Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenotypic characterization of copper-resistant mutants of Methylosinus trichosporium OB3b

Cultures of Methylosinus trichosporium OB3b grown in the presence of very low concentrations of copper synthesize a soluble methane monooxygenase (sMMO) that efficiently catalyzes the oxidation of trichloroethylene and other organic pollutants. Recently, we isolated five M. trichosporium OB3b mutants that express sMMO activity when grown in the presence of elevated copper concentrations (P.A. Phelps, S. K. Agarwal, G. E. Speitel, Jr., and G. Georgiou, Appl. Environ. Microbiol. 58:3701-3708, 1992). Here we show that, in contrast to the results for the wild-type cells, the addition of copper to mutant cultures grown on methane and nitrate as the nitrogen source has no noticeable effect on the growth rate and sMMO expression. In vitro experiments indicated that the copper-resistant phenotype does not arise from an increased stability of sMMO to copper deactivation. Furthermore, the mutant cultures exhibit altered speciation of copper in the extracellular fluid and have substantially decreased levels of cell-associated copper. On the basis of these results, we propose that the mutant phenotype arises from defects in copper uptake and metabolism rather than from changes in sMMO expression or enzyme stability.
Performance analysis of an enhanced DOA for mobile ad-hoc networks

The two ad-hoc routing protocols, Ad-hoc On demand Distance Vector (AODV) and Dynamic Source Routing (DSR) suffer a number of shortcomings. The main issues are longer path set up time in case of link failures, scalability problem because of routing overhead and etc. A combination of the two routing protocols called DOA (DSR over AODV) is used to overcome these issues. DOA is usually implemented using a model called Way Point Routing model in which the problem of position estimation errors occurs. This work enhances DOA with a new algorithm called Exponential Weighted Moving Average (EWMA) for on-line updating of nodal contact probability to minimize the possibilities of position estimation errors. In this work, new packet called Delay to Send (DTS) packets instead of NACK packets has been used in addition to RTS and CTS packets. Here DTS packets are to recover the delayed data within a certain time period instead of dropping the packet after final retransmission in case of delay due to unexpected traffic in packet delivery. A Simulation analysis is carried out to analyze the performance of DOA with EWMA compared to AODV and DSR. It proves that DOA with EWMA reduces the routing overhead by 80% and scalability problem that occurred in AODV and DSR.
Susceptibility to Alternative Oral Antimicrobial Agents in Relation to Sequence Type ST131 Status and Coresistance Phenotype among Recent Escherichia coli Isolates from U.S. Veterans

ABSTRACT The rising prevalence of resistance to first-line antimicrobial agents in Escherichia coli, which has paralleled the emergence of E. coli sequence type ST131, has created a need for alternative oral options for use in treating outpatients with infections such as cystitis and chronic prostatitis. Accordingly, we determined susceptibility to six alternative oral agents (azithromycin, chloramphenicol, doxycycline, fosfomycin, minocycline, and rifampin) by Etest or disk diffusion for 120 recently obtained E. coli clinical isolates from Veterans Affairs Medical Centers across the United States. Isolates were randomly selected in three subgroups of 40 isolates each based on coresistance to fluoroquinolones with and without extended-spectrum cephalosporins (ESCs). Results were stratified according to trimethoprim-sulfamethoxazole (TMP-SMZ) phenotype. Overall, the prevalence of susceptible (or susceptible plus intermediate) isolates varied by agent, with rifampin being lowest (0%), fosfomycin highest (98 to 99%), and others in the mid-range (37 to 88%). Substantial proportions of isolates (15 to 27%) yielded intermediate results for azithromycin, chloramphenicol, doxycycline, and minocycline. Among isolates resistant (versus susceptible) to fluoroquinolones with or without ESCs, susceptibility to the above four agents declined significantly among non-ST131 isolates but not ST131 isolates. In contrast, in the presence of resistance to TMP-SMZ, susceptibility to azithromycin, doxycycline, and minocycline was significantly reduced among both ST131 and non-ST131 isolates. These findings identify potential alternative oral agents for use with E. coli isolates resistant to fluoroquinolones, ESCs, and/or TMP-SMZ and suggest that determination of ST131 status could help guide initial antimicrobial selection, pending susceptibility results.
Is Isoflurane-induced Preconditioning Dose Related?

Background Volatile anesthetics precondition against myocardial infarction, but it is unknown whether this beneficial action is threshold- or dose-dependent. The authors tested the hypothesis that isoflurane decreases myocardial infarct size in a dose-dependent fashion in vivo. Methods Barbiturate-anesthetized dogs (n = 40) were instrumented for measurement of systemic hemodynamics including aortic and left ventricular pressures and rate of increase of left ventricular pressure. Dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion and were randomly assigned to receive either 0.0, 0.25, 0.5, 1.0, or 1.25 minimum alveolar concentration (MAC) isoflurane in separate groups. Isoflurane was administered for 30 min and discontinued 30 min before left anterior descending coronary artery occlusion. Results Infarct size (triphenyltetrazolium staining) was 29 ± 2% of the area at risk in control experiments (0.0 MAC). Isoflurane produced significant (P < 0.05) reductions of infarct size (17 ± 3, 13 ± 1, 14 ± 2, and 11 ± 1% of the area at risk during 0.25, 0.5, 1.0, and 1.25 MAC, respectively). Infarct size was inversely related to coronary collateral blood flow (radioactive microspheres) in control experiments and during low (0.25 or 0.5 MAC) but not higher concentrations of isoflurane. Isoflurane shifted the linear regression relation between infarct size and collateral perfusion downward (indicating cardioprotection) in a dose-dependent fashion. Conclusions Concentrations of isoflurane as low as 0.25 MAC are sufficient to precondition myocardium against infarction. High concentrations of isoflurane may have greater efficacy to protect myocardium during conditions of low coronary collateral blood flow.
Systemic and Mucosal Immune Responses after Intranasal Administration of Recombinant Mycobacterium bovis Bacillus Calmette-Guérin Expressing Glutathione S-Transferase from Schistosoma haematobium

ABSTRACT A major goal of current vaccine development is the induction of strong immune responses against protective antigens delivered by mucosal routes. One of the most promising approaches in that respect relies on the use of live recombinant vaccine carriers. In this study,Mycobacterium bovis BCG was engineered to produce an intracellular glutathione S-transferase fromSchistosoma haematobium (Sh28GST). The gene encoding Sh28GST was placed under the control of the mycobacterialhsp60 promoter on a replicative shuttle plasmid containing a mercury resistance operon as the only selectable marker. The recombinant Sh28GST produced in BCG bound glutathione and expressed enzymatic activity, indicating that its active site was properly folded. Both intraperitoneal and intranasal immunizations of BALB/c mice with the recombinant BCG resulted in strong anti-Sh28GST antibody responses, which were enhanced by a boost. Mice immunized intranasally produced a mixed response with the production of Sh28GST-specific immunoglobulin G1 (IgG1), IgG2a, IgG2b, and IgA in the serum. In addition, high levels of anti-Sh28GST IgA were also found in the bronchoalveolar lavage fluids, demonstrating that intranasal delivery of the recombinant BCG was able to induce long-lasting secretory and systemic immune responses to antigens expressed intracellularly. Surprisingly, intranasal immunization with the BCG producing the Sh28GST induced a much stronger specific humoral response than intranasal immunization with BCG producing the glutathioneS-transferase from Schistosoma mansoni, although the two antigens have over 90% identity. This difference was not observed after intraperitoneal administration.
Once and for all—How people change strategy to ignore irrelevant information in visual tasks

Ignoring irrelevant visual information aids efficient interaction with task environments. We studied how people, after practice, start to ignore the irrelevant aspects of stimuli. For this we focused on how information reduction transfers to rarely practised and novel stimuli. In Experiment 1, we compared competing mathematical models on how people cease to fixate on irrelevant parts of stimuli. Information reduction occurred at the same rate for frequent, infrequent, and novel stimuli. Once acquired with some stimuli, it was applied to all. In Experiment 2, simplification of task processing also occurred in a once-for-all manner when spatial regularities were ruled out so that people could not rely on learning which screen position is irrelevant. Apparently, changes in eye movements were an effect of a once-for-all strategy change rather than a cause of it. Overall, the results suggest that participants incidentally acquired knowledge about regularities in the task material and then decided to voluntarily apply it for efficient task processing. Such decisions should be incorporated into accounts of information reduction and other theories of strategy change in skill acquisition.
Cost‐effectiveness analysis of antiviral treatment in liver transplant recipients with HCV infection

Within 5–10 years, 20–40% of hepatitis C virus (HCV)‐infected liver transplant recipients can be expected to develop cirrhosis. Here, cost‐effectiveness of antiviral therapy was assessed. A Markov model was developed to simulate disease progression and calculate outcome and costs of treatment. In the baseline analysis, Peg‐IFN/RBV treatment prevented organ loss/death, gained quality‐adjusted life‐years (QALYs) and undercut the limit of cost‐effectiveness of €50 000/QALY with an incremental cost‐effectiveness ratio of approximately €40 400/QALY and €21 000/QALY for HCV genotype 1 and 2/3 patients, respectively. Furthermore, sensitivity analysis testing modified model parameters according to extreme data described in the literature confirmed cost‐effectiveness for a lower or higher rate of fibrosis progression, increased non‐HCV‐related mortality, lower limits of utilities, a time horizon of 30 years, and additional costs in the year of death. On the other hand, cost‐effectiveness was lost for patients with genotype 1 in case of doubled antiviral or life‐time costs or an increased discount rate of 7%. New treatment strategies for HCV genotype 1 infected patients remained on the same level cost‐effective, if additional costs did not exceed €10 774 per 10% sustained virologic response gain. We conclude that Peg‐IFN/RBV treatment is cost‐effective post transplant. This may support treatment decision in individual cases.
The effects of long term administration of prazosin on the microcirculation in skeletal muscles.

The effect on the microcirculation of long term administration of the alpha 1 blocker prazosin, which increases peripheral blood flow, was studied in skeletal muscles with differing metabolic profiles. Prazosin (50 mg.litre-1), given ad libitum for 5 weeks in the drinking water, resulted in an increase in capillarity in both fast glycolytic tibialis anterior cortex and slow oxidative soleus muscles of the rat. In tibialis anterior, the velocity of red blood cells through capillaries was increased, a smaller proportion of capillaries had intermittent flow, less time was spent stationary by red blood cells, and hence the calculated volume flow per capillary was increased. In soleus, capillary diameters were larger, but velocity, intermittency and calculated volume flow were unchanged. Therefore, suggested mechanisms for capillary growth induced by prazosin are different for the two muscles studied: increased shear stress and blood/endothelial cell interaction in the case of tibialis anterior, and increased capillary wall tension in the soleus.
Iloprost relaxes phenylephrine-precontracted rat aortic rings

Iloprost is a prostacyclin analogue mainly used in the treatment of pulmonary hypertension. It is also effective for renal dysfunction during renal transplant and coronary artery bypass grafting surgery, but there have been few comparative experimental studies with iloprost. We aimed to compare vasorelaxant properties of iloprost, with those of diltiazem, nitroglycerin and papaverine on rat thoracic aorta following phenylephrine-induced precontraction. Thirty-two young adult female Wistar albino rats were used in the study. After isolation of thoracic aorta distal to arcus, 3 mm aortic rings were placed in an organ bath and phenylephrine (10-6 M) was added for precontraction. Subsequently, cumulative concentrations of iloprost, nitroglycerin, diltiazem and papaverine were added to aortic rings on separate chambers and dose-response curves were recorded. The mean (± SD) maximal relaxation (Emax) was 27.1 ± 2.9% for iloprost, 111.7 ± 2.1% for nitroglycerin, 77.4±2.9% for diltiazem and 147.2 ± 2.8% for papaverine. The half maximal effective concentration (EC50) values were 2.4 × 10 -11 molar (M) for iloprost, 5.6 × 10-8 M for nitroglycerin, 7.0 × 10-7 M for papaverine and 2.1 × 10-5 M for diltiazem. There was a statistically significant difference in Emax values and EC50 values between four groups (P<0.001 and P<0.01, respectively). Although a vasorelaxant response was observed with iloprost, it was less compared to papaverine, nitroglycerin and diltiazem on the isolated rat aortic rings. Iloprost has also the lowest EC50 value which could be valuable in clinical practice.
Immune remodelling of stromal cell grafts in the central nervous system: therapeutic inflammation or (harmless) side‐effect?

Over the past two decades, several cell types with fibroblast‐like morphology, including mesenchymal stem/stromal cells, but also other adult, embryonic and extra‐embryonic fibroblast‐like cells, have been brought forward in the search for cellular therapies to treat severe brain injuries and/or diseases. Although current views in regenerative medicine are highly focused on the immune modulating and regenerative properties of stromal cell transplantation in vivo, many open questions remain regarding their true mode of action. In this perspective, this study integrates insights gathered over the past 10 years to formulate a unifying model of the cellular events that accompany fibroblast‐like cell grafting in the rodent brain. Cellular interactions are discussed step‐by‐step, starting from the day of implantation up to 10 days after transplantation. During the short period that precedes stable settlement of autologous/syngeneic stromal cell grafts, there is a complex interplay between hypoxia‐mediated cell death of grafted cells, neutrophil invasion, microglia and macrophage recruitment, astrocyte activation and neo‐angiogenesis within the stromal cell graft site. Consequently, it is speculated that regenerative processes following cell therapeutic intervention in the CNS are not only modulated by soluble factors secreted by grafted stromal cells (bystander hypothesis), but also by in vivo inflammatory processes following stromal cell grafting. Copyright © 2016 John Wiley & Sons, Ltd.
Alkaline Response Genes of Saccharomyces cerevisiaeand Their Relationship to the RIM101 Pathway*

Environmental pH exerts broad control over growth and differentiation, but the molecular responses to external pH changes are poorly understood. Here we have used open reading frame macroarray hybridization to identify alkaline response genes inSaccharomyces cerevisiae. Northern or lacZfusion assays confirmed the alkaline induction of two ion pump genes (ENA1 and VMA4), several ion limitation genes (CTR3, FRE1, PHO11/12, andPHO84), a siderophore-iron transporter gene (ARN4/ENB1), two transcription factor genes (NRG2 and TIS11), and two predicted membrane protein genes (YAR068W/YHR214W and YOL154W). Unlike ENA1 and SHC1, these new alkaline response genes are not induced by high salinity. The known pH-responsive genes in other fungi depend on the conserved PacC/Rim101p transcription factor, but induction of several of these new genes relied upon Rim101p-independent pH signaling mechanisms. Rim101p-dependent genes were also dependent on Rim13p, a protease required for Rim101p processing. The Rim101p-dependent gene VMA4 is required for growth in alkaline conditions, illustrating how Rim101p may control adaptation. Because Rim101p activates ion pump genes, we tested the role of RIM101 in ion homeostasis and found thatRIM101 promotes resistance to elevated cation concentrations. Thus, gene expression surveys can reveal new functions for characterized transcription factors in addition to uncovering physiological responses to environmental conditions.
Size at Birth and Early Childhood Growth in Relation to Maternal Smoking, Parity and Infant Breast-Feeding: Longitudinal Birth Cohort Study and Analysis

There is remarkably wide variation in rates of infancy growth, however, its regulation is not well understood. We examined the relationship between maternal smoking, parity, and breast- or bottle-feeding to size at birth and childhood growth between 0 and 5 y in a large representative birth cohort. A total of 1335 normal infants had weight, length/height, and head circumference measured at birth and on up to 10 occasions to 5 y old. Multilevel modeling (MLwiN) was used to analyze longitudinal growth data. Infants of maternal smokers were symmetrically small at birth (p < 0.0005) compared with infants of nonsmokers, however, showed complete catch-up growth over the first 12 mo. In contrast, infants of primiparous pregnancies were thin at birth (p < 0.0005), showed dramatic catch-up growth, and were heavier and taller than infants of nonprimiparous pregnancies from 12 mo onwards. Breast-fed infants were similar in size at birth than bottle-fed infants, but grew more slowly during infancy. Among infants who showed catch-up growth, males caught up more rapidly than females (p = 0.002). In conclusion, early postnatal growth rates are strongly influenced by a drive to compensate for antenatal restraint or enhancement of fetal growth by maternal-uterine factors. The mechanisms that signal catch-up or catch-down growth are unknown but may involve programming of appetite. The importance of nutrition on early childhood growth is emphasized by the marked difference in growth rates between breast- and bottle-fed infants. The sequence of fetal growth restraint and postnatal catch-up growth may predispose to obesity risk in this contemporary population.
Autoimmune Neurology of the Central Nervous System

ABSTRACT Purpose of Review: This article reviews the rapidly evolving spectrum of autoimmune neurologic disorders with a focus on those that involve the central nervous system, providing an understanding of how to approach the diagnostic workup of patients presenting with central nervous system symptoms or signs that could be immune mediated, either paraneoplastic or idiopathic, to guide therapeutic decision making. Recent Findings: The past decade has seen a dramatic increase in the discovery of novel neural antibodies and their targets. Many commercial laboratories can now test for these antibodies, which serve as diagnostic markers of diverse neurologic disorders that occur on an autoimmune basis. Some are highly specific for certain cancer types, and the neural antibody profiles may help direct the physician’s cancer search. Summary: The diagnosis of an autoimmune neurologic disorder is aided by the detection of an objective neurologic deficit (usually subacute in onset with a fluctuating course), the presence of a neural autoantibody, and improvement in the neurologic status after a course of immunotherapy. Neural autoantibodies should raise concern for a paraneoplastic etiology and may inform a targeted oncologic evaluation (eg, N-methyl-D-aspartate [NMDA] receptor antibodies are associated with teratoma, antineuronal nuclear antibody type 1 [ANNA-1, or anti-Hu] are associated with small cell lung cancer). MRI, EEG, functional imaging, videotaped evaluations, and neuropsychological evaluations provide objective evidence of neurologic dysfunction by which the success of immunotherapy may be measured. Most treatment information emanates from retrospective case series and expert opinion. Nonetheless, early intervention may allow reversal of deficits in many patients and prevention of future disability.
Nitric oxide: an important role in the maintenance of systemic and pulmonary vascular tone in man.

AIMS The aim of this study was to examine whether nitric oxide (NO) has an important role in maintaining basal vascular tone in normal man by examining the effects of nitric oxide inhibition using N(G)-monomethyl-L-arginine (L-NMMA) on systemic and pulmonary haemodynamics. METHODS Ten normal male volunteers 26 +/- 1.6 years were studied on two separate occasions in a double-blind, placebo controlled crossover study. They were randomised to receive either a continuous infusion of L-NMMA (4 mg kg(-1) h(-1)) with a front loaded bolus (4 mg kg(-1)) or volume matched placebo. Pulsed wave Doppler echocardiography was used to measure cardiac output (CO), mean pulmonary artery pressure (MPAP) and hence systemic vascular resistance (SVR) and total pulmonary vascular resistance (TPR). Measurements were made prior to infusion (t0) and after 4, 8, and 12 min (t1, t2 and t3). RESULTS Infusion of L-NMMA significantly increased mean arterial blood pressure (MAP), SVR and TPR and significantly reduced heart rate (HR), stroke volume (SV) and CO compared to placebo. These effects were observed at t1 and persisted during the entire infusion period. CONCLUSIONS These results are consistent with a role for basal nitric oxide generation in the maintenance of basal systemic and pulmonary vascular tone in normal man.
Comparison of Quantification of Histochemical Staining By Hue-Saturation-Intensity (HSI) Transformation and Color-Deconvolution

We tested a recently developed flexible method of separation and quantification of immunohistochemical staining by means of color image analysis. An algorithm was recently developed to deconvolve the color information acquired with RGB cameras, to calculate the contribution of each of the applied stains, based on the stain-specific RGB absorption. The algorithm was tested using a set of lung-tumor samples labeled for the detection of Ki-67, an antigen expressed in proliferating cells, covering a wide range of staining levels. Quantification of the labeling was compared with HSI-based segmentation and manual analysis of the same samples. The recently developed deconvolution method performed significantly better than the HSI based system when compared to manual counting as gold standard. The deconvolution system showed significantly reduced variability in the LI determination, especially of highly labeled control samples. This resulted in significant increase in sensitivity of classification of samples with increased KI-67 labeling without changing the specificity, when compared to the HSI based method.
Widely tunable wavelength converter using a double-ring fiber laser with a semiconductor optical amplifier

Widely tunable wavelength conversion has been demonstrated using broad-band orthogonal-pump four-wave mixing in a semiconductor optical amplifier placed at the intersection of two fiber ring lasers. The all-optical wavelength converter operates without using any external pump source. A 3-dB conversion-range over 40 nm is obtained. The measured power penalty is 1.5 dB for a 2.5-Gb/s converted signal at 10/sup -9/ bit error rate.