gebhart/patrepeval huggingface dataset:
Inhaled antimicrobial therapy: from cystic fibrosis to the flu. (2000)

Recent controlled clinical trials have confirmed the usefulness of aerosolized tobramycin in cystic fibrosis and have emphasized the importance of ensuring adequate lung delivery of inhaled antimicrobials. For purulent tracheobronchitis associated with prolonged mechanical ventilation it has recently been established that it is possible to deliver substantial and measurable doses of medications to the airway via aerosolization, but controlled studies are needed to determine the efficacy and safety of inhaled antibiotic therapy in this setting. However, prophylactic aerosolized antibiotic therapy in an intensive care unit setting may be counterproductive. Aerosolized pentamidine continues to provide prophylaxis against PCP in a substantial minority of subjects with human immunodeficiency virus infection who are intolerant of oral agents. The effectiveness of aerosolized amphotericin B as prophylaxis against aspergillosis in neutropenic patients needs to be evaluated in a large clinical trial. Zanamivir, an inhibitor of neuraminidase, delivered via inhalation, shows promise in the treatment of uncomplicated influenza infection, but more data are needed on its effectiveness and safety in patients with preexisting respiratory disease. The development of new chemical entities, more efficient delivery systems, and more precise measurement of dose-response and regional pulmonary drug distribution of inhaled antimicrobials suggest that this somewhat neglected topic in therapeutics may be about to receive an increased degree of attention.
The Two-Component Regulators GacS and GacA Influence Accumulation of the Stationary-Phase Sigma Factor ς S and the Stress Response in Pseudomonas fluorescens Pf-5 (1998)

Three global regulators are known to control antibiotic production by Pseudomonas fluorescens. A two-component regulatory system comprised of the sensor kinase GacS (previously called ApdA or LemA) and GacA, a member of the FixJ family of response regulators, is required for antibiotic production. A mutation in rpoS, which encodes the stationary-phase sigma factor sigmaS, differentially affects antibiotic production and reduces the capacity of stationary-phase cells of P. fluorescens to survive exposure to oxidative stress. The gacA gene of P. fluorescens Pf-5 was isolated, and the influence of gacS and gacA on rpoS transcription, sigmaS levels, and oxidative stress response of Pf-5 was determined. We selected a gacA mutant of Pf-5 that contained a single nucleotide substitution within a predicted alpha-helical region, which is highly conserved among the FixJ family of response regulators. At the entrance to stationary phase, sigmaS content in gacS and gacA mutants of Pf-5 was less than 20% of the wild-type level. Transcription of rpoS, assessed with an rpoS-lacZ transcriptional fusion, was positively influenced by GacS and GacA, an effect that was most evident at the transition between exponential growth and stationary phase. Mutations in gacS and gacA compromised the capacity of stationary-phase cells of Pf-5 to survive exposure to oxidative stress. The results of this study provide evidence for the predominant roles of GacS and GacA in the regulatory cascade controlling stress response and antifungal metabolite production in P. fluorescens.
Inhibitory role of the host apoptogenic gene PKR in the establishment of persistent infection by encephalomyocarditis virus in U937 cells (1999)

Persistent infections by viruses such as HIV-1 and hepatitis B virus can pose long-term health hazards. Because establishment of persistent infections involves close interactions and adjustments in both host and virus, it would be informative to establish a paradigm with which a normally cytolytic viral infection can be easily converted to persistent infection, so that the different stages in developing persistent infection can be examined. Such a model system is described in this paper. Highly cytolytic encephalomyocarditis virus (EMCV) infection was shifted to persistent infection as a result of repressed expression of the double-stranded RNA-dependent protein kinase (PKR) in the promonocytic U937 cells. Because of the apoptogenic potential of PKR, a deficiency of PKR resulted in a delay in virus-induced apoptosis in EMCV-infected U937 cells, allowing the eventual establishment of persistent EMCV infection in these cells (U9K-AV2). That this was a bona fide persistent infection was demonstrated by the ability of infected cells to propagate as long-term virus-shedding cultures; electron microscopy studies showing presence of intracellular EMCV virions and chromatin condensation; detection of virus-induced chromosomal DNA fragmentation and sustained expression of apoptogenic p53 and IL-1beta converting enzyme; and demonstration of active EMCV transcription by reverse transcription-PCR. In addition, a host-virus coevolution was observed in U9K-AV2 cultures over time: U9K-AV2 cells exhibited slower growth rates, resistance to viral super-infection, and cessation of IFN-alpha synthesis, whereas the infectivity of EMCV was drastically attenuated. Finally, data are presented on the suitability of this model to study establishment of persistent infection by other viruses such as Sendai virus and reovirus.
Site-Specific Role of Catechol-O-Methyltransferase in Dopamine Overflow within Prefrontal Cortex and Dorsal Striatum (2007)

Accumulating evidence from clinical and preclinical studies shows that catechol-O-methyltransferase (COMT) plays a significant role in dopamine metabolism in the prefrontal cortex, but not in the striatum. However, to what extent dopamine overflow in the prefrontal cortex and striatum is controlled by enzymatic degradation versus reuptake is unknown. We used COMT deficient mice to investigate the role of COMT in these two brain regions with in vivo voltammetry. A real-time analysis of evoked dopamine overflow showed that removal of dopamine was twofold slower in the prefrontal cortex of mice lacking COMT than in wild-type mice, indicating that half of the dopamine decline in this brain region results from COMT-mediated enzymatic degradation. Lack of COMT did not influence dopamine overflow/decline in the dorsal striatum. COMT-deficient mice demonstrated a small (20-25%) but consistent increase in evoked dopamine release in the prefrontal cortex, but not in the dorsal striatum. Cocaine affected equally dopaminergic neurotransmission in the prefrontal cortex in both genotypes by prolonging 3-4 times dopamine elimination from extracellular space. Paradoxically, this happened without increase of the peak levels of evoked dopamine release. The present findings represent the first demonstration of the significant contribution of COMT in modulating the dynamics of dopamine overflow in the prefrontal cortex and underscore the therapeutic potential of manipulating COMT activity to alter dopaminergic neurotransmission in the prefrontal cortex.
Poverty reducing potential of smallholder agriculture in Zambia: opportunities and constraints (2005)

The objective of this paper is to investigate poverty-reducing potential of smallholder agriculture in Zambia, considering suggested public actions expected to stimulate broad-based growth in the rural economy. This paper was prepared as part of the Poverty and Social Impact Analysis (PSIA) work carried out to inform the Zambia Country Economic Memorandum (CEM). Following PSIA guidelines, it combines quantitative and qualitative analyses from a variety of sources. Several analytical techniques are used to examine opportunities and constraints facing typical Zambian smallholders. These include enterprise budgets, a smallholder household model, and reviews of recent studies. Using a one-period linear programming model of agricultural production activities by smallholder households, the authors examine potential impacts of land tenure reforms, changes in fertilizer policy, infrastructure investments, and HIV/AIDS on land and labor use and income-generation.
Enzyme and Biotin Labeling of Antibody (2003)

Labeled antibodies are key reagents in many procedures, particularly immunoassays and the detection of antigens in tissue sections and on membrane blots. The ideal labeled antibody retains all the immunoreactivity of the antibody and all the signal-generating capacity of the label. In addition, these conjugates should be stable, and have defined and appropriate proportions of the two components.
Metabolic analysis of senescent human fibroblasts reveals a role for AMP in cellular senescence (2003)

Cellular senescence is considered a major tumour-suppressor mechanism in mammals, and many oncogenic insults, such as the activation of the ras proto-oncogene, trigger initiation of the senescence programme. Although it was shown that activation of the senescence programme involves the up-regulation of cell-cycle regulators such as the inhibitors of cyclin-dependent kinases p16INK4A and p21CIP-1, the mechanisms underlying the senescence response remain to be resolved. In the case of stress-induced premature senescence, reactive oxygen species are considered important intermediates contributing to the phenotype. Moreover, distinct alterations of the cellular carbohydrate metabolism are known to contribute to oncogenic transformation, as is best documented for the phenomenon of aerobic glycolysis. These findings suggest that metabolic alterations are involved in tumourigenesis and tumour suppression; however, little is known about the metabolic pathways that contribute to these processes. Using the human fibroblast model of in vitro senescence, we analysed age-dependent changes in the cellular carbohydrate metabolism. Here we show that senescent fibroblasts enter into a metabolic imbalance, associated with a strong reduction in the levels of ribonucleotide triphosphates, including ATP, which are required for nucleotide biosynthesis and hence proliferation. ATP depletion in senescent fibroblasts is due to dysregulation of glycolytic enzymes, and finally leads to a drastic increase in cellular AMP, which is shown here to induce premature senescence. These results suggest that metabolic regulation plays an important role during cellular senescence and hence tumour suppression.
Endovascular treatment of acute ischemic stroke (2013)

Early recanalization of the occluded artery leads to better clinical outcomes in patients with acute ischemic stroke (AIS) through protection of the time-sensitive penumbra. Intravenous administration of pharmacologic thrombolytic agents has been a standard treatment for AIS. To get better rates of recanalization, enhance the time window, and diminish the possibility of intracranial hemorrhage, endovascular thrombectomy was launched, with first authorization of the Merci clot retriever, a corkscrew-like apparatus, followed by approval of the Penumbra thromboaspiration system. Both devices lead to a high rate of recanalization. On the other hand, time to recanalization was on an average of 45 minutes, with most of the patients attaining only partial recanalization. More lately, retrievable stents have shown promise in decreasing the time to recanalization, and attaining a superior rate of complete clot resolution. The retrievable stent can be released within the clot to engage it within the struts of the stent, and afterwards it is taken back by pulling it under flow arrest. Neurointerventional techniques have a persistently ever-increasing and stimulating role in the management of AIS, as indicated by the advent of several important techniques. Stent retrievers have the capability to be ascertained as the most important approach to endovascular stroke treatment.
Acid Gas Capture at High Temperatures Using Molten Alkali Metal Borates (2020)

Materials designed for CO<sub>2</sub> capture provide both an opportunity and a challenge in that industrial emissions typically contain an assortment of acid gasses, which may include SO<i><sub>x</sub></i> and NO<i><sub>x</sub></i> alongside CO<sub>2</sub>. Growing pressure to reduce emissions of all acid gasses, CO<sub>2</sub> included, presents an opportunity for simultaneous capture and a challenge in handling the resultant products. Molten alkali metal borates embody a new class of high-temperature liquid-phase materials for carbon dioxide capture and we propose here that they can also be used to address the more general challenge of acid gas capture. We examine the melt capture performance at industrially relevant concentrations and mixtures, identifying the various reaction mechanisms and products, and propose designs for separating these products efficiently at high temperatures, so that they outperform the state-of-the-art CO<sub>2</sub> capture technologies in handling this opportunity challenge. We also discuss the conditions to avoid and the challenges that lie ahead for these materials in the context of emission reduction and environmental protection.
Leukotriene B4 production in human atherosclerotic plaques. (1988)

We evaluated the hypothesis that leukotriene (LT) B4, a potent chemotactic and endothelium-permeabilizing autacoid, may be a factor in the progression of the atherosclerotic lesion. Human vascular fragments, freshly obtained at vascular surgery from saphenous veins, atrial appendages, normal aortas and atherosclerotic lesions (histologically classified as fibrous plaques, fatty plaques and complicated lesions) were incubated at 37 degree C with mechanical agitation, for various times ranging between 5 and 60 minutes, sequentially, with buffer (basal), ionophore A23187 (IONO), and arachidonic acid (AA). After each step medium was assayed for LTB4 production by radioimmunoassay. Incubations were also performed in a chamber allowing selective exposure of the endothelial surface to the medium. Basal production (15 minute incubation, ng/g, mean +/- SD) was lowest for fibrous plaques (0.9 +/- 0.2, n = 38) and saphenous veins (1.0 +/- 0.3, n = 32) and much higher (P less than 0.01) for fatty plaques (7.3 +/- 2.2, n = 35) and complicated lesions (5.3 +/- 3.0, n = 28). A virtual abolition of production was observed after boiling of the vascular fragment. Production was increased in the presence of AA and IONO (in atheromas: 11.5 +/- 4.2 AND 14.3 +/- 5.3, respectively, with 15 minutes incubation), and decreased after incubation with 5-lipooxigenase inhibitors. Peak of ionophore or arachidonic acid-stimulated production in kinetic studies was reached at 20 minutes. LTB4 production was able to reach the luminal surface in both basal and stimulated conditions. There was no relationship with concomitantly measured prostacyclin production (mainly endothelial), while a correlation was found between LTB4 levels and degree of white cell infiltration in the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Glutathione Infusion Potentiates Glucose-Induced Insulin Secretion in Aged Patients With Impaired Glucose Tolerance (1992)

Glutathione infusion enhances insulin secretion in elderly people with IGT.
Perilipin-2-null mice are protected against diet-induced obesity, adipose inflammation, and fatty liver disease (2013)

The cytoplasmic lipid droplet (CLD) protein perilipin-2 (Plin2) is expressed in multiple nonadipose tissues, where it is thought to play a role in regulating their lipid storage properties. However, the extent to which Plin2 functions in nutrient utilization and metabolism, or how it influences the consequences of over-feeding, remains unclear. In this study, we demonstrate that the absence of Plin2 prevents high-fat diet(HFD)-induced obesity in male and female mice. This response is associated with increased formation of subcutaneous beige adipocyte cells with uncoupling protein 1 expression, and amelioration of inflammatory foci formation in white adipose tissue and steatosis in the liver. Experiments demonstrate that Plin2 loss results in reduced energy intake and increased physical activity in response to HFD feeding. Our study provides the first evidence that Plin2 contributes to HFD-induced obesity by modulating food intake, and that its absence prevents obesity-associated adipose tissue inflammatory foci and liver steatosis.
Aerosolized antibiotics in mechanically ventilated patients (1998)

Nebulizer delivery of aerosolized aminoglycosides is efficient and predictable. In our clinical model, aerosolized antibiotics can make a significant impact on respiratory secretions. Their efficacy in treatment of critically ill patients remains to be determined.
Modeling, Design and Experimentation of Wearable RFID Sensor Tag (2010)

Design of effective wearable tags for UHF RFID applications involving persons is still an open challenge due to the strong interaction of the antenna with the human body which is responsible of impedance detuning and efficiency degradation. A new tag geometry combining folded conductors and tuning slots is here discussed through numerical analysis and extensive experimentation also including the integration of a passive motion detector. The achieved designs, having size comparable with a credit card, may be applied to any part of the body. The measured performance indicates a possible application of these body-worn tags for the continuous tracking of human movements in a conventional room.
Circumvention of adriamycin resistance by dipyridamole analogues: A structure‐activity relationship study (1989)

Dipyridamole restores sensitivity to Adriamycin (ADR) in drug-resistant cells. In an effort to elucidate the relationship between activity and chemical structure of dipyridamole, the ability to enhance the growth inhibitory effect of ADR, in multidrug-resistant (MDR) P388 murine leukemia cells, was determined for 43 derivatives and related compounds. Since both substituted pyrimidopyrimidines and pteridines enhanced the growth-inhibitory effect of ADR in drug resistant cells, the core skeleton may not be directly involved and rather serve as a carrier for the substituents connected with this activity. The exact positions of the active substituents on the core skeleton did not seem to be critical for exertion of the activity. Activity was dependent on the presence of 3 tertiary amine groups. However, not all tertiary amines showed the same potency which might be related to the degree of basicity and/or the spatial structure of these groups. The most active derivatives carried piperidine and pyrrolidine groups while derivatives with thiomorpholine, 3-hydroxypiperidine or dimethylamine groups had low activity. Activity was also dependent on the presence of a substituent with partial electronegative charges as found in a diethanolamine group. However, this function could be carried out, with even higher efficiency, by a substituent containing 6 pi electrons.
Recognition of handwritten Arabic mathematical formulas (1990)

The author develops a hierarchical system for the recognition of on-line Arabic mathematical symbols. A precedence grammar has been also developed for the recognition of one-dimensional Arabic mathematical formulas. The segmentation of a mathematical formula is relatively simple since all characters are isolated and each consists of one stroke only, with the exception of three symbols where each consists of two strokes. Thus, the mathematical formula recognition problem reduces, after segmentation, to a pure character recognition problem. The set of characters comprising formulas includes sixteen isolated letters (ignoring diacritics), ten digits and eleven mathematical symbols. Several features are used in the recognition process, where different features are utilized sequentially in different stages of the hierarchical system. The recognition technique has been trained and tested using a large set of equations including about one thousand characters. The resulting recognition rate exceeds 99%. Thus, this system can be reliably used for the recognition of on-line handwritten Arabic mathematical formulas.<
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Growth and physiological characteristics of Bacillus subtilis L-forms. (1993)

The specific growth rate of stable Bacillus subtilis L-forms was slower (mu = 0.127) than the cell-walled form (mu = 0.219) when measured by optical density (O.D.). However, the L-form growth rate increased (mu = 0.288) when determined by viable cell counts. L-forms of B. subtilis appear to enter a phase of rapid cell division, followed by a period of cell enlargement which is associated with an increase in the number of cells with vacuoles and granules. Thus, maximum viable L-form numbers and DNA content were attained at approx. 30h, before maximum protein content was achieved (46h) and before maximum O.D. was observed at 71 h. Measurements showed that L-form cell size increased even after cell division had stopped. O.D. was therefore inaccurate for assessment of L-form growth. L-forms were sensitive to osmotic shock and unlike the cell-walled organisms from which they were derived, were resistant to penicillin, indicating a loss of peptidoglycan. The L-forms were similar to cell-walled forms in that antibiotic(s) and proteases were produced.
Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. (1998)

About one-third of sporadic basal cell carcinomas (BCCs) of the skin and 10-15% of primitive neuroectodermal tumors (PNETs) of the central nervous system show mutations in the PTCH tumor suppressor gene. The PTCH gene product (Ptch) functions as a transmembrane receptor for the Sonic hedgehog protein (Shh) and interacts with another transmembrane protein called Smoh. To further elucidate the significance of alterations in the Shh signaling pathway, we investigated 31 sporadic BCCs and 15 PNETs for the mutation and/or expression of SMOH, PTCH, SHH, and GL11. In addition, we fine-mapped the SMOH gene locus by fluorescence in situ hybridization to chromosomal band 7q32. Mutational analysis identified four BCCs with somatic missense mutations in SMOH affecting codon 535 (TGG==>TTG: Trp==>Leu) in three tumors and codon 199 (CGG==>TGG: Arg==>Trp) in one tumor. A missense mutation at codon 533 (AGC==>AAC: Ser==>Asn) was found in one PNET. PTCH mutations were detected in eight BCCs and one PNET. Two BCCs demonstrated mutations in both SMOH and PTCH. The majority of tumors showed an increased expression of SMOH, PTCH, and GL11 transcripts as compared with that of normal skin and nonneoplastic brain tissue, respectively. In contrast, only one BCC and one PNET expressed SHH mRNA at levels detectable by reverse transcription-PCR, and no SHH gene mutations were found. In summary, our results indicate that both PTCH and SMOH represent important targets for genetic alterations in sporadic BCCs and PNETs.
Reinforcement Learning, Spike-Time-Dependent Plasticity, and the BCM Rule (2007)

Learning agents, whether natural or artificial, must update their internal parameters in order to improve their behavior over time. In reinforcement learning, this plasticity is influenced by an environmental signal, termed a reward, that directs the changes in appropriate directions. We apply a recently introduced policy learning algorithm from machine learning to networks of spiking neurons and derive a spike-time-dependent plasticity rule that ensures convergence to a local optimum of the expected average reward. The approach is applicable to a broad class of neuronal models, including the Hodgkin-Huxley model. We demonstrate the effectiveness of the derived rule in several toy problems. Finally, through statistical analysis, we show that the synaptic plasticity rule established is closely related to the widely used BCM rule, for which good biological evidence exists.