gebhart/patrepeval huggingface dataset:
Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain (2004)

The factors regulating cerebral blood flow (CBF) changes in physiological activation remain the subject of great interest and debate. Recent experimental studies suggest that an increase in cytosolic NADH mediates increased blood flow in the working brain. Lactate injection should elevate NADH levels by increasing the lactate/pyruvate ratio, which is in near equilibrium with the NADH/NAD(+) ratio. We studied CBF responses to bolus lactate injection at rest and in visual stimulation by using positron-emission tomography in seven healthy volunteers. Bolus lactate injection augmented the CBF response to visual stimulation by 38-53% in regions of the visual cortex but had no effect on the resting CBF or the whole-brain CBF. These lactate-induced CBF increases correlated with elevations in plasma lactate/pyruvate ratios and in plasma lactate levels but not with plasma pyruvate levels. Our observations support the hypothesis that an increase in the NADH/NAD(+) ratio activates signaling pathways to selectively increase CBF in the physiologically stimulated brain regions.
Monoclonal Antibody-Mediated Tumor Regression by Induction of Apoptosis (1989)

To characterize cell surface molecules involved in control of growth of malignant lymphocytes, monoclonal antibodies were raised against the human B lymphoblast cell line SKW6.4. One monoclonal antibody, anti-APO-1, reacted with a 52-kilodalton antigen (APO-1) on a set of activated human lymphocytes, on malignant human lymphocyte lines, and on some patient-derived leukemic cells. Nanogram quantities of anti-APO-1 completely blocked proliferation of cells bearing APO-1 in vitro in a manner characteristic of a process called programmed cell death or apoptosis. Cell death was preceded by changes in cell morphology and fragmentation of DNA. This process was distinct from antibody- and complement-dependent cell lysis and was mediated by the antibody alone. A single intravenous injection of anti-APO-1 into nu/nu mice carrying a xenotransplant of a human B cell tumor induced regression of this tumor within a few days. Histological thin sections of the regressing tumor showed that anti-APO-1 was able to induce apoptosis in vivo. Thus, induction of apoptosis as a consequence of a signal mediated through cell surface molecules like APO-1 may be a useful therapeutic approach in treatment of malignancy.
Discharge of Identified Orexin/Hypocretin Neurons across the Sleep-Waking Cycle (2005)

Although maintained by multiple arousal systems, wakefulness falters if orexin (hypocretin), orexin receptors, or orexin neurons are deficient; narcolepsy results with hypersomnolence or sudden onset of rapid eye movement sleep [or paradoxical sleep (PS)] and loss of muscle tonus. To learn how orexin neurons maintain wakefulness, we recorded neurons in head-fixed rats across the sleep-waking cycle and then labeled them with Neurobiotin to identify them by immunohistochemistry. We show that identified orexin neurons discharge during active waking, when postural muscle tone is high in association with movement, decrease discharge during quiet waking in absence of movement, and virtually cease firing during sleep, when postural muscle tone is low or absent. During PS, they remain relatively silent in association with postural muscle atonia and most often despite phasic muscular twitches. They increase firing before the end of PS and thereby herald by several seconds the return of waking and muscle tone. The orexin neurons would thus stimulate arousal, while antagonizing sleep and muscle atonia.
In situ fabrication and regeneration of microtips for scanning tunnelling microscopy (1988)

SUMMARY Progress in STM, in particular for the interpretation of the tunnel signals of corrugated surfaces, is related to the possibility of sharpening and regenerating in situ reproducible tips for use as the probe. We proposed two techniques for the production of tips with controlled geometry at the atomic level. These two techniques are based on the production of tips with equilibrium profiles obtained under heat treatments in vacuum and in the presence of an electric field. Based on the pseudo‐stationary profile principle, the microtips can be sharpened in situ and in a reproducible manner, either from initial cylindrical (111)‐W wire, or from breakdown tips; in both cases without the need for heavy control devices (like FIM for example).
Thymic stromal lymphopoietin induces early human B‐cell proliferation and differentiation (2010)

Thymic stromal lymphopoietin (TSLP) is a cytokine that binds the IL-7-receptor-alpha chain and a unique TSLP receptor (TSLPR) chain. The role of TSLP in human B-cell development has not been elucidated. We show that TSLPR transcripts are expressed most prominently in CD34(+) cells from fetal liver and BM. In general, cell surface expression of TSLPR was low, except on a subset of multilineage-commited progenitor cells. TSLP induced the tyrosine-phosphorylation of STAT5 and the proliferation of multilineage-commited progenitor cells, pro-B cells and pre-B cells. Compared with IL-7, the levels of proliferation after stimulation of the B-cell progenitors with TSLP were lower. Expression of the BCR on the cell surface of fetal cells was inversely correlated to TSLP or IL-7 responsiveness. Pre-B cells from fetal BM, but not fetal liver, were refractory to TSLP or IL-7 stimulation. When employing an in vitro B-cell differentiation culture system starting from CD34(+)CD38(-) multipotent HSC, IL-7 induced a short wave of precursor cell expansion but did not result in long-term survival of mature B cells. TSLP was capable of increasing the proportion and the absolute numbers of more mature human B cells. Overall, we provide evidence that TSLP supports human B-cell differentiation from fetal hematopoietic progenitors.
Multiresolution video watermarking using perceptual models and scene segmentation (2002)

We introduce a watermarking procedure to embed copyright protection into digital video. Our video dependent watermarking procedure directly exploits the masking and temporal properties to embed an invisible and robust watermark. The watermark consists of static and dynamic temporal components that are generated from a temporal wavelet transform of the video scenes. To generate the watermark, the resulting wavelet coefficient frames are modified by a perceptually shaped pseudo-random sequence representing the author. The noise-like watermark is statistically undetectable to thwart unauthorized removal. Furthermore, the author representation resolves the deadlock problem. The multiresolution watermark may be detected on single frames without knowledge of the location of the frames in the video scene. We demonstrate the robustness of the watermarking procedure to several video distortions.
Chemical Studies on the Constitution of Some Pollen and Spore Membranes (1964)

(1964). Chemical Studies on the Constitution of Some Pollen and Spore Membranes. Grana Palynologica: Vol. 5, No. 2, pp. 247-252.
N-Methyl-phenacyloxycarbamidomethyl (Pocam) group: a novel thiol protecting group for solid-phase peptide synthesis and peptide condensation reactions (2011)

In the so-called thioester method for the condensation of peptide segments, protecting groups for amino and thiol groups are required for chemoselective ligation. In this study, we developed a novel thiol protecting group, N-methyl-phenacyloxycarbamidomethyl (Pocam). We used it for protection of cysteine side chains, and synthesized Pocam-containing peptides and peptide thioesters. These were condensed by the thioester method. After the condensation reaction, Pocam groups were cleaved by Zn/AcOH treatment. At the same time, the azido group, which was used for the protection of lysine side chains, was also converted to an amino group, demonstrating that this protecting group strategy simplified the deprotecting reaction after the peptide condensation reaction to only one step.
Complex Regulation of cyp26a1 Creates a Robust Retinoic Acid Gradient in the Zebrafish Embryo (2007)

Positional identities along the anterior-posterior axis of the vertebrate nervous system are assigned during gastrulation by multiple posteriorizing signals, including retinoic acid (RA), fibroblast growth factors (Fgfs), and Wnts. Experimental evidence has suggested that RA, which is produced in paraxial mesoderm posterior to the hindbrain by aldehyde dehydrogenase 1a2 (aldh1a2/raldh2), forms a posterior-to-anterior gradient across the hindbrain field, and provides the positional information that specifies the locations and fates of rhombomeres. Recently, alternative models have been proposed in which RA plays only a permissive role, signaling wherever it is not degraded. Here we use a combination of experimental and modeling tools to address the role of RA in providing long-range positional cues in the zebrafish hindbrain. Using cell transplantation and implantation of RA-coated beads into RA-deficient zebrafish embryos, we demonstrate that RA can directly convey graded positional information over long distances. We also show that expression of Cyp26a1, the major RA-degrading enzyme during gastrulation, is under complex feedback and feedforward control by RA and Fgf signaling. The predicted consequence of such control is that RA gradients will be both robust to fluctuations in RA synthesis and adaptive to changes in embryo length during gastrulation. Such control also provides an explanation for the fact that loss of an endogenous RA gradient can be compensated for by RA that is provided in a spatially uniform manner.
Dietary Energy Balance Modulation of Kras- and Ink4a/Arf+/−-Driven Pancreatic Cancer: The Role of Insulin-like Growth Factor-I (2013)

New molecular targets and intervention strategies for breaking the obesity-pancreatic cancer link are urgently needed. Using relevant spontaneous and orthotopically transplanted murine models of pancreatic cancer, we tested the hypothesis that dietary energy balance modulation impacts pancreatic cancer development and progression through an insulin-like growth factor (IGF)-I-dependent mechanism. In LSL-Kras(G12D)/Pdx-1-Cre/Ink4a/Arf(lox/+) mice, calorie restriction versus overweight- or obesity-inducing diet regimens decreased serum IGF-I, tumoral Akt/mTOR signaling, pancreatic desmoplasia, and progression to pancreatic ductal adenocarcinoma (PDAC), and increased pancreatic tumor-free survival. Serum IGF-I, Akt/mTOR signaling, and orthotopically transplanted PDAC growth were decreased in liver-specific IGF-I-deficient mice (vs. wild-type mice), and rescued with IGF-I infusion. Thus, dietary energy balance modulation impacts spontaneous pancreatic tumorigenesis induced by mutant Kras and Ink4a deficiency, the most common genetic alterations in human pancreatic cancer. Furthermore, IGF-I and components of its downstream signaling pathway are promising mechanistic targets for breaking the obesity-pancreatic cancer link.
Onset of Resin Micro-Cracks in Unidirectional Glass Fiber Laminates with Integrated SHM Sensors: Experimental Results (2009)

This article presents the results of experiments conducted in order to identify and locate the failure initiation in glass fiber/epoxy laminates with integrated structural health monitoring sensors (SHM) and electronics. Recent advances in health monitoring technologies have resulted in the development of micro-dimensional devices that can be embedded into composite laminates. Notwithstanding their small size, such inclusions may affect the response of the composite. Damage induced by the peak values of stress concentration around the embedded inclusion is, in fact, one of the main concerns in smart structures technology. To address this specific issue, unidirectional S2 glass fiber/epoxy laminated composites are fabricated with embedded small implants that mimic potential sensors and microprocessors. Quasi-static tensile tests are then performed on those samples while monitoring them by the acoustic emission (AE) technique. Additionally, the microstructure of the material with and without implants is explored. The AE results show that early low-medium amplitude events are detected at the implant location and the micrographic inspections reveal that micro-cracks initiate at the device-composite matrix interface and grow around the implant causing the debond of the external component from the surrounding resin system.
Electrogastrographic impact of multi-site functional gastric electrical stimulation (1999)

Microprocessor-controlled multi-site functional gastric electrical stimulation using synchronized higher frequency (above 25 Hz) bipolar voltages has been suggested as a possible new avenue towards efficient artificial control of gastric motility. However, the effect of this sequential stimulation on gastric electrical activity is unknown. Because of the substantial strength of the invoked sequential contractions, using implanted electrodes to assess gastric electrical activity (GEA) in experimental animals is difficult, if not impossible. Electrogastrography (EGG), the non-invasively obtained recording of GEA, provides an excellent opportunity to study the changes associated with the multi-site functional stimulation. In this study, we investigated 4 unconscious dogs with 4 circumferential sets of subserosally-implanted stimulating electrodes and 4 force transducers attached close to each stimulating electrode set at operation. The abdominal cavity of each dog was closed after the electrode implantations and 3 standard neonatal electrocardiographic electrodes were attached overlying the abdominal projection of the gastric axis. Two-channel EGG recordings were obtained for 1/2 h before any electrical stimulation and during 1/2 h of intensive sequential stimulation. Significant changes were observed in the EGG pattern during stimulation. These changes were quantified and compared to the basal recordings. Our findings indicate that the interrelation between spectral changes in cutaneous EGG and mechanical activity of the stomach could be far more complex than previously speculated.
Plant molecular biology: a practical approach. (1988)

K. H. Cox & R. B. Goldberg: Analysis of plant gene expression K. D. Jofuku & R. B. Goldberg: Analysis of plant gene structure C. Robinson & L.K. Barnett: Isolation and analysis of chloroplasts W. Schuster, R. Hiesel, B. Wissinger, W. Schobel & A. Brennicke: Isolation and analysis of plant mitochondria and their genomes C. Hawes: Subcellular localisation of macromolecules using microscopy L. Herrera-Estrella & J. Simpson: Foreign gene expression in plants R. Shillito & M. Saul: Protoplast isolation and transformation N. Shepherd: Transposable elements and gene-tagging R. Coutts, P. Wise & S. MacDowell: Molecular plant virology J.D. Rochaix, S. Mayfield, M. Goldschmidt-Clermont & J. Erickson: Molecular biology of Chlamydomonas V.A. Dzezkalns, M. Szekeres & B. Mulligan: Molecular biology of cyanobacteria.
Fisp12/Mouse Connective Tissue Growth Factor Mediates Endothelial Cell Adhesion and Migration through Integrin α v β 3 , Promotes Endothelial Cell Survival, and Induces Angiogenesis In Vivo (1999)

Fisp12 was first identified as a secreted protein encoded by a growth factor-inducible immediate-early gene in mouse fibroblasts, whereas its human ortholog, CTGF (connective tissue growth factor), was identified as a mitogenic activity in conditioned media of human umbilical vein endothelial cells. Fisp12/CTGF is a member of a family of secreted proteins that includes CYR61, Nov, Elm-1, Cop-1/WISP-2, and WISP-3. Fisp12/CTGF has been shown to promote cell adhesion and mitogenesis in both fibroblasts and endothelial cells and to stimulate cell migration in fibroblasts. These findings, together with the localization of Fisp12/CTGF in angiogenic tissues, as well as in atherosclerotic plaques, suggest a possible role for Fisp12/CTGF in the regulation of vessel growth during development, wound healing, and vascular disease. In this study, we show that purified Fisp12 (mCTGF) protein promotes the adhesion of microvascular endothelial cells through the integrin receptor alphavbeta3. Furthermore, Fisp12 stimulates the migration of microvascular endothelial cells in culture, also through an integrin-alphavbeta3-dependent mechanism. In addition, the presence of Fisp12 promotes endothelial cell survival when cells are plated on laminin and deprived of growth factors, a condition that otherwise induces apoptosis. In vivo, Fisp12 induces neovascularization in rat corneal micropocket implants. These results demonstrate that Fisp12 is a novel angiogenic inducer and suggest a direct role for Fisp12 in the adhesion, migration, and survival of endothelial cells during blood vessel growth. Taken together with the recent finding that the related protein CYR61 also induces angiogenesis, we suggest that Fisp12/mCTGF and CYR61 comprise prototypes of a new family of angiogenic regulators that function, at least in part, through integrin-alphavbeta3-dependent pathways.
The ovalbumin gene. Insertion of ovalbumin gene sequences in chimeric bacterial plasmids. (1977)

Double-stranded ovalbumin DNA was amplified and purified by the cloning of bacterial transformants. The double-stranded DNA was synthesized from a complete complementary DNA transcript of ovalbumin mRNA using Escherichia coli DNA polymerase I and the self-priming ability of the initial transcript. After S. nuclease treatment, poly(dA) was added to the 3‘ termini with terminal deoxynucleotidyltransferase and the ovalbumin gene was hybridized to a linear plasmid DNA, pMB9, containing 3‘-poly(dT) termini. This hybrid molecule was used to transform the E. coli strain X1849. The cloned transformants contained from 30 to 53% of the complete ovalbumin DNA as determined by hybridization with full length cDNA. The length of the inserts was confirmed by treatment of the isolated plasmids with the restriction enzyme Hha I. Separation of the fragments by agarose gel electrophoresis showed that the amount of inserted DNA in clones tested varied from 680 to 1090 base pairs.
Graphical analysis of 2‐[18F]FA binding to nicotinic acetylcholine receptors in rhesus monkey brain (2003)

External imaging of nicotinic acetylcholine receptors (nAChRs) using techniques such as PET would help to clarify the roles of these receptors in the physiology and pathology of brain function. Here we report the results of quantitative PET studies of cerebral nAChRs with 2-[(18)F]fluoro-A-85380 (2-[(18)F]FA) in rhesus monkeys. Data from dynamic PET scans were analyzed using graphical methods. Binding potential (BP) values of 2.0, 0.4, 0.3, and 0.03 observed in the thalamus (Th), cortex (Cx), striatum (Str), and cerebellum (Cb), respectively, were consistent with the pattern of alpha(4)beta(2) nAChR distribution in monkey brain. The high value of 2-[(18)F]FA-specific binding in the rhesus monkey Th and low level of that in Cb compared with nonspecific accumulation of radioactivity in these structures allowed use of Cb as a reference region for calculation of BP and volume of distribution of specific binding (VDsb) in Th by graphical methods, both with and without the plasma input function. In contrast, estimation of 2-[(18)F]FA specific binding in low-receptor-density regions such as Cx and Str required assessment of nondisplaceable volume of distribution (VDnd) in a separate study and measurement of nonmetabolized radioligand concentrations in the plasma. For accurate quantitation of 2-[(18)F]FA-specific binding by graphical analysis, PET studies should last up to 7 h due to the slow kinetics of 2-[(18)F]FA brain distribution. Further, to avoid substantial underestimation in measured BP values the doses of administered 2-[(18)F]FA should not exceed 0.1 nmol/kg body weight. The findings suggest that 2-[(18)F]FA is a promising ligand for quantitation of nAChRs in human brain.
Production of the chemokine RANTES by articular chondrocytes and role in cartilage degradation (2001)

Chondrocytes produce RANTES and express RANTES receptors. RANTES and CCR5 were markedly increased in OA and after in vitro treatment of normal chondrocytes with IL-1. Chondrocyte activation and cartilage degradation were identified as novel biologic and pathogenetic activities of this chemokine.
Neutralization of Macrophage-Stimulating Protein Ameliorates Renal Injury in Anti–Thy 1 Glomerulonephritis (2007)

Macrophage-stimulating protein (MSP) is a scatter factor that causes cell proliferation and migration, and receptor origin nantaise (RON) is its receptor. RON is expressed in macrophages and mesangial cells, and MSP is produced by renal tubular cells. This study investigated whether MSP/RON participate in the pathogenesis of anti-Thy 1 nephritis, a glomerular disease that is characterized by invasion of circulating monocytes into glomeruli and migration and proliferation of mesangial cells. In vivo, renal function and histopathology were studied in rats that had anti-Thy 1 disease and were untreated and treated with a neutralizing anti-MSP antibody. In vitro, whether monocytes express RON and whether MSP has a chemotactic effect on monocytes were studied. In vivo, in anti-Thy 1 disease, MSP was expressed de novo in glomeruli, and neutralization of MSP attenuated the rise in serum creatinine and proteinuria, stopped glomerular neutrophil and monocyte influx, protected from glomerular injury, and lessened mesangial cell overgrowth. In vitro, unstimulated monocytes did not express RON, but the stimulation with LPS induced de novo RON expression. LPS-stimulated monocytes were attracted by MSP. These results demonstrate a pathogenic role of the MSP/RON system in anti-Thy 1 nephritis.
Molecular cloning of the complementary DNA and gene that encode mouse brain natriuretic peptide and generation of transgenic mice that overexpress the brain natriuretic peptide gene. (1994)

Brain natriuretic peptide (BNP) is a cardiac hormone that occurs predominantly in the ventricle. To study the roles of BNP in chronic cardiovascular regulation, we isolated mouse BNP cDNA and genomic clones, and generated transgenic mice with elevated plasma BNP concentration. The mouse BNP gene was organized into three exons and two introns. Two BNP mRNA species were identified, which were generated by the alternative mRNA splicing. The ventricle was a major site of BNP production in mice. Mouse preproBNP was a 121- (or 120-) residue peptide, and its COOH-terminal 45-residue peptide was the major storage form in the heart. Transgenic mice carrying the human serum amyloid P component/mouse BNP fusion gene were generated so that the hormone expression is targeted to the liver. In the liver of these mice, considerable levels of BNP mRNA and peptide were detected, reaching up to 10-fold greater than in the ventricle. These animals showed 10- to 100-fold increase in plasma BNP concentration accompanied by elevated plasma cyclic GMP concentration, and had significantly lower blood pressure than their nontransgenic littermates. The present study demonstrates that these mice provide a useful model system with which to assess the roles of BNP in cardiovascular regulation and suggests the potential usefulness of BNP as a long-term therapeutic agent.