Chinese (13.3%), Indian (7.4%) and other ethnic groups (13.8%) which followed the population composition in Malaysia. Four factors were identified for both men and women. The factors were anthropometry, glycemia, blood pressure and dyslipidemia given the cumulative percent of variance of 69.4 and 65.9 respectively. There are 4 factors identified for Malay, Chinese and Aborigines but 5 factors for Indian ethnic groups given cumulative percent of variance explained ranged from 65.1 to 77.7. Discussion and Conclusion: BMI, neck circumference, blood pressure, Fasting TG and HDL had a high factor loading in both sexes suggesting that for field screening, diagnostic criteria would be adequate criteria. These factors also showed a similar pattern of loading by different ethnic groups. In conclusion, in Malaysian population, at least one measurement from each components namely anthropometric, blood pressure, glycemia and dyslipidemia is adequate to diagnose MetS.
The effects of self-administered alcohol-induced 'hangover' in a naturalistic setting on psychomotor and cognitive performance and subjective state.

AIMS To examine in as naturalistic a setting as possible whether having an alcohol-induced 'hangover' impairs psychomotor and cognitive performance. PARTICIPANTS AND DESIGN The sample consisted of 71 male and female social drinkers who were tested twice, once at baseline and once after exposure to the study condition. They were randomized into a control group who returned for testing on a prearranged date (n = 33), and a group who were instructed to make arrangements to return the day after a self-determined heavy drinking session (n = 38). Of the 'hangover' group, 13 participants still had a blood alcohol concentration of >1 mg/100 ml at the time of testing and these were analysed separately. All participants were students. MEASUREMENTS Psychomotor performance was assessed by means of a battery of psychomotor tasks, rate of information processing was tested by the Speed and Capacity of Language Processing Test (SCOLP) and subjective state was assessed by questionnaire measures. FINDINGS All participants in the 'hangover' group reported subjective and physical symptoms of hangover on the second testing session. Performance was significantly impaired on the hits-key components of the vigilance task, was less accurate on the primary and secondary reaction time tasks and showed greater dispersion in range of ability for participants in the 'acute and hangover' compared to 'control'. Probe memory revealed no significant group effect. Ratings of subjective state revealed significant group differences for the variables 'ability to drive', 'concentrate' and 'react quickly' as well as 'tiredness'. There were no group differences for performance on the SCOLP. CONCLUSION Hangover had negative effects on self-reported subjective and physical state and subtle effects on performance.
Finite-Time Stabilization via Sliding Mode Control

This technical note investigates the sliding mode control (SMC) design based on finite-time boundedness (FTB) for a class of nonlinear systems. A suitable SMC law is constructed to drive the state trajectories onto the specified sliding surface during a specified finite (possibly <bold><italic>short</italic></bold>) time interval. Besides, by introducing a <bold><italic>partitioning strategy</italic></bold>, the corresponding FTB over <bold><italic>reaching phase</italic></bold> and <bold><italic>sliding motion phase</italic></bold> are guaranteed, respectively. And then, the sufficient conditions are derived to ensure the FTB of the closed-loop systems over the <bold><italic>whole</italic></bold> finite-time interval. Finally, a simulation example is given to show the effectiveness of the proposed design method.
Impaired Growth Rates in Milk of Lactobacillus helveticus Peptidase Mutants Can Be Overcome by Use of Amino Acid Supplements

ABSTRACT To evaluate the contribution of intracellular peptidases to the growth of the 14-amino-acid (aa) auxotroph Lactobacillus helveticus CNRZ32, single- and multiple-peptidase-deletion mutants were constructed. Two broad-specificity aminopeptidases (PepC and PepN) and X-prolyl dipeptidyl aminopeptidase (PepX) were inactivated through successive cycles of chromosomal gene replacement mutagenesis. The inactivation of all three peptidases in JLS247 (ΔpepC ΔpepN ΔpepX) did not affect the growth rate in amino acid-defined medium. However, the peptidase mutants generally had decreased specific growth rates when acquisition of amino acids required hydrolysis of the proteins in milk, the most significant result being a 73% increase in generation time for JLS247. The growth rate deficiencies in milk were overcome by amino acid supplements with some specificity to each of the peptidase mutants. For example, milk supplementation with Pro resulted in the most significant growth rate increase for ΔpepX strains and a 7-aa supplement (Asn, Cys, Ile, Pro, Ser, Thr, and Val) resulted in a JLS247 growth rate indistinguishable from that of the wild type. Our results show that characterization of the activities of the broad-specificity aminopeptidases had little predictive value regarding the amino acid supplements found to enhance the milk growth rates of the peptidase mutant strains. These results represent the first determination of the physiological roles with respect to specific amino acid requirements for peptidase mutants grown in milk.
Heterochromatin and RNAi Are Required to Establish CENP-A Chromatin at Centromeres

Heterochromatin is defined by distinct posttranslational modifications on histones, such as methylation of histone H3 at lysine 9 (H3K9), which allows heterochromatin protein 1 (HP1)–related chromodomain proteins to bind. Heterochromatin is frequently found near CENP-A chromatin, which is the key determinant of kinetochore assembly. We have discovered that the RNA interference (RNAi)–directed heterochromatin flanking the central kinetochore domain at fission yeast centromeres is required to promote CENP-ACnp1 and kinetochore assembly over the central domain. The H3K9 methyltransferase Clr4 (Suv39); the ribonuclease Dicer, which cleaves heterochromatic double-stranded RNA to small interfering RNA (siRNA); Chp1, a component of the RNAi effector complex (RNA-induced initiation of transcriptional gene silencing; RITS); and Swi6 (HP1) are required to establish CENP-ACnp1 chromatin on naïve templates. Once assembled, CENP-ACnp1 chromatin is propagated by epigenetic means in the absence of heterochromatin. Thus, another, potentially conserved, role for centromeric RNAi-directed heterochromatin has been identified.
Extrinsic experiential value as an antecedent of customer citizenship behavior

The research on customer citizenship behavior is getting much attention in service marketing literature. However, past researches in finding antecedents of customer citizenship behavior are limited to intrinsic value while the role of extrinsic value in customer citizenship behavior is largely ignored. The aim of this study is to fill this gap by investigating the effect of extrinsic experiential value on customer citizenship behavior. The data was collected from 800 customers of four hypermarkets located in five states of Malaysia. The covariance-based structural equation modeling approach was used to analyze the data. Findings indicate that extrinsic value has significant and positive impact on all four dimensions (feedback, helping, advocacy, tolerance) of customer citizenship behavior. The findings suggest that extrinsic value, that is, customer return on investment and service excellence, are important source for developing customer citizenship behavior. Therefore, there is dire need to focus on extrinsic value to achieve customer citizenship behavior which will subsequently lead to gain competitive advantage.
Induction of oxidative cell damage by photo-treatment with zinc meta N-methylpyridylporphyrin

We have previously reported that isomeric Zn(II) N-methylpyridylporphyrins (ZnTM-2(3,4)-PyP4 + ) can act as photosensitizers with efficacy comparable to that of hematoporphyrin derivative (HpD) in preventing cell proliferation and causing cell death in vitro. To better understand the biochemical basis of this activity, the effects of photo-activated ZnTM-3-PyP4 + on GSH/GSSG ratio, lipid peroxidation, membrane permeability, oxidative DNA damage, and the activities of SOD, catalase, glutathione reductase, and glutathione peroxidase were evaluated. Light exposure of ZnTM-3-PyP4 + -treated colon adenocarcinoma cells caused a wide spectrum of oxidative damage including depletion of GSH, inactivation of glutathione reductase and glutathione peroxidase, oxidative DNA damage and peroxidation of membrane lipids. Cell staining with Hoechst-33342 showed morphological changes consistent with both necrotic and apoptotic death sequences, depending upon the presence of oxygen.
Audit, Control and Monitoring Design Patterns (ACMDP) for Autonomous Robust Systems (ARS)

This paper proposes the Audit, Control and Monitoring Design Patterns (ACMDP) for building Autonomous and Robust Systems (ARS) such as Mobile Robot Systems (MRS). These patterns are also applicable to other Mission Critical and Complex Systems (MCCS). This paper presents a proposal which will help ARS project managers and engineers design, build and estimate the probability that an ARS will succeed or fail. Furthermore, this proposal offers the possibility to ARS problems with the help of audit, monitoring and controlling components, adjust the project management pathways, and define the problem sources as well as their possible solutions, in order to deliver an ARS or an MRS.
Compact Wideband CPW Bandpass Filters With Transmission Zeros Based on Stepped Impedance Resonators (SIR)

Compact wideband and highly selective bandpass filters (BPFs) implemented in coplanar waveguide technology are presented. The high frequency selectivity is achieved by the presence of shunt-connected stepped impedance resonators which introduce a transmission zero at both band edges. The circuit model of the filter as well as the design procedure to synthesize the required bandwidth, based on such model, is presented. An order-3 prototype BPF with 38% fractional bandwidth, central frequency fo = 6.3 GHz and 0.03 dB bandpass ripple is designed and fabricated as proof-of-concept demonstrator. The measured filter response is in good agreement with the model predictions. Filter dimensions are as small as 0. 16λ0 × 0. 29λ00 , λ0 being the free-space wavelength at the central filter frequency.
Analysis of clinical, ultrasound and colour flow‐Doppler characteristics in predicting malignancy in follicular thyroid neoplasms

Fine-needle aspiration cytology (FNAC) represents the main diagnostic tool in the evaluation of thyroid nodules because of its high sensitivity, specificity and accuracy. However, while FNAC is very reliable in detecting papillary thyroid carcinomas (PTC) and anaplastic thyroid carcinomas, follicular neoplasms (FN) represent the grey zone in which cytology cannot discriminate malignant from benign tumours. 1 Consequently, in presence of nodules cytologically classified as FN, thyroidectomy is usually required and the histological evaluation reveals that about 80% are benign lesions. Thus, identification of parameters associated with malignancy is needed. In this context, several studies have focused on clinical, ultrasonographic and cytological aspects, with controversial results. 2,3
Iron homeostasis in astrocytes and microglia is differentially regulated by TNF‐α and TGF‐β1

Abnormal iron homeostasis is increasingly thought to contribute to the pathogenesis of several neurodegenerative disorders. We have previously reported impaired iron homeostasis in a mouse model of spinal cord injury and in a mouse model of amyotrophic lateral sclerosis. Both these disorders are associated with CNS inflammation. However, what effect inflammation, and in particular, inflammatory cytokines have on iron homeostasis in CNS glia remains largely unknown. Here we report that the proinflammatory cytokine TNF‐α, and the anti‐inflammatory cytokine TGF‐β1 affect iron homeostasis in astrocytes and microglia in distinct ways. Treatment of astrocytes in vitro with TNF‐α induced the expression of the iron importer “divalent iron transporter 1” (DMT1) and suppressed the expression of the iron exporter ferroportin (FPN). However, TGF‐β1 had no effect on DMT1 expression but increased the expression of FPN in astrocytes. In microglia, on the other hand, both cytokines caused induction of DMT1 and suppression of FPN expression. Iron influx and efflux assays in vitro confirmed that iron homeostasis in astrocytes and microglia is differentially regulated by these cytokines. In particular, TNF‐α caused an increase in iron uptake and retention by both astrocytes and microglia, while TGF‐β1 promoted iron efflux from astrocytes but caused iron retention in microglia. These data suggest that these two cytokines, which are expressed in CNS inflammation in injury and disease, can have profound and divergent effects on iron homeostasis in astrocytes and microglia. © 2012 Wiley Periodicals, Inc.
Effects of alcohols, povidone-iodine and hydrogen peroxide on biofilms of Staphylococcus epidermidis.

OBJECTIVES To test the effects of several biocides [N-propanol, a commercially available propanol/ethanol/chlorhexidine mixture, polyvinylpyrolidone (povidone-iodine) and hydrogen peroxide] on established biofilms of Staphylococcus epidermidis isolated from patients with cardiac implant infections and catheter-related bacteraemia. METHODS Biofilms were grown in microtitre plates for 24 h, dyed and stained with Crystal Violet. The mean optical density (OD) and the OD ratio (ODr=OD of the treated biofilm/OD of the untreated biofilm) were used for quantification. Biofilms were incubated with 60% (v/v) N-propanol, the mixture of propanol/ethanol/chlorhexidine, hydrogen peroxide at three concentrations (0.5%, 3% and 5%, v/v) and povidone-iodine for 1, 5, 15, 30 and 60 min. Unstained biofilms were sonicated and plated on Columbia agar for time-kill curves. S. epidermidis skin isolates from healthy volunteers were used as controls. RESULTS Biofilm ODs of the clinical S. epidermidis isolates and the isolates from the healthy volunteers were significantly different (1.17+/-0.512 versus 0.559+/-0.095, respectively; mean+/-SD) (P<0.01). No viable S. epidermidis was detected in biofilms treated with the alcohols, N-propanol or the propanol/ethanol/chlorhexidine mixture. Incubation with povidone-iodine and hydrogen peroxide 3% and 5% led to a log reduction of the viable cells of >5 after incubation for 5 min, however, up to 10(3) viable cells were detected in four isolates after 30 min of incubation with povidone-iodine. CONCLUSIONS S. epidermidis obtained from infected implants forms thicker biofilms than that of healthy volunteers. Hydrogen peroxide, at a concentration of 3% and 5%, and alcohols rapidly eradicate S. epidermidis biofilms, whereas povidone-iodine is less effective.
Repair of DNA Double-Strand Breaks following UV Damage in Three Sulfolobussolfataricus Strains

ABSTRACT DNA damage repair mechanisms have been most thoroughly explored in the eubacterial and eukaryotic branches of life. The methods by which members of the archaeal branch repair DNA are significantly less well understood but have been gaining increasing attention. In particular, the approaches employed by hyperthermophilic archaea have been a general source of interest, since these organisms thrive under conditions that likely lead to constant chromosomal damage. In this work we have characterized the responses of three Sulfolobus solfataricus strains to UV-C irradiation, which often results in double-strand break formation. We examined S. solfataricus strain P2 obtained from two different sources and S. solfataricus strain 98/2, a popular strain for site-directed mutation by homologous recombination. Cellular recovery, as determined by survival curves and the ability to return to growth after irradiation, was found to be strain specific and differed depending on the dose applied. Chromosomal damage was directly visualized using pulsed-field gel electrophoresis and demonstrated repair rate variations among the strains following UV-C irradiation-induced double-strand breaks. Several genes involved in double-strand break repair were found to be significantly upregulated after UV-C irradiation. Transcript abundance levels and temporal expression patterns for double-strand break repair genes were also distinct for each strain, indicating that these Sulfolobus solfataricus strains have differential responses to UV-C-induced DNA double-strand break damage.
Purification and Characterization of L,(L/D)‐Aminopeptidase from Guinea Pig Serum

Abstract Mammalian sera contain enzymes that catalyze the hydrolytic degradation of peptidoglycans and molecules of related structure and are relevant for the metabolism of peptidoglycans. We now report on a novel L,(L/D)‐aminopeptidase found in human and mammalian sera. The enzyme hydrolyses the pentapeptide L‐Ala‐D‐iso‐Gln‐meso‐DAP(ωNH2)‐D‐Ala‐D‐Ala yielding the free L‐alanine and the respective tetrapeptide (KM 18 mM). L,(L/D)‐aminopeptidase from guinea pig serum was highly purified in four chromatographic steps, up to 700‐fold. Molecular weight of the enzyme was estimated by HPLC to be approximately 175,000. The configuration of alanine obtained by hydrolysis of the pentapeptide was determined by oxidation with L‐amino acid oxidase. The amino acids sequence in the respective tetrapeptide was deduced from the results of mass spectrometry. The novel L,(L/D)‐aminopeptidase also hydrolyzed alanine‐4‐nitroanilide (KM=0.6 mM) and several peptides comprising L‐amino acids. Peptides containing D‐amino acid at the amino end and L‐Asp‐L‐Asp were not the substrates for this enzyme. The purified enzyme also exhibited enkephalin degrading activity, hydrolyzing enkephalins comprising L,L‐ and L,D‐peptide bonds. The enzyme was inhibited strongly by metal chelating agents, bestatin and amastatin.