Miracle-dz/UniFAR-FTUs huggingface dataset:
Variability in Zidovudine Serum Concentrations

This study explored the variability of zidovudine concentrations with computer simulations and measured concentrations. A one‐compartment oral absorption model was selected to characterize zidovudine disposition. Mean (± standard deviation) values for the pharmacokinetic parameters were taken from the literature. Five different Monte Carlo simulations (50 each) were performed of zidovudine concentrations following repetitive administration of 100‐mg oral doses 6 times/day in patients weighing 45–85 kg. A sixth simulation considered a weight‐adjusted regimen. Predicted concentrations were compared with those measured in 30 HIV‐infected persons receiving 100 mg/dose. Predicted concentrations 1 hour after 100 mg was administered fell in the range of 0.52–5.18 μM; measured values in 30 patients were 0.54–3.07 μM. This study confirms substantial variability in zidovudine serum concentrations. The simulation study of a weight‐adjusted regimen suggests one possibility to reduce this variability. These observations provide a basis to explore dosing strategies that control for pharmacokinetic and perhaps pharmacodynamic sources of interpatient variability.
Mitochondrial tRNA mutations and disease

Mitochondrial (mt‐) tRNA (MTT) gene mutations are an important cause of human morbidity and are associated with a wide range of pathology, from isolated organ‐specific diseases such as myopathy or hearing loss, through to multisystem disorders with encephalopathy, gastrointestinal dysmotility, and life‐threatening cardiomyopathy. Our understanding of how MTT mutations cause disease remains poor and progress has been hampered by the complex interaction of genotype with phenotype that can result in patients who harbor the same mutation exhibiting starkly contrasting phenotypes, whereas other (genetically heterogeneous) patients manifest clinically identical syndromes. A further complexity is the highly polymorphic nature of mitochondrial DNA (mtDNA), which must temper any reflex assumptions of pathogenicity for novel MTT substitutions. Nevertheless significant progress is being made and we shall review the methods employed to identify and characterize MTT mutations as pathogenic. Also important is our understanding of the molecular processes involved and we shall discuss the data available on two of the most studied MTT mutations (m.8344A > G and m.3243A > G) as well as other potential pathogenic mechanisms. Knowledge of factors influencing the inheritance of MTT mutations, and therefore the likelihood of disease transmission, is of particular importance to female patients. At present, the factors determining transmission remain elusive, but we shall examine several possible mechanisms and discuss the evidence for each. Finally, a number of different yeast and mouse models are currently used to investigate mitochondrial disease and we will assess the importance of and difficulties associated with each model as well as the future of possible therapies for patients with mitochondrial disease. Copyright © 2010 John Wiley & Sons, Inc.
Do the Flexible Employment Arrangements Increase Job Satisfaction and Employee Loyalty? Evidence from Bayesian Networks and Instrumental Variables

This study explores the relationship between job satisfaction, employee loyalty and two types of flexible employment arrangements; teleworking and flexible timing. The analysis relies on data derived from the workplace employment relations survey (WERS) in 2004 and 2011. We apply the propensity score matching approach and least squares regressions. Furthermore, we employ the Bayesian networks (BN) and directed acyclic graphs (DAGs) to confirm the causality between employment types explored and the outcomes of interest. Additionally, we propose an instrumental variables (IV) approach based on the BN framework. The results support that a positive causal effect from these employment arrangements on job satisfaction and employee loyalty is present.
Caffeine's impairment of insulin‐mediated glucose disposal cannot be solely attributed to adrenaline in humans

Caffeine (CAF) impedes insulin‐mediated glucose disposal (IMGD) and increases plasma adrenaline concentrations ([ADR]; 0.6 nm). While the antagonism of ADR abolishes the CAF effect, infusion of ADR (0.75 nm) has no effect on IMGD. We have now examined CAF and ADR in concert to determine whether or not they elicit an additive response on IMGD. We hypothesized that CAF + ADR would elicit a greater effect than either CAF or ADR alone (i.e. that CAF effects would not be solely attributed to ADR). Subjects (n= 8) completed four trials in a randomized manner. An isoglycaemic–hyperinsulinaemic clamp was performed 30 min after the following treatments were administered: (1) placebo capsules and saline infusion ([ADR]= 0.29 nm) (PL trial), (2) CAF capsules (dose = 5 mg kg−1) and saline infusion ([ADR]= 0.62 nm) (CAF trial), (3) PL capsules and ADR infusion ([ADR]= 1.19 nm) (ADR trial), and (4) CAF capsules (dose = 5 mg kg−1) and ADR infusion ([ADR]= 0.93 nm) (CAF + ADR trial). As expected, CAF, ADR and CAF + ADR decreased (P≤ 0.05) IMGD compared to PL. CAF + ADR resulted in a more pronounced decrease in IMGD versus PL (42%) compared to CAF (26%) or ADR (24%) alone; however, the effect was not fully additive (P= 0.08). Furthermore, CAF decreased IMGD to a similar magnitude as ADR despite a 50% lower [ADR]. In summary, while ADR contributes to the CAF‐induced impairment in IMGD, it is not solely responsible for caffeine's effects.
Interactive effect of apolipoprotein e genotype and age on hippocampal activation during memory processing in healthy adults.

CONTEXT Although the apolipoprotein E (APOE) ϵ4 allele is a major genetic risk factor for late-onset Alzheimer disease, its effect on hippocampal function during episodic memory is controversial because studies have yielded mixed results. The age of the studied cohorts may contribute to this apparent inconsistency: activation for ϵ4 carriers tends to be increased in studies of older adults but decreased in some studies of younger adults. Consistent with differential age effects, research in transgenic mice suggests that the ϵ4 allele may particularly affect the aging process. OBJECTIVE To define the interactions of age and this allelic variation on brain activation during episodic memory across adult life in healthy individuals. DESIGN Functional magnetic resonance imaging (fMRI) using an episodic memory paradigm to test for differences in neuroactivation across APOE genotypes and age groups. SETTING A federal research institute. PARTICIPANTS Healthy white volunteers (APOE ϵ3 homozygotes and ϵ2 and ϵ4 heterozygotes) completed the fMRI task (133 volunteers aged 19-77 years). MAIN OUTCOME MEASURE Memory-related regional blood oxygenation level-dependent (BOLD) activation. RESULTS Genotype affected the pattern of change in hippocampal BOLD activation across the adult lifespan: older age was associated with decreased activation in ϵ2 carriers and, to a lesser extent, in ϵ3 homozygotes, but this pattern was not observed in ϵ4 carriers. Among young participants, ϵ4 carriers had less hippocampal activation compared with ϵ3 homozygotes despite similar task performance. CONCLUSIONS The findings support the hypothesis that aging and APOE allele status have interacting effects on the neural substrate of episodic memory and lend clarification to disparities in the literature. The stepwise decrease in activation with age found among genotype groups resembles the order of susceptibility to Alzheimer disease, suggesting a compensatory neurobiological mechanism in older asymptomatic ϵ4 carriers.
Mortality Effects of Longer Term Exposures to Fine Particulate Air Pollution: Review of Recent Epidemiological Evidence

This article evaluates the dynamic exposure-response relationship between particulate matter air pollution (PM) and mortality risk by integrating epidemiological evidence from studies that use different time scales of exposure. The evidence suggests that short-term exposure studies are observing more than just harvesting or mortality displacement. There is little evidence of short-term compensatory reduction in deaths, and estimated PM effects are generally larger for intermediate and longer term time scales of exposure. Although proximity in time matters, with most recent exposure having the largest health impact, there is evidence that the short-term exposure studies capture only a small amount of the overall health effects of long-term repeated exposure to PM. The overall epidemiological evidence suggests that adverse health effects are dependent on both exposure concentrations and length of exposure, and that long-term exposures have larger, more persistent cumulative effects than short-term exposures.
Ultrapure Dialysate: A Desirable and Achievable Goal for Routine Hemodialysis

United States standards for the microbiologic quality of dialysate are not very stringent and have remained unchanged for more than 20 years, despite significant changes in the patient population and in the technology of hemodialysis. Numerous studies have demonstrated that bacterial products can cross dialysis membranes and stimulate an inflammatory response in the patient. Inflammation has been implicated in several complications associated with long‐term hemodialysis therapy, and the use of ultrapure dialysate has been shown to reduce the incidence of one of these complications, β2‐microglobulin amyloidosis. Since technological innovations in water treatment and improvements in dialysis machine design allow the routine production of ultrapure dialysate, its use should now become standard.
Induction of oxidative stress related responses in Arabidopsis thaliana following uranium exposure

The reactive oxygen species (ROS)-signaling pathway is very important in heavy metal toxicity. Induction of the antioxidative defense mechanism, comprising ROS-scavenging enzymes and metabolites, in plants after environmental uranium contamination has been insufficiently studied in the past. This study aimed to analyze oxidative stress related responses in Arabidopsis thaliana after uranium exposure. Seventeen-day-old seedlings were exposed to 0, 0.1, 1, 10 and 100M uranium for 3 days. After exposure to 100M uranium, a decrease in fresh weight for leaves and roots was observed, leaves colored anthocyanous and roots were stunted and yellow. To reveal the importance of oxidative stress in uranium toxicity, alterations in ROS-scavenging enzymes were studied at protein and transcriptional level. Superoxide dismutase (SOD) capacities increased in leaves and roots after exposure to 100M uranium but no differences were observed for catalase (CAT) capacities. Transcript levels of different SODs located at various cellular compartments were affected depending on the place of action. Gene expression of CAT in leaves and roots was also affected after uranium exposure. Results indicate that oxidative stress plays an important role in uranium toxicity but suggest that plant responses differ for leaves and roots.
The effect of altered sodium or potassium intake on the width and cytochemistry of the zona glomerulosa of the rat's adrenal cortex.

The cortex of the rat’s adrenal gland is divided morphologically into three major zones. The appearance of the cells and the width of the outer two zones, the glomerulosa and fasciculata, can be altered in different physiological states. Thus, the zona fasciculata enlarges and its cells appear active in conditions eliciting an increased production of adrenotropin, which stimulates the release of the cortical “sugar” factors. On the other hand, this zone shrinks and becomes inactive after hypophysectomy. Either change may occur without apparent alteration in the activity of the glomerulosa (Deane and McKibbin, 1946; Deane and Greep, 1946). The present paper will describe experiments indicating that the outer zone, the glomerulosa, undergoes morphological and cytochemical changes in physiological states that involve disturbance of the electrolyte balance of the body. These changes may occur without any demonstrable alteration of the fasciculata. Moreover, they develop in hypophysectomized as well as in inta.
Effects of Abiotic Stress (UV-C) Induced Activation of Phytochemicals on the Postharvest Quality of Horticultural Crops

Phytochemicals are bioactive non-nutrient plant components that have gained considerable attention as photoprotective agents in providing certain health benefits and are well known for their powerful antioxidant and free radical scavenging potential [1-2, 8]. Phytochemicals found in plant-based foods (fruits, vegetables, legumes, nuts, cereals, and grains) belong to several classes according to their chemical structures and physiological functions and include polyphenols, flavonoids, isoflavonoids, phytoalexins, phenols, anthocyanidins, nitrogen compounds (polyamines), chlorophyll derivatives, beta carotene (pro-vitamin A), and other carotenoids, ascorbic acid (vitamin C), folic acid, and α-tocopherol (vitamin E). Figure 1 illustrates the classification of dietary phytochemicals, which are widely distributed with different structures at the tissue, cellular, and sub-cellular levels. While it has been reported that there are over 4,000 phytochemicals, the most studied are the phenolics (largest category of phytochemicals) and carotenoids [3, 5], whereas some phytochemicals are distributed only among limited taxonomic groups. For example, glucosinolates are only found in the crucifer‐ ous vegetables crops, whereas the occurrence of sulfides is restricted to the Liliaceae. Addi‐ tionally, each fruit and vegetable species has a distinct profile of phytochemicals, which is also within a special phytochemical group [4]. Many phytochemicals, particularly the pigment molecules, are often concentrated in the outer layers of the various plant tissues [5]. Some sources of phytochemicals include lycopene from tomatoes, isoflavones from soy, β-carotene from carrots, and anthocyanins from blueberries and grapes. The phytochemicals lutein and zeaxanthin are carotenoids found in spinach, kale, and turnip greens. Another group of phytochemicals called allyl sulfides are found in garlic and onions. http://www.cancer. org/ treatment/treatmentsandsideeffects/complementaryandalternativemedicine/herbsvitamin‐ sandminerals/phytochemicals
Fate of heavy metals and major nutrients in a sludge-soil-plant-leachate system during the sludge phyto-treatment process

Land application of sewage sludge usually leads to increased levels of heavy metals in soil, plants and groundwater. Pre-treatment using plants has been proposed to reduce the contents of heavy metals and water in sludge prior to land application. This study quantified the transfer of Zn, Cd, Pb and major nutrients in a sludge-soil-plant-leachate system during the treatment of sewage sludge. To accomplish this, a two year pot experiment was carried out to collect leachate, mono- and co-cropping of Sedum alfredii and feed crops was conducted in sludge with an under-layer soil support. Sludge phyto-treatment increased Zn and Cd concentrations in the under-layer soil, but not Pb. Specifically, 70%, 70% and 80% of the original Zn, Cd and Pb, respectively, remained in the sludge, while about 40%, 70% and 60% of the original N, P and K remained. Only 3% to 5% of Cd and Zn and < 1% of Pb were transferred into the under-layer soils or leachates, while more than 12% of the N and P were transferred. Co-planting S. alfredii and feed crops led to a significant reduction of heavy metals in leachates when compared with sludge without planting. Overall, sludge leachate is more appropriate than whole sludge for recycling in agriculture since it reduces the chance of heavy metal contamination in the agro-ecosystem; therefore, co-cropping phyto-treatment of sludge can be coupled with sludge leachate recycling for crop production and re-collection of the sludge residue for landfilling.
Isolation and characterization of Rhodococcus sp. NB5 capable of degrading a high concentration of nitrobenzene

An efficient nitrobenzene degrading bacterium strain NB5, which was able to utilize nitrobenzene as a sole source of carbon, nitrogen and energy under aerobic condition, was isolated from activated sludge in an oil refinery at Hangzhou, China. Based on phenotypic features, 16S rDNA gene sequencing and G + C content analysis, strain NB5 was identified as Rhodococcus sp. NB5. Nitrobenzene degradation experiments using high performance liquid chromatograph (HPLC) showed that strain NB5 could tolerate a high nitrobenzene concentration and completely degrade nitrobenzene with initial concentration ranging from 100 mg · l–1 to 1000 mg · l–1 within 144 h. The optimal degradation and cell growth were observed at 30 °C, pH 7.0. The addition of second nitrogen source (0.1%) such as urea, peptone, yeast extract and beef extract generally enhanced degradation of nitrobenzene. Rhodococcus sp. strain NB5 could be an excellent candidate for biotreatment of industrial wastewater containing high concentration of nitrobenzene. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Visual function correlates with nerve fiber layer thickness in eyes affected by ocular hypertension.

PURPOSE To test whether the high variability observed when measuring pattern electroretinogram (PERG), visual evoked potentials (VEP), and spatial contrast sensitivity (SCS) in eyes with ocular hypertension is associated with variation in nerve fiber layer thickness, as measured by optical coherence tomography (OCT). METHODS The study involved 32 untreated eyes (32 patients; age range, 29-64 years) showing a normal whiteon-white 24/2 Humphrey (San Leandro, CA) perimetry, IOP between 23 and 28 mm Hg, best corrected acuity of 20/20 or better, and none of the following papillary signs on conventional color stereo slides: rim notch(es), peripapillary splinter hemorrhages, or increased vertical-to-horizontal cup-to-disc ratio. On recruitment, each eye underwent SCS testing, OCT, PERG, and VEP recordings. Linear regression (Pearson's test) or Spearman's rank regression was adopted for the analysis of the data. RESULTS The 95% confidence limits of the electrophysiological data were: PERG P50 latency, 59.3 to 63 msec; PERG P50 to N95 amplitude, 0.74 to 1.15 cmV; VEP P100 latency, 113 to 118 msec; VEP N75 to P100 amplitude, 3.81 to 4.90 micromV. The 360 degrees nerve fiber layer thickness overall (NFLO) ranged between 113 and 169 microm (145+/-16 microm; mean+/-SD) and significantly correlated with PERG P50 to N95 amplitude (r: 0.518; P = 0.002), PERG P50 latency (r: -0.470; P = 0.007), VEP N75 to P100 amplitude (r: 0.460; P = 0.008), VEP P100 latency (r = -0.422; P = 0.016) and SCS at 3 cyc/deg (r: -0.358; P = 0.044). CONCLUSIONS The variability of PERG, VEP, and SCS testing observed in eyes with ocular hypertension is associated with differences in NFL thickness (the thinner the layer, the worse the visual function).
Inhibitor Antibodies to Factor VIII and Factor IX: Management

Inhibitor antibodies directed against factor VIII or factor IX present challenges to the clinician. Fortunately, several management options are available, although each has disadvantages as well as advantages. Alloantibodies against factor VIII (which develop in 25 to 50% of children with severe hemophilia A, as well as in a small percentage of children with mild or moderate hemophilia A) may be low titer and transient or may be high titer. Most patients with high-titer problematic inhibitors now try to eliminate the inhibitor by using one of several immune tolerance induction (ITI) regimens. For treatment of bleeding episodes in patients who have high-titer (> or = 5 Bethesda units) inhibitors, one can use a prothrombin complex concentrate (PCC) (preferably an activated PCC [APCC]), recombinant (r) factor VIIa, or porcine factor VIII. The choice of product is generally dependent on the type and severity of the patient's bleeding, degree of cross-reactivity of the patient's inhibitor with porcine factor VIII, physician familiarity with the product, product availability, and cost. In persons with hemophilia B, alloantibodies occur in only 1 to 3% of severely affected individuals. However, in roughly half of those who develop inhibitors, anaphylaxis or severe allergic reactions occur on infusion of any type of factor IX-containing product. This phenomenon usually develops after relatively few exposures to factor IX; thus it is recommended that the first 10 to 20 infusions of factor IX given to children with severe hemophilia B be given in a setting equipped for treatment of shock. For treatment of bleeding episodes in patients with severe allergic reactions, rF VIIa is the treatment of choice. ITI has been less successful in hemophilia B patients with inhibitors than in those with hemophilia A, and in a subgroup of patients with severe allergic reactions who were desensitized to factor IX and then tried on ITI, results were even poorer. Additionally, several developed nephrotic syndrome while on ITI. For hemophilia B patients with inhibitors who do not have allergic reactions to factor IX, bleeding episodes can be treated with PCC or APCC or with rF VIIa. Autoantibodies directed against factor VIII are rare but can occur in a variety of settings. They occur mainly in adults, and bleeding is often severe and life threatening. Although some factor VIII autoantibodies disappear spontaneously, most require immunosuppression. Corticosteroids and cyclophosphamide are generally recommended. For treatment of bleeding, therapeutic options include (human) factor VIII concentrates, porcine factor VIII, APCC, and rFVIIa. The choice of product is generally determined by the consulting hematologist's familiarity with the product, product availability and cost, as well as response to treatment.
A simplified method for computation of scattered fields by the lamp-posts along a boulevard used for wireless communications in 2-GHz band

In this paper a simplified object specific ray tracing method is proposed to solve the important propagation problem of scattering by the lamp-posts. In fact, radiation from the transmitter antenna is modeled with a two ray incidence model and unknown currents on lamp-posts are computed using the Multi-Level Fast Multi-pole Method (MLFMM) which is an extension of the MoM (Method of Moments). In addition, scattering by lamp-posts is computed using the superposition of current elements electric fields based on the discrete complex image method (DCIM) in presence of a real ground with complex relative permittivity. The scattered near fields are considered instead of far fields. Based on this assumption, we use the generalized pencil-of-function (GPOF) method in DCIM. As another step in simplification, only single scattering is considered. Single scattering means that the scatterers are considered independently and their mutual effects are neglected. Another step is neglecting the scattered fields of the farther lamp-posts. To get closer to reality, lamp-post structure is considered with more details than the previous works. Although several simplifications are made and more details are added, it is shown that this method has adequate accuracy for propagation purposes. Significant gain in time and memory saving is achieved using above mentioned simplifications.
The Elements of Drawing

This paper describes the work of The Elements of Drawing, a project to digitize the teaching collection assembled by John Ruskin at the University of Oxford. It outlines John Ruskin's links with Oxford, his reasons for creating the collection as an aid to his teaching of drawing at the University, and the ways in which he organized and catalogued the collection. It then discusses the particular benefits which digitization brings to the collection, and outlines the methods being used to digitize the collection as a series of images, texts, catalogue data, and associated metadata, and how it is being made available over the world wide web.