gebhart/patrepeval huggingface dataset:
The effect of carbohydrate on the structure and stability of erythropoietin. (1991)

Erythropoietin is a glycoprotein hormone that stimulates the maturation of late erythroid progenitor cells. It has three N-linked and one O-linked carbohydrates which play an important role in the biosynthesis and biological activities of the protein. To determine the role the carbohydrate might have in maintaining the conformational stability of the protein, the protein expressed in mammalian cells (fully glycosylated), the asialo mammalian-expressed protein, and the protein expressed in Escherichia coli (no carbohydrate) were compared for their stability to guanidine HCl, pH, and temperature. Circular dichroism was used to follow protein unfolding. Both the intact and asialo mammalian-expressed proteins unfolded with a cooperative transition in guanidine HCl, with a midpoint at 1.75 M guanidine HCl. The E. coli-expressed material unfolded with a midpoint of 1.2 M guanidine HCl, and a delta G of unfolding which was 1.4 kcal/mol less than that of the two glycosylated molecules. The E. coli-derived protein was also significantly less stable to pH-induced conformational changes, showing a cooperative transition in 35% glycerol with a midpoint at pH 4.4, while both the intact and asialo mammalian-expressed molecules had a transition midpoint of pH 3.75 in the absence of glycerol, and approximately pH 3 in the presence of 35% glycerol. The E. coli-expressed molecule unfolded and precipitated upon heating to 44 degrees C, while the asialo and intact mammalian-expressed proteins remained soluble, with a Tm of 56 degrees C. From these experiments, the carbohydrate appears to play a critical role in stabilizing the erythropoietin molecule to denaturing conditions, and this increased stability does not depend on the presence of sialic acid.
Rat glioblastoma cells expressing an antisense RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and induce regression of wild-type tumors. (1994)

Insulin-like growth factor-1 (IGF-1) and IGF-2 are critical regulators of cell proliferation. The growth-promoting action of both ligands is mediated by the type 1 IGF receptor (IGF-1R). We have investigated the role of the IGF-1R in the growth and tumorigenicity of rat C6 glioblastoma cells. For this purpose, antisense RNA to IGF-1R RNA was introduced into cells by either the addition of oligodeoxynucleotides or by transfection with plasmids that express antisense RNA to IGF-1R RNA. At low cell density, C6 cells grew slowly in serum-free medium and proliferated with the sole addition of IGF-1 or IGF-2. Both antisense IGF-1R oligodeoxynucleotides and stable transfection with a plasmid expressing an antisense IGF-1R RNA inhibited IGF-1-mediated growth in monolayers and clonogenicity in soft agar. Sense oligodeoxynucleotides and sense-expressing plasmid had no effect on either parameter. In stable antisense transfectants, tyrosine-phosphorylated IGF-1 receptors were not detectable, although they were easily detected in wild-type cells. When wild-type C6 cells were injected s.c. into syngeneic immunocompetent rats, tumors developed within 1 week. In contrast, stably transfected C6 cells overexpressing antisense IGF-1R RNA were nontumorigenic. Moreover, when C6 IGF-1R antisense cells were injected, subsequent tumor formation by wild-type C6 cells was completely prevented. Finally, injection of C6 IGF-1R antisense cells into rats carrying an established wild-type C6 tumor caused complete regression of the tumors. The results demonstrate the critical importance of the IGF-1R in glioblastoma cell growth, clonogenicity, and tumorigenicity. Although the mechanism is presently unknown, the fact that the injection of C6 cells expressing an antisense RNA to IGF-1R RNA leads to regression of already established wild-type C6 tumors suggests the possibility of practical applications.
Molecular Mechanisms and Clinical Pathophysiology of Maturity-Onset Diabetes of the Young (2001)

Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous group of disorders characterized by nonketotic diabetes mellitus, an autosomal dominant mode of inheritance, an onset usually before the age of 25 years and frequently in childhood or adolescence, and a primary defect in the function of the beta cells of the pancreas. MODY can result from mutations in any one of at least six different genes (Table 1). One of these genes encodes the glycolytic enzyme glucokinase (associated with MODY 2),3 and the other five encode transcription factors: hepatocyte nuclear factor (HNF) 4α (associated with MODY 1),4 HNF-1α (MODY . . .
The Evolution of Controlled Multitasked Gene Networks: The Role of Introns and Other Noncoding RNAs in the Development of Complex Organisms (2001)

Eukaryotic phenotypic diversity arises from multitasking of a core proteome of limited size. Multitasking is routine in computers, as well as in other sophisticated information systems, and requires multiple inputs and outputs to control and integrate network activity. Higher eukaryotes have a mosaic gene structure with a dual output, mRNA (protein-coding) sequences and introns, which are released from the pre-mRNA by posttranscriptional processing. Introns have been enormously successful as a class of sequences and comprise up to 95% of the primary transcripts of protein-coding genes in mammals. In addition, many other transcripts (perhaps more than half) do not encode proteins at all, but appear both to be developmentally regulated and to have genetic function. We suggest that these RNAs (eRNAs) have evolved to function as endogenous network control molecules which enable direct gene-gene communication and multitasking of eukaryotic genomes. Analysis of a range of complex genetic phenomena in which RNA is involved or implicated, including co-suppression, transgene silencing, RNA interference, imprinting, methylation, and transvection, suggests that a higher-order regulatory system based on RNA signals operates in the higher eukaryotes and involves chromatin remodeling as well as other RNA-DNA, RNA-RNA, and RNA-protein interactions. The evolution of densely connected gene networks would be expected to result in a relatively stable core proteome due to the multiple reuse of components, implying that cellular differentiation and phenotypic variation in the higher eukaryotes results primarily from variation in the control architecture. Thus, network integration and multitasking using trans-acting RNA molecules produced in parallel with protein-coding sequences may underpin both the evolution of developmentally sophisticated multicellular organisms and the rapid expansion of phenotypic complexity into uncontested environments such as those initiated in the Cambrian radiation and those seen after major extinction events.
Clinical usefulness of testing for a heparin-dependent platelet-aggregating factor in patients with suspected heparin-associated thrombocytopenia. (1984)

It is important to confirm the diagnosis of heparin-associated thrombocytopenia, because discontinuation of heparin requires the institution of other antithrombotic therapy. Reports describing a heparin-dependent platelet-aggregating factor in the serum of patients with heparin-associated thrombocytopenia suggest the potential for a specific diagnostic test. No study has evaluated the diagnostic usefulness of testing for this factor, and we tested for a heparin-dependent platelet-aggregating factor in sera from (1) 14 patients with heparin-associated thrombocytopenia, (2) 14 nonthrombocytopenic controls given heparin, (3) 16 patients with consumptive thrombocytopenic disorders not associated with heparin, and (4) 13 healthy laboratory personnel. Coded serum samples plus varying concentrations of heparin (final concentration 0.01, 0.1, 1.0, and 5 U/ml) plus platelets from healthy individuals were incubated together, and aggregation was measured. Positive results (greater than 20% aggregation) occurred in (1) five of 14 patients with heparin-associated thrombocytopenia, (2) 0 of 16 consumptive thrombocytopenic controls not given heparin therapy, (3) one of 14 nonthrombocytopenic controls given heparin, and (4) one of 13 healthy controls, giving a sensitivity of 36% and specificities of 100%, 93%, and 92%, respectively. No unique clinical or laboratory feature distinguished those patients with heparin-associated thrombocytopenia with positive aggregation results from those patients with heparin-associated thrombocytopenia with negative results. Fourteen of the 16 patients (86%) with heparin-associated thrombocytopenia had elevated levels of platelet-associated IgG; however, the test was also positive in 67% of the 16 patients with other consumptive (and probably immune) thrombocytopenic disorders not associated with heparin administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Nanopatterning of Alkynes on Hydrogen-Terminated Silicon Surfaces by Scanning Probe-Induced Cathodic Electrografting (2003)

The electrochemical cathodic electrografting reaction, previously demonstrated on bulk silicon surfaces, can be patterned on the nanoscale utilizing conducting probe atomic force microscopy (CP-AFM). Alkyne electrografting is a particularly useful chemical technique since it leads to direct covalent attachment of conjugated alkynes to silicon. In addition, application of a forward bias during the reaction renders the surface less sensitive to oxidation and the resulting monolayers are very stable in air and basic aqueous solution. Alkyne monolayer lines can be drawn down to 40 nm resolution using a Pt-coated AFM tip, and the heights of the monolayers scale with the molecular length of the alkyne. The tip is biased (+) and the surface is biased (-) to drive the cathodic electrografting reaction under ambient conditions. The resistance of the monolayers to fluoride, as well as friction force microscopy, indicate that the alkynes are covalently bonded to the surface, not oxide-based, and hydrophobic. The reaction does not work with alkenes, and therefore hydrosilylation is not the primary mode of reaction. Wider lines (300 nm) can be produced using broadened Pt-coated AFM tips. This reaction could be important for the interfacing of conjugated molecules directly to silicon in a spatially controlled fashion.
Macrophages in cardiac homeostasis, injury responses and progenitor cell mobilisation (2014)

Macrophages are an immune cell type found in every organ of the body. Classically, macrophages are recognised as housekeeping cells involved in the detection of foreign antigens and danger signatures, and the clearance of tissue debris. However, macrophages are increasingly recognised as a highly versatile cell type with a diverse range of functions that are important for tissue homeostasis and injury responses. Recent research findings suggest that macrophages contribute to tissue regeneration and may play a role in the activation and mobilisation of stem cells. This review describes recent advances in our understanding of the role played by macrophages in cardiac tissue maintenance and repair following injury. We examine the involvement of exogenous and resident tissue macrophages in cardiac inflammatory responses and their potential activity in regulating cardiac regeneration.
Giant optical activity in dielectric planar metamaterials with two-dimensional chirality (2006)

For the first time, all-dielectric planar chiral metamaterials consisting of arrays of silicon nitride gammadions on fused silica substrates have been fabricated, and shown to be capable of inducing large changes to the polarization states of transmitted light in a manner that is dependent on the two-dimensional chirality of the microstructured silicon nitride film. The polarization response is found to reverse for opposite enantiomers, and also for the same enantiomer when it is illuminated from opposite sides of the structure. In addition, the polarization states of the various diffracted beams are found to be non-reversible. These structures therefore appear to display elements of non-reciprocal behaviour. The polarization responses of complementary designs, different chiral geometries and various silicon nitride film thicknesses have also been studied. As a result we conclude that multiple reflections within the patterned silicon nitride layer play an important role in defining the mechanism by which these structures are able to modify the polarization states of diffracted light.
A keyword match processor architecture using content addressable memory (2004)

This paper demonstrates a keyword match processor capable of performing fast dictionary search with approximate match capability. Using a content addressable memory with processor element cells, the processor can process arbitrary sized keywords and match input text streams in a single clock cycle. The processor is capable of determining approximate match and providing distance information as well. A 64-word design has been developed using 19000 transistors and it could be expanded to larger sizes easily. Using a modest 0.5 micron process, we are achieving cycle times of 8 ns and the design will scale to smaller feature sizes.
Correction of Mass Spectral Drift Using Artificial Neural Networks (1996)

For pyrolysis mass spectrometry (PyMS) to be used for the routine identification of microorganisms, for quantifying determinands in biological and biotechnological systems, and in the production of useful mass spectral libraries, it is paramount that newly acquired spectra be compared to those previously collected. Neural network and other multivariate calibration models have been used to relate mass spectra to the biological features of interest. As commonly observed, however, mass spectral fingerprints showed a lack of long-term reproducibility, due to instrumental drift in the mass spectrometer; when identical materials were analyzed by PyMS at dates from 4 to 20 months apart, neural network models produced at earlier times could not be used to give accurate estimates of determinand concentrations or bacterial identities. Neural networks, however, can be used to correct for pyrolysis mass spectrometer instrumental drift itself, so that neural network or other multivariate calibration models created using previously collected data can be used to give accurate estimates of determinand concentration or the nature of bacteria (or, indeed, other materials) from newly acquired pyrolysis mass spectra. This approach is not limited solely to pyrolysis mass spectrometry but is generally applicable to any analytical tool which is prone to instrumental drift, such as IR, ESR, NMR and other spectroscopies, and gas and liquid chromatography, as well as other types of mass spectrometry.
<title>Modeling of deterministic chaotic noise to improve target recognition</title> (1993)

We discuss three measures to determine whether a given noise time sequence or time varying image has a deterministically generated chaotic component and the strength of that component: Lyapunov coefficients, Kolmogorov entropy, and fractal dimension. Results of computer experiments show that either a neural network or a polynomial model may be successfully used to model a logistic function chaotic sequence generator. Polynomials are also shown to model a Lorentz system. In all cases, the model generates chaotic noise with the same measures as the real noise data.
Differential Phosphorylation of the Nucleoprotein of Influenza A Viruses (1989)

An analysis of the nucleoprotein (NP) of 29 different influenza A viruses by phosphopeptide fingerprinting revealed three prototype patterns. The first, which was a complex pattern consisting of six to seven phosphopeptides, another which was relatively simple consisted of two or three phosphopeptides, and a third one which was complex but was missing the main phosphopeptide shared by the two other patterns. Phosphoserine was the only labelled phosphamino acid detected. A tentative deduction of two of the phosphate attachment sites (serine residues at positions 3 and 473) could be made by comparison of the known amino acid sequences of the NPs of 25 strains. No correlation was found between species specificity or subtype or year of isolation of the strains. During the infectious cycle the fingerprint underwent significant changes, indicating subtle phosphorylation and dephosphorylation of the NP at various stages during viral multiplication. Most of the phosphopeptides were metabolically stable; however one major phosphopeptide, which was not found in the NP of mature virions, exhibited a high turnover (presumably serine at position 3). The phosphopeptide fingerprint could be significantly influenced in vivo by the specific stimulation of cellular protein kinase C by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate or by its inhibition with the isoquinoline sulphonamide H7.H7 specifically inhibited the replication of influenza A viruses by deregulation of viral protein synthesis without interfering with the multiplication of a parainfluenza virus (Newcastle disease virus), an alphavirus (Semliki Forest virus) or a flavivirus (West Nile). Therefore the correct phosphorylation of the NP of influenza viruses appears to be essential for influenza virus replication.
Genetic-Analysis Of Legume Nodule Initiation (1988)

Crop loss due to soil salinization is an increasing threat to agriculture worldwide. This review provides an overview of cellular and physiological mechanisms in plant responses to salt. We place cellular responses in a time- and tissue-dependent context ...Read More
Hemoglobin Kansas, a Human Hemoglobin with a Neutral Amino Acid Substitution and an Abnormal Oxygen Equilibrium (1968)

The structure of an abnormal human hemoglobin with a low affinity for oxygen and little heme-heme interaction has been determined. Threonine replaces asparagine in position 102 of the β chain, which is the fourth residue of the G helix. Although this is a neutral substitution, the hemoglobin is nevertheless chromatographically and electrophoretically distinguishable from normal human hemoglobin. No other abnormality has been found. The tetrameric hemoglobin dissociates at least to a dimer upon oxygenation at neutral pH and at protein concentrations at which normal hemoglobin does not dissociate significantly.
Preclinical evaluation of an anti-alpha5beta1 integrin antibody as a novel anti-angiogenic agent. (2006)

Integrin alpha5beta1, the principal fibronectin receptor, is an important survival factor, playing a key role in angiogenesis. Angiogenesis is critical for tumor growth, and anti-angiogenic therapies have met clinical success. To validate the therapeutic potential of an anti-alpha5beta1 strategy, we generated volociximab (M200) a chimeric human IgG4 version of the alpha5beta1 function-blocking murine antibody IIA1; and F200, the Fab derivative. Volociximab, F200 and IIA1 showed similar activity by ELISA (EC50= 0.2nM), Biacore (Kd= 0.1-0.4nM) and inhibition of fibronectin binding (IC50= 2-3nM). The inhibitory potential of alpha5beta1 antibodies was compared to HuMV833, an anti-VEGF antibody. Both volociximab and HuMV833 inhibited HUVEC proliferation (IC50 of volociximab = 0.2-0.5nM; IC50 of HuMV833 = 45nM). However, IIA1, volociximab and F200 were also potent inhibitors of an in vitro model of angiogenesis (HUVEC tube formation assay), unlike HuMV833. Additionally, volociximab inhibited in vitro tube formation induced by VEGF and/or bFGF, suggesting a mechanism of action independent of growth factor stimulus. In fact, inhibition of alpha5beta1 function by volociximab induced apoptosis of actively proliferating, but not resting, endothelial cells. Volociximab does not cross-react with rodent alpha5beta1, therefore in vivo validation of an anti-alpha5beta1 approach was conducted in a cynomolgus model of choroidal revascularization. Volociximab and F200 were potent inhibitors of neovessel formation in this model. These data demonstrate that volociximab has therapeutic potential in diseases in which new vessel formation is a component of the pathology.
Liberación intracerebroventricular rápida de Cu-DOTA-etanercept después de la administración periférica demostrada con imágenes PET. (2009)

Se ha demostrado que las citoquinas interleukina-1 y factor necrosis tumoral (TNF), y el bloqueador de citoquinas antagonista receptor de interleukina-1, entren en el líquido cefalorraquídeo (LCR) después de la administración periférica. \n\nRecientes informes de la rápida mejoría clínica de pacientes con enfermedad de Alzheimer y formas relacionadas de demencia después de administración periespinal de etanercept, antagonista del TNF, sugieren que etanercept también tiene la capacidad de llegar al LCR del cerebro.\n\nPara investigarlo se etiquetó el etanercept con un emisor de positrones para permitir la visualización de su distribución intracraneal después de la administración periférica mediante PET en un modelo animal.
A Psychophysical Investigation of Binary Bitter-compound Interactions (2003)

The aim of this study was to determine if taste interactions occur when bitter stimuli are mixed. Eight bitter stimuli were employed: denatonium benzoate (DB), quinine-HCl (QHCl), sucrose octaacetate (SOA), urea, L-tryptophan (L-trp), L-phenylalanine (L-phe), ranitidine-HCl, and Tetralone. The first experiment constructed individual psychophysical curves for each subject (n = 19) for each compound to account for individual differences in sensitivities when presenting bitter compounds in experiment 2. Correlation analysis revealed two groupings of bitter compounds at low intensity (1, L-trp, L-phe, and ranitidine; 2, SOA and QHCl), but the correlations within each group decreased as the perceived intensity increased. In experiment 2, intensity ratings and two-alternative forced-choice discrimination tasks showed that bitter compounds generally combine additively in mixture and do not show interactions with a few specific exceptions. The methods employed detected synergy among sweeteners, but could not detect synergy among these eight bitter compounds. In general, the perceived bitterness of these binary bitter-compound mixtures was an additive function of the total bitter-inducing stimuli in the mouth.
Self-Digitization of Sample Volumes (2010)

This paper describes a very simple and robust microfluidic device for digitizing samples into an array of discrete volumes. The device is based on an inherent fluidic phenomenon, where an incoming aqueous sample divides itself into an array of chambers that have been primed with an immiscible phase. Self-digitization of sample volumes results from the interplay between fluidic forces, interfacial tension, channel geometry, and the final stability of the digitized samples in the chambers. Here, we describe experiments and simulations that were used to characterize these parameters and the conditions under which the self-digitization process occurred. Unlike existing methods used to partition samples into an array, our method is able to digitize 100% of a sample into a localized array without any loss of sample volume. The final volume of the discretized sample at each location is defined by the geometry and size of each chamber. Thus, we can form an array of samples with varying but predefined volumes. We exploited this feature to separate the crystal growth of otherwise concomitant polymorphs from a single solution. Additionally, we demonstrated the removal of the digitized samples from the chambers for downstream analysis, as well as the addition of reagents to the digitized samples. We believe this simple method will be useful in a broad range of applications where a large array of discretized samples is required, including digital PCR, single-cell analysis, and cell-based drug screening.