gebhart/patrepeval huggingface dataset:
Importance of the Global Regulators Agr and SaeRS in the Pathogenesis of CA-MRSA USA300 Infection (2010)

CA-MRSA infection, driven by the emergence of the USA300 genetic background, has become epidemic in the United States. USA300 isolates are hypervirulent, compared with other CA- and HA-MRSA strains, in experimental models of necrotizing pneumonia and skin infection. Interestingly, USA300 isolates also have increased expression of core genomic global regulatory and virulence factor genes, including agr and saeRS. To test the hypothesis that agr and saeRS promote the observed hypervirulent phenotype of USA300, isogenic deletion mutants of each were constructed in USA300. The effects of gene deletion on expression and protein abundance of selected downstream virulence genes were assessed by semiquantitative real-time reverse-transcriptase PCR (qRT-PCR) and western blot, respectively. The effects of gene deletion were also assessed in mouse models of necrotizing pneumonia and skin infection. Deletion of saeRS, and, to a lesser extent, agr, resulted in attenuated expression of the genes encoding α-hemolysin (hla) and the Panton-Valentine leukocidin (lukSF-PV). Despite the differences in hla transcription, the toxin was undetectable in culture supernatants of either of the deletion mutants. Deletion of agr, but not saeRS, markedly increased the expression of the gene encoding protein A (spa), which correlated with increased protein abundance. Each deletion mutant demonstrated significant attenuation of virulence, compared with wild-type USA300, in mouse models of necrotizing pneumonia and skin infection. We conclude that agr and saeRS each independently contribute to the remarkable virulence of USA300, likely by means of their effects on expression of secreted toxins.
Control loop performance monitoring (1996)

Control loop monitoring can be used to improve the performance of processes in industry. The monitoring tools presented are concerned with reducing the output variance of regulation loops. As a result, three different estimators are used to determine the minimum achievable output variance, the time delay and the static input-output relationship of the process. These three properties can be used together or individually to provide insights into the process. Once the methods are introduced and their algorithms outlined, the monitoring tools are tested on data from industrial processes. These results show the capabilities and limitations of the proposed estimation methods and the potential benefits to be obtained from monitoring.
Molecular and cellular aspects of the secretory immunoglobulin system* (1995)

Adaptive immunological protection of mucous membranes is provided mainly by secretory IgA antibodies. Such "first line" defence is accomplished through a unique cooperation between the mucosal B-cell system and the secretory component (SC) expressed basolaterally on glandular epithelial cells. This transmembrane glycoprotein is quantitatively the most important receptor of the immune system because it is responsible for external transport of locally produced polymeric IgA (pIgA), which is the major product of humoral immunity. Transmembrane SC belongs to the Ig supergene family and functions as a general pIg receptor, also mediating the external translocation of pentameric IgM to form secretory IgM. The B cells responsible for local pIg production are initially stimulated in lymphoepithelial structures, particularly the Peyer's patches in the distal small intestine, from which they migrate as memory cells to exocrine tissues all over the body. Mucous membranes are thus furnished with secretory antibodies in an integrated way, ensuring a variety of specificities at every secretory site. There is currently great interest in exploiting this integrated or "common" mucosal immune system for oral vaccination against pathogenic infectious agents. However, much remains to be learned about mechanisms for antigen uptake and processing necessary to elicit mucosal immunity as well as the molecular biology and cytokine regulation of SC-dependent pIg transport. Moreover, evidence is emerging for the existence of subcompartmentalization in the mucosal immune system, particularly a dichotomy in cellular migration between the gut and the upper airway, which may complicate the design of efficient local vaccines.
The Conjunctival Provocation Test Model of Ocular Allergy: Utility for Assessment of an Ocular Corticosteroid, Loteprednol Etabonate (1998)

Two studies were conducted using the conjunctival provocation test (CPT) model of ocular allergy. The objective of the first study was to evaluate the sensitivity of the CPT model to a topical corticosteroid. Selected was loteprednol etabonate 0.5%, previously found effective in the treatment of ocular allergy and inflammation. The study was a randomized double-masked, placebo-controlled, paired-comparison of loteprednol etabonate 0.5% (LE), b.i.d. or q.i.d. Sixty subjects who had a minimum pre-determined allergic response received LE in one eye and placebo in the fellow eye for 28 days from Day 7 to Day 35. Antigen challenges were carried out on Days 0, 7 (baseline), 21 and 35. The primary endpoints were interocular differences in itching and mean redness (the average of ciliary, conjunctival and episcleral vessel beds). LE (either b.i.d. or q.i.d.) was significantly more effective than placebo for reducing mean redness and itching. No clinical or statistically significant changes in intraocular pressure were observed. Based upon the results of Study 1, we used the CPT model to aid in the selection of a concentration of loteprednol etabonate for subsequent studies in environmental seasonal allergic conjunctivitis. This was a randomized double-masked, placebo-controlled, paired-comparison of loteprednol etabonate 0.1%, 0.2% and 0.3%, q.i.d. in 88 subjects. The dosing and testing regimen was similar to the first portion of the study. Loteprednol etabonate, 0.1%, 0.2% and 0.3%, was numerically superior to the placebo in reducing mean redness and itching. At the 20-minute post allergen challenge, the 0.1% concentration was significantly superior (p < 0.05) to the placebo on Visit 4 (2 and 4 hour challenge) in reducing the mean redness; however, LE was only numerically superior in relieving itching. The 0.2% concentration was significantly superior (p < 0.05) to the placebo in the reduction of mean redness and itching on Visit 3 (Day 21) and in reduction of mean redness on Visit 4 (4 hour challenge). The 0.3% concentration was significantly superior (p < 0.05) to the placebo in the reduction of mean redness on all visits, and statistically significant in the reduction of itching on Visit 4 (4 hour challenge). While there were some elevations of IOP with LE 0.2%, they were not clinically significant. In conclusion, the CPT model of ocular allergy is useful in the evaluation of corticosteroids. Furthermore, based upon a dose-response study in this model, 0.2% loteprednol etabonate was selected for further evaluation in environmental seasonal allergic conjunctivitis studies.
Fungal cellulases: Study of hydrolytic properties of endoglucanases from Trichoderma reesei and Humicola insolens (2000)

Cellulose is one of the most abundant biopolymers on earth. Several organisms degrade cellulose, one of the most studied is the fungus <i>Trichoderma reesei</i> which produces seven genetically different cellulases. In this thesis, a thorough study of the hydrolytic characteristics of the less studied endoglucanases Cel12A (EG III), Cel45A (EG V) and Cel61A (EG IV) of <i>T. reesei</i> is presented. Cel12A showed lower endoglucanase activity than the major endoglucanases Cel5A (EG II) and Cel7B (EG I), however, the endoglucanase activity for Cel12A was significantly higher than what was observed for Cel45A and Cel61A. The need for expressing Cel12A might be found in the low molecular mass, only 25 kDa compared to about 50 kDa for the major endoglucanases. A smaller enzyme might penetrate parts of a natural cellulosic substrate to which the major enzymes cannot access. Cel45A showed high activity against glucomannan and only a low endoglucanase activity. Thus, since no activity on mannan was observed for Cel45A, the hydrolytic properties indicates that this enzyme is a glucomannanase. For Cel61A, only a low endoglucanase activity was observed. A novel approach to characterise soluble cellulose derivatives is presented. The cellulose derivative, carboxymethyl cellulose (CMC), was hydrolysed by a single endoglucanase and the products were analysed with several techniques, in particular liquid chromatography and MALDI-TOF mass spectrometry. Endoglucanases of the fungi <i>Humicola insolens</i> and <i>T. reesei</i> were used. Since the substituents inhibit the hydrolysis by the enzymes, total hydrolysis was not achieved by any endoglucanase. Furthermore, some of the endoglucanases were able to hydrolyse the CMC to higher extent than others. Thus, it is possible to use pure endoglucanases in analysing cellulose derivatives. Cellulases are able to hydrolyse cellulose in co-operation, the enzymes act in synergy. When studying the hydrolysis of lignocellulose with the exoglucanase Cel7A (CBH I) in combination with the endoglucanase Cel5A several observations were made which did not fit the most accepted synergy model. Therefore, an extension to the endo-exo synergy model is presented. The concept is introduced that the observed synergy is due to removal of obstacles for the exoglucanase by the endoglucanase activity.
1 Introduction: Stem Cell Biology (2001)

STEM CELLS: AN OVERVIEW There is still no universally acceptable definition of the term stem cell, despite a growing common understanding of the circumstances in which it should be used. According to this more recent perspective, the concept of “stem cell” is indissolubly linked with growth via the multiplication rather than the enlargement of cells. Various schemes for classifying tissues according to their mode of growth have been proposed, one of the earliest of which is that of Bizzozero (1894). This classification, which relates to the situation in the adult rather than in the embryo, recognizes three basic types of tissues: renewing, expanding, and static. Obvious examples of the first are intestinal epithelium and skin, and of the second, liver. The third category was held to include the central nervous system, although recent studies have shown that neurogenesis does continue in adulthood, for example, with regard to production of neurons that migrate to the olfactory bulbs (Gage 2000). There are various problems with such schemes of classification including, for instance, assignment of organs like the mammary gland which, depending on the circumstances of the individual, may engage in one or more cycles of marked growth, differentiation, and subsequent involution. Any attempt to find a universally acceptable definition of the term stem cell is probably doomed to fail. Nonetheless, certain attributes can be assigned to particular cells in both developing and adult multicellular organisms that serve to distinguish them from the remaining cells of the tissues to which they belong. Most...
Effects of Long-Term Storage Time and Original Sampling Month on Biobank Plasma Protein Concentrations (2016)

The quality of clinical biobank samples is crucial to their value for life sciences research. A number of factors related to the collection and storage of samples may affect the biomolecular composition. We have studied the effect of long-time freezer storage, chronological age at sampling, season and month of the year and on the abundance levels of 108 proteins in 380 plasma samples collected from 106 Swedish women. Storage time affected 18 proteins and explained 4.8-34.9% of the observed variance. Chronological age at sample collection after adjustment for storage-time affected 70 proteins and explained 1.1-33.5% of the variance. Seasonal variation had an effect on 15 proteins and month (number of sun hours) affected 36 proteins and explained up to 4.5% of the variance after adjustment for storage-time and age. The results show that freezer storage time and collection date (month and season) exerted similar effect sizes as age on the protein abundance levels. This implies that information on the sample handling history, in particular storage time, should be regarded as equally prominent covariates as age or gender and need to be included in epidemiological studies involving protein levels.
Evaluation of a Cholecystokinin 2 Receptor-Targeted Near-Infrared Dye for Fluorescence-Guided Surgery of Cancer (2013)

Surgical resection of malignant disease remains one of the most effective tools for treating cancer. Tumor-targeted near-infrared dyes have the potential to improve contrast between normal and malignant tissues, thereby enabling surgeons to more quantitatively resect malignant disease. Because the cholecystokinin 2 receptor (CCK2R and its tumor-specific splice variant CCK2i4svR) is overexpressed in cancers of the lungs, colon, thyroid, pancreas, and stomach, but absent or inaccessible to parenterally administered drugs in most normal tissues, we have undertaken to design a targeting ligand that can deliver attached near-infrared dyes to CCK2R+ tumors. We report here the synthesis and biological characterization of a CCK2R-targeted conjugate of the near-infrared dye, LS-288 (CRL-LS288). We demonstrate that CRL-LS288 binds selectively to CCK2R+ cancer cells with low nanomolar affinity (Kd = 7 × 10(-9) M). We further show that CRL-LS288 localizes primarily to CCK2R-expressing HEK 293 murine tumor xenografts and that dye uptake in these xenografts is significantly reduced when CCK2R are blocked by preinjection of excess ligand (CRL) or when mice are implanted with CCK2R-negative tumors. Because CRL-LS288 is also found to reveal the locations of distant tumor metastases, we suggest that CRL-LS288 has the potential to facilitate intraoperative identification of malignant disease during a variety of cancer debulking surgeries.
Single-feed slotted equilateral-triangular microstrip antenna for circular polarization (1999)

Novel designs of single-feed equilateral-triangular microstrip antennas for circular polarization (CP) are proposed and studied experimentally. It is demonstrated that by embedding a narrow slot or a cross slot of unequal slot lengths in the triangular patch, circularly polarized radiation of microstrip antennas can easily be achieved using a single probe feed. Furthermore, results show that for the design with a cross slot, the proposed antenna can perform CP radiation with a reduced antenna size at a given frequency (denoted as compact CP operation here); that is, the required antenna size is smaller for the proposed antenna for performing CP radiation as compared to a conventional circularly polarized triangular microstrip antenna at a fixed operating frequency. Details of the proposed CP designs are described, and typical experimental results are presented and discussed.
A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer Screening in Rotterdam, Netherlands (2010)

Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies.
Smooth muscle contractility in prostatic hyperplasia: Role of cyclic adenosine monophosphate (1994)

The role of cyclic 3'-5' adenosine monophosphate (cAMP) on alpha 1-adrenoceptor (alpha 1-receptor) induced smooth muscle contractions in symptomatic benign prostatic hyperplasia (BPH) was investigated. Application of the selective alpha 1-receptor agonist phenylephrine (PE) induced fully reversible contractions in a dose-dependent fashion. Phosphodiesterase (PDE) inhibitors blocking the degradation of cAMP suppressed the PE induced contractions as follows: theophylline (1 mM), 91.1 +/- 1.4%; papaverine (0.5 mM), 822.8 +/- 3.2%; milrinone (0.5 mM), 68.2 +/- 0.6%. Forskolin (50 microM), which elevates cAMP through direct activation of adenylatecyclase (AC), inhibited the PE induced contractions by 82.4 +/- 3.6%. To further increase the intracellular cAMP concentration ([cAMP]i), the membrane permeable cAMP analogue N6-2'-O-dibutyryladenosine derivative (dBcAMP; 1 mM) was applied and reduced the PE evoked contractions by 69.8 +/- 2.3%. We conclude that elevation of [cAMP]i is an important step in inducing smooth muscle relaxation.
Colouring matters of Australian plants. XXIII. A new synthesis of arylphenalenones and naphthoxanthenones (1980)

Condensation of naphthalene-2,7-diol with 2,4-dioxo-4-phenylbutanoic acid gives 6-hydroxy-1-oxo-9-phenyl-1H-phenalene-7-carboxylic acid which is readily converted into the lactone and on treatment with diazomethane forms only methyl 6-methoxy-1-oxo-9-phenyl-1H-phenalene-7- carboxylate. Analogous reactions of other 4-aryl-2,4-dioxobutanoic acids with naphthalene-2,7-diol or with 3,6-dimethoxynaphthalene-2,7- diol give easy access to arylphenalenones and naphthoxanthenones related to natural pigments.
Second generation sequencing allows for mtDNA mixture deconvolution and high resolution detection of heteroplasmy (2011)

The ability to routinely deconvolute mtDNA mixtures down to a level of 1:250 allows for high resolution analysis of mtDNA heteroplasmy, and for differentiation of individuals from the same maternal lineage. The pyrosequencing approach results in poor resolution of homopolymeric sequences, and PCR/sequencing artifacts require a filtering mechanism similar to that for STR stutter and spectral bleed through. In addition, chimeric sequences from jumping PCR must be addressed to make the method operational.
Safety Issues Specific to Clinical Development of Protein Therapeutics (2008)

Discoveries in molecular sciences have advanced research into therapeutics that target an array of newly identified ligands and receptors with the hope of meeting critical needs of patients with chronic or life-threatening diseases. Protein or biologic therapeutics include peptides, endogenous proteins, monoclonal antibodies, hybrids such as Fc construct molecules (including peptibodies and soluble receptors), and avimers. Proteins may be purified animal derivatives, fully human, or have portions of animal and human proteins engineered together into chimeric and humanized monoclonal antibodies. Although some reports distinguish therapeutic proteins from monoclonal antibodies, for the purposes of this article the terms biologics and proteins are used interchangeably. Clinical Pharmacology & Therapeutics (2008); 84, 5, 624–627 doi:10.1038/clpt.2008.158
Study of the trabecular projections (Chordae Willisii) of the superior sagittal sinus. (1997)

The trabecular projections or Chordae Willisii were studied in the internal surface of the human superior sagittal sinus, being defined and quantified as to having relation with afferent veins to the sinus, as to their lateral or medial location and also in the anteroposterior direction. The results indicate a predominance of trabecular projections with no relation to afferent vessels to the sinus in its medial portion and central region, as well as predominance of these projections on the left side. The number of trabecular projections related to afferent vessels was nearly the same when left and right sides of the superior sagittal sinus were compared.
Anti-Helicobacter pyloriactivity ofPlumbago zeylanicaL. (2004)

It has been shown that the presence of infection by Helicobacter pylori is strongly associated with gastric cancer and peptic ulceration. In western medicine, a 3-fold therapeutic regimen, emphasizing the use of antibiotics, is typically used to suppress H. pylori activity. However, antibiotic drug resistance frequently develops as a consequence of such treatment. In our previous study, 50 Taiwanese folk medicinal plants were screened for their anti-H. pylori activities. The results revealed that Plumbago zeylanica L. had the highest inhibitory effects against H. pylori. In this study, therefore, we have focused on establishing the anti-H. pylori activities of P. zeylanica L. Water and the organic solvents ethanol, ethyl acetate and acetone were used for P. zeylanica L. extraction, obtaining yields of 1.66-6.84% (w/w). Excluding the water extract, higher anti-H. pylori activity was demonstrated for all the extracts, both using the agar diffusion and dilution methods. The ethyl acetate extract exhibited the lowest minimum inhibitory concentrations against five H. pylori strains, of which ranged from 0.32 to 1.28 mg ml-1, followed, in ascending order, by the acetone, ethanol and water analogs. Bactericidal activity was determined for P. zeylanica L. extracts, with the lowest minimum bactericidal concentrations (5.12-20.48 mg ml-1) demonstrated for the ethyl acetate, followed, in ascending order, by the acetone and ethanol analogs. Bactericidal activity appeared to be in a dose-dependent manner. Through a broad pH range (2-7), bactericidal activity was not affected when extract concentrations were greater than or equal to the minimum bactericidal concentration. High stability was demonstrated for the ethyl acetate P. zeylanica L. extract within pH range of 1-7, exhibiting all pH treatments bactericidal activity.
Multiple roles of phosphatidylinositol 3-kinase in regulation of glucose transport, amino acid transport, and glucose transporters in L6 skeletal muscle cells (1995)

Phosphatidylinositol 3-kinase (PI3k) activity is required for the insulin stimulation of glucose transport in adipocytes and Chinese hamster ovary cells. Wortmannin (WM), an inhibitor of PI3k, inhibits the stimulation of glucose transport by insulin and the gain of glucose transporters at the cell surface. However, the effect of inhibition of PI3k on the maintenance of the basal and the insulin-stimulated glucose transport and on the intracellular donor pool of glucose transporters has not been clarified. Here we show that in L6 skeletal muscle cells in culture WM significantly inhibits the basal PI3k activity (by 40%), decreases the levels of phosphatidylinositol 3,4-phosphate and 3,4,5-phosphate (by about 50%) and abolishes the activation of the enzyme by insulin. WM inhibited the basal rate of transport of glucose (by 45%) and of amino acids through system A (by 25%) and abolished their stimulation by insulin. Insulin caused a transient increase in PI3k activity and PI3k products that returned to basal levels within 40 min, whereas glucose and amino acid transport remained elevated. Under these conditions, WM reduced the rate of glucose and amino acid transport back to basal levels. In unstimulated cells, WM decreased significantly the GLUT4 glucose transporter content at the plasma membrane and prevented the ability of insulin to recruit transporters to this membrane. Interestingly, the intracellular pools of the GLUT3 and GLUT4 glucose transporters were significantly reduced in response to WM treatment alone. We conclude that in muscle cells PI3k activity is required to maintain basal and insulin-stimulated glucose and amino acid transport, as well as to develop the stimulation of the two transport processes in response to the hormone. We hypothesize that PI3k, likely through production of phosphatidylinositol 3,4-phosphate and 3,4,5-phosphate, regulates the basal plasma membrane glucose transporter recycling and the organization of the transporter intracellular pool, in addition to being an insulin signal.