gebhart/patrepeval huggingface dataset:
Secretion of human tau fragments resembling CSF‐tau in Alzheimer's disease is modulated by the presence of the exon 2 insert (2010)

Abnormal tau cleavage is prominent in the neurofibrillary degeneration characteristic of Alzheimer's disease (AD) and related tauopathies. We recently showed that cleaved human tau is secreted by specific mechanisms when overexpressed. Here we examined the effect of expressing N-terminal and full length tau constructs in transiently and stably transfected neuronal lines. We show that secreted tau exhibits a cleavage pattern similar to CSF-tau from human AD patients and that tau secretion is specifically inhibited by the presence of the exon 2 insert. These results suggest that tau secretion may play a hitherto unsuspected role in AD and related tauopathies.
Increased surface expression of the membrane glycoprotein IIb/IIIa complex induced by platelet activation. Relationship to the binding of fibrinogen and platelet aggregation (1987)

Platelet activation altered the binding of three monoclonal antibodies (monovalent Fab' fragment) directed against the glycoprotein (GP) IIb/IIIa complex. An increased binding of two- to threefold occurred after stimulation with thrombin or phorbol myristate acetate (PMA), with slight but significant increase in the dissociation constants (Kd) of two antibodies (LJ-CP8 and LJ-P9). In contrast, no statistically significant changes were observed with ADP-stimulated platelets. The increased binding of LJ-CP3, but not of the other two antibodies, to activated platelets decreased by 30% to 40% in the presence of EDTA at 22 to 25 degrees C. Platelets stimulated by thrombin or PMA bound more fibrinogen than did those stimulated by ADP, and significant differences in the extent but not in the affinity of fibrinogen binding were observed with various platelet agonists. When the pool of GP IIb/IIIa molecules exposed on the surface of unstimulated platelets was reacted with the monoclonal antibody LJ-CP3 to block ADP-induced fibrinogen binding and platelet aggregation, stimulation with thrombin or PMA still induced substantial binding of antibody and fibrinogen, and aggregation ensued. Therefore, platelets exposed to "strong" agonists exhibit an increased number of surface-oriented epitopes associated with GP IIb/IIIa. The GP IIb/IIIa molecules bearing these newly exposed epitopes are functional in that they can bind fibrinogen and mediate platelet aggregation.
Scaling MPE Inference for Constrained Continuous Markov Random Fields with Consensus Optimization (2012)

Probabilistic graphical models are powerful tools for analyzing constrained, continuous domains. However, finding most-probable explanations (MPEs) in these models can be computationally expensive. In this paper, we improve the scalability of MPE inference in a class of graphical models with piecewise-linear and piecewise-quadratic dependencies and linear constraints over continuous domains. We derive algorithms based on a consensus-optimization framework and demonstrate their superior performance over state of the art. We show empirically that in a large-scale voter-preference modeling problem our algorithms scale linearly in the number of dependencies and constraints. 1
Are Single Molecular Wires Conducting? (1996)

Molecular wire candidates inserted into “nonconducting” n -dodecanethiol self-assembled monolayers on Au{111} were probed by scanning tunneling microscopy (STM) and microwave frequency alternating current STM at high tunnel junction impedance (100 gigohms) to assess their electrical properties. The inserted conjugated molecules, which were 4,4′-di(phenylene-ethynylene)benzenethiolate derivatives, formed single molecular wires that extended from the Au{111} substrate to about 7 angstroms above and had very high conductivity as compared with that of the alkanethiolate.
THE EFFECTS OF TETRAIODOTHYROACETIC AND TRIIODOTHYROACETIC ACIDS ON THYROID FUNCTION IN EUTHYROID AND HYPERTHYROID SUBJECTS (1979)

The effects of tetraiodothyroacetic (Tetrac) and triiodothyroacetic acids (Triac) on thyroid function have been investigated in euthyroid and hyperthyroid subjects. 50, 100, 200, 400 or 800 micrograms of Triac were administered to 8 euthyroid volunteers three times (tds) over a 24 hour period. 3 X 800 micrograms Triac/24 h was sufficient to cause a significant reduction in serum T3. Tetrac, given as an iv bolus of 3600 microgram, produced a sustained reduction in serum T3 for up to 4 days after the injection. Intermediate doses of Tetrac (1200 micrograms) or Triac (400 micrograms tds) significantly reduced the TSH response to TRH (66% and 43% respectively). Seven hyperthyroid patients received Triac 200 micrograms tds for 2 days, and in 2, a rapid decrease in serum T3 was seen. Similar changes in serum T3 were also produced with iodide administration. The results suggest that 1) in euthyroidism, Tetrac and Triac act directly at the pituitary level to inhibit the TSH response to TRH; 2) in some cases of hyperthyroidism, Triac produces a block in T3 secretion by virtue of the iodide produced by its metabolism.
Methods for utilizing maximum power from a solar array (1972)

A preliminary study of maximum power utilization methods was performed for an outer planet spacecraft using an ion thruster propulsion system and a solar array as the primary energy source. The problems which arise from operating the array at or near the maximum power point of its 1-V characteristic are discussed. Two closed loop system configurations which use extremum regulators to track the array's maximum power point are presented. Three open loop systems are presented that either: (1) measure the maximum power of each array section and compute the total array power, (2) utilize a reference array to predict the characteristics of the solar array, or (3) utilize impedance measurements to predict the maximum power utilization. The advantages and disadvantages of each system are discussed and recommendations for further development are made.
Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics (2006)

Available data on the absorption, metabolism and pharmacokinetics of coenzyme Q10 (CoQ10) are reviewed in this paper. CoQ10 has a fundamental role in cellular bioenergetics. CoQ10 is also an important antioxidant. Because of its hydrophobicity and large molecular weight, absorption of dietary CoQ10 is slow and limited. In the case of dietary supplements, solubilized CoQ10 formulations show enhanced bioavailability. The T(max) is around 6 h, with an elimination half-life of about 33 h. The reference intervals for plasma CoQ10 range from 0.40 to 1.91 micromol/l in healthy adults. With CoQ10 supplements there is reasonable correlation between increase in plasma CoQ10 and ingested dose up to a certain point. Animal data show that CoQ10 in large doses is taken up by all tissues including heart and brain mitochondria. This has implications for therapeutic applications in human diseases, and there is evidence for its beneficial effect in cardiovascular and neurodegenerative diseases. CoQ10 has an excellent safety record.
Newer Laboratory Methods for Assessing Nutriture of Selected B-Complex Vitamins (1984)

This review is limited to progress in the development of new or improved laboratory procedures to assess the nutriture of thiamin, riboflavin, niacin, vitamin B6, and folic acid. There has been marked progress in this area for the other vitamins as well. The increased availability of radioassay techniques and HPLC methodologies that have application in nutrition assessment is significant. However, for a number of the vitamins, there is still a need for additional methods that provide functionally interpretable preclinical information and give accurate assessment of body reserves of the nutrient. Often the guides used to interpret the information obtained are tentative and require validation or revision. This situation is further complicated by the frequent lack of suitable reference standards for quality controls and interlaboratory validation.
Enhanced antigen immunogenicity induced by bispecific antibodies. (1990)

The binding of protein antigens to APC with heterocrosslinked bispecific antibodies (HBAs) enhances their processing and presentation to Th cells in vitro. Here we have asked whether HBAs could also increase immune responses in vivo. We immunized mice with hen egg lysozyme (HEL) in the presence or absence of HBA, and followed antibody production after the primary challenge and after a secondary boost. We found that HBAs that bind antigen to MHC class I or II molecules, to Fc gamma R, but not to surface IgD, enhance the immunogenicity of HEL. HBAs that bound HEL to MHC class II molecules, for examples, decreased the amount of antigen required to elicit a primary anti-HEL antibody response in mice by 300-fold, and the amount required to prime for a secondary response by 10(3)- to 10(4)-fold. In fact, HBAs were as effective as IFA in generating antibody responses. Since adjuvants cannot be used in humans, HBAs could prove useful for immunizing people, especially in cases where, due to scarcity or toxicity, minute doses of antigen must be used.
Connective Tissue Growth Factor Expression and Action in Human Corneal Fibroblast Cultures and Rat Corneas after Photorefractive Keratectomy (2003)

These data demonstrate that CTGF is expressed by corneal cells after stimulation by TGF-beta, that CTGF expression increases significantly during corneal wound healing, and that CTGF mediates the effects of TGF-beta induction of collagen synthesis by corneal fibroblasts. These data support the hypothesis that CTGF promotes corneal scar formation and imply that regulating CTGF synthesis and action may be an important goal for reducing corneal scarring.
Secretion and functional display of fusion proteins through the curli biogenesis pathway (2014)

Curli are functional amyloids expressed as fibres on the surface of Enterobacteriaceae. Contrary to the protein misfolding events associated with pathogenic amyloidosis, curli are the result of a dedicated biosynthetic pathway. A specialized transporter in the outer membrane, CsgG, operates in conjunction with the two accessory proteins CsgE and CsgF to secrete curlin subunits to the extracellular surface, where they nucleate into cross-beta strand fibres. Here we investigate the substrate tolerance of the CsgG transporter and the capability of heterologous sequences to be built into curli fibres. Non-native polypeptides ranging up to at least 260 residues were exported when fused to the curli subunit CsgA. Secretion efficiency depended on the folding properties of the passenger sequences, with substrates exceeding an approximately 2 nm transverse diameter blocking passage through the transport channel. Secretion of smaller passengers was compatible with prior DsbA-mediated disulphide bridge formation in the fusion partner, indicating that CsgG is capable of translocating non-linear polypeptide stretches. Using fusions we further demonstrate the exported or secreted heterologous passenger proteins can attain their native, active fold, establishing curli biogenesis pathway as a platform for the secretion and surface display of small heterologous proteins.
Synthesis and Evaluation of Two 18F-Labeled 6-Iodo-2-(4‘-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine Derivatives as Prospective Radioligands for β-Amyloid in Alzheimer's Disease (2004)

This study evaluated (18)F-labeled IMPY [6-iodo-2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine] derivatives as agents for imaging beta-amyloid plaque with positron emission tomography (PET). The precursor for radiolabeling and reference compounds was synthesized in up to five steps from commercially accessible starting materials. One of the two N-methyl groups of IMPY was substituted with either a 3-fluoropropyl (FPM-IMPY) or a 2-fluoroethyl (FEM-IMPY) group. FPM-IMPY and FEM-IMPY were found to have moderate affinity for Abeta-aggregates with K(i) = 27 +/- 8 and 40 +/- 5 nM, respectively. A "one-pot" method for (18)F-2-fluoroethylation and (18)F-3-fluoropropylation of the precursor was developed. The overall decay-corrected radiochemical yields were 26-51%. In PET experiments with normal mouse, high uptake of activity was obtained in the brain after iv injection of each probe: 6.4% ID/g for [(18)F]FEM-IMPY at 1.2 min, and 5.7% ID/g for [(18)F]FPM-IMPY at 0.8 min. These values were similar to those of [(123)I/(125)I]IMPY (7.2% ID/g at 2 min). Polar and nonpolar radioactive metabolites were observed in both plasma and brain homogenates after injection of [(18)F]FEM or [(18)F]FPM-IMPY. In contrast to the single-exponential washout of [(123)I/(125)I]IMPY, the washouts of brain activity for the two fluorinated analogues were biphasic, with an initial rapid phase over 20 min and a subsequent much slower phase. Residual brain activity at 2 h, which may represent polar metabolites trapped in the brain, was 4.5% ID/g for [(18)F]FEM-IMPY and 2.1% ID/g for [(18)F]FPM-IMPY. Substantial skull uptake of [(18)F]fluoride was also clearly observed. With a view to slow the metabolism of [(18)F]FEM-IMPY, an analogue was prepared with deuteriums substituted for the four ethyl hydrogens. However, D(4)-[(18)F]FEM-IMPY showed the same brain uptake and clearance as the protio analogue. Metabolism of the [(18)F]FEM-IMPY was appreciably slower in rhesus monkey than in mouse. Autoradiography of postmortem brain sections of human Alzheimer's disease patients with [(18)F]FEM-IMPY showed high displaceable uptake in gray matter and low nonspecific binding in the white matter. This study demonstrates that the IMPY derivatives have favorable in vivo brain pharmacokinetics and a moderate affinity for imaging beta-amyloid plaques; however, further improvements are needed to reduce radioactive metabolites, increase binding affinity, and reduce lipophilicity.
Bacteraemia Due to Tribe Proteeae: A Review of 132 Cases During a Decade (1991–2000) (2003)

To characterize the clinical features of bacteraemia due to tribe Proteeae, 132 cases among 130 patients from 1991 to 2000 were analysed. The organisms included the Proteus species in 63 cases (P. mirabilis in 41, P. penneri in 2 and P. vulgaris in 20), the Providencia species in 8 (P. rettgeri in 3 and P. stuartii 5) and Morganella morganii in 61. Morganella bacteraemia occurred more frequently in the hospital (70.5%). Biliary and hepatic diseases were predominant in cases with Morganella bacteraemia while cardiovascular, urological and neurological diseases were more common in cases with Proteus bacteraemia. Biliary drainage catheters had more frequently been placed in cases with Morganella bacteraemia (39.3%, p < 0.001), and urinary catheters more frequently in cases with Proteus bacteraemia (17.5%). Biliary infection was most common in cases with Morganella bacteraemia (49.2%), while urinary tract infection (UTI) was most common in cases with Proteus bacteraemia (47.6%). Mortality directly related to bacteraemia due to tribe Proteeae was 20.8% (22.6, 50.0 and 15.0% for Proteus, Providencia and Morganella bacteraemia, respectively). In conclusion, Morganella bacteraemia was most frequently associated with biliary infection, while Proteus bacteraemia was most frequently with UTI. Providencia bacteraemia was relatively uncommon and it can be associated with infections other than UTI.
Improved methods for the isolation and characterization of Flavobacterium columnare (2004)

Columnaris disease, caused by the bacterium Flavobacterium columnare, is an economically significant problem in many warmwater fish species. Difficulties encountered in the isolation and culture of F. columnare have been an impediment to research on the organism and the disease it causes. The goal of this study was to improve the methods for isolation, culture, identification and maintenance of F. columnare. Following the evaluation of different culture media selective cytophaga agar was determined to be the optimum isolation medium, Flavobacterum columnare growth medium proved to be the optimum culture medium, and tryptone yeast extract agar with increased moisture was best for maintenance of cultures. Biochemical characterization of 49 F. columnare isolates was accomplished utilizing the method of Griffin et al. (1992), and the API ZYM system from BioMérieux (Hazelwood Missouri). Using these methods 48 of the 49 strains were presumptively identified as F. columnare. Ten representative F. columnare isolates were further characterized by the API NE system, and all isolates yielded identical phenotypes. Molecular characterization of various strains of F. columnare was accomplished by random amplified polymorphic DNA analysis (reference). Strains evaluated were confirmed as F. columnare by polymerase chain reaction (PCR) using primers and methodology published by Bader et al (2003). The data from RAPD analysis was used to construct three groups based on similarity comparisons. Methods for antimicrobial susceptibility testing by disk diffusion were evaluated on different formulations of dilute Mueller Hinton agar to address the problem of non distinct zones of inhibition, and to reduce the variability of resulting zone data seen when using the published dilute Mueller Hinton formulation (Hawke and Thune 1992). The improved dilute Mueller Hinton medium formulation reduced variability by 40%, increase overall bacterial growth, and also improved the zones of inhibition by producing distinct margins.
REFLECTING SAPPHO (1995)

REFLECTING SAPPHO Get access GLENN W. MOST GLENN W. MOST Ruprecht‐Karls‐Universität Heidelberg Search for other works by this author on: Oxford Academic Google Scholar Bulletin of the Institute of Classical Studies, Volume 40, Issue 1, December 1995, Pages 15–38, https://doi.org/10.1111/j.2041-5370.1995.tb00462.x Published: 12 March 2010
Development of agonists of endothelin‐1 exhibiting selectivity towards ETA receptors (2003)

(1) Endothelin-1 (ET-1) is a bicyclic 21-amino-acid peptide causing a potent and sustained vasoconstriction, mainly through the ET(A) receptor subtype. So far, no selective ET(A) agonists are described in the literature. (2) A series of truncated and chemically modified ET-1 analogues were obtained through solid-phase peptide synthesis and their biological activity was assessed on rat thoracic aorta rings (ET(A) receptors) and guinea-pig lung parenchyma strips (ET(B) receptors). (3) Structure-activity studies led to the identification of ET-1 fragments exhibiting an ET(A) selective agonistic activity. (4) In particular, [D-Lys(9)]cyclo(11-15) ET-1(9-21) was the most potent peptide. It appeared as a full agonist of ET(A) receptors, being under two orders of magnitude less potent than ET-1 (EC(50): 2.3 x 10(-7) vs 6.8 x 10(-9) M). Interestingly, even a linear formylated analogue, [Ala(11,15), Trp(For)(21)]ET-1(9-21), showed a selective ET(A) activity (EC(50): 3.0 x 10(-6) M). None of the numerous analogues of the series exhibited substantial effects in the guinea-pig lung parenchyma bioassay. (5) Thus, this study describes the first compounds showing a significant bioactivity in an ET(A) pharmacological preparation while being inactive in an ET(B) paradigm. They show that the ET-1 pharmacophores, responsible for the ET(A)-mediated actions, are located within the 9-21 segment of the molecule. Moreover, the bicyclic structure of ET-1 does not appear as essential for the ET(A)-related vasoconstriction. Results also suggest that the positive charge of the Lys(9) side chain participates in an intramolecular ionic bond with the carboxylate function of Asp(18).
In vivo imaging and characterization of hypoxia-induced neovascularization and tumor invasion (2007)

Hypoxia is a critical event in tumor progression and angiogenesis. Hypoxia can be detected noninvasively by a novel spectroscopic photoacoustic tomography technology (SPAT) and this finding is supported by our molecular biology investigation aimed to elucidate the etiopathogenesis of SPAT detected hypoxia and angiogenesis. The present study provides an integrated approach to define oxygen status (hypoxia) of intracranial tumor xenografts using spectroscopic photoacoustic tomography. Brain tumors can be identified based on their distorted vascular architecture and oxygen saturation (SO2) images. Noninvasive in vivo tumor oxygenation imaging using SPAT is based on the spectroscopic absorption differences between oxyhemoglobin (O2Hb) and deoxyhemoblobin (HHb). Sprague-Dawley rats inoculated intracranially with ENU1564, a carcinogen-induced rat mammary adenocarcinoma cell line, were imaged with SPAT three weeks post inoculation. Proteins important for tumor angiogenesis and invasion were detected in hypoxic brain foci identified by SPAT and were elevated compared with control brain. Immunohistochemistry, Western blotting, and semi-quantitative RT-PCR showed that HIF-1 alpha, VEGF-A, and VEGFR2 (Flk-1) protein and mRNA expression levels were significantly higher (P < 0.05) in brain tumor tissues compared to normal brain. Gelatin zymography and RT-PCR demonstrated the upregulation of MMP-9 in tumor foci compared with brain control. Together these results suggest the critical role of hypoxia in driving tumor angiogenesis and invasion through upregulation of target genes important for these functions. Moreover this report validates our hypothesis that a novel noninvasive technology (SPAT) developed in our laboratory is suitable for detection of tumors, hypoxia, and angiogenesis.
A Non-Nephrotoxic Gentamicin Congener That Retains Antimicrobial Efficacy (2006)

Aminoglycoside antibiotics, although of major clinical importance in the treatment of serious Gram- negative infections and a potential therapeutic agent in the amelioration of diseases that are characterized by premature stop mutations, are associated with a high incidence of acute renal failure. With the use of HPLC techniques, the four components (congeners) of gentamicin, the most commonly used aminoglycoside, were isolated and characterized. Described here is a congener with minimal cytotoxicity in cell culture and animal studies that retained normal bactericidal properties in both Bacillus subtilis and a multidrug-resistant form of Klebsiella pneumoniae. Furthermore, in animal studies, this congener failed to induce the functional and pathologic changes that are characteristic of gentamicin nephrotoxicity that is seen with the native compound. Finally, internalization of this non-nephrotoxic component was unaltered, but the subcellular distribution was different from native gentamicin or the other three cytotoxic congeners. These studies have identified a component of the native gentamicin congener mixture that retains its bactericidal properties with minimal or no apparent nephrotoxicity.
Kinetic Study of the Metal Triflate Catalyzed Benzoylation of Anisole in an Ionic Liquid (2006)

The Friedel−Crafts benzoylation of anisole with benzoic anhydride to yield 4-methoxybenzophenone has been performed in a range of ionic liquids, using homogeneous metal triflate catalysts. Of these, indium, scandium, and aluminum triflate were chosen to develop a kinetic model. A complex exchange of ligands between the metal salt, the benzoic anhydride, and the ionic liquids results in the formation of a free acid catalyst. This acid is shown to reversibly deactivated by complexation with the product; the equilibrium constant for this has been measured, and a rate equation has been developed and successfully tested.
Sequence‐Specific Recognition of DNA by a Major and Minor Groove Binding Ligand (1996)

A combination of the binding models for the simultaneous recognition of both grooves of DNA led to the design of a polyamide–oligonucleotide ligand that binds to a specific DNA sequence with an association constant of Ka > 2 × 1010 M−1. The oligonucleotide portion forms a triple helix in the major groove of DNA, and the polyamide unit forms a hairpin in the minor groove (see ribbon model below).