gebhart/patrepeval huggingface dataset:
Guidebook to Cytokines and Their Receptors (1995)

Abstract For the purposes of the present volume, cytokines are defined as secreted regulatory proteins that control the survival, growth, differentiation and effector function of tissue cells. Cytokines encompass those families of regulators variously known as growth factors, colony-stimulating factors, interleukins, lymphokines, monokines, and interferons. I have excluded most of the classical endocrine hormones because their general properties are different from those of the cytokines (see Table 1) and because they have been amply described in other texts. Nevertheless, there are no sharp boundaries that distinguish cytokines from other regulatory proteins and the selections in this book reflect my own bias.
Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O 2 -Regulated Prolyl Hydroxylation (2001)

Hypoxia-inducible factor (HIF) is a transcriptional complex that plays a central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-alpha subunits are rapidly destroyed by a mechanism that involves ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. Here we show that the interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by an enzyme we have termed HIF-alpha prolyl-hydroxylase (HIF-PH). An absolute requirement for dioxygen as a cosubstrate and iron as cofactor suggests that HIF-PH functions directly as a cellular oxygen sensor.
β-Thiophene-Fused BF2-Azadipyrromethenes as Near-Infrared Dyes (2014)

A facile synthetic route to a new class of near-IR β-thiophene-fused BF2-azadipyrromethenes (aza-BDTPs) is presented. Sharp absorption and fluorescence emission bands at around 800 nm were observed for these highly photostable aza-BDTPs, with a large absorption coefficient and very low absorptions in the visible range from 700 to 380 nm.
Direct Modulation by Androgens of the Response of Human Bone Cells (SaOS-2) to Human Parathyroid Hormone (PTH) and PTH-Related Protein* (1989)

We have investigated the actions of 17 beta-estradiol (E2) on the production of cAMP stimulated by synthetic human PTH [hPTH-(1-34)], synthetic hPTH-related protein [hPTHrP-(1-34)], and vasoactive intestinal peptide (VIP) in human (SaOS-2) and rat (ROS 17/2.8) osteoblast-like osteosarcoma cells. In SaOS-2 cells, hPTH-(1-34) (2.5 nM), hPTHrP-(1-34) (2.5 nM), and VIP (10-100 nM) stimulated the accumulation of cAMP markedly (greater than 20- to 30-fold in 1 h). Cells were preincubated in serum-free medium for 4-24 h, then in the absence or presence of E2 for 4 h before a 1-h stimulation with peptide hormone in the absence of E2. In SaOS-2 cells, pretreatment with E2 (10(-12)-10(-8) M) for 4 h inhibited by up to 50% the accumulation of cAMP stimulated by hPTH-(1-34) or hPTHrP-(1-34), but E2 had no inhibitory effect on VIP action. 17 alpha-Estradiol had no inhibitory action on hPTH- or hPTHrP-stimulated accumulation of cAMP at concentrations as high as 10(-8) M. Additional evidence against a nonspecific effect of E2 was the total lack of inhibition of cAMP accumulation stimulated by hPTH-(1-34) or hPTHrP-(1-34) in ROS 17/2.8 cells at concentrations of E2 up to 10(-6) M. We conclude that E2 can act directly and rapidly in human osteoblast-like cells to modulate selectively the ability of hPTH and hPTHrP to enhance the production of cAMP.
Kinetics of deoxyhemoglobin subunit dissociation determined by haptoglobin binding: estimation of the equilibrium constant from forward and reverse rates (1976)

Deoxyhemoglobin tetramers dissociate into dimers very slowly, with half-times on the order of several hours. It is demonstrated that absorbance changes in the Soret region which accompany this dissociation and persist upon binding of haptoglobin 1-1 to the dissociated dimers can be used for accurate kinetic determinations over the necessarily long periods required for study. This method of study for the slow reactions depends upon long-term spectral integrity of the reaction mixtures and upon accurate measurement. The variation in rate constants determined by this procedure has been correlated with variations in structural constraints at the dimer-dimer contact region. In the presence of 2,3-diphosphoglycerate the rate constant is decreased, consistent with the role of this effector in binding to both beta chains and stabilizing the constrained deoxy tetramer against dissociation into alphabeta dimers. With hemoglobin specifically modified (des-Arg-141alpha) to eliminate half the constraining salt links within the dimer-dimer contact region, the dissociation rate is increased by approximately three orders of magnitude. In hemoglobin S where the amino acid substitution is not directly in the intersubunit contact region of interest, the dissociation rate is found to be approximately the same as that for hemoglobin A. Combination of the dissociation rate constants determined by haptoglobin binding with stopped-flow determinations of the rate constant for reassociation of dissociated dimers provides an estimate of the equilibrium constant, 0K2, for the deoxyhemoglobin dimer-tetramer equilibrium. This estimate is independent of any assumptions regarding other energetic quantities, and yields a value of 2.54 +/- 0.7 X 10(10)M-1 (heme) in 0.1 M Tris-HCl, 0.1 M NaCl, and 1 mM EDTA, pH 7.4, 21.5 degrees C. Thus the intersubunit contact energy is -14.0 +/- 0.2 kcal/mol of heme. The stabilization energy between deoxy and oxy tetramers is found to be approximately 6.4 kcal/mol, under these conditions.
Three‐stage high‐performance optoelectronic asynchronous transfer mode switch: design and performance (1996)

We explore the possibility of enhancing very large scale integration (VLSI) electronic switch structures using reconfigurable freespace optical chip-to-chip interconnects. We present a novel technological approach to the realization of an output queued asynchronous transfer mode (ATM) switching fabric within a low-blocking, three-stage network configuration by employing both electronic and optical switching stages with reduced cross-office transfer rates. The first and third stages are implemented by the selective reading/writing from/to a sectorized optically accessible random access memory (known as opto-RAM) currently under development in our laboratory. The second (central) stage uses holographic fan-out/selective fan-in optics to implement a freespace photonic crossbar switch. We assess the performance of the ATM switch fabric using computer simulation as well as analytic techniques.
Improving Spectroscopic Techniques by a Scanning Multichannel Method (1990)

The conventional optical multichannel technique (MT) has improved optical spectroscopy, in comparison to single-channel methods, by at least an order of magnitude in measurement time at the same signal-to-noise ratio. In this work we show that some disadvantages (e.g., limited range of the recorded spectra, different noise and sensitivity of each detection element, and fixed spectral distance of the detection elements) can be excluded by using what we call the scanning multichannel technique (SMT). A calculation of the measurement time for characteristic single-channel and multichannel detectors results in the fact that SMT is, like MT, an order of magnitude faster than the single-channel technique (SCT). In some particular cases SMT results in measurement times shorter than those for MT. We conclude that SMT combines the advantages of MT and SCT. Moreover, measurements of sharp spectral lines made it evident that SMT also improves the reproducibility of the spectrometer used and increases the accuracy of the recorded spectra. The SMT method is not only restricted to optical spectroscopy but can be universally applied to all spectroscopic methods where multichannel detection is used.
Early Murine Polymicrobial Sepsis Predominantly Causes Renal Injury (2013)

Multiple organ failure in sepsis substantially increases mortality. This study examined if there was greater hepatic, pancreatic, splenic, or renal injury in mice that would die during sepsis induced by cecal ligation and puncture (CLP) compared with that of those that would survive. Mice were stratified into groups predicted to die (Die-P) or predicted to live (Live-P) in the first 5 days after CLP based on plasma interleukin 6 levels. Groups were sacrificed to harvest organs for histology. Separate animals were followed for survival with daily blood sampling to examine renal function. No significant histological evidence of organ injury was observed in either the Live-P or Die-P mice. Minimal hepatic injury occurred as plasma aspartate transaminase demonstrated less than a 2-fold increase over normal in both groups. In addition, pancreatic injury was minimal as there was also less than a 2-fold increase in plasma amylase levels. In contrast, blood urea nitrogen levels were nearly five times higher within 24 h in Die-P mice compared with those of mice predicted to live. Mice with blood urea nitrogen levels higher than 44 mg/dL had a 17.6 higher relative risk of dying (95% confidence interval, 4.5-69.4). Cystatin C, a more specific kidney function biomarker, was also elevated at 24 h after CLP. When the cystatin C levels were analyzed relative to the hours before death, rather than hours after CLP, they were also significantly increased in mice Dead by day 5 compared with those Alive after day 5. We conclude that limited liver, pancreas, and spleen injury develops during murine CLP-induced sepsis while significant kidney injury is present. The renal injury becomes worse closer to death.
Chiral liquid crystals for ferroelectric, electroclinic, and antiferroelectric displays and photonic devices (2000)

Ferroelectric and antiferroelectric liquid crystals have shown great promise for use in large area flat panel displays because of their fast switching and bistable operation. However, the commercialization of FLCDs and AFLCDs using surface stabilized geometries has not materialized for a number of reasons, most notably shock instability, the need to control the cell spacing of the display to between 1 and 2 micrometer, and competition from actively addressed nematic displays. Surface stabilized displays are nevertheless finding niche markets in areas such as spatial light modulators, microdisplays, and projection systems. Even though this is the present situation, it is clear that FLCs and AFLCs will be used advantageously in the future in active matrix configurations to give LCDs that operate at video-frame rates. Furthermore, there are many emerging uses for such materials in the areas of photonics and sensors e.g., novel switching and wavelength filtering components based on liquid crystal phase modulators and filters. There is also interest in utilizing LC technology in fiber optic networks, telecommunication transmission systems, interconnecting networks in large computers, optical image processors, and optically accessible electronic memory structures. All of these applications require fast switching materials that are stable and non-absorbent to light of various wavelengths.
Endothelial CD47 interaction with SIRPγ is required for human T-cell transendothelial migration under shear flow conditions in vitro (2008)

Leukocyte transendothelial migration (TEM) is a critical event during inflammation. CD47 has been implicated in myeloid cell migration across endothelium and epithelium. CD47 binds to signal regulatory protein (SIRP), SIRPalpha and SIRPgamma. So far, little is known about the role of endothelial CD47 in T-cell TEM in vivo or under flow conditions in vitro. Fluorescence-activated cell sorting and biochemical analysis show that CD3(+) T cells express SIRPgamma but not SIRPalpha, and fluorescence microscopy showed that CD47 was enriched at endothelial junctions. These expression patterns suggested that CD47 plays a role in T-cell TEM through binding interactions with SIRPgamma. We tested, therefore, whether CD47-SIRPgamma interactions affect T-cell transmigration using blocking mAb against CD47 or SIRPgamma in an in vitro flow model. These antibodies inhibited T-cell TEM by 70% plus or minus 6% and 82% plus or minus 1%, respectively, but had no effect on adhesion. In agreement with human mAb studies, transmigration of murine wild-type T helper type 1 cells across TNF-alpha-activated murine CD47(-/-) endothelium was reduced by 75% plus or minus 2% even though murine T cells appear to lack SIRPgamma. Nonetheless, these findings suggest endothelial cell CD47 interacting with T-cell ligands, such as SIRPgamma, play an important role in T-cell transendothelial migration.
Expression of sperm Ca2+‐activated K+channels inXenopusoocytes and their modulation by extracellular ATP (1998)

Ionic fluxes across the sperm membrane have been shown to be important in the initiating process of sperm activation and gamete interaction; however, electrophysiological investigation of the ion channels involved has been precluded by the small size of the sperm, especially in mammalian species. In the present study sperm ion channels were expressed in Xenopus oocytes by injection of RNAs of spermatogenic cells isolated from the rat testes. The RNA-injected oocytes responded to ATP, a factor known to regulate sperm activation, with the activation of an outwardly rectifying whole-cell current which was dependent on K+ concentrations and inhibitable by K+ channel blockers, charybdotoxin (CTX) and tetraethylammonium (TEA). The ATP-induced current could be mimicked by a Ca2+ ionophore but suppressed by a Ca2+ chelator applied intracellularly, indicating a Ca2+ dependence of the current. Single-channel measurements on RNA-injected oocytes revealed channels of large conductance which could be blocked by CTX and TEA. Co-injection of germ cell RNAs with the antisense RNA for a mouse gene encoding slowpoke 'Maxi' Ca2+-activated K+ channels resulted in significant reduction of the ATP- and ionomycin-induced current. The expression of the 'Maxi' Ca2+-activated K+ channels in sperm collected from the rat epididymis was also confirmed by Western blot analysis. These results suggest that sperm possess Ca2+-activated K+ channels which may be involved in the process of sperm activation.
S1P Is Associated with Protection in Human and Experimental Cerebral Malaria (2011)

Cerebral malaria (CM) is associated with excessive inflammatory responses and endothelial activation. Sphingosine 1-phosphate (S1P) is a signaling sphingolipid implicated in regulating vascular integrity, inflammation and T-cell migration. We hypothesized that altered S1P signaling during malaria contributes to endothelial activation and inflammation, and show that plasma S1P levels were decreased in Ugandan children with CM compared with children with uncomplicated malaria. Using the Plasmodium berghei ANKA (PbA) model of experimental CM (ECM), we demonstrate that humanized S1P lyase (hS1PL)(-/-) mice with reduced S1P lyase activity (resulting in increased bio-available S1P) had improved survival compared with wild-type littermates. Prophylactic and therapeutic treatment of infected mice with compounds that modulate the S1P pathway and are in human trials for other conditions (FTY720 or LX2931) significantly improved survival in ECM. FTY720 treatment improved vascular integrity as indicated by reduced levels of soluble intercellular adhesion molecule (sICAM), increased angiopoietin 1 (Ang1) (regulator of endothelial quiescence) levels, and decreased Evans blue dye leakage into brain parenchyma. Furthermore, treatment with FTY720 decreased IFNγ levels in plasma as well as CD4(+) and CD8(+) T-cell infiltration into the brain. Finally, when administered during infection in combination with artesunate, FTY720 treatment resulted in increased survival to ECM. These findings implicate dysregulation of the S1P pathway in the pathogenesis of human and murine CM and suggest a novel therapeutic strategy to improve clinical outcome in severe malaria.
Human platelets contain brain-derived neurotrophic factor (1990)

Neurotrophic support to peripheral sensory neurons is provided by 2 factors of related sequence, NGF and brain-derived neurotrophic factor (BDNF). NGF is present in peripheral target tissues, while BDNF has only been reported in the CNS. We now report the biological characterization and molecular cloning of a cDNA for BDNF from human platelets. BDNF in human platelets has biological activities very similar to those of BDNF obtained from adult porcine brain in neuron-enriched cultures prepared from peripheral ganglia of chick embryos at 8-12 d of incubation. BDNF from human platelets promoted the survival and neurite outgrowth of placodal and neural crest-derived sensory neurons, but not to parasympathetic or sympathetic neurons. Activity of the factor was additive to that of NGF in dorsal root ganglia (DRG) neuron cultures and is equivalent to porcine brain BDNF in nodose ganglion neuron cultures. On SDS-PAGE, BDNF from human platelets is recovered at an apparent molecular weight equivalent to porcine brain BDNF (13,000 D). A BDNF cDNA fragment was amplified from human platelet RNA by using a coupled reverse transcriptase-polymerase chain reaction. Molecular cloning and DNA sequence analysis of the amplified cDNA fragment revealed complete identity for the deduced amino acid sequences of human and porcine BDNF [amino acid (aa) 10-108 of the mature factor]. Thus, human platelets might provide an important source of BDNF for regenerating peripheral sensory neurons at the site of nerve injury.
The nac (Nitrogen Assimilation Control) Gene from Escherichia coli (1998)

The nitrogen assimilation control gene, nac, was detected in Escherichia coli but not in Salmonella typhimurium by Southern blotting, using a probe from the Klebsiella aerogenes nac (nacK) gene. The E. coli nac gene (nacE) was isolated from a cosmid clone by complementation of a nac mutation in K. aerogenes. nacE was fully functional in this complementation assay. DNA sequence analysis showed considerable divergence between nacE and nacK, with a predicted amino acid sequence identity of only 79% and most of the divergence in the C-terminal half of the protein sequence. The total predicted size of NAC(E) is 305 amino acids, the same as for NAC(K). A null mutation, nac-28, was generated by reverse genetics. Mutants bearing nac-28 have a variety of phenotypes related to nitrogen metabolism, including slower growth on cytosine, faster growth on arginine, and suppression of the failure of an Ntr-constitutive mutant to grow with serine as sole nitrogen source. In addition to a loss of nitrogen regulation of histidase formation, nac-28 mutants also showed a loss of a weak repression of glutamate dehydrogenase formation. This repression was unexpected because it is balanced by a NAC-independent activation of glutamate dehydrogenase formation during nitrogen-limited growth. Attempts to purify NAC(E) by using methods established for NAC(K) failed, and NAC(E) appears to be degraded with a half-life at 30 degrees C as short as 15 min during inhibition of protein synthesis.
Increased expression of microRNA-146a decreases myocardial ischaemia/reperfusion injury (2012)

MicroRNA-146a protects the myocardium from I/R injury. The mechanisms may involve attenuation of NF-κB activation and inflammatory cytokine production by suppressing IRAK1 and TRAF6.
Synthesis of (-)-Pseudoconhydrine through Ring Enlargement of a L-Proline Derivative (1997)

A short synthesis of (-)-pseudoconhydrine is described from L-proline by using a ring enlargement reaction.
Short communication: Thermosensitive liposomal taxol formulation: heatmediated targeted drug delivery in murine melanoma (1998)

Taxol, an antitumour alkaloid which stabilizes microtubules, demonstrates marked activity against several tumours. However, due to its low aqueous solubility, Cremophor EL (polyoxyethylated castor oil) is used as the excipient in pharmaceutical drug preparations of taxol. This has toxic side effects, thereby limiting the clinical use of taxol in cancer therapy. The aim of this study was to design a novel taxol formulation using thermosensitive liposomes in order to eliminate the Cremophor EL vehicle and improve the antitumour activity of taxol by site-specific drug delivery. Temperature-sensitive liposomes encapsulating taxol were prepared using the natural lipids egg phosphatidylcholine and cholesterol in combination with ethanol. The liposomes have a phase transition temperature (Tm) of 43 degrees C. The in vivo efficacy of thermosensitive liposome encapsulated taxol was determined in B16F10 murine melanoma transplanted into C57BI/6 mice in combination with local hyperthermia. A significant reduction in tumour volume and an increase in survival time was observed in tumour-bearing mice treated with a combination of hyperthermia and thermosensitive liposome encapsulated taxol compared with animals treated with an equivalent dose of free taxol with or without hyperthermia. These results suggest that thermosensitive liposome encapsulated taxol in combination with hyperthermia may be useful in improving the therapeutic efficacy of taxol in the treatment of melanoma.
PACAP protects cerebellar granule neurons against oxidative stress‐induced apoptosis (2002)

Oxidative stress, resulting from accumulation of reactive oxygen species, plays a critical role in neuronal cell death associated with neurodegenerative diseases and stroke. In the present study, we have investigated the potential neuroprotective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on oxidative stress-induced apoptosis. Incubation of cerebellar granule cells with PACAP inhibited hydrogen peroxide-evoked cell death in a concentration-dependent manner. The effect of PACAP on granule cell survival was not mimicked by vasoactive intestinal polypeptide and was blocked by the antagonist PACAP6-38. The protective action of PACAP upon hydrogen peroxide-induced neuronal cell death was abolished by the MAP-kinase kinase (MEK) inhibitor U0126 and mimicked by the caspase-3 inhibitor Z-DEVD-FMK. PACAP markedly inhibited hydrogen peroxide-evoked caspase-3 activation and DNA fragmentation. Taken together, these data indicate that PACAP, acting through PACAP receptor type 1, exerts a potent protective effect against neuronal degeneration induced by hydrogen peroxide. The anti-apoptotic effect of PACAP is mediated through the MAP-kinase pathway and can be accounted for by inhibition of caspase-3 activation resulting from oxidative stress.
Realizace praxí a stáží ve vybraných zemích EU a světa (2007)

Přispěvek provadi strucný exkurz do oblasti realizace praxi a
staži v některých vybraných zemich EU i v dalsich zemich světa.
Cilem je poukazat na klicove systemove prvky, ktere vysoke
skoly a jejich partneři uplatňuji v procesu vzajemne spoluprace
v teto oblasti. Mnohe z nich mohou být inspiraci pro obohaceni
dosavadniho systemu spoluprace mezi vysokými skolami a jejich
partnery v Ceske republice.