gebhart/patrepeval huggingface dataset:
Role of Protein Kinase C in the Signal Pathways That Link Na+/K+-ATPase to ERK1/2 (2001)

We have shown before that Na(+)/K(+)-ATPase acts as a signal transducer, through protein-protein interactions, in addition to being an ion pump. Interaction of ouabain with the enzyme of the intact cells causes activation of Src, transactivation of EGFR, and activation of the Ras/ERK1/2 cascade. To determine the role of protein kinase C (PKC) in this pathway, neonatal rat cardiac myocytes were exposed to ouabain and assayed for translocation/activation of PKC from cytosolic to particulate fractions. Ouabain caused rapid and sustained stimulation of this translocation, evidenced by the assay of Ca(2+)-dependent and Ca(2+)-independent PKC activities and by the immunoblot analysis of the alpha, delta, and epsilon isoforms of PKC. Dose-dependent stimulation of PKC translocation by ouabain (1-100 microm) was accompanied by no more than 50% inhibition of Na(+)/K(+)-ATPase and doubling of [Ca(2+)](i), changes that do not affect myocyte viability and are known to be associated with positive inotropic, but not toxic, effects of ouabain in rat cardiac ventricles. Ouabain-induced activation of ERK1/2 was blocked by PKC inhibitors calphostin C and chelerythrine. An inhibitor of phosphoinositide turnover in myocytes also antagonized ouabain-induced PKC translocation and ERK1/2 activation. These and previous findings indicate that ouabain-induced activation of PKC and Ras, each linked to Na(+)/K(+)-ATPase through Src/EGFR, are both required for the activation of ERK1/2. Ouabain-induced PKC translocation and ERK1/2 activation were dependent on the presence of Ca(2+) in the medium, suggesting that the signal-transducing and ion-pumping functions of Na(+)/K(+)-ATPase cooperate in activation of these protein kinases and the resulting regulation of contractility and growth of the cardiac myocyte.
Control of Ticks Systemically with Merck MK-933, an Avermectin13 (1981)

Merck MK-933 (7-[[2,6-dideoxy-4-O-(2,6-dideoxy-3-O-methyl-α-L-arabino-hexopyranosyl)-3-O-methyl-α-L-arabino-hexopyranosyl]oxy]-3’,4’,5’6,6’,7,10,11,14,15,17a,20,20a,20b-tetradecahydro-20,20b-dihydroxy-5’,6,8,19-tetramethyl-6’-(1-methylpropyl)spiro[11,15-methano-2H,13H,17H-furo[4,3,2-pq][2,6]benzodioxacyclooctadecin-13,2’-[2H]pyran]-17-one), an avermectin given orally to cattle daily by capsule, was highly effective in preventing engorgement and reproduction of adults of six species of three-host ticks—Amblyomma americanum (L.), A. cajennense (F.), A. maculatum Koch, Dermacentor andersoni Stiles, D. variabilis (Say), and Rhipicephalus sanguineus (Latreille)—and all parasitic stages of a one-host species—D. albipictus (Packard)—at dosages of >50 μg/kg per day. A daily subcutaneous injection of 10 μg/kg per day afforded complete control, but a similar injection of 5 μg/kg per day was not completely effective. MK-933 formulated as sustained-release tablets or boluses designed to release ca. 50 μg/kg per day was also effective, but the sustained-release devices eroded at rates higher or lower than those anticipated. The activity of this chemical at such low dosage levels makes it an excellent candidate as an acaricide for the control of ticks systemically.
Real-world patterns of pegloticase use for treatment of gout: descriptive multidatabase cohort study (2020)

Pegloticase is rarely used in gout, and the median duration of pegloticase therapy was 3 months. There were few anaphylaxis events captured in this claims-based study, while heart failure hospitalisations were common.
Phenyl Benzenesulfonylhydrazides Exhibit Selective Indoleamine 2,3-Dioxygenase Inhibition with Potent in Vivo Pharmacodynamic Activity and Antitumor Efficacy (2015)

Tryptophan metabolism has been recognized as an important mechanism in immune tolerance. Indoleamine 2,3-dioxygenase plays a key role in local tryptophan metabolism via the kynurenine pathway and has emerged as a therapeutic target for cancer immunotherapy. Our prior study identified phenyl benzenesulfonyl hydrazide 2 as a potent in vitro (though not in vivo) inhibitor of indoleamine 2,3-dioxygenase. Further lead optimization to improve in vitro potencies and pharmacokinetic profiles resulted in N'-(4-bromophenyl)-2-oxo-2,3-dihydro-1H-indole-5-sulfonyl hydrazide 40, which demonstrated 59% oral bioavailability and 73% of tumor growth delay without apparent body weight loss in the murine CT26 syngeneic model, after oral administration of 400 mg/kg. Accordingly, 40, is proposed as a potential drug lead worthy of advanced preclinical evaluation.
Fast Sterility Assessment by Germinable-Endospore Biodosimetry (2008)

The increased demand for sterile products has created the need for rapid technologies capable of validating the hygiene of industrial production processes. Bacillus endospores are in standard use as biological indicators for evaluating the effectiveness of sterilization processes. Currently, culture-based methods, requiring more than 2 days before results become available, are employed to verify endospore inactivation. We describe a rapid, microscopy-based endospore viability assay (microEVA) capable of enumerating germinable endospores in less than 15 min. MicroEVA employs time-gated luminescence microscopy to enumerate single germinable endospores via terbium-dipicolinate (Tb-DPA) luminescence, which is triggered under UV excitation as 10(8) DPA molecules are released during germination on agarose containing Tb(3+) and a germinant (e.g., L-alanine). Inactivation of endospore populations to sterility was monitored with microEVA as a function of thermal and UV dosage. A comparison of culturing results yielded nearly identical decimal reduction values, thus validating microEVA as a rapid biodosimetry method for monitoring sterilization processes. The simple Tb-DPA chemical test for germinability is envisioned to enable fully automated instrumentation for in-line monitoring of hygiene in industrial production processes.
Active MAC-1 (CD11b/CD18) on DCs inhibits full T-cell activation (2006)

The beta2 integrins are important for transendothelial migration of leukocytes as well as for T-cell activation during antigen presentation. Despite abundant expression of beta2 integrins on antigen-presenting cells (APCs), their functional relevance for antigen presentation is completely unclear. We show here that dendritic cells (DCs) from CD18-deficient mice, which lack all functional beta2 integrins, have no defect in antigen presentation. Moreover, DCs from normal mice express inactive beta2 integrins that do not become activated on contact with T cells, at least in vitro. Pharmacologic activation of beta2 integrins on DCs results in a significant reduction of their T cell-activating capacity. This effect is mediated by Mac-1 (CD11b/CD18) on DCs because it could be reversed via blocking antibodies against CD18 and CD11b. Furthermore, the antigen-presenting capacity of macrophages, which express constitutively active beta2 integrins, is significantly enhanced on Mac-1 blockade. We therefore conclude that active CD11b/CD18 (Mac-1) on APCs directly inhibits T-cell activation.
Automatic Image Annotation and Retrieval Using Weighted Feature Selection (2005)

The development of technology generates huge amounts of nontextual information, such as images. An efficient image annotation and retrieval system is highly desired. Clustering algorithms make it possible to represent visual features of images with finite symbols. Based on this, many statistical models, which analyze correspondence between visual features and words and discover hidden semantics, have been published. These models improve the annotation and retrieval of large image databases. However, image data usually have a large number of dimensions. Traditional clustering algorithms assign equal weights to these dimensions, and become confounded in the process of dealing with these dimensions. In this paper, we propose weighted feature selection algorithm as a solution to this problem. For a given cluster, we determine relevant features based on histogram analysis and assign greater weight to relevant features as compared to less relevant features. We have implemented four different models to link visual tokens with keywords based on the clustering results of K-means algorithm with weighted feature selection and without feature selection, and evaluated performance using precision, recall and correspondence accuracy using benchmark dataset. The results show that weighted feature selection is better than traditional ones for automatic image annotation and retrieval.
The functional interactome landscape of the human histone deacetylase family (2013)

Histone deacetylases (HDACs) are a diverse family of essential transcriptional regulatory enzymes, that function through the spatial and temporal recruitment of protein complexes. As the composition and regulation of HDAC complexes are only partially characterized, we built the first global protein interaction network for all 11 human HDACs in T cells. Integrating fluorescence microscopy, immunoaffinity purifications, quantitative mass spectrometry, and bioinformatics, we identified over 200 unreported interactions for both well-characterized and lesser-studied HDACs, a subset of which were validated by orthogonal approaches. We establish HDAC11 as a member of the survival of motor neuron complex and pinpoint a functional role in mRNA splicing. We designed a complementary label-free and metabolic-labeling mass spectrometry-based proteomics strategy for profiling interaction stability among different HDAC classes, revealing that HDAC1 interactions within chromatin-remodeling complexes are largely stable, while transcription factors preferentially exist in rapid equilibrium. Overall, this study represents a valuable resource for investigating HDAC functions in health and disease, encompassing emerging themes of HDAC regulation in cell cycle and RNA processing and a deeper functional understanding of HDAC complex stability.
Recherches dans la série des azoles (1966)

Plusieurs méthodes empiriques sont décrites, permettant d’attribuer sans ambiguïté les signaux des protons ou des méthyles en 3 et en 5 dans les spectres RMN de pyrazoles N-substitués. Les effets de solvant ont été particulièrement étudiés.
Comparison of the effects of sibutramine and other monoamine reuptake inhibitors on food intake in the rat (1997)

1. The effects of the potent 5-hydroxytryptamine (5-HT) and noradrenaline reuptake inhibitor (serotonin-noradrenaline reuptake inhibitor, SNRI), sibutramine, on the cumulative food intake of freely-feeding male Sprague-Dawley rats during an 8 h dark period were investigated and compared to those of the selective 5-HT reuptake inhibitor (selective serotonin reuptake inhibitor, SSRI), fluoxetine; the selective noradrenaline reuptake inhibitor, nisoxetine; the 5-HT and noradrenaline reuptake inhibitors, venlafaxine and duloxetine; and the 5-HT releaser and 5-HT reuptake inhibitor, (+)-fenfluramine. 2. Sibutramine (3 and 10 mg kg-1, p.o.) and (+)-fenfluramine (1 and 3 mg kg-1, p.o.) produced a significant, dose-dependent decrease in food intake over the 8 h dark period. These responses became apparent within the first 2 h following drug administration. 3. Fluoxetine (3, 10 and 30 mg kg-1, p.o.), and nisoxetine (3, 10 and 30 mg kg-1, p.o.) had no significant effect on food intake during the 8 h dark period. However, a combination of fluoxetine and nisoxetine (30 mg kg-1, p.o., of each) significantly decreased food intake 2 and 8 h after drug administration. 4. Venlafaxine (100 and 300 mg kg-1, p.o.) and duloxetine (30 mg kg-1, p.o.) also significantly decreased food intake in the 2 and 8 h following drug administration. 5. The results of this study demonstrate that inhibition of 5-HT and noradrenaline reuptake by sibutramine, venlafaxine, duloxetine, or by a combination of fluoxetine and nisoxetine, markedly reduces food intake in freely-feeding rats and suggest that this may be a novel approach for the treatment of obesity.
Heparanase gene haplotype (CGC) is associated with stage of disease in patients with ovarian carcinoma (2007)

Heparanase (HSPE-1) and vascular endothelial growth factor (VEGF), proangiogenic growth factors, play important roles in the metastatic biology of ovarian cancer. The aim of the present study was to test for association between single nucleotide polymorphisms (SNPs) in HSPE-1 and VEGF and outcome in ovarian cancer. A mutational analysis was performed on the coding sequence of the HSPE-1 gene to define high-frequency SNPs. HSPE-1 polymorphisms, together with two SNPs in the VEGF gene, were studied in 136 patients with ovarian cancer. Patients were categorized into two groups, those with FIGO stages 1 and 2 (group 1) and those with stages 3 and 4 (group 2). We identified 10 polymorphisms in the HSPE-1 gene, those in introns 2, 3 and 5b, and exons 8, 13a and 13b occurring at a minor allele frequency of >/=10%. There was an increase in frequency of those individuals with a genotype that carried at least one copy of the intron 2 (C), exon 8 (G), exon 13a (C) haplotype (CGC) in group 2. Specifically there were 24% with this haplotype in group 2 versus 5% in group 1 (P = 0.0184, odds ratio 5.986, 95% confidence interval 1.340-26.752). Most of this association was captured by the intron 2 genotype, where carriage of the C allele was associated with stage (P = 0.0148, odds ratio 6.524, 95% confidence interval 1.401-27.921). There was no association between VEGF SNPs and stage of disease. The CGC HSPE-1 haplotype associates with stage in ovarian cancer. This haplotype may affect splicing of the HSPE-1 gene, as in silico it alters the presence of a splicing motif.
Neuromorphic electronic systems (1990)

It is shown that for many problems, particularly those in which the input data are ill-conditioned and the computation can be specified in a relative manner, biological solutions are many orders of magnitude more effective than those using digital methods. This advantage can be attributed principally to the use of elementary physical phenomena as computational primitives, and to the representation of information by the relative values of analog signals rather than by the absolute values of digital signals. This approach requires adaptive techniques to mitigate the effects of component differences. This kind of adaptation leads naturally to systems that learn about their environment. Large-scale adaptive analog systems are more robust to component degradation and failure than are more conventional systems, and they use far less power. For this reason, adaptive analog technology can be expected to utilize the full potential of wafer-scale silicon fabrication.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Optimizing the use of 17P in pregnant managed Medicaid members. (2008)

The number of injections and not the time frame, which had been indicated by previous research, the initiation of 17P therapy is the factor in reducing preterm birth and decreasing NICU admissions for pregnant women with a history of preterm birth in a managed Medicaid population.
Cervical cancer: epidemiology, prevention and the role of human papillomavirus infection. (2001)

Organized screening has contributed to a decline in cervical cancer incidence and mortality over the past 50 years. However, women in developing countries are yet to profit extensively from the benefits of screening programs, and recent trends show a resurgence of the disease in developed countries. The past 2 decades have witnessed substantial progress in our understanding of the natural history of cervical cancer and in major treatment advances. Human papillomavirus (HPV) infection is now recognized as the main cause of cervical cancer, the role of coexisting factors is better understood, a new cytology reporting terminology has improved diagnosis and management of precursor lesions, and specific treatment protocols have increased survival among patients with early or advanced disease. Current research has focused on the determinants of infection with oncogenic HPV types, the assessment of prophylactic and therapeutic vaccines and the development of screening strategies incorporating HPV testing and other methods as adjunct to cytology. These are fundamental stepping stones for the implementation of effective public health programs aimed at the control of cervical cancer.
Effects of Pulsed Electromagnetic Fields on Human Articular Chondrocyte Proliferation (2001)

Low-energy, low-frequency pulsed electromagnetic fields (PEMFs) can induce cell proliferation in several cell culture models. In this work we analysed the proliferative response of human articular chondrocytes, cultured in medium containing 10% FBS, following prolonged exposure to PEMFs (75 Hz, 2.3 mT), currently used in the treatment of some orthopaedic pathologies. In particular, we investigated the dependence of the proliferative effects on the cell density, the availability of growth factors and the exposure lengths. We observed that PEMFs can induce cell proliferation of low density chondrocyte cultures for a long time (6 days), when fresh serum is added again in the culture medium. In the same conditions, in high density cultures, the PEMF-induced increase in cell proliferation was observed only in the first three days of exposure. The data presented in this study show that the availability of growth factors and the environmental constrictions strongly condition the cellular proliferative response to PEMFs.
Genes for Polyketide Secondary Metabolic Pathways in Microorganisms and Plants (2007)

Recent advances in molecular genetics have led to the isolation, sequencing and functional analysis of genes encoding synthases that catalyse the formation of several classes of polyketides. The structures of the genes and their protein products differ strikingly in the various examples. For Streptomyces aromatic polyketides, exemplified by granaticin and tetracenomycin, the synthases correspond to Type II (bacterial and plant) fatty acid synthases in consisting of distinct proteins for such processes as condensation, acyl carrier function and ketoreduction. In contrast, for actinomycete macrolides such as erythromycin, similar catalytic functions are performed by a set of multifunctional proteins resembling Type I (animal) fatty acid synthases, but with every step in chain-building being catalysed by a different enzymic domain. Penicillium patulum has a simple Type I synthase for 6-methylsalicylic acid. For plant chalcones and stilbenes, a single small polypeptide acts as a condensing enzyme for carbon chain-building and may be unrelated to any of the other polyketide and fatty acid synthases. Thus, although these systems share a common general mechanism of chain assembly, they must differ in the ways that synthase 'programming' has evolved to determine chain length, choice of chain starter and extender units, and handling of successive keto groups during chain assembly, and so control the great diversity of possible chemical products.
Apoptotic Cell Death in Mouse Models of GM2 Gangliosidosis and Observations on Human Tay-Sachs and Sandhoff Diseases (1997)

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit (Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B (beta beta homodimer) is also defective in Sandhoff disease. We previously developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs) mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff) mice succumb to a profound neurodegenerative disease by 4-6 months of age. Here we find that neuron death in Hexb-/- mice is associated with apoptosis occurring throughout the CNS, while Hexa-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. We suggest that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade.
Selected Contribution: Ambient temperature for experiments in rats: a new method for determining the zone of thermal neutrality (2002)

There is a misbelief that the same animal has the same thermoneutral zone (TNZ) in different experimental setups. In reality, TNZ strongly depends on the physical environment and varies widely across setups. Current methods for determining TNZ require elaborate equipment and can be applied only to a limited set of experimental conditions. A new, broadly applicable approach that rapidly determines whether given conditions are neutral for a given animal is needed. Consistent with the definition of TNZ [the range of ambient temperature (T(a)) at which body core temperature (T(c)) regulation is achieved only by control of sensible heat loss], we propose three criteria of thermoneutrality: 1) the presence of high-magnitude fluctuations in skin temperature (T(sk)) of body parts serving as specialized heat exchangers with the environment (e.g., rat tail), 2) the closeness of T(sk) to the median of its operational range, and 3) a strong negative correlation between T(sk) and T(c). Thermocouple thermometry and liquid crystal thermography were performed in five rat strains at 13 T(a). Under the conditions tested (no bedding or filter tops, no group thermoregulation), the T(a) range of 29.5-30.5 degrees C satisfied all three TNZ criteria in Wistar, BDIX, Long-Evans, and Zucker lean rats; Zucker fatty rats had a slightly lower TNZ (28.0-29.0 degrees C). Skin thermometry or thermography is a definition-based, simple, and inexpensive technique to determine whether experimental or housing conditions are neutral, subneutral, or supraneutral for a given animal.
Using wax crayons (2000)

There are many different types of wax crayon to choose from. Buy the best quality you can afford and introduce variations such as glitter or fluorescent crayons. Triangular shaped crayons are worth looking out for if you want to do rubbings. Avoid crayons described as ‘washable’ or ‘paint sticks’; these are water soluble and not suitable for making scratch cards or wax resist pictures.
Retrograde Transvenous Neuroperfusion: A Back Door Treatment for Stroke (1998)

We conclude that RTN treatment during MCAO effectively reverses the pathophysiological sequelae of ischemia, even when the treatment is initiated 1 hour after the onset of ischemia. Although the infarct volume in the control group was variable when quantitatively assessed 6 days after 3.5 hours of MCAO, virtually no evidence of infarcts was seen in the RTN-treated group.