gebhart/patrepeval huggingface dataset:
Nuclease-resistant chimeric ribozymes containing deoxyribonucleotides and phosphorothioate linkages (1993)

Hammerhead ribozymes are considered to be potential therapeutic agents for HIV virus because of their site-specific RNA cleavage activities. In order to elucidate structure--function relationship and also to hopefully endow ribozymes with resistance to ribonucleases, we firstly synthesized chimeric DNA/RNA ribozymes in which deoxyribonucleotides were substituted for ribonucleotides at noncatalytic residues (stems I, II, and III). Kinetic analysis revealed that (i) DNA in the hybridizing arms (stems I and III) enhanced the chemical cleavage step. (ii) stem II and its loop do not affect its enzymatic activity. Secondly, we introduced deoxyribonucleotides with phosphorothioate linkages to the same regions (stems I, II, and III) in order to test whether such thio-linkages further improve their resistance to nucleases. Kinetic measurements revealed that this chimeric thio-DNA/RNA ribozyme had seven-fold higher cleavage activity (kcat = 27 min-1) than that of the all-RNA ribozyme. In terms of stability in serum, DNA-armed ribozymes gained about 10-fold higher stability in human serum but no increase in stability was recognized in bovine serum, probably because the latter serum mainly contained endoribonucleases that attacked unmodified catalytic-loop regions of these ribozymes. Thirdly, in order to protect them from endoribonucleases, three additional modifications were made at positions U7, U4 and C3 within the internal catalytic-loop region, that succeeded in gaining more than a hundred times greater resistance to nucleases in both serums. More importantly, these catalytic-loop modified ribozymes had the comparable cleavage activity (kcat) to the wild-type ribozyme. Since these chimeric thio-DNA/RNA ribozymes are more resistant to attack by both exonucleases and endoribonucleases than the wild-type all-RNA ribozymes in vivo and since their cleavage activities are not sacrificed, they appear to be better candidates than the wild type for antiviral therapeutic agents.
Synthesis and in Vitro Activity of 3β-Substituted-3α-hydroxypregnan-20-ones:  Allosteric Modulators of the GABAA Receptor (1997)

Two naturally occurring metabolites of progesterone, 3 alpha-hydroxy-5 alpha- and 5 beta-pregnan-20-one (1 and 2), are potent allosteric modulators of the GABAA receptor. Their therapeutic potential as anxiolytics, anticonvulsants, and sedative/hypnotics is limited by rapid metabolism. To avoid these shortcomings, a series of 3 beta-substituted derivatives of 1 and 2 was prepared. Small lipophilic groups generally maintain potency in both the 5 alpha- and 5 beta-series as determined by inhibition of [35S]TBPS binding. In the 5 alpha-series, 3 beta-ethyl, -propyl, -trifluoromethyl and -(benzyloxy)methyl, as well as substituents of the form 3 beta-XCH2, where X is Cl, Br, or I or contains unsaturation, show limited efficacy in inhibiting [35S]TBPS binding. In the 5 beta-series, the unsubstituted parent 2 is a two-component inhibitor, whereas all of the 3 beta-substituted derivatives of 2 inhibit TBPS via a single class of binding sites. In addition, all of the 3-substituted 5 beta-sterols tested are full inhibitors of [35S]TBPS binding. Electrophysiological measurements using alpha 1 beta 2 gamma 2L receptors expressed in oocytes show that 3 beta-methyl- and 3 beta-(azidomethyl)-3 alpha-hydroxy-5 alpha-pregnan-20-one (6 and 22, respectively) are potent full efficacy modulators and that 3 alpha-hydroxy-3 beta-(trifluoromethyl)-5 alpha-pregnan -20-one (24) is a low-efficacy modulator, confirming the results obtained from [35S]TBPS binding. These results indicate that modification of the 3 beta-position in 1 and 2 maintains activity at the neuroactive steroid site on the GABAA receptor. In animal studies, compound 6 (CCD 1042) is an orally active anticonvulsant, while the naturally occurring progesterone metabolites 1 and 2 are inactive when administered orally, suggesting that 3 beta-substitution slows metabolism of the 3-hydroxyl, resulting in orally bioavailable steroid modulators of the GABAA receptor.
Substrate influences on CIS device performance (2002)

It has been reported that the substrate plays an active role in copper indium diselenide (CIS) devices. The physical properties of the substrate, i.e., thermal expansion coefficient, chemical composition, strain point, surface quality and cleanliness may all play a role in device efficiency and process reproducibility. For example, sodium is known to influence the conductivity of CIS, and that soda lime glass (SLG) introduces sodium into the CIS. In the experiments reported here, the sodium level in the CIS was varied by (a) changing the substrate composition and (b) the use of SiO/sub x/N/sub y/ and SiN/sub x/ barrier layers. Solar cells were fabricated on the candidate substrate and barrier layer combinations. V/sub oc/ was observed to drop with the addition of barrier layers to sodium containing glasses. The films were also analyzed for sodium by SIMS. The cell performance and SIMS analysis are presented and their significance is discussed.
Dinitrogen Chemistry from Trigonally Coordinated Iron and Cobalt Platforms (2003)

This report establishes that trigonally coordinated "[PhBPiPr3]M" platforms (M = Fe, Co) will support both pi-acidic (N2) and pi-basic (NR) ligands at a fourth binding site. The N2 complexes of iron that are described are the first thoroughly characterized examples to exhibit a 4-coordinate geometry. Methylation of monomeric {Fe0(N2)-} and {Co0(N2)-} species successfully derivatizes the beta-N atom of the coordinated N2 ligand and affords the diazenido products {FeII(N2Me)} and {CoII(N2Me)}, respectively. One-electron oxidation of the mononuclear M0(N2)- species produces dinuclear and synthetically versatile MI(N2)MI complexes. These latter species provide clean access to the chemistry of the "[PhBPiPr3]MI" subunit. For example, addition of RN3 to MI(N2)MI results in oxidative nitrene transfer to generate [PhBPiPr3]MNR with concomitant N2 release.
64.4: High‐Performance OLEDs Based on a New Class of Ir Complexes Bearing Pyrazine Structures in Their Ligands (2007)

Abstract We have developed novel Ir complexes having pyrazine structures in their ligands. The OLEDs based on these complexes showed unique properties and high performance. In particular, the red OLED achieved an extremely high efficiency of 30 cd/A with CIE color coordinates of (x, y) = (0.65, 0.35), and the luminance half‐decay time was estimated to be about 100,000 hrs at an initial luminance of 1,000 cd/m 2 .
CYCLOOXYGENASE-2-MEDIATED REGULATION OF KUPFFER CELL INTERLEUKIN-6 PRODUCTION FOLLOWING TRAUMA-HEMORRHAGE AND SUBSEQUENT SEPSIS (2001)

Studies indicate that trauma-hemorrhage results in activation of Kupffer cells to release inflammatory mediators and it leads to immunosuppression and increased susceptibility to subsequent sepsis. The cyclooxygenase (COX) product prostaglandin (PG) E2 appears to be central to this process, however, non-selective inhibition of COX activity with non-steroidal anti-inflammatory agents that block both the constitutive (COX-1) and inducible (COX-2) isoforms of cyclooxygenase has not yielded promising results in trauma patients. Nonetheless, it remains unknown whether selective inhibition of COX-2 activity has any salutary effect following trauma-hemorrhage and subsequent induction of sepsis. To study this, male C3H/HeN mice were subjected to laparotomy (i.e., soft-tissue trauma) and hemorrhagic shock (35 +/- 5 mmHg for 90 min, then resuscitated) or to sham operation. Twenty-four hours later, the mice were subjected to sepsis by cecal ligation and puncture (CLP) or to sham CLP. The mice were treated with the COX-2 inhibitor NS-398 (10 mg/kg body weight, intraperitoneally) or vehicle immediately after trauma-hemorrhage or sham operation, 12 h thereafter, and following CLP or sham CLP. At 5 h after CLP, plasma PGE2, Interleukin-(IL) 6, and TNF-alpha levels were determined along with Kupffer cell IL-6 and TNF-alpha production in vitro. NS-398 treatment markedly suppressed the elevation in plasma PGE2 levels following CLP. The increase in plasma IL-6 levels after CLP were also significantly attenuated by NS-398 treatment. In vitro Kupffer cell IL-6 production after CLP was significantly reduced by in vivo NS-398 treatment. However, NS-398 had no effect on TNF-alpha levels, in vivo and in vitro. These findings indicate that activation of COX-2 following trauma-hemorrhage and subsequent sepsis up-regulates Kupffer cell IL-6 production. Thus, selective inhibition of COX-2 activity may reduce the deleterious consequences of sepsis under such conditions.
High-Affinity H7 Head and Stalk Domain–Specific Antibody Responses to an Inactivated Influenza H7N7 Vaccine After Priming With Live Attenuated Influenza Vaccine (2015)

Recent studies have shown that live attenuated influenza vaccines (LAIVs) expressing avian influenza virus hemagglutinins (HAs) prime for strong protective antibody responses to an inactivated influenza vaccine (IIV) containing the HA. To better understand this priming effect, we compared H7 HA head and stalk domain-specific B-cell responses in H7N7 LAIV-primed subjects and non-H7-primed controls after a single dose of H7N7 IIV. As previously reported, H7N7 LAIV-primed subjects but not control subjects generated strong hemagglutination-inhibiting and neutralizing antibody responses to the H7N7 IIV. Here, we found that the quantity, epitope diversity, and affinity of H7 head-specific antibodies increased rapidly in only H7N7 LAIV-primed subjects after receipt of the IIV. However, all cohorts generated a vigorous, high-affinity, stalk-specific antibody response. Consistent increases in circulating memory B-cell frequencies after receipt of the IIV reflected the specificity of high-affinity antibody production. Our findings emphasize the value of LAIVs as a vehicle for prepandemic vaccination.
Using electroactive substrates to pattern the attachment of two different cell populations (2001)

This report describes the development of an electroactive mask that permits the patterning of two different cell populations to a single substrate. This mask is based on a self-assembled monolayer of alkanethiolates on gold that could be switched from a state that prevents the attachment of cells to a state that promotes the integrin-mediated attachment of cells. Monolayers were patterned into regions having this electroactive monolayer and a second set of regions that were adhesive. After Swiss 3T3 fibroblasts had attached to the adhesive regions of this substrate, the second set of regions was activated electrically to permit the attachment of a second population of fibroblast cells. This method provides a general strategy for patterning the attachment of multiple cell types and will be important for studying heterotypic cell-cell interactions.
Early remodelling of the left ventricle in patients with myocardial infarction (1990)

Sequential alterations of left ventricular volumes and haemodynamics were studied in 29 patients between 4 days and 4 weeks after myocardial infarction. Left ventricular volume was determined by single photon emission computerized tomography (SPECT), infarct size by creatine kinase (CK) analysis, angiography and thallium201 SPECT. Left ventricular volume index (ml m-2) decreased in patients with small infarcts (74.5 +/- 4.9 vs 62.5 +/- 3.0, P less than 0.005), but increased significantly in patients with moderate (74.6 +/- 4.7 vs 83.6 +/- 5.0, P less than 0.0001) and large (71.7 +/- 4.8 vs 90.2 +/- 6.5, P less than 0.0001) infarctions between 4 days and 4 weeks after acute myocardial infarction. The latter groups contained almost two-thirds of our patients. This dilation occurred without significant changes in filling pressures (Swan-Ganz catheter) and resulted in significant augmentation and finally, normalization of stroke volume at 4 weeks (33.2 +/- 3.3 vs 42.6 +/- 2.9), despite persistently depressed ejection fraction (conventional radionuclide ventriculography). It is concluded that left ventricular dilatation post-myocardial infarction is structural (unchanged filling pressure) and compensatory (increased stroke volume) during the interval observed in this study.
C5-substituted pyrido[2,3-d]pyrimidin-7-ones as highly specific kinase inhibitors targeting the clinical resistance-related EGFRT790M mutant (2015)

C5-substituted pyrido[2,3-<italic>d</italic>]pyrimidin-7-ones were discovered as highly potent and specific inhibitors targeting the clinical resistance-related EGFR<sup>L858R/T790M</sup> mutant.
Bovine Lactoferrin and Lactoferricin, a Peptide Derived from Bovine Lactoferrin, Inhibit Tumor Metastasis in Mice (1997)

We investigated the effect of a bovine milk protein, lactoferrin (LF-B), and a pepsin-generated peptide of LF-B, lactoferricin (Lfcin-B), on inhibition of tumor metastasis produced by highly metastatic murine tumor cells, B16-BL6 melanoma and L5178Y-ML25 lymphoma cells, using experimental and spontaneous metastasis models in syngeneic mice. The subcutaneous (s.c.) administration of bovine apo-lactoferrin (apo-LF-B, 1 mg/mouse) and Lfcin-B (0.5 mg/mouse) 1 day after tumor inoculation significantly inhibited liver and lung metastasis of L5178Y-ML25 cells. However, human apolactoferrin (apo-LF-H) and bovine holo-lactoferrin (holo-LF-B) at the dose of 1 mg/mouse failed to inhibit tumor metastasis of L5178Y-ML25 cells. Similarly, the s.c. administration of apo-LF-B as well as Lfcin-B, but not apo-LF-H and holo-LF-B, 1 day after tumor inoculation resulted in significant inhibition of lung metastasis of B16-BL6 cells in an experimental metastasis model. Furthermore, in in vivo analysis for tumor-induced angiogenesis, both apo-LF-B and Lfcin-B inhibited the number of tumor-induced blood vessels and suppressed tumor growth on day 8 after tumor inoculation. However, in a long-term analysis of tumor growth for up to 21 days after tumor inoculation, single administration of apo-LF-B significantly suppressed the growth of B16-BL6 cells throughout the examination period, whereas Lfcin-B showed inhibitory activity only during the early period (8 days). In spontaneous metastasis of B16-BL6 melanoma cells, multiple administration of both apo-LF-B and Lfcin-B into tumor-bearing mice significantly inhibited lung metastasis produced by B16-BL6 cells, though only apo-LF-B exhibited an inhibitory effect on tumor growth at the time of primary tumor amputation (on day 21) after tumor inoculation. These results suggest that apo-LF-B and Lfcin-B inhibit tumor metastasis through different mechanisms, and that the inhibitory activity of LF-B on tumor metastasis may be related to iron (Fe3+)-saturation.
Characterization of the Saccharomyces cerevisiae ARG7 Gene Encoding Ornithine Acetyltransferase, An Enzyme also Endowed with Acetylglutamate Synthase Activity (1997)

We have cloned by functional complementation and characterized the yeast ARG7 gene encoding mitochondrial ornithine acetyltransferase, the enzyme catalyzing the fifth step in arginine biosynthesis. While forming ornithine, this enzyme regenerates acetylglutamate, also produced in the first step by the ARG2-encoded acetylglutamate synthase. Interestingly, total deletion of the genomic ARG7 ORF resulted in an arginine-leaky phenotype, indicating that yeast cells possess an alternative route for generating ornithine from acetylornithine. Yeast ornithine acetyltransferase has been purified and characterized previously as a heterodimer of two subunits proposed to derive from a single precursor protein [Liu, Y-S., Van Heeswijck R., Hoj, P. & Hoogenraad, N. (1995) Eur. J. Biochem. 228, 291-296]; those authors further suggested that the internal processing of Arg7p, which is a mitochondrial enzyme, might occur in the matrix, while the leader peptide would be of the non-cleavable-type. The characterization of the gene (a) establishes that Arg7p is indeed encoded by a single gene, (b) demonstrates the existence of a cleaved mitochondrial prepeptide of eight residues, and (c) shows that the predicted internal processing site is unlike the mitochondrial proteolytic peptidase target sequence. Yeast Arg7p shares between 32-43% identity in pairwise comparisons with the ten analogous bacterial ArgJ enzymes characterized. Among these evolutionarily related enzymes, some but not all appear bifunctional, being able to produce acetylglutamate not only from acetylornithine but also from acetyl-CoA, thus catalyzing the same reaction as the apparently unrelated acetylglutamate synthase. We have addressed the question of the bifunctionality of the eucaryotic enzyme, showing that overexpressed ARG7 can complement yeast arg2 and Escherichia coli argA mutations (affecting acetylglutamate synthase). Furthermore, Arg7p-linked acetylglutamate synthase activity was measurable in an assay. The yeast enzyme is thus clearly, albeit modestly, bifunctional. As with several bacterial ornithine acetyltransferases, the activity of Arg7p was practically insensitive to arginine but strongly inhibited by ornithine, which behaved as a competitive inhibitor.
Transforming growth factor‐β1 enhances bone healing to unloaded tricalcium phosphate coated implants: An experimental study in dogs (1996)

Growth of bone into cementless prosthetic components is compromised after revision of failed joint prostheses and by osteoporosis, gaps, and micromotion. We studied the effects of recombinant human transforming growth factor-beta 1 adsorbed on ceramic coated implants on the improvement of mechanical fixation and bone growth on the implant. Unloaded cylindrical grit-blasted titanium alloy implants were inserted bilaterally into both the medial and lateral femoral condyles of 10 skeletally mature mongrel dogs. The implants measured 10 mm in length and 6 mm in diameter and were initially surrounded by a 2 mm gap. One implant had an uncoated titanium surface and three implants were coated with tricalcium phosphate and 0, 0.3, or 3.0 micrograms of recombinant human transforming growth factor-beta 1. The dogs were killed at 6 weeks. Mechanical testing showed a 3-fold increase in fixation for the 0.3 microgram dose of recombinant human transforming growth factor-beta 1 and a 2-fold increase for the 3.0 micrograms dose. Histological analysis of bone growth on the implant demonstrated that maximal stimulation occurred with the 0.3 microgram dose, but bone volume in the gap was maximally stimulated by the 3.0 micrograms dose and increased 2-fold over control values. The majority of tricalcium phosphate was resorbed after the 6-week observation period. This study suggests that recombinant human transforming growth factor-beta 1 adsorbed onto implants coated with tricalcium phosphate ceramic can enhance mechanical fixation and bone growth on the implant. The use of transforming growth factor-beta 1 on ceramic coated prosthetic components may help to improve the functional outcome of cementless total joint replacements.
Detection of Mutual Inconsistency in Distributed Systems (1983)

Many distributed systems are now being developed to provide users with convenient access to data via some kind of communications network. In many cases it is desirable to keep the system functioning even when it is partitioned by network failures. A serious problem in this context is how one can support redundant copies of resources such as files (for the sake of reliability) while simultaneously monitoring their mutual consistency (the equality of multiple copies). This is difficult since network faiures can lead to inconsistency, and disrupt attempts at maintaining consistency. In fact, even the detection of inconsistent copies is a nontrivial problem. Naive methods either 1) compare the multiple copies entirely or 2) perform simple tests which will diagnose some consistent copies as inconsistent. Here a new approach, involving version vectors and origin points, is presented and shown to detect single file, multiple copy mutual inconsistency effectively. The approach has been used in the design of LOCUS, a local network operating system at UCLA.
A New Algorithm for Retrieving Aerosol Optical Thickness Using TERRA/MODIS Satellite Images (2008)

Abstract Aerosol detection and monitoring from satellite platforms has made significant advances over the past decade. While several state-of-the-art aerosol retrieval techniques provide aerosol properties at global scale, the more detailed spatial patterns remain unknown because most of the relevant satellite sensors operate at coarse resolution. A new aerosol retrieval algorithm for the Moderate Resolution Imaging Spectroradiometer (MODIS) 500m resolution data has been developed to retrieve aerosol properties over land, which helps to address the aerosol climatic issues at local and urban scales. The results show that 500m Aerosol Optical Thickness (AOT) data from MODIS are highly correlated (r = 0.94) with AERONET sunphotometer observations in Hong Kong. This study demonstrates the feasibility of aerosol retrieval at “fine” resolution in urban areas, which can assist in studies of aerosol loading distribution and the location of pollution source areas.
Underexpression of β Cell High K m Glucose Transporters in Noninsulin-Dependent Diabetes (1990)

The role of defective glucose transport in the pathogenesis of noninsulin-dependent diabetes (NIDDM) was examined in Zucker diabetic fatty rats, a model of NIDDM. As in human NIDDM, insulin secretion was unresponsive to 20 mM glucose. Uptake of 3-O-methylglucose by islet cells was less than 19% of controls. The beta cell glucose transporter (GLUT-2) immunoreactivity and amount of GLUT-2 messenger RNA were profoundly reduced. Whenever fewer than 60% of beta cells were GLUT-2-positive, the response to glucose was absent and hyperglycemia exceeded 11 mM plasma glucose. We conclude that in NIDDM underexpression of GLUT-2 messenger RNA lowers high Km glucose transport in beta cells, and thereby impairs glucose-stimulated insulin secretion and prevents correction of hyperglycemia.
Regulation of human megakaryocytopoiesis: Analysis of proliferation, ploidy and maturation in liquid cultures (1990)

A liquid culture technique associated with either double staining and flow cytometry or electron microscopy was used to study human megakaryocytopoiesis. During development from the embryo to the adult, a progressive increase in ploidy classes associated with an enhancement of megakaryocyte (meg) size was observed. Granulocyte-macrophage colony-stimulating factor had no effects on adult marrow cultures. In contrast, interleukin (IL) 3 induced a marked proliferation, but was unable to promote polyploidization. Furthermore, it abrogated the effects on endomitosis of aplastic plasma (AP). This negative effect on polyploidization of IL-3 could be partially dissociated from its effects on proliferation by a delayed addition in culture. AP acted on both proliferation and endoreplication, which was not due to the main hematopoietic growth factors, including IL-6. A synthesis of IL-6 was detected by in situ hybridization in cultured cells including megs which also express receptors for IL-6. These results suggest that terminal meg differentiation may be regulated by an autocrine IL-6 loop, and that megakaryocytopoiesis may be independently regulated at early and late stages of differentiation.
SM22α Promoter Targets Gene Expression to Vascular Smooth Muscle Cells In Vitro and In Vivo (2000)

The SM22alpha promoter programs recombinant gene expression exclusively to vascular smcs in vitro and in vivo. Although expression levels are lower than with heterologous promoters, these vectors may provide a safe and effective tool for gene therapy of vascular diseases.