gebhart/patrepeval huggingface dataset:
Effects of covalently linked insulin dimers on receptor kinase activity and receptor down regulation (1984)

Certain covalently linked insulin dimers have previously been found to have a greater ability to bind to the insulin receptor than to stimulate lipogenesis in adipocytes. The present report presents data indicating that the same insulin dimers also have a greater ability to bind to the receptor than to stimulate the kinase activity of the insulin receptor. In particular, one such covalently linked insulin dimer had less than 1% the potency of native insulin in stimulating the receptor kinase although it could bind to the solubilized receptor with 30% the potency of native insulin. In contrast, this dimer could down regulate the insulin receptor with approximately 30% the potency of native insulin. These results suggest that stimulation of the receptor kinase may require more than simple occupancy of the receptor binding site whereas down regulation of the receptor may require only the binding of ligand to the receptor.
Pie-shaped resonant-cavity InGaAs/InAlGaAs/InP photodetector arrays for direct-coupled wavelength demultiplexing applications (1997)

Summary form only given. For parallel demultiplexing of wavelength-encoded channels, it is desirable to have arrays of wavelength-selective photodetectors, to reduce crosstalk in spatially dense arrays. In order to satisfy this requirement, we need to have a high-Q cavity which can be achieved by minimizing cavity losses and increasing cavity length. In this work a simple and thus lower-cost approach has been investigated. The photodiodes are made in the "pie"-like shape and arranged within a 60-/spl mu/m-diameter circle. The lattice-matched InAlGaAs-InGaAs-InP material system has been used in this study.
Digital voice considerations for the land-mobile radio services (1977)

This paper investigates the ability of a popular digital voice technique (Adaptive Delta Modulation, ADM/FSK) to operate compatibly in the present Private Land-Mobile Radio Services. It analyzes the technique relative to current FCC rules on cochannel coordination distance, adjacent channel coordination distance, baseband filtering, and analog/digital co-channel compatibility, and recommends rule changes to accommodate this class of digital voice equipment.
Removal of Substrate Inhibition and Increase in Maximal Velocity in the Short Chain Dehydrogenase/Reductase Salutaridine Reductase Involved in Morphine Biosynthesis (2009)

Salutaridine reductase (SalR, EC 1.1.1.248) catalyzes the stereospecific reduction of salutaridine to 7(S)-salutaridinol in the biosynthesis of morphine. It belongs to a new, plant-specific class of short-chain dehydrogenases, which are characterized by their monomeric nature and increased length compared with related enzymes. Homology modeling and substrate docking suggested that additional amino acids form a novel alpha-helical element, which is involved in substrate binding. Site-directed mutagenesis and subsequent studies on enzyme kinetics revealed the importance of three residues in this element for substrate binding. Further replacement of eight additional residues led to the characterization of the entire substrate binding pocket. In addition, a specific role in salutaridine binding by either hydrogen bond formation or hydrophobic interactions was assigned to each amino acid. Substrate docking also revealed an alternative mode for salutaridine binding, which could explain the strong substrate inhibition of SalR. An alternate arrangement of salutaridine in the enzyme was corroborated by the effect of various amino acid substitutions on substrate inhibition. In most cases, the complete removal of substrate inhibition was accompanied by a substantial loss in enzyme activity. However, some mutations greatly reduced substrate inhibition while maintaining or even increasing the maximal velocity. Based on these results, a double mutant of SalR was created that exhibited the complete absence of substrate inhibition and higher activity compared with wild-type SalR.
Telomerase activity in normal leukocytes and in hematologic malignancies (1995)

Telomeres are essential for function and stability of eukaryotic chromosomes. In the absence of telomerase, the enzyme that synthesizes telomeric DNA, telomeres shorten with cell division, a process thought to contribute to cell senescence and the proliferative crisis of transformed cells. We reported telomere stabilization concomitant with detection of telomerase activity in cells immortalized in vitro and in ovarian carcinoma cells, and suggested that telomerase is essential for unlimited cell proliferation. We have now examined the temporal pattern of telomerase expression in selected hematologic malignancies. We found that, unlike other somatic tissues, peripheral, cord blood, and bone marrow leukocytes from normal donors expressed low levels of telomerase activity. In leukocytes from chronic lymphocytic leukemia (CLL) patients, activity was lower than in controls in early disease, and comparable with controls in late disease. Relative to bone marrow, telomerase activity was enhanced in myelodysplastic syndrome (MDS) and more significantly so in acute myeloid leukemia (AML). Regardless of telomerase levels, telomeres shortened with progression of the diseases. Our results suggest that early CLL and MDS cells lack an efficient mechanism of telomere maintenance and that telomerase is activated late in the progression of these cancers, presumably when critical telomere loss generates selective pressure for cell immortality.
Diameter Base Protocol (2003)

The Diameter base protocol is intended to provide an Authentication, Authorization and Accounting (AAA) framework for applications such as network access or IP mobility. Diameter is also intended to work in both local Authentication, Authorization & Accounting and roaming situations. This document specifies the message format, transport, error reporting, accounting and security services to be used by all Diameter applications. The Diameter base application needs to be supported by all Diameter implementations.
Current ADC Linker Chemistry (2015)

The list of ADCs in the clinic continues to grow, bolstered by the success of first two marketed ADCs: ADCETRIS® and Kadcyla®. Currently, there are 40 ADCs in various phases of clinical development. However, only 34 of these have published their structures. Of the 34 disclosed structures, 24 of them use a linkage to the thiol of cysteines on the monoclonal antibody. The remaining 10 candidates utilize chemistry to surface lysines of the antibody. Due to the inherent heterogeneity of conjugation to the multiple lysines or cysteines found in mAbs, significant research efforts are now being directed toward the production of discrete, homogeneous ADC products, via site-specific conjugation. These site-specific conjugations may involve genetic engineering of the mAb to introduce discrete, available cysteines or non-natural amino acids with an orthogonally-reactive functional group handle such as an aldehyde, ketone, azido, or alkynyl tag. These site-specific approaches not only increase the homogeneity of ADCs but also enable novel bio-orthogonal chemistries that utilize reactive moieties other than thiol or amine. This broadens the diversity of linkers that can be utilized which will lead to better linker design in future generations of ADCs.
Comparison of plasma phyto-oestrogen levels in sheep and cattle after feeding on fresh clover (1971)

Wethers and heifers were fed on freshly cut pasture (red clover, Mt. Barker or Tallarook subterranean clover, or ryegrass) and the blood plasma concentration of the phyto-oestrogens and their metabolites estimated 5 hr, 24 hr, and 6 days after the beginning of the feeding. The heifers were allowed to graze the pastures after the first day. On the basis of increase in teat length in the wethers, red clover and Tallarook were estimated to have equivalent oestrogenicity ; Mt. Barker was much less active. Qualitatively, the metabolism of formononetin and biochanin A appeared similar in the two species, but there was evidence that the rates of metabolism and of conjugation were faster in cattle than in sheep. The findings are discussed in relation to an infertility syndrome in dairy cattle.
Lipoic acid inhibits cell proliferation of tumor cells in vitro and in vivo (2012)

Cancer cells convert glucose preferentially to lactate even in the presence of oxygen (aerobic glycolysis-Warburg effect). New concepts in cancer treatment aim at inhibition of aerobic glycolysis. Pyruvate dehydrogenase converts pyruvate to acetylCoA thus preventing lactate formation. Therefore, the aim of this study was to evaluate compounds that could activate pyruvate dehydrogenase in cancer cells. We investigated the effects of (R)-(+)-α-lipoic acid (LPA) and dichloroacetate (DCA), possible activators of pyruvate dehydrogenase, on suppression of aerobic glycolysis and induction of cell death. The neuroblastoma cell lines Kelly, SK-N-SH, Neuro-2a and the breast cancer cell line SkBr3 were incubated with different concentrations (0.1-30 mM) of LPA and DCA. The effects of both compounds on cell viability/proliferation (WST-1 assay), [18F]-FDG uptake, lactate production and induction of apoptosis (flow cytometric detection of caspase-3) were evaluated. Furthermore, NMRI nu/nu mice that had been inoculated s.c. with SkBr3 cells were treated daily for four weeks with LPA (i.p, 18.5 mg/kg) starting at day 7 p.i.. Tumor development was measured with a sliding caliper and monitored via [18F]-FDG-PET. Residual tumors after therapy were examined histopathologically. These data suggests that LPA can reduce (1) cell viability/proliferation, (2) uptake of [18F]-FDG and (3) lactate production and increase apoptosis in all investigated cell lines. In contrast, DCA was almost ineffective. In the mouse xenograft model with s.c. SkBr3 cells, daily treatment with LPA retarded tumor progression. Therefore, LPA seems to be a promising compound for cancer treatment.
Polymer complements to nucleotide bases. Selective binding of adenine derivatives to imprinted polymers (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolymer complements to nucleotide bases. Selective binding of adenine derivatives to imprinted polymersKenneth J. Shea, David A. Spivak, and Boerje SellergrenCite this: J. Am. Chem. Soc. 1993, 115, 8, 3368–3369Publication Date (Print):April 1, 1993Publication History Published online1 May 2002Published inissue 1 April 1993https://pubs.acs.org/doi/10.1021/ja00061a061https://doi.org/10.1021/ja00061a061research-articleACS PublicationsRequest reuse permissionsArticle Views804Altmetric-Citations208LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Improved Characterization of Fine-Texture Soils Using On-Ground GPR Full-Waveform Inversion (2013)

Ground-penetrating radar (GPR) uses the recording of electromagnetic waves and is increasingly applied for a wide range of applications. Traditionally, the main focus was on the analysis of the medium permittivity since estimates of the conductivity using the far-field approximation contain relatively large errors and cannot be interpreted quantitatively. Recently, a full-waveform inversion (FWI) scheme has been developed that is able to reliably estimate permittivity and conductivity values by analyzing reflected waves present in on-ground GPR data. It is based on a frequency-domain solution of Maxwell's equations including far, intermediate, and near fields assuming a 3-D subsurface. Here, we adapt the FWI scheme for on-ground GPR to invert the direct ground wave traveling through the shallow subsurface. Due to possible interference with the airwaves and other reflections, an automated time-domain filter needed to be included in the inversion. In addition to the obtained permittivity and conductivity values, also the wavelet center frequency and amplitude return valuable information that can be used for soil characterization. Combined geophysical measurements were carried out over a silty loam with significant variability in the soil texture. The obtained medium properties are consistent with Theta probe, electromagnetic resistivity tomography, and electromagnetic induction results and enable the formulation of an empirical relationship between soil texture and soil properties. The permittivities and conductivities increase with increasing clay and silt and decreasing skeleton content. Moreover, with increasing permittivities and conductivities, the wavelet center frequency decreases, whereas the wavelet amplitude increases, which is consistent with the radiation pattern and the antenna coupling characteristics.
Strategies for targeting primate neural circuits with viral vectors (2016)

Understanding how the brain works requires understanding how different types of neurons contribute to circuit function and organism behavior. Progress on this front has been accelerated by optogenetics and chemogenetics, which provide an unprecedented level of control over distinct neuronal types in small animals. In primates, however, targeting specific types of neurons with these tools remains challenging. In this review, we discuss existing and emerging strategies for directing genetic manipulations to targeted neurons in the adult primate central nervous system. We review the literature on viral vectors for gene delivery to neurons, focusing on adeno-associated viral vectors and lentiviral vectors, their tropism for different cell types, and prospects for new variants with improved efficacy and selectivity. We discuss two projection targeting approaches for probing neural circuits: anterograde projection targeting and retrograde transport of viral vectors. We conclude with an analysis of cell type-specific promoters and other nucleotide sequences that can be used in viral vectors to target neuronal types at the transcriptional level.
Chemically Defined Culture and Cardiomyocyte Differentiation of Human Pluripotent Stem Cells (2015)

Since the first discovery that human pluripotent stem cells (hPS cells) can differentiate to cardiomyocytes, efforts have been made to optimize the conditions under which this process occurs. One of the most effective methodologies to optimize this process is reductionist simplification of the medium formula, which eliminates complex animal-derived components to help reveal the precise underlying mechanisms. Here we describe our latest, cost-effective and efficient methodology for the culture of hPS cells in the pluripotent state using a modified variant of chemically defined E8 medium. We provide exact guidelines for cell handling under these conditions, including non-enzymatic EDTA passaging, which have been optimized for subsequent cardiomyocyte differentiation. We describe in depth the latest version of our monolayer chemically defined small molecule differentiation protocol, including metabolic selection-based cardiomyocyte purification and the addition of triiodothyronine to enhance cardiomyocyte maturation. Finally, we describe a method for the dissociation of hPS cell-derived cardiomyocytes, cryopreservation, and thawing.
The variant undecapeptide sequence of the Arcanobacterium pyogenes haemolysin, pyolysin, is required for full cytolytic activity (2002)

The cholesterol-dependent cytolysins (CDCs) are characterized by an undecapeptide sequence (ECTGLAWEWWR) that is located near the C terminus and within domain 4 of these proteins. Pyolysin (PLO), the CDC of Arcanobacterium pyogenes, has a variant undecapeptide sequence (EATGLAWDPWW). Site-directed mutants were constructed in undecapeptide residues in a recombinant PLO molecule containing a hexahistidine tag (His-PLO). Mutations in each of the three undecapeptide tryptophan residues resulted in low haemolytic activity, confirming the importance of these residues in the protein. Deletion of a proline residue (P(499)), inserted in PLO, or substitution of this residue with either phenylalanine or glycine resulted in mutant proteins with undetectable or low haemolytic activities, indicating that P(499) is essential for His-PLO haemolytic activity. Substitution of the PLO undecapeptide sequence with a consensus undecapeptide resulted in a His-PLO protein with only 0.1% activity, confirming that the variant PLO undecapeptide is required for the full cytolytic activity of this toxin. The presence of the conserved undecapeptide cysteine residue either alone (His-PLO.C(492)) or in a consensus sequence resulted in His-PLO molecules which were activated in the presence of reducing compounds, confirming the importance of this residue in the thiol-activated nature of many CDC toxins. The ability of His-PLO mutant proteins to bind cholesterol mimicked haemolytic activity, with the exception of His-PLO.C(492), which, despite having reduced haemolytic activity, showed an increased ability to bind cholesterol compared to His-PLO. Despite reductions in haemolytic activity and cholesterol-binding, all mutant proteins were still able to bind to erythrocyte membranes, suggesting that other regions of PLO may recognize host-cell membranes, through receptors other than cholesterol.
Pulsating bubble technique for evaluating pulmonary surfactant (1977)

Surface tension is determined with an apparatus which records pressure across the surface of a bubble, expanded in the sample liquid and communicating with ambient air. The disposable sample chamber, with a volume of 20 microliter, communicates with a pulsator and a pressure transducer. The volume displacement of the pulsator's moving piston is hydraulically geared down 1,000 times, which gives the pulsator a stroke volume of 0.43 microliter. When this volume is moving into the sample chamber, it causes the bubble radius to change from a maximum of 0.55 mm, accurately measured through a microscope, to a minimum of 0.4 mm. The pulsator speed is usually 20 rpm, but it can be changed from 0.02 to 80 rpm. From the known pressure gradient across bubble surface, and bubble radius, surface tension is calculated with the law of Laplace.
Pilin-based anti-Pseudomonas vaccines: latest developments and perspectives. (1997)

Among the several adhesins produced by Pseudomonas aeruginosa (Pa), the type-4 pilus promotes the majority of the adherence capability of the bacterium to epithelial cells and it is a major virulence factor in an AB.Y/SnJ mouse infection model. Vaccines targeting the disulfide loop (DSL) adherence binding domain of the pilin protein should therefore provide an effective protection against initial colonization and infection with Pa. To selectively elicit adherence blocking antibodies, the pilin DSL domain was chosen as peptide antigen for the construction of recombinant protein and live vaccines. While synthetic peptide-carrier protein conjugates provided some strain-specific protection, chimeric proteins with N- or C-terminally fused pilin DSL peptides did not engender protective IgG titers mice. Integral fusions of the pilin DSL peptide with the minor coat protein of filamentous phage or surface exposed regions of an outer membrane protein resulted in a display of the peptide on the surface of the phage particles and bacterial cells respectively. However, in immunization studies neither of these live vaccines were effective immunogens. The paracrystalline S-layer of Caulobacter crescentus combines several advantages of an effective antigen surface display system. Recombinant S-layer proteins with singlecopy insertions of a pilin peptide did not engender significant IgG titers, whereas multiple tandem insertions of the same peptide increased the serum IgG response in mice a thousand times. Multiple insertions of DSL peptides from different frequent pilin prototypes may be an interesting alternative for a recombinant cross-protective anti-Pseudomonas vaccine.
Characteristics of the shorted annular-ring patch antenna (2002)

A recent paper by Jackson et al (see IEEE Trans. Antennas Propagat., vol.41, no.8, p.1026-1037, 1993) discussed the design of a class of microstrip patch antennas that excite very little surface wave power. Their design is based on the principle that a ring of magnetic current of a particular critical radius should not excite the dominant TM/sub 0/ surface wave in the substrate. This property would allow for the design of more efficient individual patch radiators as well as provide for reduced mutual coupling in an array environment. Unfortunately, this critical radius is larger than that required for the usual dominant mode resonance for a conventional circular patch. Thus, new designs must be developed that both are resonant and satisfy the critical radius criteria. One such design, the shorted annular-ring microstrip patch, is the subject of this investigation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Microarrays in ecology and evolution: a preview (2002)

Microarray technology provides a new tool with which molecular ecologists and evolutionary biologists can survey genome-wide patterns of gene expression within and among species. New analytical approaches based on analysis of variance will allow quantification of the contributions of among individual variation, genotype, sex, microenvironment, population structure, and geography to variation in gene expression. Applications of this methodology are reviewed in relation to studies of mechanisms of adaptation and divergence; delineation of developmental and physiological pathways and networks; characterization of quantitative genetic parameters at the level of transcription ('quantitative genomics'); molecular dissection of parasitism and symbiosis; and studies of the diversification of gene content. Establishment of microarray resources is neither prohibitively expensive nor technologically demanding, and a commitment to development of gene expression profiling methods for nonmodel organisms could have a tremendous impact on molecular and genetic research at the interface of organismal and population biology.
A Formal Total Synthesis of (-)-Cephalotaxine. (1999)

A formal total synthesis of (-)-cephalotaxine (1) has been achieved. The key step is an intramolecular aldol condensation of the diketone 9, which in turn was obtained in three steps from the azabicyclic compound 6 derived from D-proline according to Seebach's procedure. Treatment of 9 with a catalytic amount of sodium 2-methyl-2-butanolate in benzene at room temperature gave the alpha, beta-unsaturated ketone 8 in 43% yield. Catalytic hydrogenation of 8 followed by reduction of the ketone 22 with sodium borohydride and acetylation of the resulting alcohol 23 gave the acetoxy derivative 24, which, after deprotection, was acylated with (methylthio)acetic acid to give the amide 26. Compound 26 was converted into optically active ketolactam 4 following the synthetic operations developed for the synthesis of the racemic compound.