gebhart/patrepeval huggingface dataset:
Is SOD1 loss of function involved in amyotrophic lateral sclerosis? (2013)

Mutations in the gene superoxide dismutase 1 (SOD1) are causative for familial forms of the neurodegenerative disease amyotrophic lateral sclerosis. When the first SOD1 mutations were identified they were postulated to give rise to amyotrophic lateral sclerosis through a loss of function mechanism, but experimental data soon showed that the disease arises from a--still unknown--toxic gain of function, and the possibility that loss of function plays a role in amyotrophic lateral sclerosis pathogenesis was abandoned. Although loss of function is not causative for amyotrophic lateral sclerosis, here we re-examine two decades of evidence regarding whether loss of function may play a modifying role in SOD1-amyotrophic lateral sclerosis. From analysing published data from patients with SOD1-amyotrophic lateral sclerosis, we find a marked loss of SOD1 enzyme activity arising from almost all mutations. We continue to examine functional data from all Sod1 knockout mice and we find obvious detrimental effects within the nervous system with, interestingly, some specificity for the motor system. Here, we bring together historical and recent experimental findings to conclude that there is a possibility that SOD1 loss of function may play a modifying role in amyotrophic lateral sclerosis. This likelihood has implications for some current therapies aimed at knocking down the level of mutant protein in patients with SOD1-amyotrophic lateral sclerosis. Finally, the wide-ranging phenotypes that result from loss of function indicate that SOD1 gene sequences should be screened in diseases other than amyotrophic lateral sclerosis.
Pharmacokinetics of all-trans-retinoic acid administered on an intermittent schedule. (1995)

An intermittent schedule of ATRA administration results in repetitive periods of exposure to concentrations of ATRA normally only observed on the first day of treatment. Phase II trials to evaluate the role of intermittent schedules of administration for ATRA are planned.
Purification and properties of D-aminoacylase of Streptomyces olivaceus. (1978)

D-Aminoacylase for enzymatic resolution of DL-amino acids was produced in the presence of inducer by Streptomyces olivaceus and almost all the activity was found in cell fraction. The partial purification and properties of this induced enzyme were studied. The enzyme had a molecular weight of about 45, 000 and was specific for the hydrolysis of N-acetyl D-amino acids. The optimum pH was found to be at pH 7.0 and the activity was remarkably inhibited by the presence of Hg2+ or Ago2+. Enzyme stability was increased by the addition of Co2+. Michaelis constants (Km) for several preferred substrates were between 1.13×10-3 and 2.95×10-3M.
Exciton and Electron Traps on Structural Defects in Molecular Crystals with Dipolar Molecules (1995)

Abstract The depths of exciton and electron traps arising due to the presence of structural defects in organic crystals consisting of dipolar molecules are calculated. In the model studied a structural defect appears if a molecule is rotated by 180° around the long axis as compared to the bulk molecules. The contribution of the electrostatic interaction to the depth of the trap state on such a defect is studied in detail. For crystals consisting of molecules which have a large dipole moment in the ground state and adopting large values in the excited state this contribution may be dominant. The calculations are carried out for triplet excitons and electrons in benzophenone crystal.
Complement Factor 3 Mediates Particulate Matter–Induced Airway Hyperresponsiveness (2002)

Epidemiologic studies have suggested that exposure to airborne particulate matter (PM) can exacerbate allergic airway responses; however, the mechanism(s) are not well understood. We and others have recently shown that development of airway hyperresponsiveness (AHR) may be a complement-mediated process. In the present study, we examined the role of complement factor 3 (C3) in the development of PM-induced AHR and airway inflammation by comparing responses between C3-deficient (C3(-/-)) and wild-type mice. Mice were exposed to 0.5 mg of ambient particulate collected in urban Baltimore. Forty-eight hours later, airway responsiveness to intravenous acetylcholine was assessed and bronchoalveolar lavage was conducted. PM exposure of wild-type mice resulted in significant increases in AHR, whereas it did not significantly increase airway reactivity in C3(-/-) mice. Interestingly, PM induced similar inflammatory responses in both wild-type and C3(-/-) mice. Immunohistochemical staining demonstrated marked C3 deposition in the airway epithelium and connective tissue of wild-type mice after PM exposure. These results suggest that exposure to PM may induce AHR through activation of complement factor 3 in the airways.
Embryonic Intermediate Filaments, Nestin and Vimentin, Expression in the Spinal Cords of Rats with Experimental Autoimmune Encephalomyelitis (2003)

Intermediate filaments, including nestin and vimentin, are found in specific cell types in central nervous system (CNS) tissues, particularly immature glial cells and multipotent progenitor cells. In the present study, the expression patterns of nestin and vimentin in the spinal cords of rats with experimental autoimmune encephalomyelitis (EAE) and the response of cells containing filaments against acute autoimmune injury were examined by immunohistochemistry. Nestin immunostaining was only weakly detected in vascular endothelial cells but not in any cell types in the spinal cord in normal and adjuvant-immunized rats. At the peak stage of EAE, nestin-immunoreativity was recognized in some astrocytes in the gray matter and white matter. Vimentin was immunopositive in some astrocytes and macrophages in EAE lesions, while vimentin was normally detected in ependymal cells of central canals in the rat spinal cords.We postulate that normal animals may contain multipotent progenitor cells in the spinal cord parenchyma as well as in the subpial lesion and ependyma. Multipotent progenitor cells may activate to transform into necessary cells, including neurons, astrocytes or oligodendrocytes, depending on CNS needs. Appropriate control of progenitor cells in the injured CNS is an alternative choice for CNS remodeling.
A new class of homogeneous nucleic acid probes based on specific displacement hybridization (2002)

We have developed a new class of probes for homogeneous nucleic acid detection based on the proposed displacement hybridization. Our probes consist of two complementary oligodeoxyribonucleotides of different length labeled with a fluorophore and a quencher in close proximity in the duplex. The probes on their own are quenched, but they become fluorescent upon displacement hybridization with the target. These probes display complete discrimination between a perfectly matched target and single nucleotide mismatch targets. A comparison of double-stranded probes with corresponding linear probes confirms that the presence of the complementary strand significantly enhances their specificity. Using four such probes labeled with different color fluorophores, each designed to recognize a different target, we have demonstrated that multiple targets can be distinguished in the same solution, even if they differ from one another by as little as a single nucleotide. Double-stranded probes were used in real-time nucleic acid amplifications as either probes or as primers. In addition to its extreme specificity and flexibility, the new class of probes is simple to design and synthesize, has low cost and high sensitivity and is accessible to a wide range of labels. This class of probes should find applications in a variety of areas wherever high specificity of nucleic acid hybridization is relevant.
Study of matrix metalloproteinases and their inhibitors in prostate cancer (2010)

Extracellular matrix metalloproteases (MMPs) have raised an extraordinary interest in cancer research because of their potential role in basal membrane and extracellular matrix degradation, consequently facilitating tumour invasion and metastases development. An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs 1, 2, 7, 9, 11, 13, 14, and their tissue inhibitors, TIMPs 1, 2 and 3. More than 2600 determinations on cancer specimens from 133 patients with clinically localised prostate carcinoma, 20 patients with prostatic intraepithelial neoplasia and 50 patients with benign prostate hyperplasia and controls, were performed. When compared with benign pathologies, prostate carcinomas had higher expression of all MMPs and TIMPs. Dendogram shows a first-order division of tumours into two distinct MMPs/TIMPs molecular profiles, one of them with high MMPs/TIMs expression profile (n=70; 52.6%). Tumours with high expression of MMP-11 or -13, or cluster thereof, were significantly associated with higher probability of biochemical recurrence. The expression of MMPs and TIMPs seems to have an important role in the molecular biology of prostate carcinomas, and their expression by tumours may be of clinical interest to used as indicators of tumour aggressiveness.
5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase. (2000)

Insulin regulates the rate of expression of many hepatic genes, including PEPCK, glucose-6-phosphatase (G6Pase), and glucose-6-phosphate dehydrogenase (G6PDHase). The expression of these genes is also abnormally regulated in type 2 diabetes. We demonstrate here that treatment of hepatoma cells with 5-aminoimidazole-4-carboxamide riboside (AICAR), an agent that activates AMP-activated protein kinase (AMPK), mimics the ability of insulin to repress PEPCK gene transcription. It also partially represses G6Pase gene transcription and yet has no effect on the expression of G6PDHase or the constitutively expressed genes cyclophilin or beta-actin. Several lines of evidence suggest that the insulin-mimetic effects of AICAR are mediated by activation of AMPK. Also, insulin does not activate AMPK in H4IIE cells, suggesting that this protein kinase does not link the insulin receptor to the PEPCK and G6Pase gene promoters. Instead, AMPK and insulin may lie on distinct pathways that converge at a point upstream of these 2 gene promoters. Investigation of the pathway by which AMPK acts may therefore give insight into the mechanism of action of insulin. Our results also suggest that activation of AMPK would inhibit hepatic gluconeogenesis in an insulin-independent manner and thus help to reverse the hyperglycemia associated with type 2 diabetes.
Epigenetic regulation of gene expression in cervical cancer cells by the tumor microenvironment. (2000)

Evidence is accumulating that the adverse tumor microenvironment both modifies the malignant progression of tumor cells and contributes to chemotherapy and radiation resistance. We hypothesized that some of the effects on malignant progression are mediated through the transcriptional regulation of genes responsive to the stresses of the microenvironment, such as low oxygen or low glucose conditions. To determine epigenetic changes in gene expression that were consistent with that hypothesis, we used an in vitro subtractive hybridization method, representational difference analysis, to identify hypoxia-induced cDNAs from cultured human cervical epithelial cells. We identified 12 induced genes: two novel genes (HIG1 and HIG2), three genes known to be hypoxia-inducible (tissue factor, GAPDH, thioredoxin), and seven genes not previously identified as hypoxia-inducible [HNRNP(a1), ribosomal L7, annexin V, lipocortin 2, Ku(70), PRPP synthase, and acetoacetyl-CoA thiolase]. In cultured cells, HIG1 and HIG2 expression is induced by hypoxia and by glucose deprivation, but their expression is not induced by serum deprivation, UV, or ionizing radiation. The putative HIG1 and HIG2 open reading frames are expressed in cells, as confirmed by epitope tagging. In addition, tumor xenografts derived from human cervical cancer cells display increased expression of HIG1 and HIG2 when they are deprived of oxygen. Taken together, these data suggest a coordinated transcriptional response of eukaryotic cells to microenvironmental stresses found in the solid tumor.
Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system (1996)

Macrolide-resistant Streptococcus pyogenes isolates from Finland, Australia, and the United Kingdom and, more recently, Streptococcus pneumoniae and S. pyogenes strains from the United States were shown to have an unusual resistance pattern to macrolides, lincosamides, and streptogramin B antibiotics. This pattern, referred to as M resistance, consists of susceptibility to clindamycin and streptogramin B antibiotics but resistance to 14- and 15-membered macrolides. An evaluation of the macrolide-lincosamide-streptogramin B resistance phenotypes among our streptococcal strains collected from 1993 to 1995 suggested that this unusual resistance pattern is not rare. Eighty-five percent (n = 66) of the S. pneumoniae and 75% (n = 28) of the S. pyogenes strains in our collection had an M phenotype. The mechanism of M resistance was not mediated by target modification, as isolated ribosomes from a pneumococcal strain bearing the M phenotype were fully sensitive to erythromycin. Further, the presence of an erm methylase was excluded with primers specific for an erm consensus sequence. However, results of studies that determined the uptake and incorporation of radiolabeled erythromycin into cells were consistent with the presence of a macrolide efflux determinant. The putative efflux determinant in streptococci seems to be distinct from the multicomponent macrolide efflux system in coagulase-negative staphylococci. The recognition of the prevalence of the M phenotype in streptococci has implications for sensitivity testing and may have an impact on the choice of antibiotic therapy in clinical practice.
Improvement of Actinic Keratoses Using Topical DNA Repair Enzymes: A Randomized Placebo-Controlled Trial. (2017)

These results suggest that topical DNA repair enzymes may help reduce the number of AKs in individuals with moderate-to-severe photodamaged skin. Additionally, there may be a lasting effect of the DNA repair if application is discontinued. Further, cutaneous malignancies were not detected in any of the subjects during the study period. Despite the brevity of the study, these preliminary results suggest the role of DNA repair enzymes for not only treatment, but also skin cancer prevention. Further study and more objective evaluation measures are required for definitive conclusions to be drawn. <em>J Drugs Dermatol. 2017;16(10):1030-1034.</em> .
The parathyroid hormone-like peptide associated with humoral hypercalcemia of malignancy and parathyroid hormone bind to the same receptor on the plasma membrane of ROS 17/2.8 cells. (1988)

[Tyr36]human adenylate cyclase stimulating peptide (1-36)-NH2, an amino-terminal analog of a tumor peptide which is associated with hypercalcemia of malignancy, and [Nle8, Nle18, Tyr34]bovine parathyroid hormone (PTH)-(1-34)-NH2 both bind with similar affinities to receptors on rat osteosarcoma cells, ROS 17/2.8, when either of the peptides is used as the radioligand. Pretreatment of the cells with either peptide down-regulates available binding sites for either radioligand and desensitizes the cAMP accumulation stimulated by either peptide. Prior exposure of the cells to dexamethasone increases these responses to both peptides. Photoderivatized radioiodinated [Tyr36]human adenylate cyclase-stimulating peptide (1-36)-NH2 and [Nle8, Nle18, Tyr34]bovine PTH-(1-34)-NH2 both specifically label a Mr = 80,000 membrane protein on ROS 17/2.8 cells. The intensity of labeling this receptor band by either photoprobe is reduced by co-incubation with either peptide over the same dose range. Equivalent dose-dependent down-regulation of receptors which bind both photoprobes is also found when ROS 17/2.8 cells are preincubated with either peptide. Dexamethasone increases the intensity of receptor labeling. Our findings strongly indicate that both peptides recognize the same plasma membrane receptor on ROS 17/2.8 cells. Although the physiological function(s) of human adenylate cyclase-stimulating peptide is unknown, these results could explain why its biological actions on mineral ion metabolism so closely simulate those of PTH and raise interesting questions about the general biological and evolutionary significance of the use of the same receptor by chemically distinct peptides.
An IPv6 Aggregatable Global Unicast Address Format (1998)

This document defines an IPv6 aggregatable global unicast address format for use in the Internet. The address format defined in this document is consistent with the IPv6 Protocol [IPV6] and the "IPv6 Addressing Architecture" [ARCH]. It is designed to facilitate scalable Internet routing. This documented replaces RFC 2073, "An IPv6 Provider-Based Unicast Address Format". RFC 2073 will become historic. The Aggregatable Global Unicast Address Format is an improvement over RFC 2073 in a number of areas. The major changes include removal of the registry bits because they are not needed for route aggregation, support of EUI-64 based interface identifiers, support of provider and exchange based aggregation, separation of public and site topology, and new aggregation based terminology.
Querying object-oriented databases (1992)

Article Querying object-oriented databases Share on Authors: Michael Kifer University of Toronto University of TorontoView Profile , Won Kim UniSQL, Inc., Austin, TX UniSQL, Inc., Austin, TXView Profile , Yehoshua Sagiv The Hebrew University of Jerusalem The Hebrew University of JerusalemView Profile Authors Info & Claims SIGMOD '92: Proceedings of the 1992 ACM SIGMOD international conference on Management of dataJune 1992 Pages 393–402https://doi.org/10.1145/130283.130342Online:01 June 1992Publication History 189citation75DownloadsMetricsTotal Citations189Total Downloads75Last 12 Months19Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Evaluation of Enzyme-Linked Immunosorbent Assays with Two Synthetic Peptides of Epstein-Barr Virus for Diagnosis of Infectious Mononucleosis (1990)

To diagnose infectious mononucleosis caused by Epstein-Barr virus (EBV), a peptide from the EBV nuclear antigen (EBNA) 1 (p107) and an EBNA 2 peptide (polyproline) were used as antigens in enzyme-linked immunosorbent assays for IgG and IgM. Well-characterized serum samples (360) from healthy individuals and patients with EBV or cytomegalovirus infections were examined. The p107 IgG and IgM assays were also tested with serum from 1000 patients with suspected EBV-related disorders. The p107 and polyproline IgG assays were 100% specific for EBV seropositivity. Low p107 IgG titers (less than 1000) were found in 98% of patients with EBV infectious mononucleosis but also in 18% of patients with other diseases. A p107-to-polyproline IgG ratio of less than 1 was 98% specific for EBV infectious mononucleosis; sensitivity was 86%. In EBV capsid antigen-IgG seropositive patients, a p107 IgG titer of less than 1000 together with a p107 IgG-to-IgM ratio of less than 1 was 98% sensitive and specific for EBV infectious mononucleosis. Thus, this ratio appears adequate to measure EBNA antibodies for diagnosis of EBV mononucleosis.
Multi-channel medical device for time domain functional near infrared spectroscopy based on wavelength space multiplexing (2013)

We have designed a compact dual wavelength (687 nm, 826 nm) multi-channel (16 sources, 8 detectors) medical device for muscle and brain imaging based on time domain functional near infrared spectroscopy. The system employs the wavelength space multiplexing approach to reduce wavelength cross-talk and increase signal-to-noise ratio. System performances have been tested on homogeneous and heterogeneous tissue phantoms following specifically designed protocols for photon migration instruments. Preliminary in vivo measurements have been performed to validate the instrument capability to monitor hemodynamic parameters changes in the arm muscle during arterial occlusion and in the adult head during a motor task experiment.
Surgical left atrial appendage occlusion: evaluation of a novel device with magnetic resonance imaging☆ (2008)

We demonstrated a safe, straightforward, persistent and effective method for LAA occlusion with this new LAA clip. MRI effectively demonstrated LAA occlusion and only minor changes in left ventricular volumes.
DIK, a Novel Protein Kinase That Interacts with Protein Kinase Cδ (2000)

A novel serine/threonine kinase, termed DIK, was cloned using the yeast two-hybrid system to screen a cDNA library from the human keratinocyte cell line HaCaT with the catalytic domain of rat protein kinase Cdelta (PKCdelta(cat)) cDNA as bait. The predicted 784-amino acid polypeptide with a calculated molecular mass of 86 kDa contains a catalytic kinase domain and a putative regulatory domain with ankyrin-like repeats and a nuclear localization signal. Expression of DIK at the mRNA and protein level could be demonstrated in several cell lines. The dik gene is located on chromosome 21q22.3 and possesses 8 exons and 7 introns. DIK was synthesized in an in vitro transcription/translation system and expressed as recombinant protein in bacteria, HEK, COS-7, and baculovirus-infected insect cells. In the in vitro system and in cells, but not in bacteria, various post-translationally modified forms of DIK were produced. DIK was shown to exhibit protein kinase activity toward autophosphorylation and substrate phosphorylation. The interaction of PKCdelta(cat) and PKCdelta with DIK was confirmed by coimmunoprecipitation of the proteins from HEK cells transiently transfected with PKCdelta(cat) or PKCdelta and DIK expression constructs.
Stereospecific Synthesis of (2Z,4E,6E)-3,7,11-Trimethyl-2,4,6,10-dodecatetraene [trans(C10)-Allofarnesene] (1982)

Abstract The stereospecific synthesis of the title acyclic sesquiterpene, isolated from Perilla frutscens f. viridis Makino (Japanese name, Aojiso) by the palladium-catalyzed cross-coupling of 2-(4,8-dimethyl-1,3,7-nonatrienyl)-1,3,2-benzodioxaborole with (Z)-2-bromo-2-butene, is described. The benzodioxaborole was prepared by the hydroboration of 4,8-dimethyl-3,7-nonadien-1-yne, newly prepared via three steps from geranial, with 1,3,2-benzodioxaborole.