gebhart/patrepeval huggingface dataset:
Surface chemistry on colloidal metals: a high-resolution NMR study of carbon monoxide adsorbed on metallic palladium crystallites in colloidal suspension (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSurface chemistry on colloidal metals: a high-resolution NMR study of carbon monoxide adsorbed on metallic palladium crystallites in colloidal suspensionJohn S. Bradley, John M. Millar, and Ernestine W. HillCite this: J. Am. Chem. Soc. 1991, 113, 10, 4016–4017Publication Date (Print):May 1, 1991Publication History Published online1 May 2002Published inissue 1 May 1991https://pubs.acs.org/doi/10.1021/ja00010a067https://doi.org/10.1021/ja00010a067research-articleACS PublicationsRequest reuse permissionsArticle Views410Altmetric-Citations75LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Selection of RNA Aptamers That Are Specific and High-Affinity Ligands of the Hepatitis C Virus RNA-Dependent RNA Polymerase (2002)

In order to find small RNA molecules that are specific and high-affinity ligands of nonstructural 5B (NS5B) polymerase, we screened by SELEX (systematic evolution of ligands by exponential amplification) a structurally constrained RNA library with an NS5BDeltaC55 enzyme carrying a C-terminal biotinylation sequence. Among the selected clones, two aptamers appeared to be high-affinity ligands of NS5B, with apparent dissociation constants in the low nanomolar range. They share a sequence that can assume a stem-loop structure. By mutation analysis, this structure has been shown to correspond to the RNA motif responsible for the tight interaction with NS5B. The aptamers appeared to be highly specific for the hepatitis C virus (HCV) polymerase since interaction with the GB virus B (GBV-B) NS5B protein cannot be observed. This is consistent with the observation that the activity of the HCV NS5B polymerase is efficiently inhibited by the selected aptamers, while neither GBV-B nor poliovirus 3D polymerases are affected. The mechanism of inhibition of the NS5B activity turned out to be noncompetitive with respect to template RNA, suggesting that aptamers and template RNA do not bind to the same site. As a matter of fact, mutations introduced in a basic exposed surface of the thumb domain severely impaired both the binding of and activity inhibition by the RNA aptamers.
Pressure marks (2007)

Selections and actions in GUI's are often separated -- i.e. an action or command typically follows a selection. This sequence imposes a lower bound on the interaction time that is equal to or greater than the sum of its parts. In this paper, we introduce pressure marks -- pen strokes where the variations in pressure make it possible to indicate both a selection and an action simultaneously. We propose a series of design guidelines from which we develop a set of four basictypes of pressure marks. We first assess the viability of this set through an exploratory study that looks at the way users draw straight and lasso pressure marks of different sizes and orientations. We then present the results of a quantitative experiment that shows that users perform faster selection-action interactions with pressure marks than with a combination of lassos and pigtails. Based on these results, we present and discuss a number of interaction designs that incorporate pressure marks.
Two different novel cis‐acting elements of erd1, a clpA homologous Arabidopsis gene function in induction by dehydration stress and dark‐induced senescence (2003)

Many plant genes have been shown to be induced by water stress and function in stress tolerance. The erd1 gene has been shown to be upregulated in response to both water stress and etiolation. Promoter studies using the erd1 promoter region fused to the luciferase (LUC) reporter gene in Arabidopsis thaliana were performed to identify the putative cis elements involved. Results indicated that the cis elements, responsible for gene expression during dehydration and etiolation, are separately located in two discrete portions of the erd1 promoter. Base substitution analysis showed that a 14-bp region from -599 to -586, and a myc recognition motif from -466 to -461 are necessary for the induction of LUC activity in dehydrated plants. On the other hand, base substitution analysis revealed that both an abscisic acid responsive element (ABRE)-like sequence (from -199 to -195) and an ACGT sequence (from -155 to -152) are required for an etiolation-induced increase in LUC activity. LUC activity measurements from etiolated transgenic plants incubated in either water, N6-benzyleadenine (BA), or a 1% sucrose solution found that while BA was able to delay the increase in LUC activity seen in water-treated plants, no increase in LUC activity was seen in plants incubated in sucrose. These results indicate that the erd1 promoter contains two different regulatory systems that are involved in upregulation by dehydration stress and dark-induced senescence.
IL‐4 induces interleukin‐6 (IL‐6) expression in human aortic endothelial cells (2008)

Previous studies have demonstrated that the pro‐oxidative and pro‐inflammatory pathways within vascular endothelium play an important role in the initiation and progression of atherosclerosis. The present study was designed to examine the hypothesis that interleukin‐4 (IL‐4) may up‐regulate expression of pro‐inflammatory cytokine IL‐6 in human aortic endothelial cells (HAEC). Quantitative real‐time RT‐PCR and enzyme‐linked immunosorbent assay (ELISA) showed that exposure of HAEC to IL‐4 significantly up‐regulated the mRNA and protein expression of IL‐6. Overexpression of IL‐6 was further confirmed in aorta and serum isolated from IL‐4‐injected mice. In addition, pretreatment with antioxidants, such as pyrrolidine dithiocarbamate (PDTC) and epigallocatechin gallate (EGCG), significantly and dose‐dependently inhibited IL‐4‐induced IL‐6 expression in HAEC. These results suggest that IL‐4 can induce IL‐6 expression through antioxidant‐sensitive mechanisms in human aortic endothelial cells. These data may contribute to understanding the cellular and molecular mechanisms involved in IL‐4‐mediated progression of atherosclerosis and development of therapeutic strategies for the prevention of atherosclerotic lesion development specifically targeted against inflammatory pathways. (This work was supported by Grant Number R15HL085229 from the National Heart, Lung, and Blood Institute)
Substrate specificity of human kallikreins 1 and 6 determined by phage display (2008)

The human tissue kallikrein (KLK) family contains 15 secreted serine proteases that are expressed in a wide range of tissues and have been implicated in different physiological functions and disease states. Of these, KLK1 has been shown to be involved in the regulation of multiple physiological processes such as blood pressure, smooth muscle contraction, and vascular cell growth. KLK6 is overexpressed in breast and ovarian cancer tissues and has been shown to cleave peptide derived from human myelin protein and Abeta amyloid peptide in vitro. Here we analyzed the substrate specificity of KLK1 and KLK6, by substrate phage display using a random octapeptide library. Consistent with earlier biochemical data, KLK1 was shown to exhibit both trypsin- and chymotrypsin-like selectivities with Tyr/Arg preferred at site P1, Ser/Arg strongly preferred at P1', and Phe/Leu at P2. KLK6 displayed trypsin-like activity, with the P1 position occupied only by Arg and a strong preference for Ser in P1'. Docking simulations of consensus peptide provide information on the identity of the enzyme residues that are responsible for substrate binding. Bioinformatic analysis suggested several putative KLK6 protein substrates, such as ionotropic glutamate receptor (GluR) and synphilin.
Gene delivery with low molecular weight linear polyethylenimines (2005)

Our study suggests that LPEIs with low MWs are promising candidates for non-viral gene delivery, because they are more efficient and substantially less toxic than their higher MW counterparts.
SCF and G-CSF lead to the synergistic induction of proliferation and gene expression through complementary signaling pathways (2000)

Abstract Stem cell factor (SCF) is a potent costimulatory molecule for many cytokines. Its synergy with granulocyte colony-stimulating factor (G-CSF) results in important biologic and clinical effects, although the mechanism by which this occurs remains poorly understood. To investigate this interaction, this study used a retroviral vector to transduce the G-CSF receptor into MO7e cells, which are known to express the SCF receptor. The transduced G-CSF receptor is functionally active, and the resultant MO7e-G cells recapitulate the proliferative synergy between SCF and G-CSF. When treated with both cytokines, a marked shortening of the G0/G1 phase of the cell cycle occurs, associated with a suppression of the cyclin-dependent kinase inhibitor p27kip-1. In addition, SCF and G-CSF induce the synergistic activation of c-fos, a proto-oncogene involved in propagation of mitogenic signals in hematopoietic cells. G-CSF, but not SCF, induces the tyrosine phosphorylation of STAT1 and STAT3, transcription factors that can mediate the induction of c-fos. However, SCF induces phosphorylation of STAT3 on serine727 (ser727), which is necessary for maximal STAT transcriptional activity, and the combination of SCF and G-CSF leads to complete STAT3 phosphorylation on ser727. The pathways by which SCF and G-CSF lead to serine phosphorylation of STAT3 are distinct and are partially dependent on phosphatidylinositol-3 kinase and ERKs, pathways that are also necessary for the synergistic effects of SCF and G-CSF on proliferation and c-fos induction. Thus, MO7e-G cells provide a powerful system in which the molecular basis of the synergy between SCF and G-CSF can be dissected.
Untersuchungen zur β‐Glycosylierung nach dem N‐Iodsuccinimid‐Verfahren: Synthese der terminalen Disaccharideinheit von Orthosomycinen (1986)

Abstract Bei der N ‐Iodsuccinimid‐Glycosylierung von Methyl‐3,4‐di‐ O ‐acetyl‐1,5‐anhydro‐2‐desoxy‐ D ‐ arabino ‐hex‐1‐enouronat ( 8 ) mit 1,6 : 2,3‐Dianhydro‐β‐ D ‐mannopyranose ( 7 ) werden als Disaccharide das kristalline 2′‐Desoxy‐2′‐iod‐β‐ D ‐ gluco ‐Derivat 9 und sein α‐ D ‐ manno ‐Isomer 10 mit ungewöhnlicher Halbbootkonformation im nichtreduzierenden Ring im Verhältnis ca. 1 : 1 gewonnen. Vergleichbare Befunde ergeben sich bei der Reaktion von 8 mit dem 1,6‐Anhydro‐2‐desoxy‐Saccharid 15a zu den interglycosidisch anomeren Trisacchariden 16 und 17 . Nach der milden Anhydroringöffnung von 16 zum Benzylglycosid 18 wird durch gleichzeitige Hydrogenolyse und Methoxycarbonyl‐Reduktion sowie eine nachfolgende regioselektive Veresterung das 6,6′‐Ditosylat 20 gewonnen. In einem abschließenden Reduktionsschritt wird das 2,2′,6,6′‐Tetradesoxydisaccharid 22 mit D ‐ arabino ‐Konfiguration in beiden Ringen erhalten, welches das terminale Disaccharidfragment B – C in verschiedenen Orthosomycinen wie z. B. 1 bis 3 darstellt.
Hyperglycemia and Inhibition of Glycogen Synthase in Streptozotocin-treated Mice (2004)

Glycogen synthase is post-translationally modified by both phosphate and O-linked N-acetylglucosamine (O-GlcNAc). In 3T3-L1 adipocytes exposed to high concentrations of glucose, O-GlcNAc contributes to insulin resistance of glycogen synthase. We sought to determine whether O-GlcNAc also regulates glycogen synthase in vivo. Glycogen synthase activity in fat pad extracts was inhibited in streptozotocin (STZ)-treated diabetic mice. The half-maximal activation concentration for glucose 6-phosphate (A(0.5)) was increased to 830 +/- 120 microm compared with 240 +/- 20 microm in control mice (C, p < 0.01), while the basal glycogen synthase activity (%I-form) was decreased to 2.4 +/- 1.4% compared with 10.1 +/- 1.8% in controls (p < 0.01). Glycogen synthase activity remained inhibited after compensatory insulin treatment. After insulin treatment kinetic parameters of glycogen synthase were more closely correlated with blood glucose (A(0.5), r(2) = 0.70; %I-form, r(2) = 0.59) than insulin levels (A(0.5), r(2) = 0.04; %I-form, r(2) = 0.09). Hyperglycemia also resulted in an increase in the level of O-GlcNAc on glycogen synthase (16.1 +/- 1.8 compared with 7.0 +/- 0.9 arbitrary intensity units for controls, p < 0.01), even though the level of phosphorylation was identical in diabetic and control mice either with (STZ: 2.9 +/- 1.0 and C: 3.2 +/- 0.8) or without (STZ: 12.2 +/- 2.8 and C: 13.8 +/- 3.0 arbitrary intensity units) insulin treatment. In all mice the percent activation of glycogen synthase that could be achieved in vitro by recombinant protein phosphatase 1 (230 +/- 30%) was significantly greater in the presence of beta-d-N-acetylglucosaminidase (410 +/- 60%, p < 0.01). This synergistic stimulation of glycogen synthase due to codigestion by protein phosphatase 1 and beta-d-N-acetylglucosaminidase was more pronounced in STZ-diabetic mice (310 +/- 70%) compared with control mice (100 +/- 10%, p < 0.05). The findings demonstrate that O-GlcNAc has a role in the regulation of glycogen synthase both in normoglycemia and diabetes.
A family of binary gene vectors with low inter- transformant variation (1994)

We have constructed a family of binary vectors for use in Agrobacterium-mediated tmosformation of plants. These vectors yield transformants with high efficiency and lead to remarkably reproducible expression of co-transferred genes. This low degree of inter-transformant variation is most likely due to . the combination of a highly &icient selectable marker gene, methotrexate resistance, with its localisation close to the l?U 'T-DNA border. Both, a Cauliflower Mosaic Virus 35s promoter and the light regulated Rubisco small subunit promoter, which exhibit a high degree of variation with other vector systems, gave reproducible levels of expression between transformants with these vectors. Several useful features such as a ply-linker, additional marker or reporter genes (kanamycin, hygromycin, R-glucuronidase), and an expression cassette were added to the basic vector.
Molecular and functional interactions of transcription factor USF with the long terminal repeat of human immunodeficiency virus type 1 (1995)

The human transcription factor USF, purified from HeLa cells, and its recombinant 43-kDa component bind to the long terminal repeat (LTR) of human immunodeficiency virus type 1. The proteins footprint over nucleotides from position -173 to -157 upstream of the transcription start site, generating strong DNAse I hypersensitivity sites at the 3' sides on both strands. As detected by methylation protection studies, the factor forms symmetric contacts with the guanines of the palindromic CACGTG core of the recognized sequence. Its binding ability is abolished by the mutation of this core sequence and is strongly reduced by the cytosine methylation of the central CpG dinucleotide. Upon binding, both recombinant and purified USFs bend the LTR DNA template. The role of USF in the control of transcription initiation from the LTR was tested by in vitro transcription assays. Upon addition of the protein, transcription from constructs containing an intact binding site is increased, while the responsiveness in constructs with a mutated sequence is abolished. Furthermore, the addition of a decoy plasmid which contains multiple repeats of the target sequence results in downregulation of transcription from the LTR. These results suggest that USF is a positive regulator of LTR-mediated transcriptional activation.
THE EPIDEMIOLOGY OF ACUTE RESPIRATORY INFECTIONS IN CHILDREN AND ADULTS: A GLOBAL PERSPECTIVE (1990)

While a number of advances have been made in our understanding of the epidemiology of acute respiratory infections in the past two decades, a number of serious questions still require urgent answers. The associations of factors such as chronic disease in adults, direct smoking, passive smoking, crowding, and breast feeding to acute respiratory infections are now well documented. Appropriate changes in public health policy need not be predicated on results from still further studies. However, in virtually all of the other areas cited in this review, further data are required. In developing countries, studies being currently conducted on vitamin A supplementation, malnutrition, and indoor air pollution will help address the most pressing issues. More studies are also needed on the relations between HIV infection and acute respiratory infections, as well as low birth weight and respiratory infection. The National Research Council studies have provided important additional data on etiologic agents in children in developing countries, but data on adult pneumonia remain sparse. In developed countries the issues that may be of greatest interest are the relation between maternal antibody levels and passive immunity in infants, the reasons for the increase in pneumonia mortality in older age groups, and the relation between air pollution and acute respiratory infections (as opposed to morbidity from bronchial reactivity). From a methodological viewpoint, the relation between previous respiratory infection (particularly in the first year of life) and subsequent acute respiratory infection morbidity has been inadequately explored. Adjustment for autocorrelation in multivariate models may be necessary if this relation is strong. Greater standardization of data collection methods in developed and developing countries also needs to be more seriously addressed. Given that some advances have been made in this area, the time may be right for development of acute symptom questionnaires, akin to the American Thoracic Society chronic respiratory questionnaire, for use in both developed and developing countries. Standardization of diaries, although somewhat more difficult, would also be extremely useful in many instances.
Therapy of Advanced Non–Small-Cell Lung Cancer With an SN-38-Anti-Trop-2 Drug Conjugate, Sacituzumab Govitecan (2017)

Purpose Trop-2, expressed in most solid cancers, may be a target for antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC). We studied sacituzumab govitecan (IMMU-132), a Trop-2 ADC, for the targeting of SN-38. Patients and Methods We evaluated IMMU-132 in a single-arm multicenter trial in patients with pretreated metastatic NSCLC who received either 8 or 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end points were safety and objective response rate (ORR). Progression-free survival and overall survival were secondary end points. Results Fifty-four patients were treated. In the response-assessable study population (n = 47), which had a median of three prior therapies (range, two to seven), the ORR was 19%; median response duration, 6.0 months (95% CI, 4.8 to 8.3 months); and clinical benefit rate (complete response + partial response + stable disease ≥ 4 months), 43%. ORR in the intention-to-treat (ITT) population was 17% (nine of 54). Responses occurred with a median onset of 3.8 months, including patients who had relapsed or progressed after immune checkpoint inhibitor therapy. Median ITT progression-free survival was 5.2 months (95% CI, 3.2 to 7.1 months) and median ITT overall survival, 9.5 months (95% CI, 5.9 to 16.7 months). Grade 3 or higher adverse events included neutropenia (28%), diarrhea (7%), nausea (7%), fatigue (6%), and febrile neutropenia (4%). One patient developed a transient immune response, despite patients receiving a median of 10 doses. More than 90% of 26 assessable archival tumor specimens were highly positive (2+, 3+) for Trop-2 by immunohistochemistry, which suggests that Trop-2 is not a predictive biomarker for response. Conclusion IMMU-132 was well-tolerated and induced durable responses in heavily pretreated patients with metastatic NSCLC. This ADC should be studied further in this disease and in other patients with Trop-2-expressing tumors.
Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes (1993)

The three classes of enzymes which inactivate aminoglycosides and lead to bacterial resistance are reviewed. DNA hybridization studies have shown that different genes can encode aminoglycoside-modifying enzymes with identical resistance profiles. Comparisons of the amino acid sequences of 49 aminoglycoside-modifying enzymes have revealed new insights into the evolution and relatedness of these proteins. A preliminary assessment of the amino acids which may be important in binding aminoglycosides was obtained from these data and from the results of mutational analysis of several of the genes encoding aminoglycoside-modifying enzymes. Recent studies have demonstrated that aminoglycoside resistance can emerge as a result of alterations in the regulation of normally quiescent cellular genes or as a result of acquiring genes which may have originated from aminoglycoside-producing organisms or from other resistant organisms. Dissemination of these genes is aided by a variety of genetic elements including integrons, transposons, and broad-host-range plasmids. As knowledge of the molecular structure of these enzymes increases, progress can be made in our understanding of how resistance to new aminoglycosides emerges.
Effects of Lutein, Lycopene, Annatto, and γ-Tocopherol on Autoxidation of Triglycerides (1996)

The effects of lycopene, lutein, annatto, and γ-tocopherol were examined on autoxidized triglycerides. Oxidation was followed by measuring hydroperoxide formation as peroxide value. The loss of the orange color of carotenoids was followed spectrophotometrically. Lutein and lycopene were prooxidants, whereas the natural food color annatto and γ-tocopherol effectively inhibited hydroperoxide formation. By adding γ-tocopherol, the prooxidant effect of carotenoids was inhibited and loss of yellow carotenoid color was retarded. Moreover, a combination of lutein and γ-tocopherol was more efficient than γ-tocopherol in inhibiting the hydroperoxide formation of triglycerides. The benefit of a combination of a carotenoid and tocopherol as an antioxidant may be due to the effect of γ-tocopherol to retard the formation of degradation products of the carotenoid. The results suggest that potential prooxidant effects of carotenoids should be considered when carotenoids are proposed for color in lipid-containing foods. Keywords: Lutein; lycopene; annatto; γ-tocopherol; autoxidation; color; antioxidant
Imidazoline derivatives: a patent review (2006 – present) (2012)

With the uncovering of the molecular mechanisms related to neurodegenerative diseases and cancer, the use of classical and novel imidazoline structures has been more frequently noted in recent (2006 - 2012) patented agents for the treatment of neurodegenerative diseases and cancer instead of agents for the treatment of cardiovascular disease noticed earlier.