gebhart/patrepeval huggingface dataset:
Prevention of neonatal hyperbilirubinemia by tin protoporphyrin IX, a potent competitive inhibitor of heme oxidation. (1981)

The effects of various metalloporphyrins on hepatic heme oxygenase (EC 1.14.99.3) activity were examined in order to identify compounds that could inhibit heme degradation to bile pigment and might therefore be utilized to suppress the development of hyperbilirubinemia in the newborn. Among nine metal-protoporphyrin IX chelates (i.e., metal-hemes) studied, Sn-heme, Mn-heme, and Zn-heme substantially diminished heme oxygenase activity in vivo in the rat. These metalloporphyrins act as competitive inhibitory substrates in the heme oxygenase reaction but are not themselves oxidatively degraded. Sn-heme was the most potent enzyme inhibitor (Ki = 0.011 microM) in liver, spleen, kidney, and skin. Sn-heme administered to newborn animals within the first 72 hr after birth blocked the postnatal increase in heme oxygenase activity that occurs in various tissues. Its effect on the enzyme levels was prompt and protracted. Sn-heme administration also entirely prevented the development of hyperbilirubinemia that normally occurs postnatally. The effect of the metalloporphyrin in lowering the increased concentrations of serum bilirubin in neonates was prompt (within 1 day) and persisted throughout the 42 days after birth. No deleterious effects of Sn-heme treatment of the newborn were observed. This demonstrates that a synthetic metalloporphyrin that is a potent competitive inhibitor of heme oxidation can, when administered to the newborn, also prevent the hyperbilirubinemia that normally develops postnatally. The potential clinical implications of these findings are evident, and it is suggested that the pharmacological properties of Sn-heme and related synthetic metalloporphyrins merit further study.
A static multiplex Fabry-Perot spectrometer (2009)

We demonstrate a static multiplex spectrometer based on a Fabry-Perot interferometric filter for measuring the mean spectral content of diffuse sources. By replacing the slit of a low-dispersion grating spectrometer with a Fabry-Perot interferometric filter, we improve the resolving power of the instrument while simultaneously overcoming the free spectral range limitation of the Fabry Perot. The resulting instrument is smaller than conventional spectrometers having the same resolving power. We present experimental results from the spectrometer using neon lamp, He-Ne laser, and diode laser sources over a wavelength range from 620 nm to 660 nm.
NAction! How Can Neuraminidase-Based Immunity Contribute to Better Influenza Virus Vaccines? (2018)

Neuraminidase is one of the two surface glycoproteins of influenza A and B viruses. It has enzymatic activity that cleaves terminal sialic acid from glycans, and that activity is essential at several points in the virus life cycle. While neuraminidase is a major target for influenza antivirals, it is largely ignored in vaccine development. Current inactivated influenza virus vaccines might contain neuraminidase, but the antigen quantity and quality are varied and not standardized. While there are data that show a protective role of anti-neuraminidase immunity, many questions remain unanswered. These questions, among others, concern the targeted epitopes or antigenic sites, the potential for antigenic drift, and, connected to that, the breadth of protection, differences in induction of immune responses by vaccination versus infection, mechanisms of protection, the role of mucosal antineuraminidase antibodies, stability, and the immunogenicity of neuraminidase in vaccine formulations. Reagents for analysis of neuraminidase-based immunity are scarce, and assays are not widely used for clinical studies evaluating vaccines. However, efforts to better understand neuraminidase-based immunity have been made recently. A neuraminidase focus group, NAction!, was formed at a Centers of Excellence for Influenza Research and Surveillance meeting at the National Institutes of Health in Bethesda, MD, to promote research that helps to understand neuraminidase-based immunity and how it can contribute to the design of better and broadly protective influenza virus vaccines. Here, we review open questions and knowledge gaps that have been identified by this group and discuss how the gaps can be addressed, with the ultimate goal of designing better influenza virus vaccines.
Defective receptor binding of low density lipoprotein from pigs possessing mutant apolipoprotein B alleles. (1988)

We previously identified a defect in the in vivo catabolism of low density lipoprotein (LDL) from hypercholesterolemic pigs carrying a mutant apolipoprotein B allele. In the present studies, we examined the in vitro metabolism of mutant LDL in cultured pig fibroblasts. A 3-fold higher concentration of mutant LDL (compared to control) was needed to displace 50% of control 125I-LDL binding. Mutant LDL had a 6-fold higher dissociation constant than control LDL. Scatchard plots of the binding data were concave upward, suggesting multiple classes of binding sites or negative cooperativity. The mutant LDL degradation rate was reduced by 40%; this decrease could be attributed to a dense LDL subspecies. Mutant and control buoyant LDL subspecies were degraded more slowly than the corresponding dense LDL subspecies. Together, these studies show that diminished LDL receptor binding can result from mutations in apolipoprotein B and from changes in the lipid composition of LDL particles.
Interleukin 2 (IL-2) and interleukin 7 (IL-7) reciprocally induce IL-7 and IL-2 receptors on gamma delta T-cell receptor-positive intraepithelial lymphocytes. (1996)

In this study, we describe the interaction between cytokine and cytokine receptor (R) for the activation and proliferation of gamma delta T-cell receptor-positive T cells (gamma delta T cells). gamma delta T cells isolated from murine intestinal intraepithelial lymphocytes (IELs) were separated into gamma delta (Dim) and gamma delta (Bright) fractions according to the intensity of gamma delta T-cell receptor expression. The gamma delta T cells express low levels of IL-2R and IL-7R as shown by flow cytometry and reverse transcriptase-PCR analysis, whereas gamma delta (Bright) T cells did not express either receptor. Our study also revealed that recombinant marine (rm)IL-2 and rmIL-7 reciprocally induced high expressions of IL-7R and IL-2R, respectively, on gamma delta (Dim) T cells but not on gamma delta (Bright) cells. Thus, treatment of gamma delta (Dim) T cells with rmIL-2 and rmIL-7 resulted in high proliferative responses, whereas gamma delta (Bright) T cells did not respond to these two cytokines. The sources of these two cytokines for gamma delta T cells were neighboring epithelial cells (IL-7) and alpha beta T cells (IL-2 and IL-7). Cytokine signaling by IL-2 and IL-7 from alpha beta T cells and epithelial cells was necessary for the expression of IL-7R and IL-2R, respectively, on a subset of gamma delta T cells (e.g., gamma delta (Dim) T cells) in mucosa-associated tissue for subsequent activation and cell division.
Intermolecular Interactions during Complex Coacervation of Pea Protein Isolate and Gum Arabic (2009)

The nature of intermolecular interactions during complexation between pea protein isolate (PPI) and gum arabic (GA) was investigated as a function of pH (4.30-2.40) by turbidimetric analysis and confocal scanning microscopy in the presence of destabilizing agents (100 mM NaCl or 100 mM urea) and at different temperatures (6-60 degrees C). Complex formation followed two pH-dependent structure-forming events associated with the formation of soluble and insoluble complexes and involved interactions between GA and PPI aggregates. Complex formation was driven by electrostatic attractive forces between complementary charged biopolymers, with secondary stabilization by hydrogen bonding. Hydrophobic interactions were found to enhance complex stability at lower pH (pH 3.10), but not with its formation.
The Heat Transfer Effects of Nanotube Surfaces Treatments and a Means for Growing the Nanotube Coated Surfaces (2006)

&lt;div class="htmlview paragraph"&gt;A method of augmenting natural convection, low-Reynolds-number single-phase forced convection and boiling heat transfer by using nanotube coated heat transfer surfaces is described, as well as a unique method of growing these nanotube surfaces from the heat transfer metal alloy, thereby achieving excellent adhesion. This paper discuses side-by-side experiments where nanotube coated and uncoated surfaces are compared. Data on the positive effects of nanotube coating the axial grooves of copper-water heat pipes is also included. Applications for this technology include improved natural convection heat sinks, enhanced boiling surfaces and improved heat pipes. The nanotube coating is also demonstrated to be a low-cost coating and has been successfully grown on several alloys.&lt;/div&gt;
Monitoring and Control of Animal Cell Bioreactors: Biochemical Engineering Considerations (2018)

This chapter focuses on the manipulation of cell metabolism using the measurement of on-line sensors such as pH and dissolved oxygen probes. It discusses the unique features of monitoring and controlling pH and dissolved oxygen in cell culture processes, since the accurate measurement and control of these parameters is essential for the estimation of process variables. The control of chemical and physical parameters in animal cell reactors is similar to that in microbial fermentations. Animal cell processes, despite their close resemblance to conventional microbial fermentation, have some unique features; three are probably most directly related to the development of instrumentation for on-line monitoring and control: a large time constant for growth and metabolism, a slow response to control action, a more stringent requirement for the chemical environment. Because of these features, the control actions usually taken to control physical and chemical variables also show some variation from those for microbial processes.
Sequential One-Pot Access to Molecular Diversity through Aniline Aqueous Borylation (2014)

On the basis of our recently reported aniline aqueous borylation, molecular diversity was achieved in a one-pot process by combining other reactions such as esterification, Suzuki-Miyaura coupling, hydrogenolysis, or Petasis borono-Mannich.
Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and Atherosclerosis (2011)

Cholesterol efflux capacity from macrophages, a metric of HDL function, has a strong inverse association with both carotid intima-media thickness and the likelihood of angiographic coronary artery disease, independently of the HDL cholesterol level. (Funded by the National Heart, Lung, and Blood Institute and others.).
Hydrogenimonas thermophila gen. nov., sp. nov., a novel thermophilic, hydrogen-oxidizing chemolithoautotroph within the ε-Proteobacteria, isolated from a black smoker in a Central Indian Ridge hydrothermal field (2004)

A novel thermophilic bacterium, strain EP1-55-1%T, was isolated from an in-situ colonization system deployed in a superheated, deep-sea, hydrothermal vent emission at the Kairei Field on the Central Indian Ridge in the Indian Ocean. The cells were highly motile rods, each possessing a single polar flagellum. Growth was observed between 35 and 65 degrees C (optimum temperature, 55 degrees C; 70 min doubling time) and between pH 4.9 and 7.2 (optimum, pH 5.9). The isolate was a microaerobic-to-anaerobic chemolithoautotroph capable of using molecular hydrogen as the sole energy source and carbon dioxide as the sole carbon source. Molecular oxygen, nitrate or elemental sulfur (S0) could serve as electron acceptors to support growth. The G+C content of the genomic DNA was 34.6 mol%. Phylogenetic analysis based on 16S rDNA sequences indicated that strain EP1-55-1%T represents the first strain for which taxonomic properties have been characterized within the previously uncultivated phylogroup classified as belonging to the uncultivated epsilon-Proteobacteria group A; the name Hydrogenimonas thermophila gen. nov., sp. nov. is proposed, with strain EP1-55-1%T (=JCM 11971T=ATCC BAA-737T) as the type strain.
Progress on novel immunomodulatory agents for HIV-1 infection and other infectious diseases (2003)

AbstractAvailability of a vast array of recombinant and synthetic immunomodulators represents a significant milestone toward the development of effective therapies for infectious diseases. This is attested by the licensing of several recombinant human cytokines, including colony-stimulating factors, interleukins, interferons and erythropoietin, for clinical use in patients. The identification of the essential role of coreceptors for the entry of HIV into the host cell focused attention on chemokines as important targets for pharmacological intervention. This generated an intense search for molecules possessing therapeutic potential as inhibitors of chemokine receptors and several new compounds have been advocated. Diverse combinations with interferons and other cytokines for the treatment of various viral infections, including hepatitis B and C, have been proposed. Considerable advances have been made on compounds exhibiting cytokine inhibitory properties useful for new treatments of infectious and inflammatory diseases. Many of the major developments and current trends in the area of cytokine biology and therapy are highlighted in this review. Novel strategies based on the engineering of cytokines and inhibitors are poised to revolutionise therapeutic options in the coming decades.Keywordschemokinechemokine inhibitorcytokinehepatitis virusHIVimmunomodulatorsinterferons
A randomized long-term trial of tacrolimus and sirolimus versus tacrolimus and mycophenolate mofetil versus cyclosporine (NEORAL) and sirolimus in renal transplantation. I. Drug interactions and rejection at one year (2004)

This 1-year interim analysis indicates that a decreasing dosage of tacrolimus with either adjunctive sirolimus or MMF may optimize future graft survival versus a less favorable outcome using a similar algorithm with CsA and sirolimus.
Glucagon gene expression in vertebrate brain. (1988)

An increasing number of regulatory peptide genes are known to be transcribed in neuroendocrine cells of the intestine and neurons of the central and peripheral nervous system. The discovery of the expression of peptide hormone genes in the nervous system has led to the suggestion that these peptides may function as neurotransmitters, neuromodulators, and releasing or inhibiting factors in different regions of the brain. Glucagon and the glucagon-like peptides are derived from proglucagon in the pancreatic islets and intestine. A role for these peptides in the central nervous system has been proposed, but evidence for the biosynthesis of proglucagon in brain has been lacking. We now report that the glucagon gene is expressed in the brainstem and hypothalamus and that a glucagon mRNA transcript identical to that produced in pancreas and intestine gives rise to proglucagon-related peptides in the brain.
Reduced tumor‐antigen density leads to PD‐1/PD‐L1‐mediated impairment of partially exhausted CD8+ T cells (2011)

Clinical progression of cancer patients is often observed despite the presence of tumor-reactive T cells. Co-inhibitory ligands of the B7 superfamily have been postulated to play a part in this tumor-immune escape. One of these molecules, PD-L1 (B7-H1, CD274), is widely expressed on tumor cells and has been shown to mediate T-cell inhibition. However, attempts to correlate PD-L1 tumor expression with negative prognosis have been conflicting. To better understand when PD-1/PD-L1-mediated inhibition contributes to the functional impairment of tumor-specific CD8(+) T cells, we varied the levels of antigen density and/or PD-L1 expression at the surface of tumor cells and exposed them to CD8(+) T cells at different levels of functional exhaustion. We found that the gradual reduction of cognate antigen expression by PD-L1-expressing tumor cells increased the susceptibility of partially exhausted T cells to PD-1/PD-L1-mediated inhibition in vitro as well as in vivo. In conclusion, chronically stimulated CD8(+) T cells become sensitive to PD-1/PD-L1-mediated functional inhibition upon low antigen detection; a setting which is likely involved during tumor-immune escape.
Jean Marquet Award. Regeneration of the neurosensory structures in the mammalian inner ear. (1997)

Regeneration of the neurosensory structures in the mammalian inner ear. Motivated by the absence of treatment of neurosensory deafness apt to restore auditory function or alter the course of progressive hearing loss, we developed two different experimental strategies to approach these diseases: one is otoprotection, designed to prevent further degradation of auditory function; the other is regeneration which is defined as the replacement of hair cells in the deaf ear and their reconnection to the central nervous system through primary auditory neurons. In this paper, we summarize our data on the regeneration of auditory neurons and hair cells. Neuronal maintenance and regeneration was studied through an initial investigation of growth factors during inner development. Once the effect of various neurotrophic molecules was determined, the factors were tested on mature auditory neurons in vitro and in vivo. The hair cell regeneration was investigated on the basis of a concept derived from comparative physiology and from the study of the development of the inner ear. We showed that in young rats it is possible to induce the regeneration/repair of hair cells in the organ of Corti in cultures using retinoïc acid and transforming growth factor alpha. The clinical prospects of these findings of inner ear regeneration are discussed.
Subcellular Localization and Biological Activity of Mr 18,000 Basic Fibroblast Growth Factor: Site-Directed Mutagenesis of a Putative Nuclear Translocation Sequence (1993)

Residues 27-31 (Lys-Asp-Pro-Lys-Arg) of the 155-amino acid form of basic fibroblast growth factor (bFGF) are in good agreement with a consensus sequence for nuclear translocation. To evaluate the role of this sequence in mediating the intracellular localization and biological activity of bFGF, basic residues Lys-27, Lys-30, and Arg-31 were changed to neutral glutamine residues by site-directed mutagenesis of the human bFGF cDNA. The bFGF mutant (M1Q-bFGF) was expressed in eukaryotic cells and in prokaryotic cells, from which it was purified to homogeneity. Transient expression of bFGF cDNA and of M1Q-bFGF cDNA in simian COS-1 cells followed by immunolocalization and by subcellular fractionation indicated that both molecules localize in the nucleus, as well as in the cytoplasm of transfected cells, and interact with nuclear chromatin and with eukaryote DNA in a similar manner. Prokaryotic expression of M1Q-bFGF cDNA yields a polypeptide endowed with a receptor-binding capacity and mitogenic activity similar to that exerted by wild-type bFGF. However, recombinant M1Q-bFGF showed a drastically reduced capacity to induce the production of urokinase-type plasminogen activator (uPA) in endothelial cells. The uPA-inducing activity of M1Q-bFGF was fully restored by the presence of soluble heparin in the culture medium. In conclusion, the sequence bFGF(27-31) does not appear to represent a nuclear translocation and/or retention sequence for bFGF. However, neutralization of its basic residues seems to modify the tertiary structure of the growth factor, thus affecting some of its biological properties.
Defect detection in textured materials using Gabor filters (2002)

Vision-based inspection of industrial materials such as textile webs, paper or wood requires the development of defect segmentation techniques based on texture analysis. In this work, a multi-channel filtering technique that imitates the early human vision process is applied to images captured online. This new approach uses Bernoulli's rule of combination for integrating images from different channels. Physical image size and yarn impurities are used as key parameters for tuning the sensitivity of the proposed algorithm. Several real fabric samples along with the result of segmented defects are presented. The results achieved show that the developed algorithm is robust, scalable and computationally efficient for detection of local defects in textured materials.
A Novel Phosphotyrosine Motif with a Critical Amino Acid at Position −2 for the SH2 Domain-mediated Activation of the Tyrosine Phosphatase SHP-1 (1997)

SHP-1 is a protein-tyrosine phosphatase associated with inhibition of activation pathways in hematopoietic cells. The catalytic activity of SHP-1 is regulated by its two SH2 (Src homology 2) domains; phosphotyrosine peptides that bind to the SH2 domains activate SHP-1. The consensus sequence (I/V)XYXX(L/V) is present in the cytoplasmic tails of several lymphocyte receptors that interact with the second SH2 domain of SHP-1. In several of these receptors, there are two or three occurrences of the motif. Here we show that the conserved hydrophobic amino acid preceding the phosphotyrosine is critical for binding to and activation of SHP-1 by peptides corresponding to sequences from killer cell inhibitory receptors. The interaction of most SH2 domains with phosphopeptides requires only the phosphotyrosine and the three residues downstream of the tyrosine. In contrast, the shortest peptide able to bind or activate SHP-1 also included the two residues upstream of the phosphotyrosine. A biphosphopeptide corresponding to the cytoplasmic tail of a killer cell inhibitory receptor with the potential to interact simultaneously with both SH2 domains of SHP-1 was the most potent activator of SHP-1. The hydrophobic residue upstream of the tyrosine was also critical in the context of the biphosphopeptide. The contribution of a hydrophobic amino acid two residues upstream of the tyrosine in the SHP-1-binding motif may be an important feature that distinguishes inhibitory receptors from those that provide activation signals.
Interaction of fibroblast growth factor and C-natriuretic peptide signaling in regulation of chondrocyte proliferation and extracellular matrix homeostasis (2005)

Overexpression of C-natriuretic peptide (CNP) in cartilage partially rescues achondroplasia in the mouse. Here, we studied the interaction of fibroblast growth factor (FGF) and CNP signaling in chondrocytes. CNP antagonized FGF2-induced growth arrest of rat chondrosarcoma (RCS) chondrocytes by inhibition of the Erk mitogen activated protein kinase pathway. This effect of CNP was protein kinase G-dependent and was mimicked by the cGMP analog pCPT-cGMP. FGF2-mediated activation of both MEK and Raf-1 but not Ras or FRS2 was abolished by CNP demonstrating that CNP blocks the Erk pathway at the level of Raf-1. CNP also counteracted the FGF2-mediated degradation of RCS extracellular matrix. CNP partially antagonized FGF2-induced expression, release and activation of several matrix-remodeling molecules including matrix metalloproteinase 2 (MMP2), MMP3, MMP9, MMP10 and MMP13. In addition, CNP compensated for FGF2-mediated matrix loss by upregulation of matrix production independent of its interference with FGF signaling. We conclude that CNP utilizes both direct and indirect ways to counteract the effects of FGF signaling in a chondrocyte environment.
Ethical challenges. -editorial- (2000)

The author urges the profession to develop a forum where matters that reach to its ethical heart are discussed. As a first step, it would be useful for the profession of pharmacy in this country to have a common ethical code that not only recognised the primacy of the patient and the pharmacist's responsibilities in that regard, but also recognised that future ethical dilemmas will challenge the very core of pharmacy practice beliefs. (non-author abstract)