gebhart/patrepeval huggingface dataset:
Platelet stimulation by thrombin and other proteases (1975)

The mechanism of stimulation of platelets by thrombin and other proteases was studied by following kinetics of secretion of Ca2+ or ATP. The progress-time curves of secretion were analyzed for rate and total amount released. The reaction of thrombin was perturbed by addition of hydroxylamine or a competitive inhibitor and by variation of pH and it was compared with the reactions of other proteases. Trypsin and papain, with specificities for arginyl residues, induced secretion with a time course that was nearly identical with that induced by thrombin when saturating levels of enzyme were used. At low levels of enzyme, trypsin and papain gave extended lags in the progress-time curves. Higher concentrations of trypsin and papain were required for saturation of the measured parameters. Human plasmin (lysly specificity) and bovine chymotrypsin (aromatic amino acid specificity) failed to induce platelet secretion. Active site inhibited thrombin was also ineffective. Both yield and kinetics depended on pH, with the pH profile for each enzyme similar to its profile for hydrolysis of synthetic substrates. Studies at low pH also showed that the early part of the reaction undergoes a change in rate-determining step from enzyme dependent at low enzyme to enzyme indepdenent at high enzyme. Hydroxylamine, a nucleophile that would be expected to accelerate hydrolytic reactions, actually decreased both the rate of initial reactions and yield. A competitive inhibitor of thrombin also decreased both rate and yield; a calculated inhibition constant was in agreement with the value for a synthetic substrate, suggesting that the interaction of thrombin with platelets is analogous to reaction with substrates. A modification of our previous model is proposed in order to accommodate the results described here and to reaoncile the apparent contradictions that enzyme was found not to turn over in the reaction (Detwiler, T. C., and Feinman, R. D. (1973), Biochemistry 12, 282), that catalytic activity is required (Davey, M. G., and Luscher, E. F. (1967), Nature (London) 216, 875; this paper), and that the reaction is characterized by an apparent equilibrium binding (Tollefsen, D. M., Feagler J. R., and Majerus, P. W. (1974), J. Biol. Chem. 249, 2646). The essential feature is a reversible catalytic step with no dissociation of enzyme from product. This is followed by irreversible, thrombin-independent platelet processes leading to secretion, with yield dependent on the equilibrium concentration of the thrombin product. The model thus has aspects of catalysis, stoichiometry, and an agonist-receptor equilibrium.
Diffuse optics for tissue monitoring and tomography (2010)

This review describes the diffusion model for light transport in tissues and the medical applications of diffuse light. Diffuse optics is particularly useful for measurement of tissue hemodynamics, wherein quantitative assessment of oxy- and deoxy-hemoglobin concentrations and blood flow are desired. The theoretical basis for near-infrared or diffuse optical spectroscopy (NIRS or DOS, respectively) is developed, and the basic elements of diffuse optical tomography (DOT) are outlined. We also discuss diffuse correlation spectroscopy (DCS), a technique whereby temporal correlation functions of diffusing light are transported through tissue and are used to measure blood flow. Essential instrumentation is described, and representative brain and breast functional imaging and monitoring results illustrate the workings of these new tissue diagnostics.
Proteome analysis of Saccharomyces cerevisiae: A methodological outline (1997)

Proteome analysis offers a unique means of identifying important proteins, characterizing their modifications and beginning to describe their function. This is achieved through the combination of two technologies: protein separation and selection by two-dimensional gel electrophoresis, and protein identification and characterization by mass spectrometry. This methodological outline sketches the strengths and weaknesses of the two central technologies used, and provides both practical tips and the theoretical background for their utilization. One application of these technologies is illustrated by the characterization of genes, revealed by sequencing, but which have no--or only weak homology--to any other known genes. Other applications, for example the identification of protein markers for particular human diseases, are only referred to. The aim of the article is thus to provide the basis for a sound understanding of the full potential and limitations of proteome analysis.
A One-Pot Formal [4 + 2] Cycloaddition Approach to Substituted Piperidines, Indolizidines, and Quinolizidines. Total Synthesis of Indolizidine (−)-209I (2005)

[reaction: see text] Heating a mixture of substituted N-benzyl gamma-chloropropylamines, conjugated alkynoates or alkynones, sodium carbonate, and a catalytic amount of sodium iodide in i-PrOH at 70-83 degrees C delivers substituted piperidines in good yields. This transformation goes through a cascade Michael addition/alkylation process and represents a facile one-pot formal [4 + 2] cycloaddition approach to piperidine ring. Using secondary cyclic gamma-chloropropylamines as substrates, this process produces substituted indolizidines or quinolizidines. On the basis of this approach, indolizidine (-)-209I is elaborated in 11 steps from methyl 2-hexenoate.
Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries. (1993)

High plasma levels of plasminogen activator inhibitor type-1 (PAI-1), the principal inhibitor of the fibrinolytic system, have been associated with thrombotic and arterial disease. To study PAI-1 expression in healthy and atherosclerotic human arteries, a detailed analysis was made by light and electron microscopy immunocytochemistry and by in situ hybridization. In healthy arteries PAI-1 was found both at the level of endothelial cells and of smooth muscle cells (SMCs) of the arterial media. In early atherosclerotic lesions PAI-1 was also detected in intimal SMCs and in extracellular areas in association with vitronectin. Immunogold analysis by electron microscopy revealed PAI-1 in vesicular structures in endothelial cells and in SMCs with normal or foam cell characteristics. In advanced atheromatous plaques, PAI-1 mRNA expression in SMCs within the fibrous cap was increased compared with SMCs located in the adjacent media or in normal arterial tissue. PAI-1 mRNA was also detected in macrophages located at the periphery of the necrotic core. The increased synthesis of PAI-1 by cellular components of the atherosclerotic plaque and the extracellular accumulation of PAI-1 may contribute to the thrombotic complications associated with plaque rupture and possibly play a role in the accumulation of extracellular matrix deposits.
An Ultra Low Power 3D Integrated Intra-Chip Silicon Electronic-Photonic Link (2015)

A record low energy (250fJ/bit) intra-chip electronic-photonic link is demonstrated at 5Gb/s on a 3D-integrated wafer using through-oxide-vias (1.45fF-per-via) for the first time. The receiver sensitivity was −19.3dBm and the on-chip laser energy was 6fJ/bit.
Identification of the Minimal Functional Unit in the Low Density Lipoprotein Receptor-related Protein for Binding the Receptor-associated Protein (RAP) (2000)

The low density lipoprotein receptor-related protein (LRP), a member of the low density lipoprotein receptor family, mediates the internalization of a diverse set of ligands. The ligand binding sites are located in different regions of clusters consisting of approximately 40 residues, cysteine-rich complement-type repeats (CRs). The 39-40-kDa receptor-associated protein, a folding chaperone/escort protein required for efficient transport of functional LRP to the cell surface, is an antagonist of all identified ligands. To analyze the multisite inhibition by RAP in ligand binding of LRP, we have used an Escherichia coli expression system to produce fragments of the entire second ligand binding cluster of LRP (CR3-10). By ligand affinity chromatography and surface plasmon resonance analysis, we show that RAP binds to all two-repeat modules except CR910. CR10 differs from other repeats in cluster II by not containing a surface-exposed conserved acidic residue between Cys(IV) and Cys(V). By site-directed mutagenesis and ligand competition analysis, we provide evidence for a crucial importance of this conserved residue for RAP binding. We provide experimental evidence showing that two adjacent complement-type repeats, both containing a conserved acidic residue, represent a minimal unit required for efficient binding to RAP.
Inducing targeted brain states utilizing merged reality systems (2015)

As virtual reality becomes more accessible and the technology becomes greatly improved to immerse the individual in real time, there will be an impact upon the human brain and its direct functioning over states of mind. For as long as humans have noted that the brain responds to lights and sounds to aid or alter moods and mind states, technology has been used in one way or another to induce some desirable mood. This paper investigates how virtual technology could be used to forward this idea.
Stimulated emission of near-infrared radiation in silicon fin light-emitting diode (2011)

We propose top-down processes to make silicon multiple quantum wells called fins for a light-emitting diode. The silicon fins are formed vertically to a substrate and embedded in a Si3N4 waveguide. By current injections into silicon fins, we have observed stimulated emission spectra peaked at the wavelengths corresponding to the periodic structures of fins. The near-field mode profiles obtained at the edge of the waveguide qualitatively agreed with theoretical calculations. It has been turned out that both transverse-electric and transverse-magnetic fields can contribute to the optical gain.
Ki-ras mutation modifies the protective effect of dietary monounsaturated fat and calcium on sporadic colorectal cancer. (1997)

The geographic differences in the incidence of colorectal cancer have been mostly attributed to variations in diet. The diversity of the Mediterranean diet and the heterogeneity of acquired genetic alterations in colorectal cancer sets the stage for investigating the possible association between dietary factors and mutations in tumor genes known to play a role in the pathogenesis of these neoplasms. With this purpose, we have studied the Ki-ras gene in 108 colorectal cancers using archival tissue and epidemiological data from our previous case-control study. Mutations in exon 1 of the Ki-ras gene were detected by a PCR-single strand conformation polymorphism approach. A polychotomous logistic regression model was used to assess the significance of observed differences between wild-type and mutated tumors with respect to population controls in the different categories of nutrient consumption. Multivariate density models were used to adjust the correlation between nutrients and total energy. Our studies show that high consumption of monounsaturated fats, mostly derived from olive oil, is associated with a statistically significant decrease in the risk of cancer with wild-type Ki-ras genotype but not of Ki-ras mutated cancers. Conversely, we find that high calcium intake is associated with a decreased risk of Ki-ras mutated tumors but not of wild-type tumors. Tumor genotyping can reveal epidemiological associations that are weak or unapparent when cases-control studies are not stratified by tumor genotype.
Resolving Individuals Contributing Trace Amounts of DNA to Highly Complex Mixtures Using High-Density SNP Genotyping Microarrays (2008)

We use high-density single nucleotide polymorphism (SNP) genotyping microarrays to demonstrate the ability to accurately and robustly determine whether individuals are in a complex genomic DNA mixture. We first develop a theoretical framework for detecting an individual's presence within a mixture, then show, through simulations, the limits associated with our method, and finally demonstrate experimentally the identification of the presence of genomic DNA of specific individuals within a series of highly complex genomic mixtures, including mixtures where an individual contributes less than 0.1% of the total genomic DNA. These findings shift the perceived utility of SNPs for identifying individual trace contributors within a forensics mixture, and suggest future research efforts into assessing the viability of previously sub-optimal DNA sources due to sample contamination. These findings also suggest that composite statistics across cohorts, such as allele frequency or genotype counts, do not mask identity within genome-wide association studies. The implications of these findings are discussed.
Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain (2003)

Diacylglycerol (DAG) lipase activity is required for axonal growth during development and for retrograde synaptic signaling at mature synapses. This enzyme synthesizes the endocannabinoid 2-arachidonoyl-glycerol (2-AG), and the CB1 cannabinoid receptor is also required for the above responses. We now report on the cloning and enzymatic characterization of the first specific sn-1 DAG lipases. Two closely related genes have been identified and their expression in cells correlated with 2-AG biosynthesis and release. The expression of both enzymes changes from axonal tracts in the embryo to dendritic fields in the adult, and this correlates with the developmental change in requirement for 2-AG synthesis from the pre- to the postsynaptic compartment. This switch provides a possible explanation for a fundamental change in endocannabinoid function during brain development. Identification of these enzymes may offer new therapeutic opportunities for a wide range of disorders.
Emerging roles of liposomal bupivacaine in anesthesia practice (2017)

Despite advances in drug technology and improvements in technology, including peripheral nerve catheters and ultrasound, postoperative pain is still a significant problem in the clinical setting worldwide. Postoperative pain can have a critical negative impact with regard to physiological consequences to the body and therefore, the role of liposomal bupivacaine as an extended release bupivacaine with approximately 72 h of duration may have far-reaching and significant impact in clinical practice. Liposomal bupivacaine has a DepoFoam multivesicular liposome technology with particle suspension in an isotonic aqueous solution and consists of tiny lipid-based particles, which contain discrete water-filled chambers dispersed through a lipid matrix. Other advantages include a reduction in opioid consumption, while not requiring a catheter or any other device, as well as easy dilution with saline. This review summarizes current research with this novel agent in postsurgical pain, and discusses potential roles in chronic pain states. Further studies are warranted for its use in epidural and intrathecal administration. Moreover, this review will explore the expansion of liposomal bupivacaine's current clinical role.
SINTAX: a simple non-Bayesian taxonomy classifier for 16S and ITS sequences (2016)

Abstract Metagenomics experiments often characterize microbial communities by sequencing the ribosomal 16S and ITS regions. Taxonomy prediction is a fundamental step in such studies. The SINTAX algorithm predicts taxonomy by using k -mer similarity to identify the top hit in a reference database and provides bootstrap confidence for all ranks in the prediction. SINTAX achieves comparable or better accuracy to the RDP Naive Bayesian Classifier with a simpler algorithm that does not require training. Most tested methods are shown to have high rates of over-classification errors where novel taxa are incorrectly predicted to have known names.
Covalent Grafting of Common Trihydroxymethylaminomethane in the Headgroup Region Imparts High Serum Compatibility and Mouse Lung Transfection Property to Cationic Amphiphile (2008)

Clinical success of cationic transfection lipids in nonviral gene therapy continues to remain critically dependent on the use of serum compatible cationic amphiphiles efficient in delivering genes into our body cells. To this end, we demonstrate that covalent grafting of simple Tris-base component of the widely used biological Tris buffer in the headgroup region is capable of imparting high serum compatibility and intravenous mouse lung transfection properties to cationic amphiphile.
Plasmonically enhanced hot electron based photovoltaic device (2013)

Hot electron photovoltaics is emerging as a candidate for low cost and ultra thin solar cells. Plasmonic means can be utilized to significantly boost device efficiency. We separately form the tunneling metal-insulator-metal (MIM) junction for electron collection and the plasmon exciting MIM structure on top of each other, which provides high flexibility in plasmonic design and tunneling MIM design separately. We demonstrate close to one order of magnitude enhancement in the short circuit current at the resonance wavelengths.
High-level expression of a novel epitope of CD59 identifies a subset of CD34+ bone marrow cells highly enriched for pluripotent stem cells. (1996)

To further define the hierarchy of human hematopoietic progenitor cells, we have attempted to identify antibodies to cell-surface molecules expressed on CD34+ progenitor cell subsets. Herein we describe the utility of a new monoclonal antibody, HCC-1, which binds to a novel epitope of CD59 differentially expressed among CD34+ progenitor cells. HCC-1 subdivides the adult marrow CD34+ population into HCC-1high and HCC-1low/- fractions of approximately equal size. Cobblestone area-forming cells (CAFC) in long-term bone marrow culture were enriched 10-30-fold in CD34+HCC-1high cells compared with CD34+HCC1-low/- cells and two-fold compared with CD34+ cells. When injected into fetal human bone fragments implanted in SCID mice, the CD34+HCC-1high population showed potent engrafting activity leading to the production of myeloid, lymphoid, and erythroid elements, as well as the retention of progenitor cell phenotype. These studies demonstrate that the CD34+HCC-1high population contains primitive pluripotent hematopoietic stem cells. No hematopoietic engrafting activity was detected in the CD34+HCC-1low/- population. Consistent with this finding, simultaneous five-color flow cytometric analysis revealed that HCC-1high cells include virtually all CD34+Thy-1+Lin- cells, a cell population previously characterized as highly enriched for primitive pluripotent hematopoietic stem cells. The ability of CD34+ cells divided into subsets by HCC-1 to produce T cells was assessed by transplantation of sorted cells into human fetal thymus implanted into SCID mice. A higher frequency of thymus-engrafting activity was observed in the CD34+HCC-1high than in the CD34+HCC-1low/- population. Consistent with the limited ability to engraft in the SCID-hu thymus model, the CD34+HCC-1low/- population was shown to contain a low frequency of CD34+CD10+ lymphoid progenitor cells. We conclude that the HCC-1 epitope is expressed at high levels on a subset of CD34+ cells that contain virtually all primitive pluripotent hematopoietic stem cells and that the population of CD59 molecules expressed on CD34+ cells is not homogeneous.
Effect of CD44 deficiency on in vitro and in vivo osteoclast formation (2004)

In vitro studies have shown that CD44 is involved in the fusion process of osteoclast precursor cells. Yet, in vivo studies do not support this, since an osteopetrotic phenotype has not been described for CD44 knock-out (CD44 k.o.) mice. This discrepancy may suggest that the role of CD44 in fusion may depend on the microenvironment of osteoclast formation. We investigated osteoclast formation of CD44 k.o. and wild-type mice under three conditions: in vitro, both on plastic and on bone and in vivo by analyzing osteoclast number, and size in long bones from wild-type and CD44 k.o. mice. Bone marrow cells from wild-type and CD44 k.o. mice were analyzed for their capacity to form osteoclasts on plastic and on bone in the presence of macrophage colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL). On plastic, the number of multinucleated tartrate resistant acid phosphatase (TRAP) positive cells in CD44 k.o. cultures was twofold higher than in wild-type cultures. On bone, however, equal numbers of osteoclasts were formed. Interestingly, the total number of osteoclasts formed on bone proved to be higher than on plastic for both genotypes, strongly suggesting that osteoclastogenesis was stimulated by the bone surface, and that CD44 is not required for osteoclast formation on bone. Functional analyses showed that bone resorption was similar for both genotypes. We further studied the osteoclastogenic potential of wild-type bone marrow cells in the presence of CD44 blocking antibodies. Osteoclastogenesis was not affected by these antibodies, a further indication that CD44 is not required for the formation of multinucleated cells. Finally, we analyzed the in vivo formation of osteoclasts by analyzing long bones from wild-type and CD44 k.o. mice. Morphometric analysis revealed no difference in osteoclast number, nor in number of nuclei per osteoclasts or in osteoclast size. Our in vitro experiments on plastic showed an enhanced formation of osteoclasts in the absence of CD44, thus suggesting that CD44 has an inhibitory effect on osteoclastogenesis. However, when osteoclasts were generated on bone, no differences in number of multinucleated cells nor in bone resorption were seen. These observations are in agreement with in vivo osteoclast characteristics, where no differences between wild-type and CD44 k.o. bones were encountered. Therefore, the modulating role of CD44 in osteoclast formation appears to depend on the microenvironment.
Proteome of Metastatic Canine Mammary Carcinomas: Similarities to and Differences from Human Breast Cancer (2010)

Mammary tumors are a major health threat to women and female dogs. In both, metastasis of the primary tumor to distant organs is the most common cause of tumor-related death. Nevertheless, the molecular mechanisms of tumor metastasis are far from being understood, and it is still unknown why some human and canine carcinomas metastasize and others do not. Using 2D-DIGE and MALDI-TOF-MS we identified 21 proteins with significant changes (fold change >1.5; p < 0.05) in protein expression between metastasizing (n = 6) and nonmetastasizing (n = 6) canine mammary carcinomas. Quantitative RT-PCR was used to identify transcriptional or post-transcriptional regulation of protein expression. Up-regulated proteins in metastatic carcinomas included proliferating cell nuclear antigen, ferritin light chain, bomapin, tropomyosin 3, thioredoxin-containing domain C5, adenosin, ornithine aminotransferase, coronin 1A, RAN-binding protein 1,3-phosphoglycerate dehydrogenase, and eukaryotic translation elongation factor 1. Down-regulated proteins in metastatic carcinomas included calretinin, myosin, light chain 2, peroxiredoxin 6, maspin, ibrinogen beta chain, vinculin, isocitrate dehydrogenase 1, tropomyosin 1, annexin A5, and Rho GTPase activating protein 1. Interestingly, 19 of these 21 proteins have been described with a malignancy-associated expression in human breast cancer and other human cancer types before. Further investigations are now necessary to test whether these markers are of prognostic value for canine mammary carcinomas and whether their expression is directly involved in canine mammary carcinogenesis or represent solely a secondary reactive phenotype.