gebhart/patrepeval huggingface dataset:
Targeting Heme-Oxidized Soluble Guanylate Cyclase in Experimental Heart Failure (2007)

Soluble guanylate cyclase is a heterodimeric enzyme with a prosthetic heme group that, on binding of its main ligand, NO, generates the second messenger cGMP. Unlike conventional nitrovasodilators, the novel direct NO- and heme-independent soluble guanylate cyclase activator BAY 58-2667 is devoid of non-cGMP actions, lacks tolerance development, and preferentially activates NO-insensitive heme-free or oxidized soluble guanylate cyclase. BAY 58-2667, therefore, represents a novel therapeutic advance in mediating vasodilation. To date, its cardiorenal actions in congestive heart failure (CHF) are undefined. We, therefore, hypothesized that BAY 58-2667 would have beneficial preload- and afterload-reducing actions in experimental severe CHF together with renal vasodilating properties. We assessed the cardiorenal actions of intravenous administration of 2 doses of BAY 58-2667 (0.1 and 0.3 microg/kg per minute, respectively) in a model of tachypacing-induced severe CHF. In CHF, BAY 58-2667 dose-dependently reduced mean arterial, right atrial, pulmonary artery, and pulmonary capillary wedge pressure (from baseline 19+/-1 to 12+/-2 mm Hg). Cardiac output (2.4+/-0.3 to 3.2+/-0.4 L/min) and renal blood flow increased. Glomerular filtration rate and sodium and water excretion were maintained. Consistent with cardiac unloading, atrial and B-type natriuretic peptide decreased. Plasma renin activity (P=0.31) and aldosterone remained unchanged (P=0.19). In summary, BAY 58-2667 in experimental CHF potently unloaded the heart, increased cardiac output and renal blood flow, and preserved glomerular filtration rate and sodium and water excretion without further neurohumoral activation. These beneficial properties make direct soluble guanylate cyclase stimulation with BAY 58-2667 a promising new therapeutic strategy for cardiovascular diseases, such as heart failure.
A phase I/IItrial of MYO‐029 in adult subjects with muscular dystrophy (2008)

This trial supports the hypothesis that systemic administration of myostatin inhibitors provides an adequate safety margin for clinical studies. Further evaluation of more potent myostatin inhibitors for stimulating muscle growth in muscular dystrophy should be considered.
Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia (2016)

Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.
Optical fiber meta-tips (2016)

We realize the first optical-fiber “meta-tips” implementing in the near-infrared the beam-steering with increasing angles, up to the limit case of surface-waves excitation. We also explore their capability to work as local refractive index sensor.
A Simple Method for Preparation of Secondary Aromatic Amines (1991)

A simple and efficient method for the preparation of secondary N-alkylarylamines via reductive amination of ketones with primary aromatic amines using activated zinc/acetic acid is described. It requires only equimolar amounts of the starting compounds and affords good yields of the corresponding amines (50-90%). It is not applicable to aldehydes nor aliphatic amines.
Post-synthesis grafting of Al onto MCM-41 (1997)

Al-containing MCM-41 materials are prepared by grafting Al onto purely siliceous MCM-41; the resulting materials retain the hexagonal order and physical properties of the purely siliceous parent MCM-41 and exhibit higher Brønsted acid content compared to Al-MCM-41 prepared by direct hydrothermal synthesis.
Platelet Factor 4: An Inhibitor of Angiogenesis (2004)

Platelet factor 4 (PF4) is an antiangiogenic ELR-negative chemokine. PF4 inhibits endothelial cell proliferation and migration and angiogenesis in vitro and in vivo. Three different mechanisms have been proposed to explain PF4's antiangiogenic effects. First, PF4 may bind proteoglycans and interfere with the proteoglycan-bystander effect on growth factor activity. Second, PF4 is able to interact directly with angiogenesis growth factors such as fibroblast growth factors or vascular endothelial growth factors and inhibits their interaction with cell surface receptors. Third, PF4 may activate cell surface receptors on endothelial cells and induce inhibitory signals. Recently, one such receptor, CXCR3-B, was identified. In cardiovascular disease, PF4 may possibly intervene in collateral vessel formation, plaque neovascularization, heparin-induced thrombocytopenia and stent endothelialization. Several PF4 fragments such as PF4-CTF and modified molecules have been made that exhibit antiangiogenesis properties and may serve as leads for further therapeutic development.
What's real about virtual reality? (1999)

The author presents a personal assessment of the state of the art of VR. In 1994, he surveyed the field of VR. His assessment then was that VR almost worked, but that we were not yet there. There were lots of demos and pilot systems, but except for vehicle simulators and entertainment applications, VR was not yet in production use doing real work. This year he was invited to do an up-to-date assessment of VR, with funding to visit major centers in North America and Europe. Every one of the component technologies has made big strides. Moreover, I found that there now exist some VR applications routinely operated for the results they produce.
Polymer particles that switch shape in response to a stimulus (2010)

Particle engineering for biomedical applications has unfolded the roles of attributes such as size, surface chemistry, and shape for modulating particle interactions with cells. Recently, dynamic manipulation of such key properties has gained attention in view of the need to precisely control particle interaction with cells. With increasing recognition of the pivotal role of particle shape in determining their biomedical applications, we report on polymeric particles that are able to switch their shape in real time in a stimulus-responsive manner. The shape-switching behavior was driven by a subtle balance between polymer viscosity and interfacial tension. The balance between the two forces was modulated by application of an external stimulus chosen from temperature, pH, or chemical additives. The dynamics of shape switch was precisely controlled over minutes to days under physiological conditions. Shape-switching particles exhibited unique interactions with cells. Elliptical disk-shaped particles that are not phagocytosed by macrophages were made to internalize through shape switch, demonstrating the ability of shape-switchable particles in modulating interaction with cells.
Incomplete Cd8+ T Lymphocyte Differentiation as a Mechanism for Subdominant Cytotoxic T Lymphocyte Responses to a Viral Antigen (2000)

CD8(+) cytotoxic T lymphocytes (CTLs) recognize antigen in the context of major histocompatibility complex (MHC) class I molecules. Class I epitopes have been classified as dominant or subdominant depending on the magnitude of the CTL response to the epitope. In this report, we have examined the in vitro memory CTL response of H-2(d) haplotype murine CD8(+) T lymphocytes specific for a dominant and subdominant epitope of influenza hemagglutinin using activation marker expression and staining with soluble tetrameric MHC-peptide complexes. Immune CD8(+) T lymphocytes specific for the dominant HA204-210 epitope give rise to CTL effectors that display activation markers, stain with the HA204 tetramer, and exhibit effector functions (i.e., cytolytic activity and cytokine synthesis). In contrast, stimulation of memory CD8(+) T lymphocytes directed to the subdominant HA210-219 epitope results in the generation of a large population of activated CD8(+) T cells that exhibit weak cytolytic activity and fail to stain with the HA210 tetramer. After additional rounds of restimulation with antigen, the HA210-219-specific subdominant CD8(+) T lymphocytes give rise to daughter cells that acquire antigen-specific CTL effector activity and transition from a HA210 tetramer-negative to a tetramer-positive phenotype. These results suggest a novel mechanism to account for weak CD8(+) CTL responses to subdominant epitopes at the level of CD8(+) T lymphocyte differentiation into effector CTL. The implications of these findings for CD8(+) T lymphocyte activation are discussed.
A Novel Peptide Probe for Studying the Transbilayer Movement of Phosphatidylethanolamine (1994)

Ro09-0198 is a cyclic peptide isolated from Streptoverticillium griseoverticillatum which recognizes strictly the structure of phosphatidylethanolamine (PE) and forms an equimolar complex with the phospholipid on biological membranes. To use the peptide as a probe for analyzing the transbilayer movement of PE, we labeled the amino-terminal amino acid of the peptide with biotin without changing either the reactivity or specificity of the peptide. The amount of the peptide bound to the membrane was measured by enzyme linked immunosorbent assay (ELISA) after extraction of the peptide from the membrane. The peptide showed a strict temperature-dependent binding to human erythrocytes and the binding increased with increasing temperature. Since the peptide bound to PE in a temperature-independent manner and the binding to membrane PE is not affected by membrane proteins, the present temperature-dependent binding of the peptide to the cell membranes was likely to reflect temperature-dependent translocation of PE. The binding of the peptide to erythrocytes differed greatly among animal species. The peptide also showed temperature-dependent binding to a human histocytic lymphoma cell line, U937, suggesting that the peptide will provide a novel and convenient probe for analyzing the transbilayer movement of PE in eukaryotic cells.
A monoclonal antibody against a laminin-heparan sulfate proteoglycan complex perturbs cranial neural crest migration in vivo. (1988)

INO (inhibitor of neurite outgrowth) is a monoclonal antibody that blocks axon outgrowth, presumably by functionally blocking a laminin-heparan sulfate proteoglycan complex (Chiu, A. Y., W. D. Matthew, and P. H. Patterson. 1986. J. Cell Biol. 103: 1382-1398). Here the effect of this antibody on avian neural crest cells was examined by microinjecting INO onto the pathways of cranial neural crest migration. After injection lateral to the mesencephalic neural tube, the antibody had a primarily unilateral distribution. INO binding was observed in the basal laminae surrounding the neural tube, ectoderm, and endoderm, as well as within the cranial mesenchyme on the injected side of the embryo. This staining pattern was indistinguishable from those observed with antibodies against laminin or heparan sulfate proteoglycan. The injected antibody remained detectable for 18 h after injection, with the intensity of immuno-reactivity decreasing with time. Embryos ranging from the neural fold stage to the 9-somite stage were injected with INO and subsequently allowed to survive for up to 1 d after injection. These embryos demonstrated severe abnormalities in cranial neural crest migration. The predominant defects were ectopic neural crest cells external to the neural tube, neural crest cells within the lumen of the neural tube, and neural tube deformities. In contrast, embryos injected with antibodies against laminin or heparan sulfate proteoglycan were unaffected. When embryos with ten or more somites were injected with INO, no effects were noted, suggesting that embryos are sensitive for only a limited time during their development. Immunoprecipitation of the INO antigen from 2-d chicken embryos revealed a 200-kD band characteristic of laminin and two broad smears between 180 and 85 kD, which were resolved into several bands at lower molecular mass after heparinase digestion. These results indicate that INO precipitates both laminin and proteoglycans bearing heparan sulfate residues. Thus, microinjection of INO causes functional blockage of a laminin-heparan sulfate proteoglycan complex, resulting in abnormal cranial neural crest migration. This is the first evidence that a laminin-heparan sulfate proteoglycan complex is involved in aspects of neural crest migration in vivo.
Ionizing radiation and short wavelength UV activate NF-κB through two distinct mechanisms (1998)

We examined the mechanisms by which two different types of photonic radiation, short wavelength UV (UV-C) and gamma radiation, activate transcription factor NF-kappaB. Exposure of mammalian cells to either form of radiation resulted in induction with similar kinetics of NF-kappaB DNA binding activity, nuclear translocation of its p65(RelA) subunit, and degradation of the major NF-kappaB inhibitor IkappaBalpha. In both cases, induction of NF-kappaB activity was attenuated by proteasome inhibitors and a mutation in ubiquitin-activating enzyme, suggesting that both UV-C and gamma radiation induce degradation of IkappaBs by means of the ubiquitin/proteasome pathway. However, although the induction of IkappaBalpha degradation by gamma rays was dependent on its phosphorylation at Ser-32 and Ser-36, UV-C-induced IkappaBalpha degradation was not dependent on phosphorylation of these residues. Even the "super repressor" IkappaBalpha mutant, which contains alanines at positions 32 and 36, was still susceptible to UV-C-induced degradation. Correspondingly, we found that gamma radiation led to activation of IKK, the protein kinase that phosphorylates IkappaBalpha at Ser-32 and Ser-36, whereas UV-C radiation did not. Furthermore, expression of a catalytically inactive IKKbeta mutant prevented NF-kappaB activation by gamma radiation, but not by UV-C. These results indicate that gamma radiation and UV-C activate NF-kappaB through two distinct mechanisms.
Electrocatalytic intercalator-induced winding of double-stranded DNA with polyaniline (2003)

The intercalation of doxorubicin into double-stranded DNA stimulates the electocatalyzed oxidation of aniline to polyaniline and its winding on the DNA template.
Tumor necrosis factor α– and interleukin‐1β–dependent induction of CCL3 expression by nucleus pulposus cells promotes macrophage migration through CCR1 (2012)

Our findings indicate that TNFα and IL-1β modulate the expression of CCL3 in NP cells by controlling the activation of MAPK, NF-κB, and C/EBPβ signaling. The CCL3-CCR1 axis may play an important role in promoting macrophage infiltration in degenerated, herniated discs.
Electrostatic melting in a single-molecule field-effect transistor with applications in genomic identification (2017)

The study of biomolecular interactions at the single-molecule level holds great potential for both basic science and biotechnology applications. Single-molecule studies often rely on fluorescence-based reporting, with signal levels limited by photon emission from single optical reporters. The point-functionalized carbon nanotube transistor, known as the single-molecule field-effect transistor, is a bioelectronics alternative based on intrinsic molecular charge that offers significantly higher signal levels for detection. Such devices are effective for characterizing DNA hybridization kinetics and thermodynamics and enabling emerging applications in genomic identification. In this work, we show that hybridization kinetics can be directly controlled by electrostatic bias applied between the device and the surrounding electrolyte. We perform the first single-molecule experiments demonstrating the use of electrostatics to control molecular binding. Using bias as a proxy for temperature, we demonstrate the feasibility of detecting various concentrations of 20-nt target sequences from the Ebolavirus nucleoprotein gene in a constant-temperature environment.
Stereochemistry of asymmetric silicon. XV. Stereospecific hydrosilation and exchange reactions of R3SiH(D) catalyzed by Group VIII metal centers (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereochemistry of asymmetric silicon. XV. Stereospecific hydrosilation and exchange reactions of R3SiH(D) catalyzed by Group VIII metal centersLeo H. Sommer, J. E. Lyons, and Hiroshi FujimotoCite this: J. Am. Chem. Soc. 1969, 91, 25, 7051–7061Publication Date (Print):December 1, 1969Publication History Published online1 May 2002Published inissue 1 December 1969https://pubs.acs.org/doi/10.1021/ja01053a027https://doi.org/10.1021/ja01053a027research-articleACS PublicationsRequest reuse permissionsArticle Views367Altmetric-Citations81LEARN 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-Alertsclose Get e-Alerts
Comparison of Phosphodiesterase Inhibitors of Differing Isoenzyme Selectivity Added to St. Thomas' Hospital Cardioplegic Solution Used for Hypothermic Preservation of Rat Lungs (2000)

Raising intracellular cAMP or cGMP concentrations protects lungs from ischemia-reperfusion injury. These nucleotides are catabolized by a number of distinct phosphodiesterase (PDE) isoenzyme subfamilies. We examined the ability of PDE inhibitors of differing selectivities to protect lungs from the effects of prolonged hypothermic storage. Rat lungs were perfused with bicarbonate buffer mixed with rat blood (4:1 vol/vol, 37 degrees C), ventilated, and vascular resistance, airway compliance, and resistance, and gas exchange measured. Lungs were then flushed with, and immersed in, St. Thomas' Hospital Solution (STH) (4 degrees C) or STH containing rolipram, milrinone, zaprinast, or theophylline. After 8 h storage, function was reassessed during 40 min reperfusion. Lungs stored in STH containing rolipram or theophylline had improved function on reperfusion. After 40 min reperfusion, pulmonary compliance (Cstat) was 0.07 +/- 0.01 ml/cm H(2)O in lungs stored in STH alone. Adding rolipram (100 microM) or theophylline (3,000 microM) to the STH used for flushing and storage improved Cstat after reperfusion to 0.17 +/- 0.02 ml/cm H(2)O (p < 0.05) and 0.17 +/- 0.02 ml/cm H(2)O (p < 0. 05), respectively. Theophylline also improved the increase in perfusate PO(2) on transit through the lung after storage to 25.16 +/- 2.33 compared with 4.72 +/- 2.18 mm Hg in lungs stored in STH alone (p < 0.05). Of the selective PDE inhibitors tested, rolipram (type IV inhibitor) was most effective. However, the nonselective agent, theophylline, provided the best protection of function after storage and reperfusion of rat lungs.
Linkage and sequence homology of two human immunoglobulin gamma heavy chain constant region genes. (1982)

We report the nucleotide sequence of a gene encoding a human immunoglobulin C gamma 2 region. Comparison with the previously determined C gamma 4 sequence reveals that these two genes share extensive (approximately 95%) homology in the three CH domain exons and adjacent noncoding regions. In contrast, hinge exons have diverged to a much greater degree, implying that natural selection has favored the generation of diversity in these coding regions. We have used the noncoding nucleotide differences to estimate that approximately 6-7 million years have elapsed since the occurrence of the gene duplication or correction event which generated the two identical ancestral genes. In addition we show that the two C gamma genes are arranged in human chromosomal DNA in the configuration 5'-C gamma 2-17 kilobase pairs -C gamma 4-3'.
Mcl-1 Is a Key Regulator of Apoptosis Resistance in Chlamydia trachomatis-Infected Cells (2008)

Chlamydia are obligate intracellular bacteria that cause variety of human diseases. Host cells infected with Chlamydia are protected against many different apoptotic stimuli. The induction of apoptosis resistance is thought to be an important immune escape mechanism allowing Chlamydia to replicate inside the host cell. Infection with C. trachomatis activates the Raf/MEK/ERK pathway and the PI3K/AKT pathway. Here we show that inhibition of these two pathways by chemical inhibitors sensitized C. trachomatis infected cells to granzyme B-mediated cell death. Infection leads to the Raf/MEK/ERK-mediated up-regulation and PI3K-dependent stabilization of the anti-apoptotic Bcl-2 family member Mcl-1. Consistently, interfering with Mcl-1 up-regulation sensitized infected cells for apoptosis induced via the TNF receptor, DNA damage, granzyme B and stress. Our data suggest that Mcl-1 up-regulation is primarily required to maintain apoptosis resistance in C. trachomatis-infected cells.
An estrogen-dependent secretory protein, which shares identity with chitinases, is expressed in a temporally and regionally specific manner in the sheep oviduct at the time of fertilization and embryo development. (1995)

An estrogen (E2)-dependent 90,000-92,000 M(r) protein is synthesized and released by the sheep oviduct in a temporally and regionally specific manner during the first few days of pregnancy, where it associates with the embryo. The present study was undertaken to further define the nature of this protein and its regulation at a time when fertilization and early embryonic cleavage occur in the oviduct. The complete complementary DNA (cDNA) sequence for the 90,000-92,000 M(r) protein was determined, and steady state messenger RNA (mRNA) levels were measured during early pregnancy (estrus and days 1, 2, 3, 4, 6, and 16). The composite cDNA possessed an open reading frame of 1633 bases with a single potential N-glycosylation site. The inferred amino acid (aa) sequence predicted a prepolypeptide of 539 aa (69,151 M(r)) and a mature polypeptide of 518 aa (66,477 M(r)). Nucleotide and deduced aa sequence shared identity with translated E2-dependent cow, human, and partially sequenced baboon oviduct protein cDNAs; a human articular cartilage protein, gp 39; and chitinases. Northern blot hybridization revealed a single RNA species (2.2 kilobases) in the fimbria and ampulla, which was not detected in the isthmus or other reproductive and nonreproductive tract tissue RNAs. Steady state levels of mRNA encoding the 90,000-92,000 M(r) were highest in the fimbria and ampulla at estrus and on day 1 of pregnancy, when gamete transport and fertilization occur in the E2-dominated fallopian tube. Oviduct protein mRNA levels declined significantly (P < 0.05) on day 2 and underwent a further significant reduction on day 3 of pregnancy coincident with transport of the embryo from the oviduct to the uterus, a reproductive stage associated with rising progesterone levels. By day 16 of pregnancy, the mRNA encoding the E2-dependent oviduct protein was virtually undetectable. The temporally and regionally specific regulation of gene expression for the 90,000-92,000 M(r) E2-dependent protein correlates with protein synthesis data and emphasizes the precise regulation of its synthesis at a time when fertilization and embryonic cleavage are taking place in the oviduct. Identity with a growing class of steroid-regulated oviduct secretory proteins and chitinase enzymes suggests a possible structural and/or functional relationship, which may be important in mediating these latter reproductive events.