gebhart/patrepeval huggingface dataset:
Average modeling and analysis of a Flyback with Active Clamp topology based on a very simple transformer (2007)

This paper presents the average model and analyzes the dynamics of a low power (10W) topology derived from Flyback with Active Clamp based on very simple and low cost transformers. The main feature of this Flyback topology is that the ratio between magnetizing inductance and the series inductance (leakage or integrated inductor) is very low (around 10/1). Operation of the topology is analyzed. The relationship between variables allows for reducing the order of the large signal average model. The average model is validated in a prototype (VIN =42V, VOUT = 3.3V, IOUT = 5A). The proposed solution, presented in [1], achieves a promising trade-off between efficiency and cost in low power applications with medium or high input/output voltage ratio.
Prostaglandin E Receptor EP4 Antagonism Inhibits Breast Cancer Metastasis (2006)

Cyclooxygenase-2 (COX-2) expression in epithelial tumors is frequently associated with a poor prognosis. In a murine model of metastatic breast cancer, we showed that COX-2 inhibition is associated with decreased metastatic capacity. The COX-2 product, prostaglandin E(2) (PGE(2)), acts through a family of G protein-coupled receptors designated EP1-4 that mediate intracellular signaling by multiple pathways. We characterized EP receptor expression on three murine mammary tumor cell lines and show that all four EP isoforms were detected in each cell. Stimulation of cells with either PGE(2) or the selective EP4/EP2 agonist PGE(1)-OH resulted in increased intracellular cyclic AMP and this response was inhibited with either EP2 or EP4 antagonists. Nothing is known about the function of EP receptors in tumor metastasis. We tested the hypothesis that the prevention of EP receptor signaling would, like inhibition of PGE(2) synthesis, inhibit tumor metastasis. Our results show for the first time that antagonism of the EP4 receptor with either AH23848 or ONO-AE3-208 reduced metastasis as compared with vehicle-treated controls. The therapeutic effect was comparable to that observed with the dual COX-1/COX-2 inhibitor indomethacin. EP3 antagonism had no effect on tumor metastasis. Mammary tumor cells migrated in vitro in response to PGE(2) and this chemotactic response was blocked by EP receptor antagonists. Likewise, the proliferation of tumor cells was also directly inhibited by antagonists of either EP4 or EP1/EP2. These studies support the hypothesis that EP receptor antagonists may be an alternative approach to the use of COX inhibitors to prevent tumor metastasis.
Binding of purified multiple antibiotic-resistance repressor protein (MarR) to mar operator sequences. (1995)

Elevated expression of the marORAB multiple antibiotic-resistance operon enhances the resistance of Escherichia coli to various medically significant antibiotics. Transcription of the operon is repressed in vivo by the marR-encoded protein, MarR, and derepressed by salicylate and certain antibiotics. The possibility that repression results from MarR interacting with the marO operator-promoter region was studied in vitro using purified MarR and a DNA fragment containing marO. MarR formed at least two complexes with marO DNA, bound > 30-fold more tightly to it than to salmon sperm DNA, and protected two separate 21-bp sites within marO from digestion by DNase I. Site I abuts the downstream side of the putative -35 transcription-start signal and includes 4 bp of the -10 signal. Site II begins 13 bp downstream of site I, ending immediately before the first base pair of marR. Site II, approximately 80% homologous to site I, is not required for repression since a site II-deleted mutant (marO133) was repressed in trans by wild-type MarR. The absence of site II did not prevent MarR from complexing with the site I of marO133. Salicylate bound to MarR (Kd approximately 0.5 mM) and weakened the interaction of MarR with sites I and II. Thus, repression of the mar operon, which curbs the antibiotic resistance of E. coli, correlates with the formation of MarR-site I complexes. Salicylate appears to induce the mar operon by binding to MarR and inhibiting complex formation, whereas tetracycline and chloramphenicol, which neither bind MarR nor inhibit complex formation, must induce by an indirect mechanism.
THE MONTANA-STUDY: IDEALISTIC FAILURE OR INNOVATIVE SUCCESS (1991)

University System and funded by the Rockefeller Foundation. The project experimented with study groups and community research as a technique for stabilizing and improving community living. The purpose of this current study was to examine critically why the Montana Study was not institutionalized and whether the Montana Study&amp;apos;s techniques were viable methods for adult education and community development. This investigation employed a case study approach using historical analysis of primary documents and oral histories from study group participants. Primary sources used
Single copy shRNA configuration for ubiquitous gene knockdown in mice (2005)

RNA interference through the expression of small hairpin RNA (shRNA) molecules has become a very promising tool in reverse mouse genetics as it may allow inexpensive and rapid gene function analysis in vivo. However, the prerequisites for ubiquitous and reproducible shRNA expression are not well defined. Here we show that a single copy shRNA-transgene can mediate body-wide gene silencing in mice when inserted in a defined locus of the genome. The most commonly used promoters for shRNA expression, H1 and U6, showed a comparably broad activity in this configuration. Taken together, the results define a novel approach for efficient interference with expression of defined genes in vivo. Moreover, we provide a rapid strategy for the production of gene knockdown mice combining recombinase mediated cassette exchange and tetraploid blastocyst complementation approaches.
Exendin-4 Decelerates Food Intake, Weight Gain, and Fat Deposition in Zucker Rats (2000)

Exendin-4 is a 39 amino acid peptide produced in the salivary gland of the Gila monster lizard. It has a 53% amino acid homology to the incretin hormone glucagon-like peptide-1 (GLP-1). Exendin-4 induces insulin release through activation of the GLP- 1 receptor but is a much more potent insulinotropic agent than GLP-1. Of critical importance for its potential use as a treatment for diabetes is its much longer biological effect in vivo. Previous studies involving once daily administration of exendin-4 over 13 weeks to db/db mice demonstrated that it lowers hemoglobin A1c (HbA1c), a marker of mean blood glucose levels. Food consumption in the treated animals dropped over the first 4 days and then increased to a level comparable with that of the untreated animals. In this study, we initially examined the effect of once daily injections (over 14 days) on the food consumption of Zucker fatty rats. We observed an immediate reduction in food intake which then leveled off(after 5 days) to match that of the untreated animals. Subsequently we injected the same animals twice daily (treatment period of 56 days in total) and observed a sustained reduction in food intake and weight-gain. This was matched by a reduction in the critical parameters of HbA1c, fasting blood glucose and plasma insulin. MRI imaging of the abdominal regions of the animals showed that initially only the amount of fat deposited in the sc region was reduced after 4 weeks exendin-4 treatment. At the 8-week time point there was a corresponding decrease in the amount of visceral fat deposition. The combination of appetite reduction, decreased fat deposition and an improvement in the parameters associated with glucose intolerance makes a case for the use of exendin-4 as a treatment for diabetes.
Glassy State and Secondary Structures of Chiral Macromolecules:  Polyisocyanates and Polyketones (2000)

The temperature dependence of the optical activity in the amorphous and therefore nonbirefringent solid state is used here to study the conformational properties of polyisocyanates and isotactic polyketones. Optically active polyisocyanates, which are not entirely amorphous in the solid state, were rendered amorphous by blending, while the glass transition temperature of the inherently amorphous polyketones was varied from 145 to 1 °C by terpolymerization of alternating styrenic/CO units with alternating 1-alkene/CO units. In both polymer systems, the optical activity changed significantly at temperatures only above Tg. This result, which was controlled for the contribution of degradation and epimerization of stereocenters in the polyketones, requires that the chiral optical properties of these polymers arise from long-range conformational properties of the chain that are impeded from changing with temperature only in the glassy state. This is consistent with the known character of the polyisocyanates but acts to reveal the previously uncertain basis of the optical activity in the isotactic polyketones studied here.
Calcium‐dependent neutral proteinase (calpain) in fracture healing in rats (1994)

Calpain refers to Ca(2+)-dependent neutral cysteine proteinase, which originally was thought to be an intracellular proteinase but recently has been shown to function extracellularly as well. This report describes the immunohistochemical demonstration of calpain and biochemical changes in the amount of calpain during fracture healing in rats. The tibiae of 6-week-old Wistar rats were fractured, and calluses were obtained 5-28 days after fracture. A frozen section of the fracture callus was stained by the immunoperoxidase method with use of polyclonal antibodies of calpains I and II. Positive staining was noted with the anti-calpain II antibody in the perivascular areas, chondrocytes, and cartilage matrix in calluses at 5, 7, and 10 days. Less intense staining was seen in older calluses. The caseinolytic activity of calpain II reached its maximum on the 5th day, was high on the 7th and 10th days, and decreased rapidly thereafter. The quantity of calpain II was dependent on the process of fracture healing. It was concluded that calpain was working as one of the matrix proteinases in fracture callus.
Evolving Accelerated Amidation by SpyTag/SpyCatcher to Analyze Membrane Dynamics (2017)

SpyTag is a peptide that forms a spontaneous amide bond with its protein partner SpyCatcher. This protein superglue is a broadly useful tool for molecular assembly, locking together biological building blocks efficiently and irreversibly in diverse architectures. We initially developed SpyTag and SpyCatcher by rational design, through splitting a domain from a Gram-positive bacterial adhesin. In this work, we established a phage-display platform to select for specific amidation, leading to an order of magnitude acceleration for interaction of the SpyTag002 variant with the SpyCatcher002 variant. We show that the 002 pair bonds rapidly under a wide range of conditions and at either protein terminus. SpyCatcher002 was fused to an intimin derived from enterohemorrhagic Escherichia coli. SpyTag002 reaction enabled specific and covalent decoration of intimin for live cell fluorescent imaging of the dynamics of the bacterial outer membrane as cells divide.
Studies of the reactive ion etching of SiGe alloys (1991)

Reactive-ion etching (RIE) of epitaxial, strained Si1−xGex alloys, x≤0.20, in fluorine-chlorine-, and bromine-based low-pressure plasmas has been investigated. The reactive-ion etch rates of the Si1−xGex alloys increase with the Ge content of the alloy for most etching gases. This effect is most pronounced for fluorine (CF4 and SF6) plasmas where the etch rate of a Si80Ge20 alloy is increased by a factor of ≂2 over that of Si. The etch rate enhancement is of reduced importance for chlorine (CF2Cl2) and bromine (HBr) plasmas, where the etch rate increases by less than 50% for a Si80Ge20 alloy relative to that of elemental Si. Analysis shows that the etch rate increase is not accounted for by the greater rate of gasification of Ge atoms alone but that the presence of Ge atoms in the SiGe alloy increases the Si etch product formation rate. Directional SiGe profiles are observed for CF2Cl2 and HBr plasmas which are identical to those obtained with Si. After etching in CF4 or SF6 plasmas the Ge surface concentration of the SiGe alloy is increased relative to its bulk value and both fluorinated Si and Ge are observed by in situ x-ray photoemission spectroscopy. On the other hand, for CF2Cl2 and HBr plasmas the SiGe surface is Si rich. The effect of band-gap narrowing, strain and plasma-induced surface modifications on the etching of the SiGe alloys is discussed.
Thermal alteration of oleic acid in the presence of clay catalysts with co‐catalysts (1985)

Abstract The effects of added co‐catalysts on the clay catalyzed polymerization of oleic acid have been investigated. Heating oleic acid at 230 C for 3 hr with a clay catalyst gave a polymer fraction (dimer and trimer acids, 35% yield) and a monomer fraction (branched chain isomers of oleic acid, 27% yield) as the major products. The variation in yield between the polymer and monomer products was found to be dependent upon the co‐catalyst used with the clay catalyst. For example, with both acidic and basic clays, polymer formation is favored (55% yield) in the presence of water and/or metal ions. In contrast, when Bronsted acids such as methanesulfonic or phosphoric acid are used as co‐catalysts, the yield of branched monomer increased significantly (50%). Studies on the adsorption of oleic and Bronsted acids onto the clay surface showed that isomer formation is favored when both the oleic acid and the Bronsted acids are adsorbed onto the clay surface at selected molar ratios.
Lipid detection in atherosclerotic human coronaries by spectroscopic intravascular photoacoustic imaging (2013)

The presence of lipids in atherosclerotic coronary lesions is an important determinant of their potential to trigger acute coronary events. Spectroscopic intravascular photoacoustic imaging (sIVPA) has the potential to automatically detect lipids in atherosclerotic lesions. For real-time in vivo imaging, limiting the number of excitation wavelengths is crucial. We explored methods for plaque lipid detection using sIVPA, with the aim to minimize the number of laser pulses per image line. A combined intravascular ultrasound (IVUS) and photoacoustic imaging system was used to image a vessel phantom and human coronary arteries ex vivo. We acquired co-registered cross-sectional images at several wavelengths near 1200 nm, a lipid-specific absorption band. Correlating the photoacoustic spectra at 6 or 3 wavelengths from 1185 to 1235 nm with the absorption spectrum of cholesterol and peri-adventitial tissue, we could detect and differentiate the lipids in the atherosclerotic plaque and peri-adventitial lipids, respectively. With two wavelengths, both plaque and peri-adventitial lipids were detected but could not be distinguished.
Keeping checkpoint kinases in line: new selective inhibitors in clinical trials (2008)

Chk kinases are part of the DNA damage recognition and response pathways and as such represent attractive targets. Agents that target checkpoint kinases have demonstrated impressive evidence preclinically that this approach will provide tumour-specific potentiating agents and may have broad therapeutic utility.
Monoclonal antibodies to the major feline allergen Fel d I. II. Single step affinity purification of Fel d I, N-terminal sequence analysis, and development of a sensitive two-site immunoassay to assess Fel d I exposure. (1988)

Abstract Two mAb were used to develop new techniques for the purification and quantitation of the major feline salivary allergen, Felis domesticus allergen I (Fel d I). The allergen was purified from aqueous house dust extract with a high Fel d I content by affinity chromatography over a monoclonal immunosorbent and elution with 4 mM HCl, pH 2.5. This single step procedure gave 40 to 50% recovery of 90% pure allergen which, following final purification by size exclusion HPLC, showed a single line on immunodiffusion and crossed immunoelectrophoresis against monospecific anti-Fel d I and polyclonal anti-cat dander antibodies. The m.w. of native Fel d I was 39,000 on size exclusion HPLC, and 17,000 under nonreducing conditions on gel electrophoresis. The N-terminal amino acid sequence (33 residues) showed no homology with other known protein sequences. The combination of the SDS-PAGE and N-terminal sequence data suggests that Fel d I is a non-covalently linked homodimer. A two-site RIA was developed using mAb directed against different epitopes on Fel d I. This assay was species-specific, highly sensitive (0.0004 U/ml), and showed an excellent correlation with a polyclonal inhibition RIA (n = 27, r = 0.93, p less than 0.001). Cat allergen extracts used for immediate skin tests showed marked differences in Fel d I content (from 0.1 to 30 U/ml). Consistently high Fel d I levels were found at monthly intervals in six dust samples from four houses with cats (10 to 100 mu/g of dust). Comparisons of Fel d I and mite and pollen allergen levels showed that house dust can contain greater than 100 micrograms/g of either of these allergens and is a potent source of foreign environmental antigens. Monoclonal affinity chromatography provides a major breakthrough in the purification of Fel d I, from a source material that would otherwise have been considered impossible (house dust). The mAb assay for Fel d I is both more sensitive and more easily standardized than existing techniques. These techniques will allow full structural and antigenic analysis of Fel d I and more detailed studies on the relationship between cat antigen exposure and the development of asthma.
First synthesis of ortho-trifluoromethylated aryl triflates (1997)

An efficient method for the preparation of trifluoromethylated aryl triflates (trifluoromethanesulfonates) has been developed. Treatment of 2-iodophenol with trifluoromethanesulfonic anhydride in the presence of triethylamine gives triflate 3. Then, reaction of compound 3 with FSO2CF2CO2Me and CuI in DMF–HMPA affords trifluoromethylated aryl triflate 2. This reaction sequence is also successful for meta- and para-trifluoromethylated aryl triflates. Based on this methodology, the trifluoromethylated aryl triflate 11, a key intermediate for the preparation of the conformationally restricted retinoid 8 containing a trifluoromethyl group, has been synthesized. The cross-coupling of aryl triflate 11 with vinylstannane 17 under palladium catalysis provides compound 18, the methyl ester of retinoid 8, in moderate yield.
Origin of Low Mammalian Cell Toxicity in a Class of Highly Active Antimicrobial Amphipathic Helical Peptides (2008)

We recently described a novel antimicrobial peptide, RTA3, derived from the commensal organism Streptococcus mitis, with strong anti-Gram-negative activity, low salt sensitivity, and minimal mammalian cell toxicity in vitro and in vivo. This peptide conforms to the positively charged, amphipathic helical peptide motif, but has a positively charged amino acid (Arg-5) on the nonpolar face of the helical structure that is induced upon membrane binding. We surmised that disruption of the hydrophobic face with a positively charged residue plays a role in minimizing eukaryotic cell toxicity, and we tested this using a mutant with an R5L substitution. The greatly enhanced toxicity in the mutant peptide correlated with its ability to bind and adopt helical conformations upon interacting with neutral membranes; the wild type peptide RTA3 did not bind to neutral membranes (binding constant reduced by at least 1000-fold). Spectroscopic analysis indicates that disruption of the hydrophobic face of the parent peptide is accommodated in negatively charged membranes without partial peptide unfolding. These observations apply generally to amphipathic helical peptides of this class as we obtained similar results with a peptide and mutant pair (Chen, Y., Mant, C. T., Farmer, S. W., Hancock, R. E., Vasil, M. L., and Hodges, R. S. (2005) J. Biol. Chem. 280, 12316-12329) having similar structural properties. In contrast to previous interpretations, we demonstrate that these peptides simply do not bind well to membranes (like those of eukaryotes) with exclusively neutral lipids in their external bilayer leaflet. We highlight a significant role for tryptophan in promoting binding of amphipathic helical peptides to neutral bilayers, augmenting the arsenal of strategies to reduce mammalian toxicity in antimicrobial peptides.
A novel putative receptor protein tyrosine kinase of the met family. (1993)

By successive screenings of cDNA libraries prepared from human tumours and from human foreskin keratinocytes, we have isolated overlapping cDNAs coding for a novel protein which we call Ron, with sequence characteristics of a receptor protein tyrosine kinase. Ron is a 1400 amino acid protein structurally similar to the 1408 amino acid product of the C-MET proto-oncogene, the receptor for hepatocyte growth factor and scatter factor. The two proteins have 63% overall sequence identity in their intracellular regions. We have localised the RON gene to human chromosome region 3p21, a region frequently deleted in small cell carcinoma of the lung and in renal cell carcinoma, and which is believed to harbour unidentified tumour suppressor genes. Interestingly, normal lung tissue contains transcripts of the RON gene.
Chronic hepatitis B: Are we close to a cure? (2015)

Approximately 300 million people worldwide are persistently infected with the hepatitis B virus and are at risk of developing hepatocellular carcinoma and liver cirrhosis, which can progress to end-stage liver disease. Despite the effectiveness of the current vaccination policy, the prevalence of the disease remains high, and the burden for health services is considerable. The currently available antiviral strategies are either poorly effective or only effective for non-curative suppression of viral replication. Recent efforts have been focused on improving the cure rate for chronic hepatitis B and developing strategies to eliminate infected cells. Several approaches are under evaluation, and these include targeting the virus at different stages of its life cycle and boosting the antiviral immune response. This article reviews these latest approaches and comments on their feasibility and potential translation into clinical applications.
Identification of a novel phosphatase sequence motif (1997)

We have identified a novel, conserved phosphatase sequence motif, KXXXXXXRP-(X12-54)-PSGH-(X31-54)-SRXXXXX HXXXD, that is shared among several lipid phosphatases, the mammalian glucose-6-phosphatases, and a collection of bacterial nonspecific acid phosphatases. This sequence was also found in the vanadium-containing chloroperoxidase of Curvularia inaequalis. Several lines of evidence support this phosphatase motif identification. Crystal structure data on chloroperoxidase revealed that all three domains are in close proximity and several of the conserved residues are involved in the binding of the cofactor, vanadate, a compound structurally similar to phosphate. Structure-function analysis of the human glucose-6-phosphatase has shown that two of the conserved residues (the first domain arginine and the central domain histidine) are essential for enzyme activity. This conserved sequence motif was used to identify nine additional putative phosphatases from sequence databases, one of which has been determined to be a lipid phosphatase in yeast.
Determination of influenza virus proteins required for genome replication (1990)

An artificial vaccinia virus vector-driven replication system for influenza virus RNA has been developed. In this system, a synthetic NS-like gene is replicated and expressed by influenza virus proteins supplied through infection with vaccinia virus recombinant vectors. The minimum subset of influenza virus proteins needed for specific replication and expression of the viral ribonucleoprotein was found to be the three polymerase proteins (PB1, PB2, and PA) and the nucleoprotein.