Miracle-dz/UniFAR-FTUs huggingface dataset:
The initiation and pharmacologic reactivity of a ventricular pacemaker in the intact animal.

A new method is presented by which the function and reactivity of a ventricular pacemaker may be studied. This was accomplished by stimulating a vagus nerve so that the sino-atrial pacemaker was depressed to a critical level and in this circumstance superimposing sympathetic activity through injection of a sympathomimetic amine. In this way the automaticity of the ventricular pacemaker is raised and atrio-ventricular rhythms result. The smallest dose of a sympathomimetic amine to produce atrio-ventricular rhythms during vagal stimulation was considered threshold. Threshold comparisons of certain sympathomimetic amines in the cat and dog revealed isopropylarterenol to be approximately ten times more potent than either l-epinephrine or levarterenol. In the cat, phenylephrine and ephedrine were between fifty and one hundred times less active than isopropylarterenol. Methoxamine was found to be considerably weaker than any of the other amines tested. Although direct comparison of the sino-atrial and the ventricular pacemakers were not made certain observations suggest that the sino-atrial node is more sensitive to sympathomimetic stimulation. Isopropylarterenol was found significantly more effective on the sino-atrial pacemaker than either epinephrine or levarterenol, as was the case for the ventricular pacemaker. The greater effectiveness of isopropylarterenol on the sino-atrial and ventricular pacemaker and its negligible action on myocardial automaticity suggests that this drug may be of value in those instances where an increase in myocardial automaticity may be undesirable. The results of these investigations reveal that the influence of the vagus on automaticity of the sino-atrial node is great as opposed to a minor influence on ventricular pacemaker automaticity.
Pheromone response elements are necessary and sufficient for basal and pheromone-induced transcription of the FUS1 gene of Saccharomyces cerevisiae

The FUS1 gene of Saccharomyces cerevisiae is transcribed in a and alpha cells, not in a/alpha diploids, and its transcription increases dramatically when haploid cells are exposed to the appropriate mating pheromone. In addition, FUS1 transcription is absolutely dependent on STE4, STE5, STE7, STE11, and STE12, genes thought to encode components of the pheromone response pathway. We now have determined that the pheromone response element (PRE), which occurs in four copies within the FUS1 upstream region, functions as the FUS1 upstream activation sequence (UAS) and is responsible for all known aspects of FUS1 regulation. In particular, deletion of 55 bp that includes the PREs abolished all transcription, and a 139-bp fragment that includes the PREs conferred FUS1-like expression to a CYC1-lacZ reporter gene. Moreover, three or four copies of a synthetic PRE closely mimicked the activity conferred by the 139-bp fragment, and even a single copy of PRE conferred a trace of activity that was haploid specific and pheromone inducible. In the FUS1 promoter context, four copies of the synthetic PRE inserted at the site of the 55-bp deletion restored full FUS1 transcription. Sequences upstream and downstream from the PRE cluster were important for maximal PRE-directed expression but, by themselves, did not have UAS activity. Other yeast genes with PREs, e.g., STE2 and BAR1, are more modestly inducible and have additional UAS elements contributing to the overall activity. In the FUS1 promoter, the PREs apparently act alone to confer activity that is highly stimulated by pheromone.
Tuberculosis may be underestimated in Rwandan women.

BACKGROUND AND HYPOTHESIS The majority of adult tuberculosis (TB) cases reported to the surveillance system in Rwanda are male. If this results from detection mechanisms that are less sensitive to TB in women, notified cases should be more severe in women than in men. METHODS We analysed the 2006 series of TB cases among persons aged ≥ 15 years in Huye District and Kigali. Severe TB was defined as disease leading to death, or extra-pulmonary or disseminated TB. RESULTS Of 1673 cases identified, 40% involved women, who were younger than men (65% vs. 54% aged <35 years). Overall severity was similar in both sexes. Considering age <35 years, women were at higher risk of severe TB than men, although the difference was not statistically significant. Smear-negative pulmonary TB (SNPTB), and human immunodeficiency virus (HIV) infection were more frequent in women than in men (59% vs. 42%, P < 0.001). For women with smear-positive pulmonary TB (SPPTB), the risk of death was twice that among men (adjusted hazard ratio 1.8; 95%CI 1.0-3.2). CONCLUSIONS Among female TB patients, the higher risk of death with SPPTB, the higher frequency of SNPTB and the higher prevalence of HIV infection suggest that the passive system of case detection may underestimate the burden of TB in Rwandan women.
Einbettungsprobleme in der Differentialgaloistheorie

Die Differentialgaloistheorie ist analog zur gewoehnlichen Galoistheorie aufgebaut. Statt Polynomgleichungen ueber Koerpern studiert man lineare Differentialgleichungen ueber einem Differentialkoerper K mit Konstantenkoerper C. Wir nehmen an, dass C algebraisch abgeschlossen und von Charakteristik 0 ist. Die Begriffe "Galoiserweiterung" und "Galoisgruppe" und der Hauptsatz der Galoistheorie haben eine Entsprechung in der Differentialgaloistheorie. Auch Einbettungsprobleme koennen wie in der gewoehnlichen Galoistheorie definiert werden. Zuerst verallgemeinern wir den Begriff eines Frattini-Einbettungsproblems von endlichen auf lineare algebraische Gruppen. Dies erlaubt die Zerlegung eines Einbettungsproblems in ein zerfallendes und ein Frattini-Einbettungsproblem wie in der gewoehnlichen Galoistheorie. Als Hauptresultat fuer zusammenhaengende Einbettungsprobleme erhalten wir: --- Im Fall K=C(t) hat jedes zusammenhaengende Einbettungsproblem eine eigentliche Loesung. --- Wir koennen sogar mehr zeigen: Ist der Transzendenzgrad von K ueber C endlich, dann hat jedes zusammenhaengende, effektive Einbettungsproblem eine eigentliche Loesung. Hier ist die Effektivitaet eine technische Bedingung, die im Fall K=C(t) automatisch erfuellt ist. Diese Resultate koennen fuer einige nicht zusammenhaengende Einbettungsprobleme verallgemeinert werden. Hiermit kann das inverse Problem ueber Funktionenkoerper geloest werden: --- Ist K ein Funktionenkoerper in endlich vielen Variablen ueber C, dann kann jede lineare algebraische Gruppe als Differentialgaloisgruppe ueber K realisiert werden. ---
Uncoupling conformational change from GTP hydrolysis in a heterotrimeric G protein α-subunit

Heterotrimeric G protein α (Gα) subunits possess intrinsic GTPase activity that leads to functional deactivation with a rate constant of ≈2 min-1 at 30°C. GTP hydrolysis causes conformational changes in three regions of Gα, including Switch I and Switch II. Mutation of G202→A in Switch II of Gαi1 accelerates the rates of both GTP hydrolysis and conformational change, which is measured by the loss of fluorescence from Trp-211 in Switch II. Mutation of K180→P in Switch I increases the rate of conformational change but decreases the GTPase rate, which causes transient but substantial accumulation of a low-fluorescence Gαi1·GTP species. Isothermal titration calorimetric analysis of the binding of (G202A)Gαi1 and (K180P)Gαi1 to the GTPase-activating protein RGS4 indicates that the G202A mutation stabilizes the pretransition state-like conformation of Gαi1 that is mimicked by the complex of Gαi1 with GDP and magnesium fluoroaluminate, whereas the K180P mutation destabilizes this state. The crystal structures of (K180P)Gαi1 bound to a slowly hydrolyzable GTP analog, and the GDP·magnesium fluoroaluminate complex provide evidence that the Mg2+ binding site is destabilized and that Switch I is torsionally restrained by the K180P mutation. The data are consistent with a catalytic mechanism for Gα in which major conformational transitions in Switch I and Switch II are obligate events that precede the bond-breaking step in GTP hydrolysis. In (K180P)Gαi1, the two events are decoupled kinetically, whereas in the native protein they are concerted.
The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients

Solid organ transplantations have been performed successfully in selected HIV‐positive patients with highly active antiretrovirus therapy (HAART). However, some of the medications in the HAART regimen require metabolism via the cytochrome P4503A, the same enzyme complex responsible for clearance of the calcineurin inhibitors cyclosporine and tacrolimus. Several case reports have described significant interactions between the agents used in HAART and immunosuppressive drugs. The goal of this report is to examine the extent of potential drug interactions between antiretroviral agents and tacrolimus after liver and kidney transplantation. Seven liver transplant (LTx) patients (M = 6, F = 1) and four kidney transplant (KTx) patients (M = 4) infected with HIV underwent surgery between September 1997 and January 2001. Initial immunosuppression consisted of tacrolimus and steroids for LTx patients or tacrolimus, steroids, and mycophenolate mofetil for KTx recipients. Their current baseline immunosuppression and HAART regimen were examined retrospectively. Of the seven liver recipients, one (case 4) died 2 weeks after LTx and never received HAART therapy posttransplantation. The remaining six patients were placed on a regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI) (nelfinavir in 5, indinavir in 1) based on known viral sensitivities or history of a previous clinical response. Kidney recipients received NRTI and nonnucleoside reverse transcriptase inhibitors (NNRTI). The mean dose of tacrolimus in liver recipients was 0.6 mg/d, with mean trough concentration of 9.7 mg/mL. Compared with historic controls (liver transplant patients not on HAART), the average tacrolimus dose was 16‐fold lower in patients on HAART. In contrast to liver recipients, HIV‐positive kidney recipients not on PI therapy required a mean tacrolimus dose of 9.5 mg/d to maintain a mean trough concentration of 9.6 ng/mL. Of the two protease inhibitors used, nelfinavir seems to have a more profound effect than indinavir. When patients on nelfinavir alone (n = 5) were compared with a control group not on antiretroviral therapy, the need for a tacrolimus dose was 38 times lower (mean dose, 0.26 mg/d). Profound drug interactions between PI and tacrolimus have been observed requiring up to 50‐fold reductions in dosage. This effect seems to be most pronounced with the use of nelfinavir as opposed to indinavir, although further experience is required to confirm this observation. In contrast, HAART using NRTI and NNRTI without the use of PI, as shown in kidney recipients, produces less significant effects on tacrolimus metabolism. Great caution and frequent drug level monitoring are necessary when HAART is introduced or withdrawn in HIV‐positive recipients of organ transplants.
The myth of the eternal return : cosmos and history

This founding work of the history of religions, first published in English in 1954, secured the North American reputation of the Romanian emigre-scholar Mircea Eliade (1907-1986). Making reference to an astonishing number of cultures and drawing on scholarship published in no less than half a dozen European languages, Eliade's The Myth of the Eternal Return makes both intelligible and compelling the religious expressions and activities of a wide variety of archaic and "primitive" religious cultures. While acknowledging that a return to the "archaic" is no longer possible, Eliade passionately insists on the value of understanding this view in order to enrich our contemporary imagination of what it is to be human. Jonathan Z. Smith's new introduction provides the contextual background to the book and presents a critical outline of Eliade's argument in a way that encourages readers to engage in an informed conversation with this classic text.
The study of Cutaneous Lupus Erythematosus Disease Area and Severity Index in Indian patients with systemic lupus erythematosus

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a newly described tool used to assess the activity of and damage caused by cutaneous lupus erythematosus (CLE). There is a paucity of data on CLASI from the Indian subcontinent. We sought to determine the applicability of CLASI in specific lesions of CLE in patients with systemic lupus erythematosus (SLE) attending a tertiary care hospital in India. In this prospective, cross-sectional study, 93 patients of SLE with cutaneous lesions were recruited. CLASI activity and damage scores of lupus erythematosus (LE)-specific skin lesions were done in 75 patients with SLE. The mean CLASI activity score was 15.4 ± 9.4 (range 0–39) and the mean damage score was 6.87 ± 7.75 (range 0–30). Higher mean CLASI activity scores were seen in patients with a combination of acute, subacute and chronic CLE and in those with widespread lesions. Patients with longstanding disease and long duration of skin lesions had higher damage scores. This study shows that CLASI is an effective tool to assess cutaneous activity of LE-specific lesions, and the damage caused by them, in Indian patients.
Glutamine inhibits the lowering effect of glucose on the level of phosphoenolpyruvate carboxykinase mRNA in isolated rat hepatocytes.

The expression of phosphoenolpyruvate carboxykinase (P-pyruvate CK) was shown to be decreased by hypoosmolarity and increased by glutamine in perfused liver from fed rats [Newsome, W. P., Warskulat, U. , Noe, B. , Wettstein, M. , Stoll, B. , Gerok, W. & Häussinger, D. (1994) Biochem, J. 304, 555-560]. This work was undertaken to specify the mechanisms of glutamine action, using isolated hepatocytes from rats that had been starved for 24 h. At low concentrations (up to 5 mM), glutamine elicited a decrease in the level of P-pyruvate CK mRNA through cell swelling and, at higher concentrations, an increase in the mRNA level was observed. Experiments with combinations of glucose and glutamine or glucose and various amino acids demonstrated that glutamine counteracted the inhibitory effect of glucose on P-pyruvate CK mRNA at a transcriptional, level, and strongly suggested that the amide group of glutamine was involved in this effect. The metabolism of glucose was required for the reinforcement of the apparent stimulatory effect of glutamine, as demonstrated by the use of various sugars. Glucosamine, but not mannosamine, increased the level of P-pyruvate CK mRNA, as did glucose plus glutamine. These results suggest that the pathway leading from glucosamine-6-phosphate production might be responsible, at least partly, for the effect observed on P-pyruvate CK mRNA.
Effect of smoking cessation on the microbial flora.

OBJECTIVE To determine the effect of smoking cessation on the frequency of recovery of potential pathogens and aerobic and anaerobic interfering bacteria in the nasopharynges of smokers. DESIGN Nasopharyngeal cultures were taken from 20 smokers before and 12 to 15 months after cessation of smoking. Potential pathogens and aerobic and anaerobic bacteria with interfering capabilities against these organisms were identified. RESULTS Eleven potential pathogens (0.92 pathogens per subject) were isolated from nasopharyngeal cultures obtained from 9 individuals before smoking cessation, and 2 (0.17 per subject) were recovered from 2 individuals after smoking cessation (P < .05). Bacterial interference between 2 aerobic (alpha and nonhemolytic streptococci) and 2 anaerobic species (Prevotella and Peptostreptococcus species) and 4 potential pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes) was observed. Bacterial interference was noted in 35 instances against the 4 potential pathogens by 14 normal flora isolates that were recovered from the smokers before cessation and in 116 instances by 42 isolates after cessation (P < .01). CONCLUSION To our knowledge, these findings illustrate for the first time that the high number of pathogens and low number of interfering organisms found in the nasopharynx of smokers revert to normal levels after complete cessation of smoking.
SU-8 as a Torsional Spring: Viscoelastic Creeping and Closed Loop Control

The torsional viscoelastic creeping and recovery of an SU-8 spring is reported by studying the deflection angle variation of a vertical comb-drive actuator suspended by an SU-8 spring at three different stress levels. A maximum creep of 0.43° (corresponding to a relative change of strain of 5.7%) is observed under a constant stress of 8.3 MPa in 1 h (V = 22.7 V). A capacitive readout circuit is designed to sense the torsional deflection of the comb-drive actuator. The circuit is capable of actuating and sensing the capacitance change by the same combdrives with a resolution of 0.03° (corresponding to a capacitance resolution of 0.05 pF). The readout capacitance is then used as the input variable for a proportional-integral (PI) controller in order to eliminate the time and load dependent drift by creeping of the SU-8 spring. The PI controller is tuned by the Ziegler-Nichols method and has a settling time of ~2.3 s for the output. Compared with the open loop deflection of 0.43°, the closed-loop deflection is reduced by a factor of 7 down to 0.06°. This controller error is prominent at high actuation voltages, and is attributed to the actuator's lateral and vertical cross-sensitivity.
Analysis of bacterial carbapenem antibiotic production genes reveals a novel β‐lactam biosynthesis pathway

Carbapenems are β‐lactam antibiotics which have an increasing utility in chemotherapy, particularly for nosocomial, multidrug‐resistant infections. Strain GS101 of the bacterial phytopathogen, Erwinia carotovora, makes the simple β‐lactam antibiotic, 1‐carbapen‐2‐em‐3‐carboxylic acid. We have mapped and sequenced the Erwinia genes encoding carbapenem production and have cloned these genes into Escherichia coli where we have reconstituted, for the first time, functional expression of the β‐lactam in a heterologous host. The carbapenem synthesis gene products are unrelated to enzymes involved in the synthesis of the so‐called sulphur‐containing β‐lactams, namely penicillins, cephamycins and cephalosporins. However, two of the carbapenem biosynthesis genes, carA and carC, encode proteins which show significant homology with proteins encoded by the Streptomycesclavuligerus gene cluster responsible for the production of the β‐lactamase inhibitor, clavulanic acid. These homologies, and some similarities in genetic organization between the clusters, suggest an evolutionary relatedness between some of the genes encoding production of the antibiotic and the β‐lactamase inhibitor. Our observations are consistent with the evolution of a second major biosynthetic route to the production of β‐lactam‐ring‐containing antibiotics.
Transplantation of Purified Islet Cells in Diabetic Rats: II. Immunogenicity of Allografted Islet β-Cells

This study examines whether the survival of allografted rat islet β-cells is influenced by the presence of other pancreatic donor cells. Grafts (RT1u/l) of different cellular composition were intraportally transplanted in streptozocin-induced diabetic rats (RT1n/n). All grafts corrected the diabetic state within 3 days. Implants of freshly isolated islets contained various endocrine and nonendocrine cell types; they became diffusely infiltrated within 1 wk and were completely destroyed within 2 wk. A 4-day culture period did not lead to major changes in the cellular composition of the islets or in their survival as allograft. Islet cell aggregates prepared after islet dissociation and cell purification were less acutely infiltrated and less rapidly rejected. Aggregates composed of sorted MHC class II–negative cells maintained basal normoglycemia in 3 of 5 recipients for 5 wk but only in 1 of 5 for 20 wk. Aggregates of purified islet β-cells remained relatively free of diffuse infiltrations during the 1st wk and preserved the normalized state in 7 of 13 recipients for 5 wk; after 20 wk, 6 of 13 were still aglucosuric, but 40% of the implants were diffusely infiltrated and depleted of insulin. Reaggregation of purified islet β-cells with purified islet endocrine non–²-cells promoted their long-term survival as allograft: 11 of 13 recipients of mixed islet endocrine cells maintained normal basal glycemia over 20 wk; their implants contained relatively constant insulin reserves and remained virtually devoid of diffuse infiltrations. These results demonstrate that techniques aiming at the elimination of surface MHC class II–positive cells are less successful in preparing rat islet allografts of low immunogenicity than methods of positive cell selection. Pure islet β-cells are immunogenic as an allograft but illicit a milder and less-acute immune attack than undissociated islet tissue. Nonendocrine and damaged islet cells are suspected of enhancing the rapidity and intensity of the cytotoxic reaction. Survival of allografted β-cells is markedly prolonged by the presence of islet endocrine non–²-cells within the graft. The mechanisms underlying this effect have not yet been elucidated; they may involve immune and metabolic interactions of the endocrine non–²-cells. We conclude that purification of islet endocrine cells represents a new and powerful method for preparing insulin-producing allografts that can survive in hosts without pharmacological immunosuppression.
Vloga učitelja pri razvijanju tujejezikovne sporazumevalne zmožnosti za poslovne sestanke v angleškem jeziku: primer simulacije poslovnih sestankov

Namen raziskave je bil prispevati k izboljsanju ucinkovitosti poucevanja poslovnega angleskega jezika na visokosolski stopnji izobraževanja z ucinkovitim razvijanjem tujejezikovne sporazumevalne zmožnosti s simulacijami poslovnega sestanka v angleskem jeziku za nadaljnje avtonomno in vseživljenjsko ucenje tujih jezikov in lažje vkljucevanje v mednarodno poslovno okolje. Korpusna analiza simulacij poslovnih sestankov studentov Ekonomske fakultete Univerze v Ljubljani je pokazala, kako se razvijajo nabor, struktura in nadzor nad jezikovnimi, sociolingvisticnimi in pragmaticnimi prvinami tujejezikovne sporazumevalne zmožnosti ob prisotnosti in odsotnosti ucitelja in ugotovila, da je vloga ucitelja kljucna predvsem pri razvijanju sociolingvisticnih in pragmaticnih prvin. Primerjava korpusa simulacij poslovnih sestankov studentov in korpusa poslovnih sestankov poslovnežev je poleg podobnosti in razlik v pojavnicah, razlicnicah, sopojavnicah, pozitivnih in negativnih kljucnih besedah pokazala, da se korpusa razlikujeta predvsem po sociolingvisticnih in pragmaticnih prvinah, kar skupaj s kvalitativno analizo pricevanj uciteljev in studentov omogoca vpogled v specifiko in vlogo ucitelja pri razvijanja in ozavescanju celostnega razvoja tujejezikovne sporazumevalne zmožnosti, da bodo ta spoznanja lahko postala del sirse izobraževalne in poslovne skupnosti in posledicno omogocila boljso ucinkovitost.