Miracle-dz/UniFAR-FTUs huggingface dataset:
Continued Production of Drug-Sensitive Human Immunodeficiency Virus Type 1 in Children on Combination Antiretroviral Therapy Who Have Undetectable Viral Loads

ABSTRACT Highly active antiretroviral therapy (HAART) can suppress plasma human immunodeficiency virus type 1 (HIV-1) levels to below the detection limit of ultrasensitive clinical assays. However, HIV-1 persists in cellular reservoirs, and in adults, persistent low-level viremia is detected with more sensitive assays. The nature of this viremia is poorly understood, and it is unclear whether viremia persists in children on HAART, particularly those who start therapy shortly after birth. We therefore developed a reverse transcriptase PCR (RT-PCR) assay that allows genotyping of HIV-1 protease even when viremia is present at levels as low as 5 copies of HIV-1 RNA/ml. We demonstrated that viremia persists in children with plasma virus levels below the limit of detection of clinical assays. Viremia was detected even in children who began HAART in early infancy and maintained such strong suppression of viremia that HIV-1-specific antibody responses were absent or minimal. The low-level plasma virus lacked protease inhibitor resistance mutations despite the frequent use of nelfinavir, which has a low mutational barrier to resistance. Protease sequences resembled those of viruses in the latent reservoir in resting CD4+ T cells. Thus, in most children on HAART with clinically undetectable viremia, there is continued virus production without evolution of resistance in the protease gene.
Comparative CNS Toxicity of Lidocaine, Etidocaine, Bupivacaine, and Tetracaine in Awake Dogs Following Rapid Intravenous Administration

The comparative central nervous system (CNS) toxicity of serially administered intravenous doses of lidocaine, bupivacaine, etidocaine, and tetracaine was investigated in awake dogs. The mean cumulative dose required for convulsive activity was 4.0 mg/kg tetracaine, 5.0 mg/kg bupivacaine, 8.0 mg/kg etidocaine, and 22.0 mg/kg lidocaine. The cumulative convulsive dose of lidocaine was significantly greater than that of the other three agents (P < 0.01). A comparison of the in vivo anesthetic potency and the acute CNS toxicity of these various agents suggests little difference in the therapeutic ratio between less potent anesthetics such as lidocaine and more potent drugs, i.e., tetracaine, bupivacaine, and etidocaine. The relative CNS toxicity of the different agents as determined in awake dogs in this study was compared with their relative cardiovascular toxicity previously evaluated in a series of ventilated dogs anesthetized with pentobarbital. The dose of lidocaine, etidocaine, tetracaine, and bupivacaine required to produce irreversible cardiovascular depression was 3.5–6.7 times greater than that which produced convulsions. These results suggest that the CNS is the primary target organ for the toxic effects of both highly lipid-soluble and highly protein-bound local anesthetics (i.e., bupivacaine, etidocaine, and tetracaine) and less lipid-soluble and less protein-bound drugs (i.e., lidocaine) following rapid intravenous administration.
Oxidation of Dihydrotestosterone by Human Cytochromes P450 19A1 and 3A4*

Background: The fate of dihydrotestosterone has been characterized only in terms of reduction of the 3-ketone. Results: Human P450s 19A1 and 3A4 oxidized dihydrotestosterone to several new products, detected in vivo. Conclusion: The new P450 19A1 and 3A4 pathways introduce an oxidative dimension to the metabolism of dihydrotestosterone. Significance: Small changes in the steroid A ring can produce major changes in P450 3A4 catalytic selectivity. Dihydrotestosterone is a more potent androgen than testosterone and plays an important role in endocrine function. We demonstrated that, like testosterone, dihydrotestosterone can be oxidized by human cytochrome P450 (P450) 19A1, the steroid aromatase. The products identified include the 19-hydroxy- and 19-oxo derivatives and the resulting Δ1,10-, Δ5,10-, and Δ9,10-dehydro 19-norsteroid products (loss of 19-methyl group). The overall catalytic efficiency of oxidation was ∼10-fold higher than reported for 3α-reduction by 3α-hydroxysteroid dehydrogenase, the major enzyme known to deactivate dihydrotestosterone. These and other studies demonstrate the flexibility of P450 19A1 in removing the 1- and 2-hydrogens from 19-norsteroids, the 2-hydrogen from estrone, and (in this case) the 1-, 5β-, and 9β-hydrogens of dihydrotestosterone. Incubation of dihydrotestosterone with human liver microsomes and NADPH yielded the 18- and 19-hydroxy products plus the Δ1,10-dehydro 19-nor product identified in the P450 19A1 reaction. The 18- and 19-hydroxylation reactions were attributed to P450 3A4, and 18- and 19-hydroxydihydrotestosterone were identified in human plasma and urine samples. The change in the pucker of the A ring caused by reduction of the Δ4,5 bond is remarkable in shifting the course of hydroxylation from the 6β-, 2β-, 1β-, and 15β-methylene carbons (testosterone) to the axial methyl groups (18, 19) in dihydrotestosterone and demonstrates the sensitivity of P450 3A4, even with its large active site, to small changes in substrate structure.
Order Imbalance and the Pricing of Index Futures

This study examines whether the direction and magnitude of the aggregate order-imbalance of the index stocks can explain the arbitrage spread between index futures and the underlying cash index. The data are for the Asian financial crisis period and hence entail wide variations in order imbalance and the index-futures basis. The analysis controls for realistic trading costs and actual dividend payments. The results indicate that the arbitrage spread is positively related to the aggregate order imbalance in the underlying index stocks; negative order-imbalance has a stronger impact than positive order imbalance. Violations of the upper no-arbitrage bound are related to positive order imbalance and violations of the lower no-arbitrage bound are related to negative order imbalance. Asymmetric response times to negative and positive spreads can be attributed to the difficulty, cost, and risk of short stock arbitrage when the futures is below its no-arbitrage value. The significant relationship between order imbalance and arbitrage spread confirm that index arbitrageurs are important providers of liquidity in the futures market when the stock market is in disequilibrium.
STUDIES ON MEDIATOR PRODUCTION BY HIGHLY PURIFIED HUMAN T AND B LYMPHOCYTES

Highly purified populations of T and B lymphocytes obtained by affinity column separation were stimulated by antigen and their ability to produce two mediators, migration inhibitory factor (MIF) and lymphocyte mitogenic factor (LMF) was assessed. Both T- and B-cell populations made MIF; the production of MIF was antigen-specific using purified protein derivative of tuberculin, streptokinase-streptodornase, and Candida antigens. The MIF activity from both populations could not be attributed to antigen-antibody complexes as the inhibitory activity eluted from Sephadex G-100 columns in the same region corresponding to mol wt 23,000 daltons. Further studies indicate that the T cells producing MIF are proliferating cells whereas the B cells producing this mediator are not. In contrast, LMF was made only by T cells and not B cells when these populations were stimulated by antigen. The LMF induced the [3H]thymidine incorporation into both T and B cells obtained from donors lacking sensitivity to the antigens used to elicit the factor. Chromatographic studies indicate that LMF eluted from Sephadex G-100 in a fraction of mol wt 23,000 daltons where MIF is also found; however, since B cells produce MIF but not LMF, these two factors appear to be distinct from one another. Some of the implications of these findings are discussed. The explanation for the production or lack of production of MIF by lymphocytes obtained from patients with immunodeficiency disorders requires reinterpretation.
Development, Analysis, And Application Of A Well By Well Method For Estimating Surface Heat Flow For Regional Geothermal Resource Assessment

To accurately map local temperature variations, resource assessments have relied largely on bottom hole temperature (BHT) measurements, primarily from oil and gas wells because of the high density of well sites in explored areas. As the volume of BHT data grows due to increased drilling activity, the ability to quickly analyze and incorporate additional data is critical. Currently, in the Appalachian basin of West Virginia and Pennsylvania, more than 1,000 wells are being drilled every year. Incorporating this number of BHT points using current techniques may take weeks to months. This paper presents an approach to quickly and efficiently incorporate additional well data into existing geothermal resource maps.
Human immunodeficiency virus type 1 T-cell tropism is determined by events prior to provirus formation

Different strains of human immunodeficiency virus type 1 (HIV-1) vary in the ability to replicate in cells that bear the HIV-1 receptor, CD4. The mechanism responsible for these cell tropism differences is unknown. We examined different isolates of HIV-1 with regard to replication in specific tumor-derived CD4-positive T-cell lines and normal peripheral blood lymphocytes. To investigate early events in the virus life cycle at low multiplicities of infection, we used a modification of the polymerase chain reaction method. Use of a molecularly cloned primary HIV-1 isolate, HIV-1 JR-CSF, restricted for replication in T-cell lines, demonstrated that little or no viral DNA or RNA was synthesized in nonpermissive cells after infection. However, transfection of proviral DNA resulted in efficient transient virus production from these cells. Therefore, we conclude that at least one block to infection for HIV-1 strains in nonpermissive T cells occurs at a point in entry or uncoating before provirus formation.
Salinity Interactions with Other Abiotic and Biotic Stresses in Citrus

Multiple stresses almost always have synergistic effects on plants. In citrus, there are direct and indirect interactions between salinity and other physical abiotic stresses like poor soil drainage, drought, irradiance, leaf temperature, and atmospheric evaporative demand. In addition, salinity interacts with biotic pests and diseases including root rot (Phytophthora spp.), nematodes, and mycorrhizae. Improving tree water relations through optimum irrigation/drainage management, maintaining nutrient balances, and decreasing evaporative demand can alleviate salt injury and decrease toxic ion accumulation. Irrigation with high salinity water not only can have direct effects on root pathogens, but salinity can also predispose citrus rootstocks to attack by root rot and nematodes. Rootstocks known to be tolerant to root rot and nematode pests can become more susceptible when irrigated with high salinity water. In addition, nematodes and mycorrhizae can affect the salt tolerance of citrus roots and may increase chloride (Cl–) uptake. Not all effects of salinity are negative, however, as moderate salinity stress can reduce physiological activity and growth, allowing citrus seedlings to survive cold stress, and can even enhance fl owering after the salinity stress is relieved.
FORMULATION DEVELOPMENT OF ENTERAL NUTRITION PRODUC TS

Th is review ma inly deals with the Formulation Development of Enteral Nutrition P roducts. Nutrition plays an important role in the prevention and management of many diseases. Chronic illness is associated with many compli cations such as anorexia, hyper metabol ism, malabsorption, atrophy of muscles, liver, kidney, gastrointestinal tract heart, and impaired cell mediated immunity, suscepti bility to infection, poor wound healing, anaemia, death. Hence it is important to correct caloric and nutrient deficiencies wh enever possible. The term enteral means “within or by th e way of gastrointestinal tract”. The nutrition product given by enteral route called as enteral nutrition product. The different types of enteral nutrition are classified as Short term and long term enteral nutrition. Enteral tubes are made of PVC, Polyurethane etc. The selection of the enteral formula is patient specific thus its nutritional requirements, the ingredients used in it a re taken into consideration. The classification of formulas is also done on the basis of the patient’s needs and ingredients used in it. The enteral feeds can be given in the form of solutions and powders which require reconstitution. The quality control test like Osmolality, pH, etc is also taken into consideration. Thus, the purpose here is to point out explicitly the formulation development of enteral nutrition products.
Adrenergic mechanisms in hypertension.

hydrochloride (15 mg/kg i.v.). The pressor responses to propranolol and tyramine hydrochloride (100 jg) were not seen when the animals had been pretreated with reserpine, 10 mg/kg I.P., 48 hr and 24 hr before the experiment. A slow intravenous infusion of noradrenaline (10-15 [Lg in 20-30 min) in the presence of bretylium tosylate (1 mg/kg i.v.) as suggested by Clark & Leach (1968), restored the response to tyramine but not to propranolol. The response due to propranolol was also lost by pithing the rat by the method of Shipley & Tilden (1947).
Tumours of the thymus: a cohort study of prognostic factors from the European Society of Thoracic Surgeons database

OBJECTIVES : A retrospective database was developed by the European Society of Thoracic Surgeons, collecting patients submitted to surgery for thymic tumours to analyse clinico-pathological prognostic predictors. METHODS : A total of 2151 incident cases from 35 institutions were collected from 1990 to 2010. Clinical-pathological characteristics were analysed, including age, gender, associated myasthenia gravis stage (Masaoka), World Health Organization histology, type of thymic tumour [thymoma, thymic carcinoma (TC), neuroendocrine thymic tumour (NETT)], type of resection (complete/incomplete), tumour size, adjuvant therapy and recurrence. Primary outcome was overall survival (OS); secondary outcomes were the proportion of incomplete resections, disease-free survival and the cumulative incidence of recurrence (CIR). RESULTS : A total of 2030 patients were analysed for OS (1798 thymomas, 191 TCs and 41 NETTs). Ten-year OS was 0.73 (95% con ﬁ dence interval 0.69 – 0.75). Complete resection (R0) was achieved in 88% of the patients. Ten-year CIR was 0.12 (0.10 – 0.15). Predictors of shorter OS were increased age ( P < 0 – 001), stage [III vs I HR 2.66, 1.80 – 3.92; IV vs I hazard ratio (HR) 4.41, 2.67 – 7.26], TC (HR 2.39, 1.68 – 3.40) and NETT (HR 2.59, 1.35 – 4.99) vs thymomas and incomplete resection (HR 1.74, 1.18 – 2.57). Risk of recurrence increased with tumour size ( P = 0.003), stage (III vs I HR 5.67, 2.80 – 11.45; IV vs I HR 13.08, 5.70 – 30.03) and NETT (HR 7.18, 3.48 – 14.82). Analysis using a propensity score indicates that the administration of adjuvant therapy was bene ﬁ cial in increasing OS (HR 0.69, 0.49 – 0.97) in R0 resections. CONCLUSIONS : Masaoka stages III – IV, incomplete resection and non-thymoma histology showed a signi ﬁ cant impact in increasing recurrence and in worsening survival. The administration of adjuvant therapy after complete resection is associated with improved survival.
Identification of an Escherichia coli genetic locus involved in thermoregulation of the pap operon

We previously showed, using a single-copy papBAp-lac fusion (previously designated papBA-lac), that pyelonephritis-associated pili (pap) pilin gene transcription is subject to both phase variation and thermoregulatory control mechanisms (L. B. Blyn, B. A. Braaten, C. A. White-Ziegler, D. H. Rolfson, and D. A. Low, EMBO J. 8:613-620, 1989). At 37 degrees C, Escherichia coli strains carrying the papBAp-lac fusion displayed both Lac+ and Lac- colony phenotypes. In contrast, at 23 degrees C, colonies displayed a uniform Lac- phenotype, suggesting that pilin was not transcribed at this temperature. In this study, a strain carrying the papBAp-lac fusion was subjected to mini-Tn10 (mTn10) mutagenesis to isolate mutants that could initiate transcription of pilin at the nonpermissive temperature. Two classes of thermoregulatory mutants were identified in which the mTn10 mutation was linked to the mutant phenotype. Class I mutants displayed a phase variation phenotype at both 37 degrees C and 23 degrees C, whereas class II mutants displayed a uniform Lac+ colony phenotype at both temperatures. Preliminary analysis of these mutants showed that the mTn10 insertions in the class I mutants were chromosomally located, whereas the mTn10 insertions in the class II mutants were located within the papBAp-lac fusion phage. Southern blot analysis of the class I mutants demonstrated that mTn10 was present in the same 5.9-kilobase SalI DNA fragment in each mutant. Two of the class I mTn10 mutations were mapped to approximately 23.4 min on the E. coli K-12 chromosome. The locus defined by the class I mTn10 mutations was designated tcp, for thermoregulatory control of pap. Analysis of phase transition rates of the class I mutants showed that the phase-off (Lac-)----phase-on (Lac+) transition rates were higher than those observed with the nonmutant E. coli strain.
Use of guidelines when planning home care of a girl with severe congenital myopathy

We use issues that arose in the management of a 4‐year old girl with a congenital myopathy to consider the tension between respecting the choices and decisions of the child's parents and applying clinical practice guidelines that emphasise minimising risk to the child. This case raises the issue of when it is reasonable to override parents’ choice of management options.
Identification of Interactions in the E1E2 Heterodimer of Hepatitis C Virus Important for Cell Entry*

Several conserved domains critical for E1E2 assembly and hepatitis C virus entry have been identified in E1 and E2 envelope glycoproteins. However, the role of less conserved domains involved in cross-talk between either glycoprotein must be defined to fully understand how E1E2 undergoes conformational changes during cell entry. To characterize such domains and to identify their functional partners, we analyzed a set of intergenotypic E1E2 heterodimers derived from E1 and E2 of different genotypes. The infectivity of virions indicated that Con1 E1 did not form functional heterodimers when associated with E2 from H77. Biochemical analyses demonstrated that the reduced infectivity was not related to alteration of conformation and incorporation of Con1 E1/H77 E2 heterodimers but rather to cell entry defects. Thus, we generated chimeric E1E2 glycoproteins by exchanging different domains of each protein in order to restore functional heterodimers. We found that both the ectodomain and transmembrane domain of E1 influenced infectivity. Site-directed mutagenesis highlighted the role of amino acids 359, 373, and 375 in transmembrane domain in entry. In addition, we identified one domain involved in entry within the N-terminal part of E1, and we isolated a motif at position 219 that is critical for H77 function. Interestingly, using additional chimeric E1E2 complexes harboring substitutions in this motif, we found that the transmembrane domain of E1 acts as a partner of this motif. Therefore, we characterized domains of E1 and E2 that have co-evolved inside a given genotype to optimize their interactions and allow efficient entry.
Effect of Cisplatinum on the Liver of the Adult Albino Rat and the Possible Protective Role of Vitamin E (Histological and Ultrastructural Study)

Background: Cisplatinum is one of the older chemotherapy drugs which is been used for decades. In spite of its significant anticancer activity, its clinical use is often limited by its undesirable side effects. The liver is known to accumulate significant amounts of cisplatinum thus hepatotoxicity could be associated with cisplatinum treatment. Aim: The aim of the present study is to detect the histopathological effect of cisplatinum on the liver of the adult albino rat and the possible protective role of vitamin E in prevention of cisplatinum-induced hepatotoxicity. Material and methods: Thirty adult male albino rats were used in the current study. The rats were divided into3 groups; control, cisplatinum and cisplatinum +vitamin E groups. Histological, transmission electro-microscopic as well as morphometric studies were used in the study. Results: Histological examination of the liver of the cisplatinum treated rats exhibited the presence of congestion of the central veins and hepatic sinusoids. Massive intracytoplasmic vacuolations, margination of chromatin with the occurrence of karryorehxis, pyknosis in the nuclei were also constant features. Kupffer cells were observed with the presence of hemosiderin granules . The ultrathin sections exhibited degeneration of the nuclei with margination of the nucleoli and irregularities of the nuclear membranes. Slight improvement of the histological findings was observed in the liver of the cisplatinum and vitamin E treated rats. Degeneration of the hepatocytes, margination of the nucleoli, karryorehxis, apoptotic nuclei and apoptotic bodies were observed in this group. Conclusion: Thus, it is recommended to investigate the liver capacity before the use of cisplatinum and throughout the course of treatment. Once, the liver changes start to develop, shifting to another more safe antitumor drug must be considered. As regard using vitamin E to reduce the toxic effect of the cisplatinum on the liver, it was found that vitamin E had a minimum protective role.
Very-low-voltage testing for weak CMOS logic ICs

In this paper we propose a very-low-voltage (VLV) testing technique for CMOS logic ICs. Voltage dependence of CMOS logic circuit operation in the presence of resistive shorts and hot carrier damage is studied. It is shown that at certain much-lower-than-normal power supply voltage, weak CMOS logic ICs due to the presence of these flaws can be forced to malfunction while truly good ICs continue to function. Very-low-voltage testing also detects pattern dependent faults caused by resistive shorts. Because of its simplicity and because there is no overhead associated with it, very-low-voltage testing can easily be applied to chips and circuit boards as a production test, field test, or failure diagnosis technique. <<ETX>>
Post‐prandial chylomicron response may be predicted by a single measurement of plasma apolipoprotein B48 in the fasting state

The clearance of chylomicron remnants was assessed in normolipaemic, dyslipidaemic and obese male subjects by monitoring the plasma kinetics of apolipoprotein (apo) B48, retinyl palmitate and triglyceride after a lipid meal. Regression analysis of fasting plasma apo B48 with the area under the post‐prandial curves of apo B48, retinyl ester and triglyceride was carried out in order to determine whether the post‐prandial response could be predicted by the fasting concentration of this exclusive chylomicron marker.