gebhart/patrepeval huggingface dataset:
Guanosine binding to the Tetrahymena ribozyme: thermodynamic coupling with oligonucleotide binding. (1993)

The L-21 Sca I ribozyme derived from the group I intron of Tetrahymena thermophila pre-rRNA catalyzes an endonuclease reaction analogous to the first step of self-splicing. Guanosine (G) is bound by the ribozyme, and its 3'-hydroxyl group acts as the nucleophile. Here, we provide evidence that Km for G in several single-turnover reactions is equal to the equilibrium dissociation constant for G. This evidence includes the observation that removal of the 2'-hydroxyl group at the cleavage site of the oligoribonucleotide substrate [from CCCUCUA to CCCUC(dU)A] decreases the rate of cleavage approximately 1000-fold but has no effect on either the Km for G (0.17 mM) or for guanosine 5'-monophosphate (pG) (0.09 mM). In the course of this study, it was observed that Km for G or pG was lower by a factor of 5 for reactions with the ribozyme-CCCUC(dU)A complex compared with the free ribozyme, indicating a modest amount of thermodynamic coupled binding of the two substrates. The decrease in the rate of oligonucleotide dissociation upon addition of saturating pG provides independent support for this coupling. Coupling is lost with a substrate that cannot make the normal tertiary interactions with the ribozyme, providing evidence that coupled binding requires docking of the substrate into the catalytic core. Surprisingly, the binding of product CCCUCU and G is slightly anticooperative, indicating that the cleaved pA is important for coupling with substrate. Coupled binding suggests a splicing model in which the intron binds G tightly to promote the first step of reaction, after which its binding is an order of magnitude weaker, thereby facilitating the second step.
Narrow‐band (TL‐01) ultraviolet B phototherapy for chronic plaque psoriasis: three times or five times weekly treatment? (1998)

Three and five times weekly narrow-band TL-01 (311-313 nm) ultraviolet (UV) B phototherapy regimens for chronic plaque psoriasis were compared in a randomized, observer-blinded, half-body, within-patient paired study. Twenty-one patients [13 men, eight women, age range 21-68 years, skin phototypes I (two patients), II (14) and III (five)] entered the study. Sixteen reached clearance or minimal residual activity (MRA) on both sides. Of the other five, three withdrew because they did not reach clearance or MRA on the 5x weekly side by a maximum of 30 treatments, one when he was satisfied with moderate improvement and one because of repeated failure to attend. Those who completed treatment reached clearance or MRA after a median of 35 days with 5x weekly treatment compared with 40 days with 3x weekly treatment (P = 0.007), but required a median of 23.5 compared with 17 UVB exposures (P = 0.001) and 94 minimal erythema dose multiples (MEDs) compared with 64 MEDs (P = 0.01). Fifteen (of 16) developed at least one episode of well-demarcated erythema during 5x weekly treatment compared with just three of 16 treated 3x weekly (P < 0.001). There was no significant difference between regimens in duration of remission. For this skin phototype I-III population, the more rapid clearance of psoriasis with 5x weekly phototherapy is not, for the majority of patients, sufficient to justify the extra exposures and higher UVB dose. We no longer use 5x weekly phototherapy for psoriasis.
Resistance of Transgenic Mice Expressing Human Group II Phospholipase A2 toEscherichia coliInfection (2000)

Group II phospholipase A2 (PLA2) is a newly recognized antibacterial acute-phase protein. Recently we observed that transgenic mice expressing group II PLA2 (PLA2(+) mice) were able to resist experimental Staphylococcus aureus infection by killing the bacteria, as indicated by improved survival and by the small numbers of live bacteria in their tissues (V. J. O. Laine, D. S. Grass, and T. J. Nevalainen, J. Immunol. 162:7402-7408, 1999). To establish the role of group II PLA2 in Escherichia coli infection, the host responses of PLA2(+) mice and their PLA2-deficient C57BL/6J littermates (PLA2(-) mice) were studied after intraperitoneal administration of E. coli. The levels of group II PLA2 in sera of PLA2(+) mice increased after the administration of E. coli, and the concentration of group II PLA2 correlated significantly with the catalytic activity of PLA2 in serum. PLA2(+) mice showed lower rates of mortality and less bacterial growth in peritoneal lavage fluid, blood, and spleen and liver tissues than PLA2(-) mice. Unlike the observations with staphylococcal infection, serum and peritoneal lavage fluid did not inhibit the growth of E. coli in vitro. The results indicate that expression of the group II PLA2 transgene improves the host defense of mice against E. coli infection.
Transparent Metal Nanowire Thin Films Prepared in Mesostructured Templates (2009)

The preparation of conductive and transparent gold/silver nanowire mesh films is reported. The nanowires formed after the reduction of the metal ions was triggered and a thin growth solution film was spread on a substrate. Metal reduction progressed within a template of a highly concentrated surfactant liquid crystalline mesostructure formed on the substrate during film drying to form ordered bundles of ultrathin nanowires. The films exhibited metallic conductivity over large areas, high transparency, and flexibility.
Sequences Within the Coding Regions of Clotting Factor VIII and CFTR Block Transcriptional Elongation (1995)

The clotting factor VIII (FVIII) and cystic fibrosis transmembrane conductance regulator (CFTR) cDNAs have dramatically reduced levels of expression compared to clotting factor IX (FIX) and other cDNAs (100 and 1,000-fold lower, respectively), when produced in cells by using an expression vector. Part of the inhibitory signal in the FVIII cDNA has been localized to a 1.2-kb inhibitory sequence (FVIII INS), which decreased steady-state RNA levels from a retroviral vector by 30- to 100-fold. An analysis of RNA degradation indicated that the FVIII INS vector RNA is relatively stable. Nuclear run-on experiments with the FVIII INS vector demonstrated a low signal for FVIII, in contrast to the high signal for a FIX vector. The low signal for FVIII INS was not due to a decrease in transcriptional initiation. Thus, FVIII expression is reduced through a block to transcriptional elongation, as has been found in c-myc and other genes. We show that the inhibitory effect of FVIII INS is orientation dependent with regard to the promoter. In addition, the inhibitory effect is position dependent, because expression of FVIII INS sequence increased when it was moved 1 kb further from the promoter in a retroviral vector. Similar results were observed by using a retroviral vector for expression of the CFTR cDNA. The CFTR retroviral vector produced 1,000-fold decreased steady-state RNA levels, compared to the parent vector. Nuclear run-on analysis with the CFTR vector revealed a block to transcriptional elongation within the CFTR cDNA. The presence of blocks to transcriptional elongation within the FVIII and CFTR cDNAs complicates efforts to produce high levels of these proteins for therapeutic purposes and to develop high-titer retroviral expression vectors for human gene therapy.
Epidermal growth factor upregulates intestinal electrolyte and nutrient transport (1991)

The role of epidermal growth factor (EGF) in the acute regulation of intestinal transport of electrolytes and glucose was examined. In vivo transport studies were performed in New Zealand White rabbits (500-900 g) using a single-pass perfusion technique. In vitro net fluxes were determined under short-circuited conditions in Ussing chambers. Kinetic parameters of glucose transport in the presence and absence of EGF were measured in brush-border membrane vesicles. In vivo studies showed that the addition of 60 ng/ml EGF to the perfusate resulted in increased absorption of H2O, Na+, Cl-, and glucose from the jejunum. In Ussing chambers, the presence of EGF caused an increase in jejunal net fluxes of glucose-stimulated Na+ and 3-O-methylglucose due to an increase in mucosal-to-serosal movements. Verapamil abolished the EGF effect. In the absence of glucose, net fluxes of Na+ and Cl- were enhanced in the presence of EGF due to a decrease in the serosal-to-mucosal movement of both ions. Verapamil had no effect on this decrease. The incubation of EGF with brush-border membrane vesicles had no effect on either the maximal flux or the Michaelis constant of glucose transport. These results indicate that EGF is capable of regulating absorption of electrolytes and nutrients from the small intestine and suggest a role for this peptide in the control of intestinal transport.
Depression and sleep: pathophysiology and treatment (2006)

This review examines the relationship between sleep and depression. Most depressive disorders are characterized by subjective sleep disturbances, and the regulation of sleep is intricately linked to the same mechanisms that are implicated in the pathophysiology of depression. After briefly reviewing the physiology and topography of normal sleep, the disturbances revealed in studies of sleep in depression using polysomnographic recordings and neuroimaging assessments are discussed. Next, treatment implications of the disturbances are reviewed at both clinical and neurobiologic levels. Most antidepressant medications suppress rapid eye movement (REM) sleep, although this effect is neither necessary nor sufficient for clinical efficacy. Effects on patients' difficulties initiating and maintaining sleep are more specific to particular types of antidepressants. Ideally, an effective antidepressant will result in normalization of disturbed sleep in concert with resolution of the depressive syndrome, although few interventions actually restore decreased slow-wave sleep. Antidepressants that block central histamine 1 and serotonin 2 tend to have stronger effects on sleep maintenance, but are also prone to elicit complaints of daytime sedation. Adjunctive treatment with sedative hypnotic medications--primarily potent, shorter-acting benzodiazepine and gamma-aminobutyric acid (GABA A)-selective compounds such as zolpidem--are often used to treat associated insomnia more rapidly. Cognitive behavioral therapy and other nonpharmacologic strategies are also helpful.
ChemInform Abstract: ORGANOBORANES PART 17, REACTION OF ORGANOMETALLICS WITH DIALKYLBORANE DERIVATIVES, THE SYNTHESIS OF MIXED ORGANOBORANES NOT AVAILABLE VIA HYDROBORATION (1974)

Abstract Das Boran (II) reagiert mit HCl in n‐Pentan zu den Boranchlorid (I) und mit Methanol (III) in THF zu dem Borinat (IV).
On determinants, matchings, and random algorithms. (1979)

Immobilization of WGA considerably enhances the binding as well as the uptake of PLGA-nanospheres by Caco-2 monolayers. For bioadhesion studies, the vertical setup is recommended instead of the horizontal setup.
A molecular dissection of the carboxyterminal tails of the major neurofilament subunits NF‐M and NF‐H (1991)

We have initiated a multidisciplinary project that aims to dissect and ultimately define the functions of the long and unusual C-terminal "tail" sequences of the two high molecular weight neurofilament subunits, NF-M and NF-H. A series of recombinant fusion proteins containing selected NF-M and NF-H tail sequences were constructed using appropriate cDNAs. These fusion proteins were used to further define the epitopes for a variety of widely used neurofilament antibodies, including NN18 and N52, which are now available commercially from several companies. We also measured the SDS-PAGE mobility of the fusion proteins and found that, like the native neurofilament tails, the fusion proteins ran considerably slower than predicted from their molecular weight. Since all fusion proteins produced so far exhibit this characteristic we conclude that all segments of the NF-M and NF-H tail share this unusual property. Finally we were able to produce novel and potentially useful polyclonal and monoclonal antibodies to selected segments of NF-M and NF-H sequence. These antibody studies showed that the extreme C-termini of NF-M and NF-H are immunologically absolutely distinct from one another and also indicate that the extreme C-terminus of NF-M is immunologically much more conserved than the analogous region of NF-H. These findings are in complete agreement with our conclusions derived from amino acid sequence analysis, and further underline the possible functional importance of the extreme C-terminus of NF-M. We also show that the unusual immunological properties of the bovine NF-M tail we have previously observed do not extend to the extreme C-terminal region, which appears immunologically no different from the analogous region of other NF-M molecules. The peculiarities of bovine NF-M could be explained by the presence of a KSP motif that resembles the NF-H KSP prototype.
Adapting motion capture data using weighted real-time inverse kinematics (2005)

In this article we present a technique that enhances an inverse kinematics (IK) solver such that when the results are applied to a computer character, we can generate a level of individualization tailored to both the character and the environment, e.g., a walking motion can become "stiffer" or can be turned into a limping motion. Since the technique is based on an IK solver, we also have the desirable effect of solving retargetting issues when mapping motion data between characters. As the individualization aspect of our technique is very tightly coupled with the inverse kinematics solver, we can achieve both the individualization and retargetting of characters in real time.
Oligodeoxynucleotide analogs with 5′‐linked anthraquinone (1989)

We report here the synthesis of novel 5'-linked oligodeoxynucleotides, both normal phosphodiester and phosphorothioate analogs, in which a covalently attached group at the 5'-terminus is an anthraquinone. These compounds represent a new class of antisense compounds in which the base sequence of the oligodeoxynucleotide serves to deliver a nuclease-resistant reactive drug-like molecule to a cellular target nucleic acid (mRNA or DNA).
REDOX REGULATION: A Broadening Horizon (2005)

Initially discovered in the context of photosynthesis, regulation by change in the redox state of thiol groups (S-S <--> 2SH) is now known to occur throughout biology. Several systems, each linking a hydrogen donor to an intermediary disulfide protein, act to effect changes that alter the activity of target proteins: the ferredoxin/thioredoxin system, comprised of reduced ferredoxin, a thioredoxin, and the enzyme, ferredoxin-thioredoxin reductase; the NADP/thioredoxin system, including NADPH, a thioredoxin, and NADP-thioredoxin reductase; and the glutathione/glutaredoxin system, composed of reduced glutathione and a glutaredoxin. A related disulfide protein, protein disulfide isomerase (PDI) acts in protein assembly. Regulation linked to plastoquinone and signaling induced by reactive oxygen species (ROS) and other agents are also being actively investigated. Progress made on these systems has linked redox to the regulation of an increasing number of processes not only in plants, but in other types of organisms as well. Research in areas currently under exploration promises to provide a fuller understanding of the role redox plays in cellular processes, and to further the application of this knowledge to technology and medicine.
Mechanisms of Soluble β-Amyloid Impairment of Endothelial Function (2004)

Alzheimer's disease (AD) has been recently associated with vascular risk factors. beta-amyloid peptides (AbetaP), the main component of senile plaques typical of AD, circulate in soluble globular form in bloodstream. Interestingly, AbetaP is able to induce endothelial dysfunction, and this effect may represent the link between vascular and neuronal pathophysiological factors involved in AD. We aimed to clarify the molecular mechanisms underlying globular AbetaP-induced vascular toxicity. Using several methodological approaches, we have observed that in vascular tissues globular AbetaP is unable to induce oxidative stress, one of the mechanisms hypothesized involved in beta-amyloid toxicity. More important, we have demonstrated that globular AbetaP is able to localize on vascular endothelium, where it inhibits eNOS enzymatic activity. In particular, AbetaP enhances eNOS phosphorylation on threonine 495 and serine 116 and reduces acetylcholine-induced phosphorylation on serine 1177. Such an effect depends on a PKC signaling pathway, as suggested by its phosphorylation on serine 660. In fact, selective inhibition of the calcium-dependent group of PKC is able to rescue beta-amyloid-induced alteration of eNOS phosphorylation, NO production, and endothelial vasorelaxation. The activation of these Ca(2+)-dependent pathways is probably due to the ability of AbetaP to evoke Ca(2+) leakage from inositol 1,4,5-triphosphate receptors on endoplasmic reticulum. Our data demonstrate that globular AbetaP-induced endothelial NO dysfunction can be attributed to an alteration of intracellular Ca(2+) homeostasis, which could lead to the activation of calcium-dependent group of PKC with a consequent change of the eNOS phosphorylation pattern. These mechanisms could contribute to shed further light on the toxic effect of beta-amyloid in vascular tissues.
Specific detection of carcinoembryonic antigen-expressing tumor cells in bone marrow aspirates by polymerase chain reaction. (1994)

Since approximately 30% of the colorectal carcinoma patients that score negative in immunocytology staining of bone marrow samples have been reported to relapse, earlier diagnosis of the presence of malignant cells is needed. Our result that samples scoring positive in the described CEA-specific PCR test remained negative by two immunostaining methods suggests a higher sensitivity. We conclude that PCR amplification of CEA mRNA may lead to an earlier diagnosis of micrometastatic bone disease in patients with CEA-expressing carcinomas.
Optical Multibead Arrays for Simple and Complex Odor Discrimination (2001)

A fiber optic bead-based sensor array platform has been employed to discriminate between six different odors and air carrier gas. Six different bead sensor types, with over 250 replicates of each, were monitored before, during, and after odor exposure to produce time-dependent fluorescence response patterns that were unique for each sensor-analyte combination. A total of 2,683 sensors were analyzed with respect to changes in their fluorescence, and signals from identical sensor beads were averaged to improve signal-to-noise ratios. Analyte classification rates of 100% were achieved for three complex (coffee bean) odors and three pure (simple) odors (toluene, acetone, 1,3-dinitrotoluene) measured at their highest relative concentrations. When lower odor concentrations were employed, the system exhibited better than 85% classification rates for analyte discrimination. Sensor response repeatability to these odor stimuli has also been quantified statistically, which is vital in defining the detection limit of the overall system. These results demonstrate, for the first time, the utility of our bead array technology for discriminating between different odor types at various dilution levels.
Implications of Leukocytosis and Fever at Conclusion of Antibiotic Therapy for Intra-abdominal Sepsis (1982)

Outcomes of 65 patients after operation who had exhibited a clinical response to treatment for intra-abdominal sepsis were compared based on the presence or absence of leukocytosis and fever at the conclusion of antibiotic therapy. Fifty-one patients were afebrile when antibiotics were stopped. Intra-abdominal infection developed in 7 of 21 (33%) who had a persistent leukocytosis, but no intra-abdominal infections developed after operation in 30 patients who had normal WBC counts at the end of antibiotic treatment (p less than 0.005). Nosocomial infections developed in 6 (12%) of the 51 patients, and there was no difference in the incidence between patients with or without leukocytosis. Eleven of 14 (79%) patients who were still febrile when antibiotics were discontinued developed infections after operation. Nosocomial infections occurred in three (21%) and intra-abdominal infections in eight (57%). Of the 15 patients who developed intra-abdominal infection after operation, only four responded to appropriate antibiotic treatment without requiring further surgery. The other patients required surgical management for definitive control within two months of the initial operation. In conclusion, patients at risk of developing infection after operation after exhibiting a clinical response to treatment of intra-abdominal sepsis are those who are afebrile with a persistent leukocytosis or who are still febrile when antibiotics are stopped.
VOR/DME system improvements (1970)

The VOR/DME/TACAN system of short distance navigation in the United States has provided service over the past decade to all civil and military air traffic. Improvements have been incorporated which have been in the nature of refinements, assuring adequate performance for all current aircraft needs. Recent analyses indicate that continued use of VOR/DME to meet increased civil air traffic demands through 1980 will require that the system demonstrate a capability for greater accuracy for terminal area operations, an improvement in signal quality to support area navigation, and the potential for increased traffic handling capacity of the DME component. Development activities now underway indicate that such improvements are feasible. Evaluation results and new techniques are described in support of this conclusion.
Increasing Prevalence of Multidrug-ResistantStreptococcus pneumoniaein the United States (2000)

Multidrug-resistant pneumococci are common and are increasing. Because a limited number of serotypes account for most infections with drug-resistant strains, the new conjugate vaccines offer protection against most drug-resistant strains of S. pneumoniae.
Different Mechanisms Confer Gradual Control and Memory at Nutrient- and Stress-Regulated Genes in Yeast (2015)

Cells respond to environmental stimuli by fine-tuned regulation of gene expression. Here we investigated the dose-dependent modulation of gene expression at high temporal resolution in response to nutrient and stress signals in yeast. The GAL1 activity in cell populations is modulated in a well-defined range of galactose concentrations, correlating with a dynamic change of histone remodeling and RNA polymerase II (RNAPII) association. This behavior is the result of a heterogeneous induction delay caused by decreasing inducer concentrations across the population. Chromatin remodeling appears to be the basis for the dynamic GAL1 expression, because mutants with impaired histone dynamics show severely truncated dose-response profiles. In contrast, the GRE2 promoter operates like a rapid off/on switch in response to increasing osmotic stress, with almost constant expression rates and exclusively temporal regulation of histone remodeling and RNAPII occupancy. The Gal3 inducer and the Hog1 mitogen-activated protein (MAP) kinase seem to determine the different dose-response strategies at the two promoters. Accordingly, GAL1 becomes highly sensitive and dose independent if previously stimulated because of residual Gal3 levels, whereas GRE2 expression diminishes upon repeated stimulation due to acquired stress resistance. Our analysis reveals important differences in the way dynamic signals create dose-sensitive gene expression outputs.