gebhart/patrepeval huggingface dataset:
HU-308: A specific agonist for CB 2 , a peripheral cannabinoid receptor (1999)

Two cannabinoid receptors have been identified: CB(1), present in the central nervous system (CNS) and to a lesser extent in other tissues, and CB(2), present outside the CNS, in peripheral organs. There is evidence for the presence of CB(2)-like receptors in peripheral nerve terminals. We report now that we have synthesized a CB(2)-specific agonist, code-named HU-308. This cannabinoid does not bind to CB(1) (K(i) > 10 microM), but does so efficiently to CB(2) (K(i) = 22.7 +/- 3.9 nM); it inhibits forskolin-stimulated cyclic AMP production in CB(2)-transfected cells, but does so much less in CB(1)-transfected cells. HU-308 shows no activity in mice in a tetrad of behavioral tests, which together have been shown to be specific for tetrahydrocannabinol (THC)-type activity in the CNS mediated by CB(1). However, HU-308 reduces blood pressure, blocks defecation, and elicits anti-inflammatory and peripheral analgesic activity. The hypotension, the inhibition of defecation, the anti-inflammatory and peripheral analgesic effects produced by HU-308 are blocked (or partially blocked) by the CB(2) antagonist SR-144528, but not by the CB(1) antagonist SR-141716A. These results demonstrate the feasibility of discovering novel nonpsychotropic cannabinoids that may lead to new therapies for hypertension, inflammation, and pain.
Characterization of a New Type of Human Papillomavirus That Causes Skin Warts (1977)

A human papillomavirus (HPV) was isolated from the lesions of a patient (ML) bearing numerous hand common warts. This virus was compared with the well-characterized HPV found in typical plantar warts (plantar HPV). ML and plantar HPV DNAs have similar molecular weights (5.26 x 10(6) and 5.23 x 10(6), respectively) but were shown to be different by restriction enzyme analysis. When the cleavage products of both DNAs by endonuclease EcoRI, BamI, HpaI, or Hind were analyzed by electron microscopy, one, two, one, and four fragments were detected for ML HPV DNA instead of the two, one, two, and six fragments, respectively, detected for plantar HPV DNA. In contrast to plantar HPV DNA, a high proportion of ML HPV DNA molecules were resistant to these restriction enzymes. Most, if not all, of the molecules were either resistant to BamI and sensitive to EcoRI or sensitive to BamI and resistant to EcoRI. After denaturation and renaturation of the cleavage products of ML HPV DNA by a mixture of the two enzymes, the circular "heteroduplexes" formed showed one to three heterology loops corresponding to about 4 to 8% of the genome length. No sequence homology was detected between ML and plantar HPV DNAs by cRNA-DNA filter hybridization, by measuring the reassociation kinetics of an iodinated plantar HPV DNA in the presence of a 25-fold excess of ML HPV DNA, or by the heteroduplex technique. The two viruses had distinct electrophoretic polypeptide patterns and showed no antigenic cross-reaction by immunodiffusion or immunofluorescence techniques. Preliminary cRNA-DNA hybridization experiments, using viral DNAs from single or pooled plantar or hand warts, suggest that hand common warts are associated with viruses similar or related to ML HPV. The existence of at least two distinct types of HPVs that cause skin warts was demonstrated; they were provisionally called HPV type 1 and HPV type 2, with plantar HPV and ML HPV as prototypical viruses, respectively.
Psychoacoustics: facts and models (1991)

Psychoacoustics - Facts and Models offers a unique, comprehensive summary of information describing the processing of sound by the human hearing system. It includes quantitative relations between sound stimuli and auditory perception in terms of hearing sensations, for which quantitative models are given, as well as an unequalled collection of data on the human hearing system as a receiver of acoustic information. In addition, many examples of the practical application of the results of basic research in fields such as noise control, audiology, or sound quality engineering are detailed. The t
Chemokines and innate immunity. (2000)

Our environment contains a great variety of infectious microbes that may be potentially destructive and threaten our survival. As soon as microbes try to establish a site of infection, the host launches a complex defense system. Innate immunity is a non-specific response and serves as the first-line of defense where phagocytes, such as neutrophils and macrophages, and NK cells play central roles in neutralizing and clearing microorganisms. Thus, migration of cells into infectious foci and subsequent activation of these cells appear to be a critical step, enabling the host to achieve effective and efficient removal of microbes. Over the past decade, chemokines have been identified as chemotactic cytokines that attract and activate specific types of leukocyte populations in vitro. There is now evidence that the magnitude of chemokines' expression in infectious diseases is strongly associated with the severity of the inflammatory responses. Blocking chemokines or their receptors with neutralizing antibodies or gene targeting technology has allowed us to understand the pathological significance of chemokines in animal models of infectious diseases. Growing evidence suggests that chemokines play an important beneficial role in immune system development, homeostasis and in innate immunity, which may pave the way for new therapeutic strategies for the treatment of infectious diseases.
A fast automaton-based method for detecting anomalous program behaviors (2002)

Anomaly detection on system call sequences has become perhaps the most successful approach for detecting novel intrusions. A natural way for learning sequences is to use a finite-state automaton (FSA). However previous research indicates that FSA-learning is computationally expensive, that it cannot be completely automated or that the space usage of the FSA may be excessive. We present a new approach that overcomes these difficulties. Our approach builds a compact FSA in a fully automatic and efficient manner, without requiring access to source code for programs. The space requirements for the FSA is low - of the order of a few kilobytes for typical programs. The FSA uses only a constant time per system call during the learning as well as the detection period. This factor leads to low overheads for intrusion detection. Unlike many of the previous techniques, our FSA-technique can capture both short term and long term temporal relationships among system calls, and thus perform more accurate detection. This enables our approach to generalize and predict future behaviors from past behaviors. As a result, the training periods needed for our FSA based approach are shorter. Moreover false positives are reduced without increasing the likelihood of missing attacks. This paper describes our FSA based technique and presents a comprehensive experimental evaluation of the technique.
Subcellular localization and tissue distribution of sialic acid-forming enzymes. N-acetylneuraminate-9-phosphate synthase and N-acetylneuraminate 9-phosphatase (1984)

The activities of N-acetylneuraminate 9-phosphate synthase and N-acetylneuraminate 9-phosphatase, the two enzymes involved in the final steps of the biosynthetic pathway of N-acetylneuraminic acid, were measured with the substrates N-acetyl[14C]mannosamine 6-phosphate and N-acetyl[14C]neuraminic acid 9-phosphate respectively. Subcellular localization studies in rat liver indicated that both enzymes are localized in the cytosolic fraction after homogenization in sucrose medium. To test the possibility of misinterpretation due to the hydrolysis of N-acetylneuraminic acid 9-phosphate by non-specific phosphatases, the hydrolysis of various phosphate esters by the cytosolic fraction was tested. Only p-nitrophenyl phosphate was hydrolysed; however, competition studies with N-acetylneuraminic acid 9-phosphate and p-nitrophenyl phosphate indicated that two different enzymes were involved and that no competition existed between the two substrates. In various other rat tissues N-acetylneuraminate-9-phosphate synthase and N-acetylneuraminate 9-phosphatase activities were detected, suggesting that N-acetylmannosamine 6-phosphate is a general precursor for N-acetylneuraminic acid biosynthesis in all the tissues studied.
Degradability of Polysaccharides Multilayer Films in the Oral Environment:  an in Vitro and in Vivo Study (2005)

Biomedical devices and modified biomaterial surfaces constitute an expanding research domain in the dental field. However, such oral applications have to face a very particular environment containing specific physiological conditions and specific enzymes. To evaluate their suitability in the development of novel oral applications, the degradability of polyelectrolyte multilayer films made of the natural polysaccharides chitosan and hyaluronan (CHI/HA) was investigated in vitro and in vivo in a rat mouth model. The films were either native or cross-linked using a water-soluble carbodiimide (EDC) in combination with N-hydroxysulfosuccinimide. The in vitro degradation of the films by different enzymes present in the oral environment, such as lysozyme and amylase, was followed by quartz crystal microbalance measurements and confocal laser scanning microscopy observations after being film labeled with CHI(FITC). Whereas native films were subjected to degradation by all the enzymes, cross-linked films were more resistant to enzymatic degradation. Films were also put in contact with whole saliva, which induced a slow degradation of the native films over an 18 h period. The in vivo degradation of the films deposited on polymer disks and sutured in the rat mouth was followed over a 3 day period. Whereas film degradation is fast for native films, it is much slower for the cross-linked ones. More than 60% of these films remained on the disks after 3 days in the mouth. Taken together, these results suggest that the multilayer films made of natural polysaccharides are of high potential interest for oral applications, especially as drug release systems, offering various degradation rates and consequent release characteristics.
Helical Complexes Containing Diamide‐Bridged Benzene‐o‐dithiolato/Catecholato Ligands (2006)

The benzene-o-dithiol/catechol ligands H4-2 and H4-3 react with [TiO(acac)2] to give the dinuclear, double-stranded anionic complexes [Ti2(L)2(mu-OCH3)2](2-) ([22](2-), L=2(4-); [23](2-), L=3(4-)). NMR spectroscopic investigations reveal that the complex anion [Ti2(2)2(mu-OCH3)(2)](2-) is formed as a mixture of three of four possible isomers/pairs of enantiomers, whereas only one isomer of the complex anion [Ti2(3)2(mu-OCH3)(2)](2-) is obtained. The crystal structure analysis of (PNP)2[Ti2(3)2(mu-OCH3)2] shows a parallel orientation of the ligand strands, whereas the structure determination for (AsPh4)2[Ti2(2)2(mu-OCH3)2] does not yield conclusive results about the orientation of the ligand strands due the presence of different isomers in solution, the possible co-crystallisation of different isomers and severe disorder in the crystal. NMR spectroscopy shows that ligand H4-3 reacts at elevated temperature with [TiO(acac)2] to give the triple-stranded helicate (PNP)4[Ti2(3)3] ((PNP)4[24]) as a mixture of two isomers, one with a parallel orientation of the ligand strands and one with an antiparallel orientation. Exclusively the triple-stranded helicates [Ti2(L)(3)](4-) ([25](4-), L=1(4-); [26](2-), L=4(4-)) are formed in the reaction of ligands H4-1 and H4-4 with [TiO(acac)2]. The molecular structures of Na(PNP)3[Ti2(1)3]CH(3)OHH(2)OEt(2)O (Na(PNP)3[25]CH(3)OHH(2)OEt(2)O) and Na(1.5)(PNP)(6.5)[Ti2(4)3]2.3 DMF (Na(1.5)(PNP)(6.5)[26]2.3 DMF) reveal a parallel orientation of the ligand strands in both complexes, which is retained in solution. The sodium cations present in the crystal structures lead to two different kinds of aggregation in the solid state. Na-[25]-Na-[25]-Na polymeric chains are formed from compound Na(PNP)3[25], with the sodium cations coordinated by the carbonyl groups of two ligand strands from two different [Ti2(1)3](4-) ions in addition to solvent molecules. In contrast to this, two [Ti2(4)3](4-) ions are connected by a sodium cation that is coordinated by the three meta oxygen atoms of the catecholato groups of each complex tetraanion to form a central {NaO6} octahedron in the anionic pentanuclear complex {[26]-Na-[26]}(7-).
T Cell Antigen Receptor-Mediated Activation of Phospholipase C Requires Tyrosine Phosphorylation (1990)

Triggering of the antigen-specific T cell receptor-CD3 complex (TCR-CD3) stimulates a rapid phospholipase C-mediated hydrolysis of inositol phospholipids, resulting in the production of second messengers and in T cell activation and proliferation. The role of tyrosine phosphorylation in these events was investigated with a tyrosine protein kinase (TPK) inhibitor, genistein. At doses that inhibited TPK activity and tyrosine phosphorylation of the TCR zeta subunit, but not phospholipase C activity, genistein prevented TCR-CD3-mediated phospholipase C activation, interleukin-2 receptor expression, and T cell proliferation. These findings indicate that tyrosine phosphorylation is an early and critical event that most likely precedes, and is a prerequisite for, inositol phospholipid breakdown during receptor-mediated T cell activation.
Genomic Analysis of Non- NF2 Meningiomas Reveals Mutations in TRAF7 , KLF4 , AKT1 , and SMO (2013)

We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive-nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics.
Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia (1979)

In a prelminary communication, we described the establishment of a continuous human myeloid cell line (HL-60). Here we report the detailed properties of this cell line and document its derivation from the peripheral blood leukocytes of a patient with acute promyelocytic leukemia. As characterized by light and electron microscopy, the predominant cell type in both the fresh and cultured sources is a neutrophilic promyelocyte with prominent nuclear/cytoplasmic asynchrony. Up to 10% of the cultured cells spontaneously differentiate beyond the promyelocyte stage, and the proportion of terminally differentiated cells is markedly enhanced by compounds known to stimulate differentiation of mouse (Friend) erythroleukemia cells. The HL-60 cells lack specific markers for lymphoid cells, but express surface receptors for Fc fragment and complement (C3), which have been associated with differentiated granulocytes. They exhibit phagocytic activity and responsiveness to a chemotactic stimulus commensurate with the proportion of mature cells. As characteristic of transformed cells, the HL-60 cells form colonies in semisolid medium and produce subcutaneous myeloid tumors (chloromas) in nude mice. A source of colony-stimulating activity stimulated the cloning efficiency in soft agar 5--30-fold. Despite adaptations to culture, the morphological phenotype and responsiveness to chemical induction of differentiation is essentially unchanged through at least 85 passages. Cytogenetic studies reveal aneuploidy. Metaphases with 44 chromosomes predominated in vivo and in early culture passages; however, clones with 45 or 46 chromosomes became predominant with continued passaging. The most consistent karyotypic abnormalities were the deletion of chromosomes 5, 8, and X and the addition of a marker resembling a D-group acrocentric and of a submetacentric marker, most likely an abnormal E-group chromosome. No DNA herpesvirus or RNA retrovirus was isolated in the fresh or cultured cells. The HL-60 cultured cell line provides a continuous source of human cells for studying the molecular events of myeloid differentiation and the effects of physiologic, pharmacologic, and virologic elements on this process.
Bulk-Heterojunction Solar Cells with Benzotriazole-Based Copolymers as Electron Donors: Largely Improved Photovoltaic Parameters by Using PFN/Al Bilayer Cathode (2010)

Three benzotriazole (BTA)-based conjugated polymers PF-DTBTA, PCz-DTBTA, and PPh-DTBTA, with electron-donating segments of fluorene, carbazole, and dialkoxybenzene, respectively, were successfully synthesized as new polymeric donors in bulk-heterojunction (BHJ) photovoltaic cells (PVCs). All the copolymers exhibited good solubility in common organic solvents and good thermal stability. The optical band gaps for PF-DTBTA, PCz-DTBTA, and PPh-DTBTA are 2.24, 2.18, and 1.87 eV, respectively. The HOMO levels for PF-DTBTA, PCz-DTBTA, and PPh-DTBTA are −5.67, −5.54, and −5.20 eV, respectively, which were determined by the electron-donating segments. The LUMO levels for PF-DTBTA, PCz-DTBTA, and PPh-DTBTA are −3.43, −3.36, and −3.33 eV, respectively, which were mainly dominated by the BTA unit. For a blend ratio of polymer:PCBM = 1:2, BHJ PVCs with Al cathode displayed power conversion efficiencies (PCE) of 0.9%, 1.51%, and 1.16% for PF-DTBTA, PCz-DTBTA, and PPh-DTBTA, respectively. Alcohol-soluble poly[(9,9-dioctyl-2,7-fluorene)-alt-(9,9-bis(3′-(N,N-dimethylamino)propyl)-2,7-fluorene)] (PFN) was selected for cathode modification. For BHJ PVCs with PF-DTBTA and PCz-DTBTA as the donors, open-circuit voltages (Voc) of the PVCs could all be elevated with the PFN/Al bilayer cathode, whereas no such improvements were found for PVCs with PPh-DTBTA as the donor. The behaviors could be attributed to the different Voc losses when using Al cathode. Using PFN/Al bilayer cathode could also improve short-curcuit current and fill factor for the three BTA-based copolymers. The N−N interactions between the BTA-based polymers and the PFN may modify interfacial contact, resulting in enhancement of the electron extraction from the acceptor phase to the cathode and decreasing hole−electron recombination in the active layer. Consequently, PFN/Al bilayer cathode elevated PCE values to 1.3%, 2.75%, and 1.39% for PF-DTBTA, PCz-DTBTA, and PPh-DTBTA, respectively. The most significant increasing of PCE with a calculated value of 80% was found for PCz-DTBTA as the donor, and this might be related to the additional N−N interactions between the carbazole segments and the PFN. The results would supply useful information to understand the contribution of an interfacial layer on the photovoltaic performance. Our results also suggest that the bilayer cathode would have great potential to elevate PCE of BHJ PVCs.
Comparative Release of Phenylpropanolamine HC1 from Long-Acting Appetite Suppressant Products: Acutrim Vs. Dexatrim (1984)

The release of phenylpropanolamine HC1 from two commercially available long-acting appetite suppressant products, Acutrim and Dexatrim, was evaluated by using a dissolution apparatus modified from the well-calibrated Ghannam-Chien diffusion cells. The solubility profile of phenylpropanolamine showed extreme dependency on pH. The release of phenylpropanolamine from Acutrim tablets was observed to be fairly independent of pH and fluid dynamics, but is affected by the osmotic pressure in the dissolution medium. The release profiles of phenylpropanolamine from both Dexatrim and Acutrim were observed to consist of two stages: an initial, fast-release phase and a sustained-release phase at steady state. While both products achieve 100% release of the loading dose, the sustained-release portion of the phenylpropanolamine dose was observed to release from Acutrim tablets at zero-order kinetics over a 8-hr period, but showed a gradual dissolution from Dexatrim granules for over a 4-hr duration. Therefore, a prolonged release of phenylpropanolamine over the target 16-hr period was achieved by Acutrim tablets, but not by Dexatrim capsules.
Retrospective evaluation of possible renal toxicity associated with continuous infusion of vancomycin in critically ill patients (2011)

AKI is frequently observed during continuous vancomycin infusion, particularly when conditions that cause acute (shock) or chronic (diabetes) renal dysfunction are present and vancomycin levels above target range are achieved. Although this study challenges the concept that continuous vancomycin infusion might alleviate the risk of nephrotoxicity in critically ill patients, a direct relationship between vancomycin and nephrotoxicity remains to be proven.
Neurabin is a synaptic protein linking p70 S6 kinase and the neuronal cytoskeleton (1998)

p70 S6 kinase (p70(S6k)) is a mitogen-activated protein kinase that plays a central role in the control of mRNA translation. It physiologically phosphorylates the S6 protein of the 40s ribosomal subunit in response to mitogenic stimuli and is a downstream component of the rapamycin-sensitive pathway, which includes the 12-kDa FK506 binding protein and includes rapamycin and the 12-kDa FK506 binding protein target 1. Here, we report the identification of neurabin (neural tissue-specific F-actin binding protein), a neuronally enriched protein of 1,095 amino acids that contains a PDZ domain and binds p70(S6k). We demonstrate the neurabin-p70(S6k) interaction by yeast two-hybrid analysis and biochemical techniques. p70(S6k) and neurabin coimmunoprecipitate from transfected HEK293 cells. Site-directed mutagenesis of neurabin implicates its PDZ domain in the interaction with p70(S6k), and deletion of the carboxyl-terminal five amino acids of p70(S6k) abrogates the interaction. Cotransfection of neurabin in HEK293 cells activates p70(S6k) kinase activity. The mRNA of neurabin and p70(S6k) show striking colocalization in brain sections by in situ hybridization. Subcellular fractionation of rat brain demonstrates that neurabin and p70(S6k) both localize to the soluble fraction of synaptosomes. By way of its PDZ domain, the neuronal-specific neurabin may target p70(S6k) to nerve terminals.
Effect of surface properties on the antithrombogenicity of silk fibroin/S-carboxymethyl kerateine blend films (1998)

Polymeric blends of silk fibroin (SF) and S-carboxymethyl kerateine (SCMK) were prepared by the solvent casting method to study the effect of surface properties on the antithrombogenicity. The films of SF/SCMK showed better antithrombogenic properties than SF or SCMK alone. Among them, the film containing 50 wt% SCMK showed the best antithrombogenicity. When the SF/SCMK films were treated with methanol, the antithrombogenicity of the films was scarcely affected except the SF-rich ones. The enhanced antithrombogenic properties were explained in terms of polarity of the surface. The blend films showed an enhancement of polar contribution to surface free energy (gamma(P)S and polar stabilization energy (I(SW)). SF-rich films showed high gamma(P)S and I(SW) values when treated with methanol. This change of surface properties was considered to be due to the fact that the conformational transition from random coil structure to beta-structure of proteins may have affected the surface properties, especially the polar properties.