gebhart/patrepeval huggingface dataset:
Design and Evaluation of Inclusion Resolutions, Based on Readily Available Host Compounds (2005)

Abstract Resolution of enantiomers through selective crystallisation of diastereomeric inclusion compounds can extend the scope of traditional racemate resolution beyond salt forming compounds. To assess the practical value of this approach the literature was carefully screened and promising results were checked. Also an extensive range of new inclusion hosts suitable for resolution processes, derived from simple hydroxy‐ and amino acids were prepared and tested. Several techniques, including the Dutch Resolution approach utilizing mixtures of resolving agents, were applied. Over 70 potential resolving agents were tested in combinations with 34 racemates (over 100 racemates if literature results are included). Reproducibility of literature results was found to be problematic. Also the number of successful new resolutions found was very limited: only two efficient resolutions out of 1200 combinations of racemate and resolving agent tested in over 10.000 experiments! Crystal studies of representative combinations of resolving agents and inclusion compounds revealed some of the causes for the low rate of success in inclusion resolution. Compared to diastereomeric salts, the absence of strong electrostatic interactions substantially reduces the probability of forming crystals including both components. Molecular structure features allowing formation of intricate intramolecular and intermolecular H‐bond networks were found to be responsible for inclusion crystal formation, and for the quality of the ensuing resolution through selective diastereomer crystallisation, in the successful cases. Whereas diastereomeric salt resolution continues to be of scientific and industrial interest, inclusion resolution should be viewed as of very limited scope; useful in specific instances, but lacking the wide applicability of classical resolution. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)
Carthamus, SalviaandStachysspecies protect neuronal cells against oxidative stress-induced apoptosis (2014)

The above-mentioned plants seem to have important biological activities and their further study may lead to the discovery of new natural therapeutics useful against disorders such as Alzheimer and Parkinson diseases.
Nanotechnology for the Progress of Lithium Battery R&D (2003)

Rechargeable lithium batteries are well established devices which have acquired a key role in the consumer electronics marketHoweverthere is still a need for further improvement in the peormance and thusin the technological impact of these important electrochemical power sourcesIndeedit would be greatly desirable to replace the pre-
Innate Immune Responses of Synthetic Lipid A Derivatives of Neisseria meningitidis (2007)

Differences in the pattern and chemical nature of fatty acids of lipid A of Neisseria meningitides lipooligosaccharides (LOS) and Escherichia coli lipopolysaccharides (LPS) may account for differences in inflammatory properties. Furthermore, there are indications that dimeric 3-deoxy-D-manno-oct-2-ulosonic acid (KDO) moieties of LOS and LPS enhance biological activities. Heterogeneity in the structure of lipid A and possible contaminations with other inflammatory components have made it difficult to confirm these observations. To address these problems, a highly convergent approach for the synthesis of a lipid A derivative containing KDO has been developed, which relies on the ability to selectively remove or unmask in a sequential manner an isopropylidene acetal, 9-fluorenylmethoxycarbonyl (Fmoc), allyloxycarbonate (Alloc), azide, and thexyldimethylsilyl (TDS) ether. The strategy was employed for the synthesis of N. meningitidis lipid A containing KDO (3). Mouse macrophages were exposed to the synthetic compound and its parent LOS, E. coli lipid A (2), and a hybrid derivative (4) that has the asymmetrical acylation pattern of E. coli lipid A, but the shorter lipids of meningococcal lipid A. The resulting supernatants were examined for tumor necrosis factor alpha (TNF-alpha) and interferon beta (IFN-beta) production. The lipid A derivative containing KDO was much more active than lipid A alone and just slightly less active than its parent LOS, indicating that one KDO moiety is sufficient for full activity of TNF-alpha and IFN-beta induction. The lipid A of N. meningitidis was a significantly more potent inducer of TNF-alpha and IFN-beta than E. coli lipid A, which is due to a number of shorter fatty acids. The compounds did not demonstrate a bias towards a MyD88- or TRIF-dependent response.
Mechanism and Specificity of Human α-1,3-Fucosyltransferase V (1996)

Human alpha-1,3-fucosyltransferase catalyzes the transfer of the L-fucose moiety from guanosine diphosphate-beta-L-fucose (GDP-Fuc) to acceptor sugars to form biologically important fucoglycoconjugates, including sialyl Lewis x (SLex). Evidence for a general base mechanism is supported by a pH-rate profile that revealed a catalytic residue with a pKa of 4.1. The characterized solvent kinetic isotope effect (Dv = 2.9, Dv/k = 2.1) in a proton inventory study indicates that only one-proton transfer is involved in the catalytic step leading to the formation of the transition state. Evidence for Mn2+ as an electrophilic catalyst was supported by the observation that the nonenzymatic transfer of L-fucose from GDP-Fuc to the hydroxyl group of water in the presence of 10 mM MnCl2 at 20 degrees C was accelerated from K(obs)= 3.5 x 10(-6) to 3.8 x 10(-5) min-1. Using the GDP-Fuc hydrolysis as the nonenzymatic rate, the enzymatic proficiency of FucT V, (Kcat/Ki,GDP-fuc. K(m),1.acNAc)/K(non), was estimated to be 1.2 x 10(10) M-1 with a transition-state affinity of 8.6 x 10(-11) M. The Km for Mn2+ was determined to be 6.1 mM, and alternative divalent metal cofactors were identified as Ca2+, Co2+, and Mg2+. Detailed kinetic characterization of the acceptor sugar specificity indicated that incorporation of hydrophobic functionality [e.g. -O-(CH2)5CO2CH3] to the reducing end of the acceptor sugar substantially decreased the K(m),acceptor by over 100-fold. The role of the nucleotide was investigated by studying the inhibition of nucleotides, including the guanosine series. The inhibitory potency trend (GTP approximately GDP > GMP > > guanosine) is consistent with bidentate chelation of Mn2+ by GDP-Fuc. The role of charge and distance in the synergistic inhibitory effect by the combination of GDP, an aza sugar, and the acceptor sugar was probed. A mechanism for fucosyl transfer incorporating these findings is proposed and discussed.
Association of complement factor H polymorphisms with exudative age-related macular degeneration. (2006)

We have found differences in the association between the CFH gene and exudative AMD in Chinese from Caucasians and Japanese. We detected SNP rs3753394 in the CFH promoter carrying a significantly increased risk for exudative AMD.
Engineering a Material Surface for Drug Delivery and Imaging using Layer‐by‐Layer Assembly of Functionalized Nanoparticles (2010)

DOI: 10.1002/adma.200903069 The affiliation in the above article was incorrect. The correct affiliation is shown here: [*] Prof. V. P. Shastri Institute for Macromolecular Chemistry and Bioss-Center for Biological Signalling Studies University of Freiburg 79104 Freiburg (Germany) E-mail: prasad.shastri@bioss.uni-freiburg.de; prasad.shastri@makro.uni-freiburg.de Prof. V. P. Shastri, T. Soike, A. K. Streff, C. M. Guan, R. Ortega, Dr. C. Pino Department of Biomedical Engineering Vanderbilt University Nashville, TN 37232 (USA) Dr. M. N. Tantawy Department of Radiology Vanderbilt Institute of Imaging Sciences Nashville, TN 37232 (USA) The editorial office apologizes for any inconvenience caused.
Blistering in keratinocyte cultures: a regular phenomenon associated with differentiation. (1986)

Blisters have previously been observed in keratinocyte cultures depleted of vitamin A, and in cultures of keratinocytes from patients with epidermolysis bullosa. We have found that blistering may occur in keratinocyte cultures from normal human epidermis, grown under standard conditions, and our aim was to further characterize the mechanism of blister formation. Keratinocytes were seeded at 10(5) cells per 35 mm collagen-coated dish with a 3T3 feeder layer. Blisters were macroscopic, fluid-filled structures which formed irrespective of donor site, or donor age, and were noted on various alternative substrates (collagen, 3T3 + plastic, plastic alone). Blistering commenced around day 12, prior to confluency, and new blisters were formed for up to 5 weeks post-plating. Maximal numbers (up to 70 per dish) were present around days 12 to 20. Cleavage occurred at the cell/collagen interface to form a blister roof composed of 6 to 9 cell layers. The lowest layer appeared metabolically active, but, in contrast to peri-blister regions, lacked hemidesmosomes. The central 2 to 3 layers contained membrane-coating granules and keratohyalin granules while the superficial strata resembled rudimentary corneocytes. Cultures supplemented with 10(-5) M vitamin A formed no blisters, which correlated with suppressed differentiation. Ouabain (10(-7) M) caused blister collapse and a reversible inhibition of new blister formation. We conclude that blisters are a consistent finding in keratinocyte cultures grown under standard conditions. Their formation may be associated with active transport and triggered during differentiation. Further examination of this phenomenon might shed light on whether differentiation itself has an influence on keratinocyte attachment to substrate.
Dopaminergic and Ligand-Independent Activation of Steroid Hormone Receptors (1991)

The current view of how steroid hormone receptors affect gene transcription is that these receptors, on binding ligand, change to a state in which they can interact with chromatin and regulate transcription of target genes. Receptor activation is believed to be dependent only on this ligand-binding event. Selected steroid hormone receptors can be activated in a ligand-independent manner by a membrane receptor agonist, the neurotransmitter dopamine. In vitro, dopamine faithfully mimicked the effect of progesterone by causing a translocation of chicken progesterone receptor (cPR) from cytoplasm to nucleus. Dual activation by progesterone and dopamine was dissociable, and a serine residue in the cPR was identified that is not necessary for progesterone-dependent activation of cPR, but is essential for dopamine activation of this receptor.
Turbidimetric Assessment of the Compatibility of Taxol with 42 other Drugs During Simulated Y-site Injection (1993)

Journal Article Turbidimetric Assessment of the Compatibility of Taxol with 42 other Drugs During Simulated Y-site Injection Get access Lawrence A. Trissel, FASHP, Lawrence A. Trissel, FASHP Director Investigational Pharmaceutical Services, Division of Pharmacy, The University of Texas, M. D. Anderson Cancer Center, Houston, T.X. Search for other works by this author on: Oxford Academic Google Scholar Juan F. Martinez Juan F. Martinez Laboratory Technician II Investigational Pharmaceutical Services, Division of Pharmacy, The University of Texas, M. D. Anderson Cancer Center, Houston, T.X. Search for other works by this author on: Oxford Academic Google Scholar American Journal of Hospital Pharmacy, Volume 50, Issue 2, 1 February 1993, Pages 300–304, https://doi.org/10.1093/ajhp/50.2.300 Published: 01 June 1993
Agonist-selective endocytosis of mu opioid receptor by neurons in vivo. (1996)

Opiate alkaloids are potent analgesics that exert multiple pharmacological effects in the nervous system by activating G protein-coupled receptors. Receptor internalization upon stimulation may be important for desensitization and resensitization, which affect cellular responsiveness to ligands. Here, we investigated the agonist-induced internalization of the mu opioid receptor (MOR) in vivo by using the guinea pig ileum as a model system and immunohistochemistry with an affinity-purified antibody to the C terminus of rat MOR. Antibody specificity was confirmed by the positive staining of human embryonic kidney 293 cells transfected with epitope-tagged MOR cDNA, by the lack of staining of cells transfected with the delta or kappa receptor cDNA, and by the abolition of staining when the MOR antibody was preadsorbed with the MOR peptide fragment. Abundant MOR immunoreactivity (MOR-IR) was localized to the cell body, dendrites, and axonal processes of myenteric neurons. Immunostaining was primarily confined to the plasma membrane of cell bodies and processes. Within 15 min of an intraperitoneal injection of the opiate agonist etorphine, intense MOR-IR was present in vesicle-like structures, which were identified as endosomes by confocal microscopy. At 30 min, MOR-IR was throughout the cytoplasm and in perinuclear vesicles. MOR-IR was still internalized at 120 min. Agonist-induced endocytosis was completely inhibited by the opiate antagonist naloxone. Interestingly, morphine, a high-affinity MOR agonist, did not cause detectable internalization, but it partially inhibited the etorphine-induced MOR endocytosis. These results demonstrate the occurrence of agonist-selective MOR endocytosis in neurons naturally expressing this receptor in vivo and suggest the existence of different mechanisms regulating cellular responsiveness to ligands.
Pharmacological evidence that α1‐ and α2‐adrenoceptors mediate vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs (1999)

Vasoconstriction of carotid arteriovenous anastomoses may be involved in the therapeutic action of acutely acting anti-migraine agents, including the triptans and ergot alkaloids. While 5-HT1B/1D receptors mediate the effect of triptans, ergotamine and dihydroergotamine also interact with alpha-adrenoceptors. In the present study, we investigated the potential role of alpha1- and alpha2-adrenoceptors in mediating vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs. Ten minute intracarotid infusions of phenylephrine (1, 3 and 10 microg kg(-1) min(-1)) or BHT 933 (3, 10 and 30 microg kg(-1) min(-1)) produced dose-dependent decreases in total carotid and arteriovenous anastomotic conductances; no changes were observed in the capillary fraction. The carotid vascular effects of phenylephrine and BHT 933 were selectively abolished by prazosin (100 microg kg(-1), i.v.) and rauwolscine (300 microg kg(-1), i.v.), respectively. The responses to phenylephrine and BHT 933 were not affected by the selective 5-HT1B/1D receptor antagonist GR127935 (500 microg kg(-1), i.v.). These results show that both alpha1- and alpha2-adrenoceptors can mediate vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs. Since vasoconstrictor activity in this in vivo model is predictive of anti-migraine activity, an agonist activity at particularly the alpha2-adrenoceptor subtypes, in view of their less ubiquitous nature, could provide migraine abortive potential. Thus, the present results may aid further understanding of the mode of action of some current anti-migraine agents and may eventually be helpful in the development of future treatment in migraine.
Functional protein domains from the thermally driven motion of polypeptide chains: A proposal (1998)

It is proposed that the thermally driven motion of certain polypeptide chains, including those that are part of an otherwise stable folded protein, produces time-averaged three-dimensional domains that confer unique functions to a protein. These domains may be controlled by collapsing the polypeptide into an enthalpically favored structure, or extending it into an entropically dominated form. In the extended form, these domains occupy a relatively large space, which may be used to regulate protein-protein interactions and confer mechanical properties to proteins. This "entropic bristle" model makes several predictions about the structure and properties of these domains, and the predictions are used to reevaluate a range of biophysical studies on proteins. The outcome of the analysis suggests that the entropic bristle can be used to explain a wide range of disparate and apparently unrelated experimental observations.
Efficacy and Safety of Orally/Sublingually, Intranasally, and Intraperitoneally Administered Recombinant Murine Interferon in the Treatment of Murine Encephalomyocarditis Virus (2001)

Interferons (IFN) have been shown to be effective in protecting animals against lethal viral infections when administered systemically in relatively high doses. Intraperitoneal (i.p.) injection of mice with encephalomyocarditis virus (EMCV) gives rise to a rapidly progressive fatal disease characterized by central nervous system involvement and encephalitis. IFN-alpha has been shown to be effective in protecting mice against lethal EMCV infection when given via parenteral and oral/sublingual routes. The current study was designed to explore the ability of orally/sublingually and intranasally (i.n.) administered IFN-alpha to treat mice infected with EMCV in support of a planned clinical trial to evaluate efficacy of oral IFN-alpha in human viral infections. The primary objective of the study was to determine the efficacy of recombinant murine IFN-alpha (rMuIFN-alpha) in the treatment of mice infected with 100 LD(50) EMCV following oral, i.n., and i.p. administration at doses of 20,000 and 100,000 IU. The results of the current experiment did not indicate protection from infection with EMCV in mice that received IFN by the i.n. or oral/sublingual routes. The negative controls, infection of mice with 100 LD(50) of EMCV followed by treatment with excipient via all three routes, resulted in death of nearly all mice, as expected. The positive control, treatment of EMCV-infected (100 LD(50)) mice with rMuIFN-alpha via the i.p. route, was successful in protecting a significant number of mice from death compared with matched controls. This study points out the need to determine the optimum conditions for administration of oral/sublingual or i.n. IFN to insure maximum efficacy against viral infections.
Multimolecular Forms of Pyruvate Kinase from Rat and Other Mammalian Tissues* (1972)

Journal Article Multimolecular Forms of Pyruvate Kinase from Rat and Other Mammalian Tissues: I. Electrophoretic Studies Get access Kiichi IMAMURA, Kiichi IMAMURA The Department of Nutrition and Physiological Chemistry, Osaka University Medical SchoolJoancho, Kita-ku, Osaka Search for other works by this author on: Oxford Academic PubMed Google Scholar Takehiko TANAKA Takehiko TANAKA The Department of Nutrition and Physiological Chemistry, Osaka University Medical SchoolJoancho, Kita-ku, Osaka Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Biochemistry, Volume 71, Issue 6, June 1972, Pages 1043–1051, https://doi.org/10.1093/oxfordjournals.jbchem.a129852 Published: 01 June 1972 Article history Received: 15 December 1971 Published: 01 June 1972
Transferred nuclear Overhauser effect spectroscopy study of a peptide from the PapG pilus subunit bound by the Escherichia coli PapD chaperone (1997)

Interaction of the Escherichia coli PapD chaperone with the synthetic peptide PapG308-314 (Thr-Met-Val-Leu-Ser-Phe-Pro), corresponding to the seven C-terminal residues of the PapG pilus subunit, was studied by transferred nuclear Overhauser effect (TRNOE) spectroscopy. The observation of cross-peaks corresponding to either intraresidue or sequential C(alpha)H/NH and C(beta)H/NH TRNOEs and the absence of sequential NH(i)/NH(i+1) TRNOEs indicate that the peptide binds to PapD in an extended conformation. In addition, line-broadening effects gave information of the peptide's mode of interaction with PapD. These observations were in excellent agreement with a recent crystal structure of a PapG peptide complexed with PapD.
Heart rate increase in otherwise subclinical seizures is different in temporal versus extratemporal seizure onset: support for temporal lobe autonomic influence. (2005)

Ictal heart rate was investigated in otherwise subclinical epileptic seizures to test the hypothesis as to whether ictal tachycardia is physiological and not a physical or psychological stress response. In addition, we aimed to evaluate the localizing significance of pure ictal tachycardia. We included 21 epilepsy patients, who showed an ictal EEG seizure pattern during 22, otherwise subclinical seizures. All patients underwent ictal video-EEG recordings to evaluate the possibility of resective epilepsy surgery. The changes in heart rate in these patients were investigated in order to determine their relationship to localization and duration of EEG seizure patterns. Ictal tachycardia was observed in 41% of the otherwise subclinical seizures (nine out of 22), and significantly more often in seizures arising from the temporal lobe than from extratemporal regions (62% versus 11%, p < 0.0018). The seizure duration as defined by EEG was significantly positively correlated with an increase of heart rate (p = 0.043). Ictal heart rate can increase as a result of epileptic activation of autonomic cortex, reflecting a temporal lobe autonomic influence. Thus, measurement of heart rate should be included in the evaluation of otherwise subclinical epileptic seizures, because of its localizing value.
The Decomposition Algorithm for Linear Programs (1961)

A procedure is presented for the efficient computational solution of linear programs having a certain structural property characteristic of a large class of problems of practical interest. The property makes possible the decomposition of the problem into a sequence of small linear programs whose iterated solutions solve the given problem through a generalization of the simplex method for linear programming. 1. THE DECOMPOSED LINEAR PROGRAM MANY LINEAR programming problems of practical interest have the property that they may be described, in part, as composed of separate linear programming problems tied together by a number of constraints considerably smaller than the total number imposed on the problem. When the matrix of coefficients of such a problem, suitably ordered, is displayed in the usual way, a pattern emerges like that shown in Figure 1. In this figure the constraint matrix has been partitioned into nonzero blocks A1 and By, the right-hand side column of constants correspondingly into b, bl,..., bn; and the costs,
Solid-phase synthesis of peptide-dendrimer conjugates for an investigation of integrin binding (2001)

Peptide-dendrimer conjugates, bearing up to eight peptide ligands (LDV) targeted against the 4 integrin VLA-4 were prepared by solid-phase synthesis. Solid phase synthesis allowing the dendrimer conjugates to be prepared in high purity for an investigation of the multivalent effect in ligand integrin interactions. An ELISA was used to screen the peptide-dendrimer conjugates for their ability to compete with a biotinylated peptide component of the CS1 region of fibronectin. The inhibition potential of the different generation peptide-dendrimer conjugates was found to increase with higher generations.