gebhart/patrepeval huggingface dataset:
Indole Metabolism in the Pineal Gland: A Circadian Rhythm in <i>N</i> -Acetyltransferase (1970)

The activity of N-acetyltransferase in the rat pineal gland is more than 15 times higher at night than during the day. This circadian rhythm persists in complete darkness, or in blinded animals, and is suppressed in constant lighting. The N-acetyltransferase rhythm is 180 degrees out of phase with the serotonin rhythm and is similar to the norepinephrine and melatonin rhythms. Experiments in vitro indicate that norepinephrine, not serotonin, regulates the activity of N-acetyl-transferase through a highly specific receptor.
Intra-articular hyaluronan therapy (2000)

The hyaluronan in normal synovial fluid plays an important role in joint homeostasis. It contributes to joint lubrication, buffers load transmission across articular surfaces, provides a renewed source of hyaluronan to joint tissues, and imparts antinociceptive and anti-inflammatory properties to synovial fluid. In osteoarthritis, the molecular weight and concentration of hyaluronan in synovial fluid are diminished. This has led to the proposition that removal of pathologic osteoarthritic synovial fluid and replacement with hyaluronan-based products that restore the molecular weight and concentration of hyaluronan toward normal levels can have beneficial therapeutic effects. This form of treatment for osteoarthritis has been termed viscosupplementation. Within the musculoskeletal community there are diverse opinions, ranging from skepticism to acceptance, about viscosupplementation as a mainstream symptom-modifying osteoarthritis therapy. This review focuses on recent basic and clinical studies dealing with mechanism of action, symptomatic efficacy, safety, and disease modification, and places these studies in context with earlier studies.
Cytokine Transgene Expression and Promoter Usage in Primary CD34 <sup>+</sup> Cells Using Particle-Mediated Gene Delivery (1998)

Induction or short-term transgenic expression of specific cytokines, growth factors, or other candidate therapeutic genes in hematopoietic progenitor or stem cells is potentially applicable to gene therapy for cancer. In this study, we explored the application of a gene gun technique, as an alternative to viral vectors, for ex vivo gene transfer into and transient gene expression in highly enriched CD34+ cells derived from human umbilical cord blood. Twenty-four hours posttransfection, 32.6 to 1500 pg/l x 10(6) CD34+ cells of transient gene expression was routinely obtained for specific cytokine and reporter genes. Transgene expression at the single-cell level was revealed by X-Gal staining of lacZ cDNA-transfected CD34+ cells. Expression of four candidate therapeutic genes, namely human granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, interleukin 2, and interferon gamma, was detectable for 4 to 7 days in CD34+ cells. A human elongation factor 1alpha promoter/intron 1 transcription unit was identified as a strong cellular promoter for CD34+ cells, exhibiting strength similar to that of the commonly employed cytomegalovirus immediate-early promoter. These results suggest that the nonviral, gene gun technique offers an efficient alternative approach for transient transgenic studies of hematopoietic cells and may provide new possibilities for certain cancer gene therapy strategies using CD34+ cells.
Partial purification and characterization of free and immobilized lipases from <i>Mucor miehei</i> (1987)

An extracellular lipase, a glycoprotein, produced by fermentation with a selected strain ofMucor miehei has been partially purified in two forms, A and B. The two forms have a high degree of antigenic identity and have similar pH-activity profiles with tributyroylglycerol as a substrate with optima at pH 7. They differ as follows: A, in contrast to B, requires activation at alkaline pH before analysis; A binds with concanavalin-A more completely than B; the net charges are slightly different at pH 8; and the isoelectric points are different. Our results indicate that the B lipase is formed by partial deglycosylation of the A lipase and that this influences the activity toward emulsions.In addition, the two enzymes have been immobilized by adsorption. These preparations and the soluble forms were highly specific for primary esters of triacylglycerols (TG); they usually hydrolyzed TG of 12∶0, 14∶0, 16∶0, and 18∶1 more rapidly than those of 4∶0, 6∶0, and 8∶0 and 10∶0 in mixtures of monoacid TG (4∶0 to 18∶1); and they were not stereospecific for TG. Immobilization altered the specificity of the preparations somewhat, in that slightly more 14∶0 and 16∶0 were released.
Negative regulation of histone H1 kinase expression by mimosine, a plant amino acid. (1994)

The plant amino acid mimosine has been shown to reversibly arrest mammalian cells in late G1 phase of the cell cycle. However, the underlying molecular mechanisms of this block are not as yet understood. Here we show that mimosine prevents the serum-stimulated synthesis and activation of histone H1 kinase, a crucial regulator of cell cycle progression. The same effect is observed in logarithmically growing primary cells as well as transformed cells. Concomitantly, hyperphosphorylation of the retinoblastoma tumor suppressor gene product is partially inhibited. These effects are fully reversible, because removal of mimosine restores histone H1 kinase activity and the cells resume growth. Because the activity of histone H1 kinase has been shown to be absolutely required for cell cycle progression, it is conceivable that the cytostatic effect of mimosine is due to its negative effects on synthesis and activity of this enzyme.
[(NHC)<sub>2</sub>Cu]X Complexes as Efficient Catalysts for Azide–Alkyne Click Chemistry at Low Catalyst Loadings (2008)

Geklickt! Ein Katalysesystem auf der Grundlage eines [(NHC)2Cu]X-Komplexes (NHC=N-heterocyclisches Carben) wurde für die [3+2]-Cycloaddition von Aziden mit Alkinen unter Klickbedingungen entwickelt (siehe Schema). Dieses System ist breit anwendbar und selbst bei sehr niedriger Katalysatorbeladung (nur 40 ppm) hoch effizient (Umsatzfrequenzen bis 5000 h−1). Erste mechanistische Studien weisen auf eine spezifische Präkatalysatoraktivierung hin.
Multi-silicon ridge nanofabrication by repeated edge lithography (2009)

We present a multi-Si nanoridge fabrication scheme and its application in nanoimprint lithography (NIL). Triple Si nanoridges approximately 120 nm high and 40 nm wide separated by 40 nm spacing are fabricated and successfully applied as a stamp in nanoimprint lithography. The fabrication scheme, using a full-wet etching procedure in combination with repeated edge lithography, consists of hot H(3)PO(4) acid SiN(x) retraction etching, 20% KOH Si etching, 50% HF SiN(x) retraction etching and LOCal Oxidation of Silicon (LOCOS). Si nanoridges with smooth vertical sidewalls are fabricated by using Si 110 substrates and KOH etching. The presented technology utilizes a conventional photolithography technique, and the fabrication of multi-Si nanoridges on a full wafer scale has been demonstrated.
Systematic Research of Peptide Spacers Controlling Drug Release from Macromolecular Prodrug System, Carboxymethyldextran Polyalcohol−Peptide−Drug Conjugates (2008)

The primary purpose of this study was to comprehensively delineate specificity of the peptide spacer sequence to tumor-expressed proteases for the design of macromolecular carrier-peptide spacer-drug conjugate system. 225 conjugates of carboxymethyldextran polyalcohol (CM-Dex-PA) as water-soluble carrier and a dansyl derivative (N-(4-aminobutyl)-5-(dimethylamino)-1-naphthalenesulfonamide, DNS) as the model drug linked with different tetrapeptide spacers (Gly-Gly-P(2)-P(1), P(2), P(1): Ala, Asn, Gly, Cit, Gln, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, and Val) were combinatorially synthesized. First, the drug release assay of all of the fluorogenic model conjugates was performed in murine Meth A solid tumor homogenates. The drug release rate was higher with conjugates having hydrophobic amino acids at P(2). It was also found that conjugates with Asn release the drug rapidly and, in contrast, those with Pro does not. Second, we selected three peptide spacers (Gly-Gly-Phe-Gly, Gly-Gly-Ile-Gly, Gly-Gly-Pro-Leu), which release only DNS at different rates, and applied them to doxorubicin (DXR) conjugates. These three DXR conjugates were used for investigating relationships with drug release, pharmacokinetics, and antitumor activity against Meth A bearing mice of these conjugates. The release of DXR from the conjugates corresponded well with that of DNS conjugates in tumor homogenates. CM-Dex-PA-Gly-Gly-Phe-Gly-DXR and CM-Dex-PA-Gly-Gly-Ile-Gly-DXR indicated strong antitumor activity, with the comparable pharmacokinetic profile of released DXR in tumor. Taken with the fact that the drug release rate in tumor homogenates was approximately 10-fold different between these two DXR conjugates, it is likely that cellular uptake of the conjugate would be rate-limiting, rather than the drug release process under the in vivo situation. However, much weaker antitumor activity was observed with CM-Dex-PA-Gly-Gly-Pro-Leu-DXR, of which the drug release was extremely slow.
Broad and thematic remodeling of the surfaceome and glycoproteome on isogenic cells transformed with driving proliferative oncogenes (2020)

The cell surface proteome, the surfaceome, is the interface for engaging the extracellular space in normal and cancer cells. Here we apply quantitative proteomics of <i>N</i>-linked glycoproteins to reveal how a collection of some 700 surface proteins is dramatically remodeled in an isogenic breast epithelial cell line stably expressing any of six of the most prominent proliferative oncogenes, including the receptor tyrosine kinases, EGFR and HER2, and downstream signaling partners such as KRAS, BRAF, MEK, and AKT. We find that each oncogene has somewhat different surfaceomes, but the functions of these proteins are harmonized by common biological themes including up-regulation of nutrient transporters, down-regulation of adhesion molecules and tumor suppressing phosphatases, and alteration in immune modulators. Addition of a potent MEK inhibitor that blocks MAPK signaling brings each oncogene-induced surfaceome back to a common state reflecting the strong dependence of the oncogene on the MAPK pathway to propagate signaling. Cell surface protein capture is mediated by covalent tagging of surface glycans, yet current methods do not afford sequencing of intact glycopeptides. Thus, we complement the surfaceome data with whole cell glycoproteomics enabled by a recently developed technique called activated ion electron transfer dissociation (AI-ETD). We found massive oncogene-induced changes to the glycoproteome and differential increases in complex hybrid glycans, especially for KRAS and HER2 oncogenes. Overall, these studies provide a broad systems-level view of how specific driver oncogenes remodel the surfaceome and the glycoproteome in a cell autologous fashion, and suggest possible surface targets, and combinations thereof, for drug and biomarker discovery.
Applications of Lie Group to Nonholonomic Electromechanical System (2012)

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Hydrodynamic properties of complex, rigid, biological macromolecules: theory and applications (1981)

Among the Various methods for characterizing macromolecules in solution, hydrodynamic techniques play a major role. Since the advent of the ultracentrifuge and the development of viscometric apparatus, sedimentation coefficients and intrinsic viscosities have been extensively used to learn about the size and shape of synthetic and biological polymers. More recently, refined techniques such as quasielastic light scattering, transient electric birefringence and fluorescence anisotropy decay have made it possible to obtain in a simple and rapid way quantitative information of high precision on the translational and rotational brownian dynamics of dissolved macromolecules.
Correlating Structural and Energetic Changes in Glycine Receptor Activation (2015)

Pentameric ligand-gated ion channels (pLGICs) mediate fast chemoelectrical transduction in the nervous system. The mechanism by which the energy of ligand binding leads to current-conducting receptors is poorly understood and may vary among family members. We addressed these questions by correlating the structural and energetic mechanisms by which a naturally occurring M1 domain mutation (α1(Q-26'E)) enhances receptor activation in homo- and heteromeric glycine receptors. We systematically altered the charge of spatially clustered residues at positions 19' and 24', in the M2 and M2-M3 linker domains, respectively, which are known to be critical to efficient receptor activation, on a background of α1(Q-26'E). Changes in the durations of single receptor activations (clusters) and conductance were used to determine interaction coupling energies, which we correlated with conformational displacements as measured in pLGIC crystal structures. Presence of the α1(Q-26'E) enhanced cluster durations and reduced channel conductance in homo- and heteromeric receptors. Strong coupling between α1(-26') and α1(19') across the subunit interface suggests an important role in receptor activation. A lack of coupling between α1(-26') and α1(24') implies that 24' mutations disrupt activation via other interactions. A similar lack of energetic coupling between α1(-26') and reciprocal mutations in the β subunit suggests that this subunit remains relatively static during receptor activation. However, the channel effects of α1(Q-26'E) on α1β receptors suggests at least one α1-α1 interface per pentamer. The coupling-energy change between α1(-26') and α1(19') correlates with a local structural rearrangement essential for pLGIC activation, implying it comprises a key energetic pathway in activating glycine receptors and other pLGICs.
Laser tweezers in cell biology (1998)

Basic laser tweezers, R. Sterba, M.P. Sheetz limitations - photodamage and heating, S. Kuo dual beam traps, J. Spudich trap and cut, M. Berns AFM-like microscope, A. Stout, W. Webb single molecules imaging and nano-manipulation of biomolecules, T. Yanagida et al signals and noise in micromechanical measurements, F. Gittes, C.F. Schmidt cell membrane mechanics, J. Dai, M.P. Sheetz application of laser tweezers to studies of the fences and tethers of the membrane skeleton which regulate the movements of plasma membrane proteins, A. Kusumi et al internal organelles, M. Schliwa.
<title>Laser-annealed Fabry-Perot fiber optic temperature sensor</title> (1994)

A fiber-optic temperature sensor has been fabricated by first sputtering a silicon film onto the end of an optical fiber. The approximately one-micrometer thick silicon film serves as a Fabry-Perot etalon whose resonant wavelengths change as a function of temperature. The silicon film is annealed in order to stabilize its structure. This will provide a sensor with acceptable long term stability. The use of wavelength encoding fiber optic sensors provides a high degree of immunity from cable and connector effects. The benefits of this technology include reduced volume and weight, reduced cost, and improved reliability.
Acylation of<i>Escherichia coli</i>Hemolysin: A Unique Protein Lipidation Mechanism Underlying Toxin Function (1998)

The pore-forming hemolysin (HlyA) of Escherichia coli represents a unique class of bacterial toxins that require a posttranslational modification for activity. The inactive protoxin pro-HlyA is activated intracellularly by amide linkage of fatty acids to two internal lysine residues 126 amino acids apart, directed by the cosynthesized HlyC protein with acyl carrier protein as the fatty acid donor. This action distinguishes HlyC from all bacterial acyltransferases such as the lipid A, lux-specific, and nodulation acyltransferases, and from eukaryotic transferases such as N-myristoyl transferases, prenyltransferases, and thioester palmitoyltransferases. Most lipids directly attached to proteins may be classed as N-terminal amide-linked and internal ester-linked acyl groups and C-terminal ether-linked isoprenoid groups. The acylation of HlyA and related toxins does not equate to these but does appear related to a small number of eukaryotic proteins that include inflammatory cytokines and mitogenic and cholinergic receptors. While the location and structure of lipid moieties on proteins vary, there are common effects on membrane affinity and/or protein-protein interactions. Despite being acylated at two residues, HlyA does not possess a "double-anchor" motif and does not have an electrostatic switch, although its dependence on calcium binding for activity suggests that the calcium-myristoyl switch may have relevance. The acyl chains on HlyA may provide anchorage points onto the surface of the host cell lipid bilayer. These could then enhance protein-protein interactions either between HlyA and components of a host signal transduction pathway to influence cytokine production or between HlyA monomers to bring about oligomerization during pore formation.
Dietary Fat in Breast Cancer Survival (2013)

Laboratory evidence suggests a plausible role for dietary fat in breast cancer pathophysiology. We conducted a systematic literature review to assess the epidemiological evidence on the impact of total dietary fat and fat subtypes, measured pre- and/or postcancer diagnosis, in relation to breast cancer-specific and all-cause mortality among breast cancer survivors. Studies were included if they were in English, had a sample size ≥200, and presented the hazard ratio/rate ratio for recurrence, disease-specific mortality, or all-cause mortality (n = 18). Although the results are mixed, most studies suggested that higher saturated fat intake prediagnosis was associated with increased risk of breast cancer-specific and all-cause mortality. Postdiagnostic trans fat intake was associated with a 45% and 78% increased risk of all-cause mortality. Higher monounsaturated fat intake before and after diagnosis was generally associated with increased risk of all-cause and breast cancer-specific mortality, albeit the majority of the studies were statistically nonsignificant. Two studies evaluating omega-3 fat intake suggested an inverse association with all-cause mortality. Although there were too few studies on fat subtypes to draw definitive conclusions, high consumption of saturated fat may exert a detrimental effect on breast cancer-specific and all-cause mortality, whereas omega-3 fat may be beneficial. The inconsistent and limited evidence warrants research to assess the impact of consumption of fat subtypes on breast cancer recurrence and mortality.
Dermal Absorption and Metabolism of the Antipsoriatic Drug Dithranol Triacetate (1984)

Percutaneous absorption, excretion kinetics, and metabolism of dithranol triacetate (2) have been investigated in Wistar rats. By the use of two differently labelled molecules--3H in the anthracene nucleus and 14C in the acetoxy groups of 2, resp.--the fate of the different parts of the dithranol triacetate molecule could be followed. After injection, large amounts of 2 are cleaved under the influence of enzymes into acetate and dithranol. These deacetylated metabolites lose half their 3H label with formation of 3H2O. In urine, 1,8-diacetoxy-9-anthrone, 1-acetoxy-8-hydroxy-9-anthrone, 1,8-dihydroxy-9,10-anthraquinone and its diacetate were found as metabolites. After dermal application, unchanged 2 is practically not absorbed at all. Arylesterases which, according to in vitro studies, are present in or on the skin, hydrolyse dithranol triacetate to give free dithranol. Up to 33% of the latter are absorbed from under an occlusive dressing. Dithranol triacetate, therefore, shows pro-drug characteristics for the treatment of psoriasis.
IMLS-SLAM: Scan-to-Model Matching Based on 3D Data (2018)

The Simultaneous Localization And Mapping (SLAM) problem has been well studied in the robotics community, especially using mono, stereo cameras or depth sensors. 3D depth sensors, such as Velodyne LiDAR, have proved in the last 10 years to be very useful to perceive the environment in autonomous driving, but few methods exist that directly use these 3D data for odometry. We present a new low-drift SLAM algorithm based only on 3D LiDAR data. Our method relies on a scan-to-model matching framework. We first have a specific sampling strategy based on the LiDAR scans. We then define our model as the previous localized LiDAR sweeps and use the Implicit Moving Least Squares (IMLS) surface representation. We show experiments with the Velodyne HDL32 with only 0.40% drift over a 4 km acquisition without any loop closure (i.e., 16 m drift after 4 km). We tested our solution on the KITTI benchmark with a Velodyne HDL64 and ranked among the best methods (against mono, stereo and LiDAR methods) with a global drift of only 0.69%.
Modifying Weather on a Large Scale (1958)

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AT<sub>1</sub> Angiotensin Receptors Mobilize Intracellular Calcium in a Subclone of NG108–15 Neuroblastoma Cells (1992)

The effects of angiotensin II (AII) and related peptides on the mobilization of internal Ca2+ were studied in a subclone of NG 108-15 cells. The subclone, C1, was prepared by fluorescence-activated cell cloning using a rapid response kinetics and a large response magnitude following stimulation by AII as the selection criteria. Angiotensin I, AII, and angiotensin III (AIII) stimulated Ca2+ mobilization in the C1 cells in a concentration-dependent manner (1 nM-100 microM), yielding EC50 values of 437 +/- 80 nM (n = 4; slope = 1.6 +/- 0.3), 57 +/- 8 nM (n = 12; slope = 1.5 +/- 0.3), and 36 +/- 5 nM (n = 7; slope = 1.4 +/- 0.3), respectively. AIII was significantly more potent than AII (p less than 0.05). In contrast, Des-Phe8-AII, AII-hexapeptide (AII 3-8), and p-NH2-Phe6-AII (1-10 microM) were inactive as agonists. Although the effects of AII and AIII in C1 and parent NG108-15 cells were totally inhibited by the AT1 receptor-selective nonpeptide antagonist, DUP-753 (0.3-1 microM), the AT2-selective antagonists, EXP-655 and CGP42112A (1-10 microM), failed to block the effects of AII. DUP-753 (0.3-100 nM) produced dextral shifts of the AII-induced concentration-response curves and yielded an estimated affinity constant (pA2) of 8.5 +/- 0.2 (n = 16) using single-point analysis involving different concentrations of DUP-753. These data compared well with those obtained for the inhibition of AII-induced aortic contractions by DUP-753 (pA2 = 8.5) reported previously by others.(ABSTRACT TRUNCATED AT 250 WORDS)