gebhart/patrepeval huggingface dataset:
hSK4, a member of a novel subfamily of calcium-activated potassium channels (1997)

The gene for hSK4, a novel human small conductance calcium-activated potassium channel, or SK channel, has been identified and expressed in Chinese hamster ovary cells. In physiological saline hSK4 generates a conductance of approximately 12 pS, a value in close agreement with that of other cloned SK channels. Like other members of this family, the polypeptide encoded by hSK4 contains a previously unnoted leucine zipper-like domain in its C terminus of unknown function. hSK4 appears unique, however, in its very high affinity for Ca2+ (EC50 of 95 nM) and its predominant expression in nonexcitable tissues of adult animals. Together with the relatively low homology of hSK4 to other SK channel polypeptides (approximately 40% identical), these data suggest that hSK4 belongs to a novel subfamily of SK channels.
Syntheses of substituted 1,4-naphthoquinones by Diels–Alder addition of methoxycyclohexadienes to substituted 1,4-benzoquinones (1976)

Additions of 1-methoxycyclohexa-1,3-diene to 2-methoxy-3-methyl-1,4-benzoquinone and to chloro-1,4-benzoquinone give Diels–Alder adducts which are coverted in high yield into substituted juglone methyl ethers. Reactions between 1-methoxy-3-methylcyclohexa-1,3-diene and methoxy-1,4-benzoquinone follow a similar course. Addition of 1,3-dimethoxycyclohexa-1,3-diene to chloro- or methoxy-benzoquinone affords a dihydrodibenzofuran rather than a Diels–Alder adduct.
Biofilms, Infection, and Antimicrobial Therapy (2005)

SECTION I Biofilms: Background, Significance, and Roles of Catheters and Indwelling Devices Microbial Biofilms Xiuping Jiang and John L. Pace Economic Impact of Biofilms on Treatment Costs John G. Thomas, Isaiah Litton, and Harald Rinde Biofilm-Related Indwelling Medical Device Infections Matthew K. Schinabeck and Mahmoud A. Ghannoum Medical Device Composition and Biological Secretion Influences on Biofilm Formation Sean P. Gorman and David S. Jones SECTION II Biofilm-Forming Pathogens Role of Biofilms in Infections Caused by Escherichia coli Gregory Jubelin, Corinne Dorel, and Philippe Lejeune Staphylococcus aureus Biofilms Julie M. Higashi and Paul M. Sullam Coagulase-Negative Staphylococci Dietrich Mack, Matthias A. Horstkotte, Holger Rohde, and Johannes K.-M. Knobloch Pseudomonas aeruginosa Biofilm Infections in Cystic Fibrosis Andrea Smiley and Daniel J. Hassett Candida Stephen Hawser and Khalid Islam SECTION III Emerging Issues, Assays, and Models Current Perspectives on the Regulation of the ica Operon and Biofilm Formation in Staphylococcus epidermidis Paul D. Fey and Luke D. Handke Cell-to-Cell Communication in Bacteria Kenneth D. Tucker and Luciano Passador Persisters: Specialized Cells Responsible for Biofilm Tolerance to Antimicrobial Agents Kim Lewis, Amy L. Spoering, Niilo Kaldalu, Iris Keren, and Devang Shah Minimal Biofilm Eradication Concentration (MBEC) Assay: Susceptibility Testing for Biofilms Howard Ceri, Merle E. Olson, Douglas W. Morck, and Douglas G. Storey Environmental Cues Regulate Virulence and Biofilm Formation John L. Pace and Steven M. Frey In Vivo Models for the Study of Biomaterial-Associated Infection by Biofilm-Forming Staphylococci Luke D. Handke and Mark E. Rupp Host Response to Biofilms Susan Meier-Davis SECTION IV Overview of Antiinfective Agents and Clinical Therapy Pharmacodynamics and the Treatment of IMD-Related Infections Roger Finch and Sarah Gander Protein Synthesis Inhibitors, Fluoroquinolones, and Rifampin for Biofilm Infections Steven L. Barriere *-Lactams for the Treatment of Biofilm-Associated Infections Ingrid L. Dodge, Karen Joy Shaw, and Karen Bush Glycopeptide Antibacterials and the Treatment of Biofilm-Related Infections John L. Pace, Roasaire Verna, and Jan Verhoef Antibiotic Resistance in Biofilms Nafsika H. Georgopapadakou Treatment Protocols for Infections of Vascular Catheters Russell E. Lewis and Issam I. Raad Treatment Protocols for Bacterial Endocarditis and Infection of Electrophysiologic Cardiac Devices Martin E. Stryjewski and G. Ralph Corey Treatment Protocol of Infections of Orthopedic Devices Vera Antonios, Elie Berbari, and Douglas Osmon Index ...
Chromosomal location and expression of the genes coding for Ku p70 and p80 in human cell lines and normal tissues (1994)

Ku protein is a relatively abundant DNA-binding nuclear protein complex composed of two polypeptide subunits, p70 and p80. Ku has been recently identified as the regulatory component of the DNA-dependent protein kinase that phosphorylates RNA polymerase II. To further characterize in vivo regulation of Ku protein, we studied the expression of the transcripts coding for the Ku p70 and p80 subunits in different human cell lines and normal tissues by Northern blot hybridization, using specific cDNA probes. The expression level of both genes was approximately 10-fold higher in established cell lines than in normal tissues. However, mRNA expression levels in permanent cell lines correlated more strongly with their proliferative state than with their level of malignant transformation. In purified T lymphocytes induced to proliferate by the combined action of monoclonal antibodies directed against the CD2 and CD28 adhesion molecules, Ku p70 and p80 mRNA steady-state levels increased as soon as 6 h after activation and lasted at least 72 h. The human genes coding for the Ku p70 and p80 subunits were localized by cytogenetic mapping, using fluorescence in situ hybridization, to 22q13 and 2q33-->q35, respectively.
Visualization of lipoprotein receptors by ligand blotting. (1983)

This paper describes the visualization of the low density lipoprotein (LDL) receptor by ligand blotting. Preparations of detergent-solubilized membranes are subjected to one- or two-dimensional sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, after which the proteins are transferred to nitrocellulose paper. The paper is incubated with native LDL and then with an 125I-labeled antibody against LDL, and the bound antibody is visualized by autoradiography. The success of LDL blotting depends on the omission of sulfhydryl reducing agents from the electrophoresis system. Intrachain disulfide bonds allow the receptor to retain its binding activity even after electrophoresis in the presence of SDS. In identifying LDL receptors, the ligand blotting technique is as sensitive as immunoblotting with a monoclonal antibody against the LDL receptor; it can therefore be used to identify receptors when no anti-receptor antibodies are available. We use this technique to show that the LDL receptor of the rabbit adrenal gland has the same molecular weight as the LDL receptor of the bovine adrenal cortex and human fibroblasts. The ligand blotting technique may be generally applicable for visualization of other plasma membrane receptors after SDS-gel electrophoresis.
Future Cyclotrons (1972)

This paper reviews future trends in cyclotron design, first briefly from the point‐of‐view of cyclotrons now in construction and second from the point‐of‐view of design features. The topics covered include the choice of a conventional or separated‐sector magnet, the use of dees or cavities for acceleration, possible flat‐topping of the rf wave, the impact of new technologies on design and operation, and extensions of the cyclotron concept to higher energies.
The NanA Neuraminidase of Streptococcus pneumoniae Is Involved in Biofilm Formation (2009)

Streptococcus pneumoniae remains a major cause of bacteremia, pneumonia, and otitis media despite vaccines and effective antibiotics. The neuraminidase of S. pneumoniae, which catalyzes the release of terminal sialic acid residues from glycoconjugates, is involved in host colonization in animal models of infection and may provide a novel target for preventing pneumococcal infection. We demonstrate that the S. pneumoniae neuraminidase (NanA) cleaves sialic acid and show that it is involved in biofilm formation, suggesting an additional role in pathogenesis, and that it shares this property with the neuraminidase of Pseudomonas aeruginosa even though we show that the two enzymes are phylogenetically divergent. Using an in vitro model of biofilm formation incorporating human airway epithelial cells, we demonstrate that small-molecule inhibitors of NanA block biofilm formation and may provide a novel target for preventative therapy. This work highlights the role played by the neuraminidase in pathogenesis and represents an important step in drug development for prevention of colonization of the respiratory tract by this important pathogen.
Pharmacokinetics of two lorazepam formulations, oral and sublingual, after multiple doses (1983)

The pharmacokinetic profiles of a sublingual and a conventional oral lorazepam tablet formulation were established following chronic administration to twelve healthy male volunteers. Fitting a multi-dose equation based on a one-compartment model to the observed data, the average elimination half-lives for the sublingual and oral doses are estimated to be 11 and 8 h, respectively, while the corresponding absorption half-lives are 15 and 55 min; this confirms earlier reports that the sublingual formulation is more rapidly absorbed. The observed time to steady-state for both formulations was approximately 3 days, which agrees well with that predicted from previous single dosing studies. Although the sublingual formulation yields a higher average steady-state minimum plasma concentration than the oral formulation (41.6 versus 38.1 ng ml-1), the maximum lorazepam concentration achieved during steady state was approximately 83 ng ml-1 for both formulations. The average steady-state plasma concentration is estimated to be 63 ng ml-1, independent of the formulation used.
A hierarchical decision module based on multiple neural networks (2002)

A new approach to source localization in the human brain, an important problem of neuroscience, is presented. A multiple neural network-based hierarchical decision-making system is developed. Each network is assigned to an independent model, and the output is evaluated in the higher level of the decision-making system. Utility functions are designed in the framework of decision-making. The network with the highest utility value is selected as the best network, representing the best model in EEG based inverse mapping. Simulation results show that the multiple neural network based decision-making system has successfully produced preferred decisions in source localization.
Treatment of Cutaneous T-Cell Lymphoma by Extracorporeal Photochemotherapy (1987)

Systemically disseminated cutaneous T-cell lymphoma is generally resistant to chemotherapy and radiotherapy. We tested a treatment involving the extracorporeal photoactivation of biologically inert methoxsalen (8-methoxypsoralen) by ultraviolet A energy to a form that covalently cross-links DNA. After oral administration of methoxsalen, a lymphocyte-enriched blood fraction was exposed to ultraviolet A (1 to 2 J per square centimeter) and then returned to the patient. The combination of ultraviolet A and methoxsalen caused an 88 +/- 5 percent loss of viability of target lymphocytes, whereas the drug alone was inactive. Twenty-seven of 37 patients with otherwise resistant cutaneous T-cell lymphoma responded to the treatment, with an average 64 percent decrease in cutaneous involvement after 22 +/- 10 weeks (mean +/- SD). The responding group included 8 of 10 patients with lymph-node involvement, 24 of 29 with exfoliative erythroderma, and 20 of 28 whose disease was resistant to standard chemotherapy. Side effects that often occur with standard chemotherapy, such as bone marrow suppression, gastrointestinal erosions, and hair loss, did not occur. Although the mechanism of the beneficial effect is uncertain, an immune reaction to the infused damaged cells may have restricted the activity of the abnormal T cells. This preliminary study suggests that extracorporeal photochemotherapy is a promising treatment for widespread cutaneous T-cell lymphoma.
Respiratory tract disease and mucosal colonization by Pasteurella haemolytica in transported cattle (1996)

Vaccination can reduce the frequency of colonization of the upper respiratory tract by PH.
One-Pot Asymmetric Synthesis of Either Diastereomer of tert-Butanesulfinyl-protected Amines from Ketones (2006)

A one-pot method for the asymmetric synthesis of tert-butanesulfinyl-protected amines is described. Condensation of aryl alkyl and dialkyl ketones with tert-butanesulfinamide followed by in situ reduction with the appropriate reagent provides either diastereomer of the sulfinamide products in good yields and with diastereomeric ratios of up to 99:1.
Neuropathologic Outcome of Mild Cognitive Impairment Following Progression to Clinical Dementia (2006)

The neuropathologic outcome of amnestic MCI following progression to dementia is heterogeneous, and it includes AD at a high frequency. Complex neuropathologic findings including 2 or more distinct pathologic entities contributing to dementia may be common in community-based cohorts. Neither demographic variables nor cognitive measures had predictive value in determining which patients diagnosed with MCI will develop the neuropathologic features of AD.
Can Heparin Immobilized Surfaces Maintain Nonthrombogenic Activity During In Vivo Long-Term Implantation? (1996)

The authors previously demonstrated that heparin immobilized surfaces showed excellent nonthrombogenic properties for extracorporeal membrane oxygenation experiments as long as 168 hr. The characteristics of the heparin immobilized surfaces include high heparin bioactivity and prevention of platelet adhesion and complement activation. However, it is not known whether the heparin immobilized surfaces would be effective for in vivo long-term implantation. Heparin bioactivity may be lost because of complete degradation or blocking of binding sites on heparin by adsorbed proteins. This study attempted to elucidate the in vivo long-term fate of heparin immobilized surfaces. The blood contacting surfaces of the ventricular assist device (VAD) made from polyurethane was modified with heparin immobilization and evaluated in a long-term sheep left VAD (LVAD) model for as long as 3 months. After removal of the VAD, heparin bioactivity was measured by Factor Xa assay. The blood contacting surfaces were analyzed with a scanning electron microscope, and the adsorbed proteins on the surfaces of the diaphragm were analyzed by SDS-PAGE and Western blotting. The thickness of adsorbed proteins on the surfaces also was measured by a confocal laser microscope. For the control ventricular assist devices, thrombus formation was observed within 1 month, whereas heparin immobilized VADs were able to operate thrombus free for periods as long as 3 months. The control surfaces demonstrated a thick adsorbed protein layer on thin surfaces, whereas heparin immobilized surfaces maintained thinner adsorbed proteins on thin surfaces. Anti Factor Xa activity of the heparinized surfaces disappeared after 15 days, but the surfaces remained nonthrombogenic even after heparin bioactivity was completely lost. The protein composition analyzed by SDS-PAGE showed an albumin dominant pattern on the heparinized surfaces. The band of 110 kD corresponding to C3b was detected only on the control surfaces, which possibly activated complement, and subsequently activated platelets and coagulation. Immunoblot showed degradation products of fibronectin and vitronectin on the control surfaces, which probably were promoted by surface generated protease, whereas the heparinized surfaces showed minimal degradation throughout the experimental periods. These results suggest that the heparin moiety has an ability to control adsorbed proteins, thereby inhibiting thrombus formation during in vivo long-term implantation.
Single-well genotyping of diallelic sequence variations by a two-color ELISA-based oligonucleotide ligation assay (1996)

Single nucleotide substitutions and unique insertions/deletions are the most common form of DNA sequence variation and disease-causing mutation in the human genome. Because of the biological and medical importance of these variations, a wide array of methods have been developed for their typing. We have applied an approach that combines the amplification of polymorphic regions by the polymerase chain reaction (PCR) with a system for typing diallelic variants using an oligonucleotide ligation assay (OLA). In this report, we describe a significant advance in this technology that permits the typing of two alleles in a single microtiter well. By marking each of the allele-specific primers with a unique hapten, i.e. digoxigenin and fluorescein, each OLA reaction can be detected by using hapten specific antibodies that are labeled with different enzyme reporters, alkaline phosphatase or horseradish peroxidase. This system permits the detection of the two alleles using a high throughput format that leads to the production of two different colors. We demonstrate the specificity, sensitivity and ease of data interpretation with this system. Furthermore, we show that multiplex PCR/OLA not only increases the throughput of DNA typing but also increases its accuracy in typing diallelic sequence variations using an approach that can be broadly applied for human genome analysis (in evaluating genotype/phenotype links), in typing infectious agents and in forensic analysis.
Chemical mechanism of the endogenous argininosuccinate lyase activity of duck lens δ2-crystallin (1998)

The endogenous argininosuccinate lyase activity of duck delta2-crystallin was specifically inactivated by the histidine-specific reagent, diethyl pyrocarbonate. The protein was protected by l-citrulline or l-arginine from the diethyl pyrocarbonate inactivation. To characterize further the chemical mechanism of the delta2-crystallin-catalysed reaction, deuterium-labelled argininosuccinate was enzymically synthesized from fumarate and l-arginine with delta2-crystallin in 2H2O. The argininosuccinate synthesized contained about 19% of the anhydride form; however, the deuterium was clearly demonstrated to be incorporated enantioselectively. Only the pro-HR atom at C-9 of the succinate moiety was labelled in the [2H]argininosuccinate-9-d synthesized, which indicates an anti-elimination mechanism for the endogenous argininosuccinate lyase activity of delta2-crystallin. The enzymic activity of duck lens delta2-crystallin in the pH range 5.5-8.5 was investigated using both protium- and deuterium-labelled argininosuccinate as the substrate. From the logkcat versus pH plot, two molecular pKa values of 6.18+/-0.02 and 8.75+/-0.03 were detected in the delta2-crystallin-argininosuccinate binary complex. The former must be dehydronated and the latter hydronated to achieve an optimum reaction rate. The logkcat/Km versus pH plot suggested two molecular pKa values of 5.96+/-0.09 and 8.29+/-0.10 for the free delta2-crystallin to be involved in the substrate binding. Small kinetic isotope effects of 1.17+/-0.02 and 1.05+/-0.09 were found for kcat and kcat/Km respectively. Combining results from labelling and kinetic analysis indicates that the endogenous argininosuccinate lyase activity of duck delta2-crystallin is compatible with a stepwise E1cB mechanism, the rate-limiting step probably at the C-N bond-cleavage step.
Discourse-Based Approach to Involvement of Background Knowledge for Question Answering (2019)

We introduce a concept of a virtual discourse tree to improve question answering (Q/A) recall for complex, multisentence questions. Augmenting the discourse tree of an answer with tree fragments obtained from text corpora playing the role of ontology, we obtain on the fly a canonical discourse representation of this answer that is independent of the thought structure of a given author. This mechanism is critical for finding an answer that is not only relevant in terms of questions entities but also in terms of interrelations between these entities in an answer and its style. We evaluate the Q/A system enabled with virtual discourse trees and observe a substantial increase of performance answering complex questions such as Yahoo! Answers and www.2carpros.com.
Group I permuted intron-exon (PIE) sequences self-splice to produce circular exons (1992)

Circularly permuted group I intron precursor RNAs, containing end-to-end fused exons which interrupt half-intron sequences, were generated and tested for self-splicing activity. An autocatalytic RNA can form when the primary order of essential intron sequence elements, splice sites, and exons are permuted in this manner. Covalent attachment of guanosine to the 5' half-intron product, and accurate exon ligation indicated that the mechanism and specificity of splicing were not altered. However, because the exons were fused and the order of the splice sites reversed, splicing released the fused-exon as a circle. With this arrangement of splice sites, circular exon production was a prediction of the group I splicing mechanism. Circular RNAs have properties that would make them attractive for certain studies of RNA structure and function. Reversal of splice site sequences in a context that allows splicing, such as those generated by circularly permuted group I introns, could be used to generate short defined sequences of circular RNA in vitro and perhaps in vivo.
Metabotropic glutamate receptors in the thalamocortical network: Strategic targets for the treatment of absence epilepsy (2011)

Metabotropic glutamate (mGlu) receptors are positioned at synapses of the thalamocortical network that underlie the development of spike-and-wave discharges (SWDs) associated with absence epilepsy. The modulatory role of individual mGlu receptor subtypes on excitatory and inhibitory synaptic transmission in the cortico-thalamo-cortical circuitry makes subtype-selective mGlu receptor ligands potential candidates as novel antiabsence drugs. Some of these compounds are under clinical development for the treatment of numerous neurologic and psychiatric disorders, and might be soon available for clinical studies in patients with absence seizures refractory to conventional medications. Herein we review the growing evidence that links mGlu receptors to the pathophysiology of pathologic SWDs moving from the anatomic localization and function of distinct mGlu receptor subtypes in the cortico-thalamo-cortical network to in vivo studies in mouse and rat models of absence epilepsy.
Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin (2004)

One Japanese pedigree of familial essential thrombocythemia (FET) inherited in an autosomal-dominant manner is presented. A unique point mutation, serine 505 to asparagine 505 (Ser505Asn), was identified in the transmembrane domain of the c-MPL gene in all of the 8 members with thrombocythemia, but in none of the other 8 unaffected members in this FET family. The Ba/F3 cells expressing the mutant Asn505 acquired interleukin 3 (IL-3)-independent survival capacity, whereas those expressing wild-type Ser505 did not. The autonomous phosphorylation of Mek1/2 and Stat5b was observed in the mutant Ba/F3 cells in the absence of IL-3. The former was also found in platelets derived from the affected individual in the absence of thrombopoietin. These results show that the Asn505 is an activating mutation with respect to the intracellular signaling and survival of the cells. This is the first report of FET deriving from a dominant-positive activating mutation of the c-MPL gene.
Entrainment of Free-Running Circadian Rhythms by Melatonin in Blind People (2000)

Administration of melatonin can entrain circadian rhythms in most blind people who have free-running rhythms.