Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic function and properties of 4-hydroxyphenylacetic acid 1-hydroxylase from Pseudomonas acidovorans

The enzyme 4-hydroxyphenylacetate, NAD(P)H:oxygen oxidoreductase (1-hydroxylating) (EC 1.14.13 .; 4-hydroxyphenylacetate 1-monooxygenase; referred to here as 4-HPA 1-hydroxylase) was induced in Pseudomonas acidovorans when 4-hydroxyphenylacetate (4-PHA) was utilized as carbon source for growth; homogentisate and maleylacetoacetate were intermediates in the degradation of 4-HPA. A preparation of the hydroxylase that was free from homogentisate dioxygenase and could be stored at 4 C in the presence of dithioerythritol with little loss of activity was obtained by ultracentrifuging cell extracts; but when purified 18-fold by affinity chromatography the enzyme became unstable. Flavin adenine dinucleotide and Mg2+ ions were required for full activity. 4-HPA 1-hydrocylase was inhibited by KCl, which was uncompetitive with 4-HPA. Values of Ki determined for inhibitors competitive with 4-HPA were 17 muM dl-4-hydroxymandelic acid, 43 muM 3,4-dihydroxyphenylacetic acid, 87 muM 4-hydroxy-3-methylphenylacetic acid, and 440 muM 4-hydroxyphenylpropionic acid. Apparent Km values for substrates of 4-HPA 1-hydroxylase were 31 muM 4-HPA, 67 muM oxygen, 95 muM reduced nicotinamide adenine dinucleotide (NADH); AND 250 muM reduced nicotinamide adenine dinucleotide phosphate (NADPH). The same maximum velocity was given by NADH and NADPH. A chemical synthesis is described for 2-deutero-4-hydroxyphenylacetic acid. This compound was enzymatically hydroxylated with retention of half the deuterium in the homogentisic acid formed. Activity as substrate or inhibitor of 4-HPA 1-hydroxylase was shown only by those analogues of 4-HPA that possessed a hydroxyl group substituent at C-4 of the benze nucleus. A mechanism is suggested that accounts for this structural requirement and also for the observation that when 4-hydroxyphenoxyacetic acid was attacked by the enzyme, hydroquinone was formed by release of the side chain, probably as glycolic acid. Only one enantiometer of racemic 4-hydroxyhydratropic acid was attacked by 4-HPA 1-hydroxylase; the product, alpha-methylhomogentisic acid (2-(2,5-dihydroxyphenyl)-propionic acid), exhibited optical activity. This observation suggests that, during its shift from C-1 to C-2 of the nucleus, the side chain of the substrate remains bound to a site on the enzyme while a conformational change of the protein permits the necessary movement of the benzene ring.
An overview of computer forensics

The core goals of computer forensics are fairly straightforward: the preservation, identification, extraction, documentation, and interpretation of computer data. There are several policies and procedures that need to be out-lined and defined with regard to computer forensics are analyzed in this paper. Data must be able to be retrieved and analyzed without it is damaged. The authenticity of the data is also ensured. The widespread usage of computer forensics has resulted from the convergence of two factors: the increasing dependence of law enforcement on computing and the ubiquity of computers that followed from the microcomputer revolution. There is a plethora of hardware and software tools available to assist with the interpretation of forensic data. The AccessData Forensic Toolkit can be used by both law enforcement and the private sector to run complete forensic examinations of a computer.
An Isoflow-Volume Technique for Assessing Airway Dynamics in Children and Adults

Background: We propose a new approach to the measurement of small airway function as an alternative to recordings of maximal expiratory flow-volume (MEFV) curves. Objectives: A newly developed technique to record isoflow-volume (IFV) curves to be tested against maximal respiratory flow curves. Methods: An isoflow whistle (IFW; Iflopen®) measures the length of a constant expiration after full inspiration. The note of the whistle enables a subject to generate an even expiration, and the isoflow maintenance times at 1 l·s–1 (IFMT1) and 2 l·s–1 (IFMT2) are recorded. The accuracy and reproducibility of the IFV technique were evaluated in 17 healthy adults (age 17–55 years) and in 14 asthmatic children (age 6–14 years). Comparisons with standard lung function parameters, such as forced expiratory volume in 1 s (FEV1), maximal expiratory flow at 50% (MEF50) and 25% (MEF25) vital capacity and peak expiratory flow (PEF), obtained with a Wright® Peakflow Meter were undertaken in 102 healthy (aged 8–14 years) and 101 asthmatic children (aged 6–17 years). A bronchial challenge test was performed in 13 asthmatic children. Results: The expired volume measured by the IFW showed an acceptable agreement with that of a pneumotachograph (mean error of 4.32% for IFMT1 and 5.93% for IFMT2). In healthy and in asthmatic children, the correlations between FEV1 and IFMT1 or IFMT2 (r = 0.92 and 0.94, respectively) were found to be greater than that between FEV1 and PEF (r = 0.68). During bronchial challenge tests in 13 asthmatic children, the FEV1 decreased to 69% of baseline and IFMT1 to 58% of baseline. Conclusions: The IFV technique accurately measured airway obstruction and closely followed changes in standard parameters of the MEFV curve.
A novel matrix-based lumped-element analysis method for CMOS distributed amplifiers

This paper presents a matrix-based lumped-element theoretical analysis of CMOS distributed amplifiers that employ the image impedance technique for the input/output terminating networks. The design of distributed amplifiers can be more efficient in CMOS technology by using lumped-element modelling of the distributed amplifiers rather than the one commonly based on transmission line parameters. The simulation results clearly indicate an improved voltage gain and a better gain uniformity over the bandwidth of the proposed amplifier design. Moreover, this matrix-based lumped-element method is suitable for analysis of any distributed amplifier with an arbitrary terminating network.
Body Mass Index, Weight, and Oral Contraceptive Failure Risk

OBJECTIVE: This project was supported by grant 1 R01 HD-34712 from the U.S. National Institute of Child Health and Human Development. To estimate the effect of body mass index (BMI) and weight on risk of pregnancy while using oral contraceptives (OCs). METHODS: We conducted a case-control study of 248 health maintenance organization enrollees who became pregnant while using OCs between 1998 and 2001 and 533 age-matched enrollees who were nonpregnant OC users during the same period. Using logistic regression we calculated adjusted odds ratios (ORs) to estimate the risk of pregnancy according to BMI and weight quartile. RESULTS: Among all OC users, when compared with women having a BMI of 27.3 or less, the risk of pregnancy was nearly 60% higher in women with BMI greater than 27.3 (OR 1.58, 95% confidence interval [CI] 1.11–2.24) and over 70% higher in women with BMI greater than 32.2 (OR 1.72, 95% CI 1.04–2.82). Among consistent users (women who missed no pills in reference month), the risk of pregnancy was more than doubled in women with BMI greater than 27.3 (OR 2.17, 95% CI 1.38–3.41) or BMI greater than 32.2 (OR 2.22, 95% CI 1.18–4.20). When compared with women weighing 74.8 kg or less, among consistent OC users the risk of pregnancy was over 70% higher in women weighing more than 74.8 kg (OR 1.71, 95% CI 1.08–2.71) and nearly doubled in women weighing more than 86.2 kg (OR 1.95, 95% CI 1.06–3.67). CONCLUSION: Our results suggest that being overweight may increase the risk of becoming pregnant while using OCs. If causal, this association translates to an additional 2–4 pregnancies per 100 woman-years of use among overweight women, for whom consideration of additional or effective alternative contraceptive methods may be warranted. LEVEL OF EVIDENCE: II-2
Symptoms of depression and anxiety during adult life: evidence for a decline in prevalence with age

Background. To test the hypothesis that the prevalence, in the general population, of symptoms of depression and anxiety declines with age. Methods. A general population sample of 2725 persons aged 18 to 79 years was administered two inventories for current symptoms of depression and anxiety, together with measures of neuroticism and of exposures that may confer increased risk of such symptoms. Results. Symptoms of depression showed a decline with age in both men and women. For anxiety, the decline was statistically significant for women but not consistently so for men. For the risk factors examined, there was a decline with age in the neuroticism score, the frequency of adverse life events, being seriously short of money and having had parents who separated or divorced. Further analysis showed that the association between age and a declining symptom score cannot be entirely attributed to these risk factors, with the single exception of neuroticism. The latter is itself likely to be contaminated by current symptoms. Conclusion. Unless these findings are due to bias in the sample of those who agreed to participate, they add to the evidence that symptoms of depression and to a lesser extent of anxiety decline in prevalence with age. Some risk factors also decline with age. It now has to be determined if these cross-sectional observations are also to be found in longitudinal data; and what process may underlie this striking change in mental health during adulthood.
Road casualties and changes in risky driving behavior in France between 2001 and 2004 among participants in the GAZEL cohort.

OBJECTIVES We investigated behavioral changes in a large cohort of drivers to identify underlying causes of the decline in road casualties in France. METHODS In 2001 and 2004, 11,240 participants used self-administered questionnaires to report attitudes toward road safety and driving behaviors. Injury road traffic collisions were recorded from 2001 to 2005 through the cohort's annual questionnaire. RESULTS Between 2001 and 2004, speeding and cell phone use decreased concomitantly with a decrease in injury road traffic collision rates among participants. Reported driving while sleepy remained unchanged and driving while alcohol intoxicated was reported by a higher proportion in 2004 than in 2001. Decreases in speeding between 2001 and 2004 were strongly linked with positive attitudes toward road safety in 2001. CONCLUSIONS In this cohort, speeding and using a cell phone while driving decreased over the 2001 to 2004 period concomitantly with increases in traffic law enforcement and a dramatic decline in road mortality in France. However, the deterrent effect of traffic enforcement policies may have been reduced by negative attitudes toward traffic safety and having had a history of traffic penalty cancellations.
Asymptotic variance expressions for identified black-box transfer function models

Identification of black-box transfer function models is considered. It is assumed that the transfer function models possess a certain shift-property, which is satisfied for example by all polynomial-type models. Expressions for the variances of the transfer function estimates are derived, that are asymptotic both in the number of observed data and in the model orders. The result is that the joint covariance matrix of the transfer functions from input to output and from driving white noise source to the additive output disturbance, respectively, is proportional to the inverse of the joint spectrum matrix for the input and driving noise multiplied by the spectrum of the additive output noise. The factor of proportionality is the ratio of model order to number of data. This result is independent of the particular model structure used. The result is applied to evaluate the performance degradation due to variance for a number of typical model uses. Some consequences for input design are also drawn.
Azole-Anion-Based Aprotic Ionic Liquids: Functional Solvents for Atmospheric CO2 Transformation into Various Heterocyclic Compounds.

The chemical transformation of atmospheric CO2 is of great significance yet still poses a great challenge. Herein, azole-anion-based aprotic ionic liquids (ILs) were synthesized by the deprotonation of weak proton donors (e.g., 2-methylimidazole, 4-methylimidazole, and 2,4-dimethylimidazole) with tetrabutylphosphonium hydroxide, [Bu4 P][OH]. We found that these ILs, such as [Bu4 P][2-MIm], could activate atmospheric CO2 through the formation of carbamates. The resultant carbamate intermediates could further react with various types of substrate, including propargylic alcohols, 2-aminobenzonitriles, ortho-phenylenediamines, and 2-aminothiophenol, thereby producing α-alkylidene cyclic carbonates, quinazoline-2,4(1 H,3 H)-diones, benzimidazolones, and benzothiazoline, respectively, in moderate-to-good yields. Thus, we have achieved the transformation of CO2 at atmospheric pressure, and we expect this method to open up new routes for the synthesis of various oxygen-containing heterocyclic compounds under metal-free conditions.
Enhancement of apoptosis by nitric oxide released from α‐phenyl‐tert‐butyl nitrone under hyperthermic conditions

The aim of this study was to examine whether a neuroprotector, PBN (α‐phenyl‐tert‐butyl nitrone), enhances apoptosis induced by hyperthermia, which generates superoxide (O 2− ) intracellularly, since the release of nitric oxide (NO) from PBN under oxidative stress has been reported. When human myelomonocytic lymphoma U937 cells were treated with hyperthermia (44°C, 10 min) and PBN, an increase in the concentration of nitrite in the culture medium, and a decrease in the hyperthermia‐induced production of O 2− was observed. Imaging using a fluorescence dye for intracellular NO, diaminofluorescein‐2 diacetate (DAF‐2 DA), revealed the formation of NO in the apoptotic cells treated with hyperthermia and PBN combined. Apoptotic endpoints were significantly enhanced by the combined treatment: a decrease in mitochondrial trans‐membrane potential, cleavage of Bid, release of cytochrome c, and activation of caspase‐8 and ‐3. An increase in the intracellular Ca2+ concentration ([Ca2+]i), externalization of Fas, and decrease in Hsp70 and phosphorylated HSF1 were observed following the combined treatment. Furthermore, scavengers of NO and ONOO− significantly inhibited the enhancement of apoptosis, the externalization of Fas and the increase in [Ca2+]i. These results suggest that, (1) NO is released from PBN by hyperthermia, and subsequently reacts with O 2− to form ONOO−, (2) NO and ONOO− are involved in the enhancement of apoptosis through Fas‐mitochondria‐caspase and [Ca2+]i‐dependent pathways, and (3) a decrease in Hsp70 and phosphorylated HSF1 also contributed to the enhancement of apoptosis. J. Cell. Physiol. 206: 468–476, 2006. © 2005 Wiley‐Liss, Inc.
White Matter Alteration in Metabolic Syndrome

OBJECTIVE We explored the regional pattern of white matter alteration in subjects with metabolic syndrome. We also investigated whether white matter alteration was correlated with BMI. RESEARCH DESIGN AND METHODS Seven middle-aged men with metabolic syndrome and seven without metabolic syndrome underwent diffusion tensor imaging with a 3T magnetic resonance imaging imager. We analyzed the fractional anisotropy (FA) values by using a tract-based spatial statistics technique (whole-brain analysis). We subsequently focused on measuring the mean FA values of the right inferior fronto-occipital fasciculus (IFOF) of all subjects by tract-specific analysis (regional brain analysis). We used a Pearson correlation coefficient to evaluate the relationship between BMI and mean FA values of the right IFOF. RESULTS In the whole-brain analysis, subjects with metabolic syndrome had significantly lower FA values than control subjects in part of the right external capsule (part of the right IFOF), the entire corpus callosum, and part of the deep white matter of the right frontal lobe. In the regional brain analysis, the mean FA value of the right IFOF was 0.41 ± 0.03 for subjects with metabolic syndrome and 0.44 ± 0.05 for control subjects. A significant negative correlation was observed between BMI and FA values in the right IFOF (r = −0.56, P < 0.04). CONCLUSIONS Our results show that microstructural white matter changes occur in patients with metabolic syndrome. FA values may be useful indices of white matter alterations in patients with metabolic syndrome.
Age‐adjusted reference limits for carotid intima‐media thickness as better indicator of vascular risk: population‐based estimates from the VITA project

Summary. Background: An increase of carotid intima‐media thickness (CIMT) has been demonstrated to be associated in many studies with the subsequent risk of cardio‐ and cerebrovascular events, but the threshold level of CIMT for an increased risk at different ages remains uncertain. Objectives: We aimed at establishing optimal reference limits associated with a definite increased vascular risk in the general population. Methods: A cohort of 2580 subjects was enrolled in a population‐based cross‐sectional survey. CIMT was measured on both left and right common carotid arteries, and age‐specific, percentile‐based reference ranges for CIMT were computed together with the Framingham risk score. Results: A significant, steady increase of CIMT reference ranges was observed within different age strata. CIMT levels were linearly related with an increase of the Framingham risk score, but after age‐adjustment only the upper CIMT quintile was associated with a higher Framingham risk score. Conclusions: Age‐specific reference limits provide better estimate of vascular risk in the population and correlation with established risk factors.
Citrulline as a Biomarker in the Non-human Primate Total- and Partial-body Irradiation Models: Correlation of Circulating Citrulline to Acute and Prolonged Gastrointestinal Injury

AbstractThe use of plasma citrulline as a biomarker for acute and prolonged gastrointestinal injury via exposure to total- and partial-body irradiation (6 MV LINAC-derived photons; 0.80 Gy min−1) in nonhuman primate models was investigated. The irradiation exposure covered gastrointestinal injuries spanning lethal, mid-lethal, and sub-lethal doses. The acute gastrointestinal injury was assessed via measurement of plasma citrulline and small intestinal histopathology over the first 15 d following radiation exposure and included total-body irradiation at 13.0 Gy, 10.5 Gy, and 7.5 Gy and partial-body irradiation at 11.0 Gy with 5% bone marrow sparing. The dosing schemes of 7.5 Gy total-body irradiation and 11.0 Gy partial-body irradiation included time points out to day 60 and day 180, respectively, which allowed for correlation of plasma citrulline to prolonged gastrointestinal injury and survival. Plasma citrulline values were radiation-dependent for all radiation doses under consideration, with nadir values ranging from 63–80% lower than radiation-naïve NHP plasma. The nadir values were observed at day 5 to 7 post irradiation. Longitudinal plasma citrulline profiles demonstrated prolonged gastrointestinal injury resulting from acute high-dose irradiation had long lasting effects on enterocyte function. Moreover, plasma citrulline did not discriminate between total-body or partial-body irradiation over the first 15 d following irradiation and was not predictive of survival based on the radiation models considered herein.
Genetic Analysis of Purine Metabolism in Leishmania donovani *

To dissect the contributions of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenine phosphoribosyltransferase (APRT), and adenosine kinase (AK) to purine salvage in Leishmania donovani, null mutants genetically deficient in HGPRT and/or APRT were generated by targeted gene replacement in wild type cells and preexisting mutant strains lacking either APRT or AK activity. These knockouts were obtained either by double targeted gene replacement or by single gene replacement followed by negative selection for loss-of-heterozygosity. Genotypes were confirmed by Southern blotting and the resultant phenotypes evaluated by enzymatic assay, resistance to cytotoxic drugs, ability to incorporate radiolabeled purine bases, and growth on various purine sources. All mutant strains could propagate in defined growth medium containing any single purine source and could metabolize exogenous [3H]hypoxanthine to the nucleotide level. The surprising ability of mutant L. donovani lacking HGPRT, APRT, and/or AK to incorporate and grow in hypoxanthine could be attributed to the ability of the parasite xanthine phosphoribosyltransferase enzyme to salvage hypoxanthine. These genetic studies indicate that HGPRT, APRT, and AK, individually or in any combination, are not essential for the survival and growth of the promastigote stage of L. donovani and intimate an important, if not crucial, role for xanthine phosphoribosyltransferase in purine salvage.
A sparse sampling algorithm for self-optimisation of coverage in LTE networks

Coverage optimisation is an important self-organising capability that operators would like to have in LTE networks. This paper applies a Reinforcement Learning (RL) based Sparse Sampling algorithm for the self-optimisation of coverage through antenna tilting. This algorithm is better than supervised learning and Q-learning based algorithms as it has the ability to adapt to network environments without prior knowledge, handle large state spaces, perform self-healing and potentially focus on multiple coverage problems.
Mutations at Two Invariant Nucleotides in the 3′-Minor Domain of Escherichia coli 16 S rRNA Affecting Translational Initiation and Initiation Factor 3 Function (*)

We have investigated the highly conserved GAUCA sequence of small subunit ribosomal RNA. Within this region, the invariant nucleotides G1530 and A1531 of Escherichia coli 16 S rRNA were mutagenized to A1530/G1531. These base changes caused a lethal phenotype when expressed from a high copy number plasmid. In low copy number plasmids, the mutant ribosomes had limited effects when expressed in vivo but caused significant deficiencies in translation in vitro, affecting enzymatic tRNA binding, non-enzymatic tRNA binding, subunit association, and initiation factor 3 (IF3) binding. Mutant 30 S ribosomal subunits showed a 10-fold decrease in affinity for IF3 as compared to wild-type subunits but showed an increased affinity for IF3 when in 70 S ribosomes. Additionally, IF3 did not promote dissociation of 70 S ribosomes, which had mutated subunits as monitored by light-scattering experiments. However, extension inhibition experiments (toeprinting) showed that IF3 retained its ability to discriminate between initiator and elongator tRNAs on mutated subunits. The results indicate that the two functions of IF3, tRNA discrimination and subunit dissociation, are separable and that the invariant nucleotides are important for correct subunit function during initiation.