gebhart/patrepeval huggingface dataset:
Antisense oligonucleotide inhibition of hepatitis C virus gene expression in transformed hepatocytes (1996)

Genetic and biochemical studies have provided convincing evidence that the 5' noncoding region (5' NCR) of hepatitis C virus (HCV) is highly conserved among viral isolates worldwide and that translation of HCV is directed by an internal ribosome entry site (IRES) located within the 5' NCR. We have investigated inhibition of HCV gene expression using antisense oligonucleotides complementary to the 5' NCR, translation initiation codon, and core protein coding sequences. Oligonucleotides were evaluated for activity after treatment of a human hepatocyte cell line expressing the HCV 5' NCR, core protein coding sequences, and the majority of the envelope gene (E1). More than 50 oligonucleotides were evaluated for inhibition of HCV RNA and protein expression. Two oligonucleotides, ISIS 6095, targeted to a stem-loop structure within the 5' NCR known to be important for IRES function, and ISIS 6547, targeted to sequences spanning the AUG used for initiation of HCV polyprotein translation, were found to be the most effective at inhibiting HCV gene expression. ISIS 6095 and 6547 caused concentration-dependent reductions in HCV RNA and protein levels, with 50% inhibitory concentrations of 0.1 to 0.2 microM. Reduction of RNA levels, and subsequently protein levels, by these phosphorothioate oligonucleotides was consistent with RNase H cleavage of RNA at the site of oligonucleotide hybridization. Chemically modified HCV antisense phosphodiester oligonucleotides were designed and evaluated for inhibition of core protein expression to identify oligonucleotides and HCV target sequences that do not require RNase H activity to inhibit expression. A uniformly modified 2'-methoxyethoxy phosphodiester antisense oligonucleotide complementary to the initiator AUG reduced HCV core protein levels as effectively as phosphorothioate oligonucleotide ISIS 6095 but without reducing HCV RNA levels. Results of our studies show that HCV gene expression is reduced by antisense oligonucleotides and demonstrate that it is feasible to design antisense oligonucleotide inhibitors of translation that do not require RNase H activation. The data demonstrate that chemically modified antisense oligonucleotides can be used as tools to identify important regulatory sequences and/or structures important for efficient translation of HCV.
Analysis of fractal electrodes for efficient neural stimulation (2013)

Planar electrodes are increasingly used in therapeutic neural stimulation techniques such as functional electrical stimulation, epidural spinal cord stimulation (ESCS), and cortical stimulation. Recently, optimized electrode geometries have been shown to increase the efficiency of neural stimulation by increasing the variation of current density on the electrode surface. In the present work, a new family of modified fractal electrode geometries is developed to enhance the efficiency of neural stimulation. It is shown that a promising approach in increasing the neural activation function is to increase the "edginess" of the electrode surface, a concept that is explained and quantified by fractal mathematics. Rigorous finite element simulations were performed to compute electric potential produced by proposed modified fractal geometries. The activation of 256 model axons positioned around the electrodes was then quantified, showing that modified fractal geometries required a 22% less input power while maintaining the same level of neural activation. Preliminary in vivo experiments investigating muscle evoked potentials due to median nerve stimulation showed encouraging results, supporting the feasibility of increasing neural stimulation efficiency using modified fractal geometries.
Unique single-domain antigen binding fragments derived from naturally occurring camel heavy-chain antibodies (1999)

The humoral immune response of camels, dromedaries and llamas includes functional antibodies formed by two heavy chains and no light chains. The amino acid sequence of the variable domain of the naturally occurring heavy-chain antibodies reveals the necessary adaptations to compensate for the absence of the light chain. In contrast to the conventional antibodies, a large proportion of the heavy-chain antibodies acts as competitive enzyme inhibitors. Studies on the dromedary immunoglobulin genes start to shed light on the ontogeny of these heavy-chain antibodies. The presence of the heavy-chain antibodies and the possibility of immunizing a dromedary allows for the production of antigen binders consisting of a single domain only. These minimal antigen-binding fragments are well expressed in bacteria, bind the antigen with affinity in the nM range and are very stable. We expect that such camelid single domain antibodies will find their way into a number of biotechnological or medical applications. The structure of the camelid single domain is homologous to the human VH, however, the antigen-binding loop structures deviate fundamentally from the canonical structures described for human or mouse VHs. This has two additional advantages: (1) the camel or llama derived single domain antibodies might be an ideal scaffold for anti-idiotypic vaccinations; and (2) the development of smaller peptides or peptide mimetic drugs derived from of the antigen binding loops might be facilitated due to their less complex antigen binding site.
Correlates Among Nocturnal Agitation, Sleep, and Urinary Incontinence in Dementia (2014)

Family caregivers of elders with dementia often face the challenging behaviors of nighttime agitation, sleep disturbances, and urinary incontinence. To date, no study has examined the interrelationships of these behaviors in community-dwelling persons. This single group, descriptive study employs wireless body sensors to objectively collect data on nighttime agitation, sleep, and urinary incontinence in patients with dementia in their homes over a 5- to 7-day period. The aims are to (1) examine the feasibility and acceptability of the use of body sensors in community-dwelling persons with dementia; (2) describe patterns of nocturnal agitation, sleep continuity and duration, and nighttime urinary incontinence; and (3) examine the relationships among nocturnal agitation, sleep continuity and duration, and nighttime urinary incontinence. Data collection is in early stages and is still in progress. Challenges and advantages from preliminary data collection are reported.
Synthesis of N10-methyl-4-thiofolic acid and related compounds (1975)

Compound 21 (N10-methyl-4-thiofolic acid) and related compounds were prepared as potential inhibitors of the cofactor forms of tetrahydrofolate. The preparation of 2-acetylamino-4-(benzylthio)-6-chloro-5-nitropyrimidine (4) provided an intermediate that was allowed to react with methyl p-[(3-aminoacetonyl)methylamino]benzoate oxime (16). The oxime function of the resulting 6-substituted aminopyrimidine 6 was hydrolyzed to give the corresponding acetonylaminopyrimidine 7, which on reductive cyclization gave methyl p-[[[2-amino-4-(benzylthio)-7,8-dihydro-6-pteridinyl]methyl]methylamino]benzoate (9). This dihydropteridine was oxidized with potassium permanganate, and the product was treated successively with sodium hydrosulfide to replace the benzylthio group and with aqueous sodium hydroxide to hydrolyze the ester function to give p-[[(2-amino-3,4-dihydro-4-thioxo-6-pteridinyl)methyl]methylamino]benzoic acid (N10-methyl-4-thiopteroic acid, 12). Another route to 12 involved the interaction of 2,5-diamino-4,6-dichloropyrimidine (15) with 16 to give methyl p-[[(2-amino-4-chloro-7,8-dihydro-6-pteridinyl)methyl]methylamino]benzoate (13). Displacement of the chloro group of 13 with sodium hydrosulfide followed by the simultaneous air oxidation of the dihydropteridine ring and saponification of the ester group gave 12. After protection of the 2-amino and 4-thioxo moieties of 12, the resulting intermediate benzoic acid was coupled with diethyl L-glutamate. The product of this reaction was deblocked to give 21. Methylation of 21 gave the corresponding 4-(methylthio) derivative 22, which on reaction with hydrazine gave the 4-hydrazino analog 23 of methotrexate. Reduction of 12 and 21 with sodium hydrosulfite gave the dihydropteridines 24 and 25, respectively. The title compound was an excellent inhibitor of the growth of Streptococcus faecium ATCC 8043. However, this and related compounds were ineffective inhibitors of dihydrofolic reductase and showed no significant activity in either the KB cell culture screen or against L1210 leukemia cells in mice.
Statistical Molecular Design of Building Blocks for Combinatorial Chemistry (2000)

The reduction of the size of a combinatorial library can be made in two ways, either base the selection on the building blocks (BB's) or base it on the full set of virtually constructed products. In this paper we have investigated the effects of applying statistical designs to BB sets compared to selections based on the final products. The two sets of BB's and the virtually constructed library were described by structural parameters, and the correlation between the two characterizations was investigated. Three different selection approaches were used both for the BB sets and for the products. In the first two the selection algorithms were applied directly to the data sets (D-optimal design and space-filling design), while for the third a cluster analysis preceded the selection (cluster-based design). The selections were compared using visual inspection, the Tanimoto coefficient, the Euclidean distance, the condition number, and the determinant of the resulting data matrix. No difference in efficiency was found between selections made in the BB space and in the product space. However, it is of critical importance to investigate the BB space carefully and to select an appropriate number of BB's to result in an adequate diversity. An example from the pharmaceutical industry is then presented, where selection via BB's was made using a cluster-based design.
Techniques of cutaneous examination for the detection of skin cancer (1995)

Skin cancers are the most common cancers in humans. The American Cancer Society estimates that in the United States more than 700,000 new skin cancers are diagnosed annually. Although the majority of nonmelanoma skin cancers occur on visibly exposed anatomic areas, most malignant melanomas occur on body sites obscured by clothing. The high mortality associated with advanced melanomas emphasizes the importance of performing regular total cutaneous examinations in all patients to detect early, easily curable lesions. A number of techniques aid in these examinations: (1) physical and psychologic preparation of the patient; (2) appropriate lighting and a suitable examination table; (3) when indicated, use of Wood's light, dermoscopy, and photography. In addition, any suspicious lesion should be biopsied promptly either in parte or in toto. Lastly, the patient should be educated about the signs and symptoms of skin cancer, the role of sunlight in causing skin cancer, and the need for sun avoidance and/or protection. By heightening public awareness of the high incidence of cancers of the skin and by emphasizing the need for routine examination of the entire cutaneous surface, most cutaneous malignancies can be diagnosed early when they can be cured by simple surgical procedures.
New sutureless aortic valve prosthesis (2012)

This new technology may offer improved results. Cost-effectiveness and fine-tuning of patient selection are two aspects that future investigation should address.
RuO2 Bottom Electrodes for Ferroelectric (Pb, La)(Zr, Ti)O3 Thin Films by Metalorganic Chemical Vapor Deposition (1995)

RuO 2 thin films were grown on various substrates by metalorganic chemical vapor deposition (MOCVD) using Ru(C 11 H 19 O 2 ) 3 . The films produced at 350° C in O 2 had a tetragonal rutile structure and a resistivity of 60 µΩ cm with excellent adhesion. From the viewpoint of integrated device applications, lanthanum-modified lead zirconate titanate (PLZT) films were also prepared by MOCVD. The RuO 2 films were found to serve as effective diffusion barriers for PLZT and MgO. Significant interdiffusion at RuO 2 /Si and RuO 2 /SiO 2 interfaces occurred during the deposition of PLZT films, and annealing of RuO 2 film considerably depressed the interface reactions. Ta 2 O 5 film served as an excellent barrier against the interface reaction between RuO 2 and Si. The dielectric and ferroelectric properties of PLZT thin films on the RuO 2 /MgO and RuO 2 /Ta 2 O 5 /Si substrates were superior compared to those observed with RuO 2 /Si and RuO 2 /SiO 2 /Si substrates.
Cytometry of DNA replication and RNA synthesis: Historical perspective and recent advances based on “click chemistry” (2011)

This review covers progress in the development of cytometric methodologies designed to assess DNA replication and RNA synthesis. The early approaches utilizing autoradiography to detect incorporation of (3) H- or (14) C-labeled thymidine were able to identify the four fundamental phases of the cell cycle G(1) , S, G(2) , and M, and by analysis of the fraction of labeled mitosis (FLM), to precisely define the kinetics of cell progression through these phases. Analysis of (3) H-uridine incorporation and RNA content provided the means to distinguish quiescent G(0) from cycling G(1) cells. Subsequent progress in analysis of DNA replication was based on the use of BrdU as a DNA precursor and its detection by the quenching of the fluorescence intensity of DNA-bound fluorochromes such as Hoechst 33358 or acridine orange as measured by flow cytometry. Several variants of this methodology have been designed and used in studies to detect anticancer drug-induced perturbations of cell cycle kinetics. The next phase of method development, which was particularly useful in studies of the cell cycle in vivo, including clinical applications, relied on immunocytochemical detection of incorporated halogenated DNA or RNA precursors. This approach however was hampered by the need for DNA denaturation, which made it difficult to concurrently detect other cell constituents for multiparametric analysis. The recently introduced "click chemistry" approach has no such limitation and is the method of choice for analysis of DNA replication and RNA synthesis. This method is based on the use of 5-ethynyl-2'deoxyuridine (EdU) as a DNA precursor or 5-ethynyluridine (EU) as an RNA precursor and their detection with fluorochrome-tagged azides utilizing a copper (I) catalyzed [3+2] cycloaddition. Several examples are presented that illustrate incorporation of EdU or EU in cells subjected to DNA damage detected as histone H2AX phosphorylation that have been analyzed by flow or laser scanning cytometry.
Sentinel-a technology for practical automatic monitoring of busy and complex scenes (2003)

The author reviews the problems which surveillance missions present to automation and includes examples that cause conventional systems to fail. Sentinel is an automated scene monitoring system specifically designed to overcome these problems. The technological approach used in the Sentinel system is presented, the advantages this gives and how they may best be exploited are discussed. A practical example is shown and the way that Sentinel is deployed, including the necessary setting up, is illustrated. Surveillance performance results are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Two-way applications for cable television systems in the '70s (1971)

Two-way communications on a cable television system can be achieved in many different ways. This special report surveys the various approaches that have been proposed and are being tried experimentally in the field. The emphasis is on the basic engineering configurations rather than on the uses to which the systems can be put. For almost all of the systems, the possible two-way uses are limited only by one's imagination. The capability for any communications task exists if one is willing to pay the price.
Children's sense of place as literacy learners in their classroom (2005)

This paper focuses on children's sense of place that they find in their classroom literacy situations This paper presents findings of child interviews and samples of classroom observations from the author's classroom-based research, to explore the pleasures and passions that children bring to or find in their classroom literacy situations and the provocations they encounter there. Children's pleasures, passions and provocations provide a backdrop for exploring and understanding their patterns of participation. This paper examines how particular kinds of classroom situations may help or hinder children's participation and the sense of place that they find as literacy learners at school.
Structural basis for recognition by an in vitro evolved affibody (2003)

The broad binding repertoire of antibodies has permitted their use in a wide range of applications. However, some uses of antibodies are precluded due to limitations in the efficiency of antibody generation. In vitro evolved binding proteins, selected from combinatorial libraries generated around various alternative structural scaffolds, are promising alternatives to antibodies. We have solved the crystal structure of a complex of an all alpha-helical in vitro selected binding protein (affibody) bound to protein Z, an IgG Fc-binding domain derived from staphylococcal protein A. The structure of the complex reveals an extended and complementary binding surface with similar properties to protein-antibody interactions. The surface region of protein Z recognized by the affibody is strikingly similar to the one used for IgG(1) Fc binding, suggesting that this surface contains potential hot-spots for binding. The implications of the selected affibody binding-mode for its application as a universal binding protein are discussed.
Nonmuscle Myosin IIB Is Involved in the Guidance of Fibroblast Migration (2003)

Although myosin II is known to play an important role in cell migration, little is known about its specific functions. We have addressed the function of one of the isoforms of myosin II, myosin IIB, by analyzing the movement and mechanical characteristics of fibroblasts where this protein has been ablated by gene disruption. Myosin IIB null cells displayed multiple unstable and disorganized protrusions, although they were still able to generate a large fraction of traction forces when cultured on flexible polyacrylamide substrates. However, the traction forces were highly disorganized relative to the direction of cell migration. Analysis of cell migration patterns indicated an increase in speed and decrease in persistence, which were likely responsible for the defects in directional movements as demonstrated with Boyden chambers. In addition, unlike control cells, mutant cells failed to respond to mechanical signals such as compressing forces and changes in substrate rigidity. Immunofluorescence staining indicated that myosin IIB was localized preferentially along stress fibers in the interior region of the cell. Our results suggest that myosin IIB is involved not in propelling but in directing the cell movement, by coordinating protrusive activities and stabilizing the cell polarity.
Procedure for the Preparation of Pure Dithiocarbamates (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProcedure for the Preparation of Pure DithiocarbamatesPascale Giboreau and Christophe MorinCite this: J. Org. Chem. 1994, 59, 5, 1205–1207Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/jo00084a046https://doi.org/10.1021/jo00084a046research-articleACS PublicationsRequest reuse permissionsArticle Views729Altmetric-Citations15LEARN 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
Medicinal Inorganic Chemistry:  Introduction (1999)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMedicinal Inorganic Chemistry: IntroductionChris Orvig and Michael J. AbramsView Author Information Medicinal Inorganic Chemistry Group, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada and AnorMED, Incorporated, 100 20353 64th Avenue, Langley, British Columbia, V2Y 1N5, CanadaCite this: Chem. Rev. 1999, 99, 9, 2201–2204Publication Date (Web):July 30, 1999Publication History Published online30 July 1999Published inissue 8 September 1999https://pubs.acs.org/doi/10.1021/cr980419whttps://doi.org/10.1021/cr980419wresearch-articleACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views6981Altmetric-Citations403LEARN 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 SUBJECTS:Elements,Inorganic chemistry,Ions,Metals,Pharmaceuticals Get e-Alerts