gebhart/patrepeval huggingface dataset:
Short interfering RNA (siRNA): tool or therapeutic? (2005)

Gene silencing by siRNA (short interfering RNA) is a still developing field in biology and has evolved as a novel post-transcriptional gene silencing strategy with therapeutic potential. With siRNAs, virtually every gene in the human genome contributing to a disease becomes amenable to regulation, thus opening unprecedented opportunities for drug discovery. Besides the well-established role for siRNA as a tool for target screening and validation in vitro, recent progress of siRNA delivery in vivo raised expectations for siRNA drugs as the up-and-coming 'magic bullet'. Whether siRNA compounds will make it as novel chemical entities from 'bench to bedside' will probably depend largely on improving their pharmacokinetics in terms of plasma stability and cellular uptake. Whereas locally administered siRNAs have already entered the first clinical trials, strategies for successful systemic delivery of siRNA are still in a preclinical stage of development. Irrespective of its therapeutic potential, RNAi (RNA interference) has unambiguously become a valuable tool for basic research in biology and thereby it will continue to have a major impact on medical science. In this review, we will give a brief overview about the history and current understanding of RNAi and focus on potential applications, especially as a therapeutic option to treat human disease.
2.2-kilobase class of early transcripts encoded by cell-related sequences in human cytomegalovirus strain AD169 (1986)

In this report we describe the kinetics of appearance and fine mapping of a 2.2-kilobase (kb) class of transcripts arising from a region of the human cytomegalovirus genome which contains cell-related sequences. These transcripts are encoded by adjacent EcoRI fragments R and d (map units 0.682 to 0.713), located within the long unique segment of the genome. The 2.2-kb RNAs were first detected at 8h postinfection and appeared at comparable or slightly lower levels at 28 and 72 h postinfection. At late times (72 h) additional transcripts were detected with probes from this region. RNase, S1 nuclease, and exonuclease VII protection analyses of 8- and 28-h RNA indicated that the 2.2-kb RNAs had a complex spliced structure consisting of invariable 5' and internal exons and a heterogeneous 3' exon. The position of the 5' end of the RNA was determined with respect to the nucleotide sequence. Analysis of this sequence showed that the cell-related sequences were contained within a long open reading frame in the 5' exon.
A Systematic Review of T-cell Epitopes in Hepatitis B Virus: Identification, Genotypic Variation and Relevance to Antiviral Therapeutics (2008)

Identification of HBV-specific epitopes in non-HLA-A2-positive individuals and recognition of genotypic variation across epitopes are important for the future development of novel immunotherapeutic strategies for the management of chronic HBV infection.
Optofluidic Microscope: A Novel High Resolution Microscope-on-a-Chip System (2006)

In this paper, a novel on-chip optical imaging device, termed optofluidic microscope (OFM) is presented, which features compact size and high resolution along with high-speed imaging.
Field-effect transistor on SrTiO3 with sputtered Al2O3 gate insulator (2003)

A field-effect transistor has been constructed that employs a perovskite-type SrTiO3 single crystal as the semiconducting channel. This device functions as an n-type accumulation-mode device. The device was fabricated at room temperature by sputter-deposition of amorphous Al2O3 films as a gate insulator on the SrTiO3 substrate. The field-effect (FE) mobility is 0.1 cm2/V s and on-off ratio exceeds 100 at room temperature. The temperature dependence of the FE mobility down to 2 K shows a thermal-activation-type behavior with an activation energy of 0.6 eV.
CALCIUM CHANNEL DIVERSITY AND NEUROTRANSMITTER RELEASE: The ω-Conotoxins and ω-Agatoxins (1994)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
108. The condensation of phthalaldehydic acid and related compounds with various heterocyclic systems (1965)

C. W. Rees and C. R. Sabet, J. Chem. Soc., 1965, 687 DOI: 10.1039/JR9650000687
The triple-helical region of human type XIX collagen consists of multiple collagenous subdomains and exhibits limited sequence homology to alpha 1(XVI) (1994)

We previously isolated a clone from a human rhabdomyosarcoma (RH) cDNA library coding for a collagen chain different from those constituting the 18 reported types (Myers, J. C., Sun, M. J., D'Ippolito, J. A., Jabs, E. W., Neilson, E. G., and Dion, A. S. (1993) Gene (Amst.) 123, 211-217). The sequence translated to a 186-amino acid noncollagenous region, a 524-residue three-subdomain collagenous region, and a presumed 8-amino acid COOH-terminal peptide. To further elucidate the primary structure of this collagen, we have now determined the sequence of additional cDNA clones. Overlapping 3' clones, found to diverge exactly where the noncollagenous 8-residue COOH sequence began, encode two additional collagenous subdomains of 168 and 70 residues and a 19-residue COOH-terminal peptide. Analysis of genomic DNA spanning the region in question revealed several 45- and 51-base pair exons linked by 4 introns totaling over 5 kilobases (kb). A 2-kb intron, absent from the clones coding for the extended collagenous region, was used in Northern blot hybridization to detect an apparently prevalent splicing intermediate 2 kb larger than the major 12.4-kb RH transcript. Therefore, the triple-helical region of this collagen chain is likely to be composed of 832 amino acids divided into five collagenous subdomains separated by 20-44 residue interruptions. Two interruptions are similar in sequence and position to those located in the type XVI chain. Furthermore, the arrangement of 2 cysteines near the COOH terminus and two imperfections in collagenous subdomain 1 are conserved in the related subclass composed of type IX, XII, XIV, and XVI collagens. However, in contrast to the COOH-terminal interchain bridging in this latter collagen group, molecular modeling strongly predicts that the cysteines in RH collagen participate in intrachain disulfide bonds. Taken together, the data clearly show that RH collagen does not represent another chain of one of the known collagen types. We propose that it be designated the alpha 1 chain of type XIX collagen.
Delay test simulation (1977)

The delay test simulator described here has two functions. First, it computes the actual timing to be used for each delay test. This computation requires delay distributions and tester tolerances. Second, it performs a parallel fault simulation to determine which delay faults have been detected.
The prevalence and characteristics of fibromyalgia in the general population (1995)

Fibromyalgia is common in the population, and occurs often in older persons. Characteristic features of fibromyalgia--pain threshold and symptoms--are similar in community and clinic populations, but overall severity, pain, and functional disability are more severe in the clinic population.
CXCL12 chemokine up‐regulates bone resorption and MMP‐9 release by human osteoclasts: CXCL12 levels are increased in synovial and bone tissue of rheumatoid arthritis patients (2003)

Chemokines are involved in a number of inflammatory pathologies and some of them show a pivotal role in the modulation of osteoclast development. Therefore, we evaluated the role of CXCL12 chemokine on osteoclast differentiation and function and we analyzed its expression on synovial and bone tissue biopsies from rheumatoid arthritis (RA) patients. Osteoclasts were obtained by 7 days in vitro differentiation with RANKL and M-CSF of CD11b positive cells in the presence or absence of CXCL12. The total number of osteoclast was analyzed by Tartrate-resistant acid phosphatase (TRAP)-staining and bone-resorbing activity was assessed by pit assay. MMP-9 and TIMP-1 release was evaluated by ELISA assay. CXCL12 expression on biopsies from RA patients was analyzed by immunohistochemistry. Osteoclasts obtained in the presence of CXCL12 at 10 nM concentration displayed a highly significant increase in bone-resorbing activity as measured by pit resorption assay, while the total number of mature osteoclasts was not affected. The increased resorption is associated with overexpression of MMP-9. Immunostaining for CXCL12 on synovial and bone tissue biopsies from both rheumatoid arthritis (RA) and osteoarthritis (OA) samples revealed a strong increase in the expression levels under inflammatory conditions. CXCL12 chemokine showed a clear activating role on mature osteoclast by inducing bone-resorbing activity and specific MMP-9 enzymatic release. Moreover, since bone and synovial biopsies from RA patients showed an elevated CXCL12 expression, these findings may provide useful tools for achieving a full elucidation of the complex network that regulates osteoclast function in course of inflammatory diseases.
Determinants of RNA Quality from FFPE Samples (2007)

The large archives of formalin-fixed paraffin-embedded (FFPE) tissue specimens that exist are a highly valuable source of sample material for molecular biological analysis, including gene expression profiling. However, current data on adverse effects of standard pathological practice on the usefulness of biomolecular analytes obtained from such archived specimens is largely anecdotal. Here, we present a systematic examination of the most relevant parameters for integrity and useability of RNA obtained from FFPE samples, including storage time and conditions, fixation time, and specimen size. The results are particularly relevant for any application relying on cDNA synthesis as an initial step of the procedure, such as RT-PCR, and microarray analysis.
UCN-01: a Potent Abrogator of G2 Checkpoint Function in Cancer Cells With Disrupted p53 (1996)

UCN-01 is a potent abrogator of G2 checkpoint control in cancer cells with disrupted p53 function. UCN-01 might be capable of enhancing the effectiveness of DNA-damaging agents in the treatment of tumors with cells lacking normal p53 function.
A Progressive Deposition of Paired Helical Filaments (PHF) in the Brain Characterizes the Evolution of Dementia in Alzheimerʼs Disease. (1991)

Using the monoclonal antibody (mAb) 6.423 which recognizes epitopes of the pronase-resistant core of paired helical filaments (PHF), we studied postmortem frontal cortex from Alzheimer's disease (AD) patients with short (Group II) and long (Group III) histories of clinical dementia. Four cases with clinically unconfirmed dementia and a postmortem diagnosis of AD (Group I) were also studied. In Group I, the 6,423 mAb was negative whereas in Group II, the antibody recognized primarily neurofibrillary tangles (NFT). In contrast, brains in Group III contained a dense network of 6,423-immunoreactive (IR) thread-like structures ("ghost" neurites) and plaque-like structures with granular appearance, in addition to NFT. The number of 6,423-IR structures appeared to be related to the duration of clinical dementia and the age of onset. Furthermore, "ghost" neurites were more abundant in young AD cases. The possible significance of the 6,423-IR pattern in the pathogenesis of AD is discussed.
The RNA binding protein FXR1 is a new driver in the 3q26-29 amplicon and predicts poor prognosis in human cancers (2015)

Aberrant expression of RNA-binding proteins has profound implications for cellular physiology and the pathogenesis of human diseases such as cancer. We previously identified the Fragile X-Related 1 gene (FXR1) as one amplified candidate driver gene at 3q26-29 in lung squamous cell carcinoma (SCC). FXR1 is an autosomal paralog of Fragile X mental retardation 1 and has not been directly linked to human cancers. Here we demonstrate that FXR1 is a key regulator of tumor progression and its overexpression is critical for nonsmall cell lung cancer (NSCLC) cell growth in vitro and in vivo. We identified the mechanisms by which FXR1 executes its regulatory function by forming a novel complex with two other oncogenes, protein kinase C, iota and epithelial cell transforming 2, located in the same amplicon via distinct binding mechanisms. FXR1 expression is a candidate biomarker predictive of poor survival in multiple solid tumors including NSCLCs. Because FXR1 is overexpressed and associated with poor clinical outcomes in multiple cancers, these results have implications for other solid malignancies.
Fas-Associated Factor 1 is a negative regulator of PYRIN-containing Apaf-1-like protein 1 (2009)

PYRIN-containing apoptotic protease-activating factor 1-like proteins (PYPAFs, also called NALPs) participate in inflammatory signaling by regulating nuclear factor-κB (NF-κB) activation and cytokine processing, and have been implicated in autoimmune and inflammatory disorders. However, the precise mechanisms that regulate the signal pathway leading to NF-κB activation are not completely understood. Here, we used yeast two-hybrid assays to identify Fas-associated factor 1 (FAF1) as a protein interacting with the pyrin domains of several PYPAFs. In these assays, FAF1 interacted strongly with PYPAF1, PYPAF3 and PYPAF7, moderately with PYPAF2 and PYNOD but not at all with the pyrin domains of pyrin or the adaptor molecule apoptosis-associated speck-like protein containing a caspase activation and recruit domain (ASC). The interaction between FAF1 and PYPAF1 in mammalian cells was confirmed by immunoprecipitation assays, and the Fas-interacting domain of FAF1 was critical for this interaction. When co-expressed in HEK293 cells, FAF1 interfere with the NF-κB activation induced by PYPAF1 and ASC. A FAF1 mutant lacking the Fas-interacting domain showed significantly reduced ability to inhibit NF-κB activation. In THP-1 cells, the stimulation of NF-κB up-regulated the level of endogenous FAF1. Taken together, these findings suggest that FAF1 functions as a negative regulator of an NF-κB signal pathway that involves PYPAF1 and ASC.
A chaotic PSO approach to multi-mode resource-constraint project scheduling with uncertainty (2011)

In this paper, a new optimisation method based on chaotic particle swarm optimisation (CPSO) algorithm for solving multi-mode resource-constraint project scheduling problem (MRCPSP) under uncertainty is proposed. Fuzzy set theory is used to represent the uncertainties of activity duration. A searching technique using CPSO algorithm is adopted to search for the minimum of fuzzy project completion time. A case with uncertain activity duration is used to illustrate the performance of the proposed method. The result indicates that CPSO algorithm can assist project managers in selecting a schedule with the least possibility of being late in an uncertain scheduling environment.
Pharmacokinetics and tissue distribution of 3-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)benzamide; a novel ALK5 inhibitor and a potential anti-fibrosis drug (2008)

The authors investigated the pharmacokinetics and metabolism of 3-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)benzamide (IN-1130), a novel ALK5 inhibitor, which suppresses renal and hepatic fibrosis, and also exerts anti-metastatic effects on breast cancer-bearing MMTV-cNeu mice model. Plasma half-lives of orally administered IN-1130 were 62.6 min in mice, 76.6 +/- 10.6 min in dogs, 156.1 +/- 19.3 min in rats, and 159.9 +/- 59.9 min in monkeys. IN-1130 showed a high apparent permeability coefficient (P(app)) of (45.0 +/- 2.3) x 10(-6) cm s(-1) in in vitro permeability tests in a Caco-2 cell monolayer model. The bioavailability of orally administered IN-1130 was 84.9% in dogs and 34.4% in monkeys (oral dose, 5.5 mg kg(-1)), 11.4% in rats and 8.95% in mice (oral dose, 50.3 mg kg(-1)), respectively. Orally given IN-1130 was readily distributed into liver, kidneys and lungs. The major metabolite of IN-1130 (M1) was detected in the systemic circulation of rat and mouse and was purified and tentatively identified as 3-((4-(3-hydroxyquinoxaline-6-yl)-5-(6-methylpyridine-2-yl)-1H-imidazol-2-yl)methyl)benzamide or 3-((4-(2-hydroxyquinoxalin-6-yl)-5-(6-methylpyridine-2-yl)-1H-imidazol-2-yl)methyl)benzamide. The highest levels of M1 were found in liver. The results of this study suggest that IN-1130 has the potential to serve as an effective oral anti-fibrotic drug.
Sulfonamidopyrrolidinone Factor Xa Inhibitors:  Potency and Selectivity Enhancements via P-1 and P-4 Optimization (1999)

Sulfonamidopyrrolidinones were previously disclosed as a selective class of factor Xa (fXa) inhibitors, culminating in the identification of RPR120844 as a potent member with efficacy in vivo. Recognizing the usefulness of the central pyrrolidinone template for the presentation of ligands to the S-1 and S-4 subsites of fXa, studies to optimize the P-1 and P-4 groups were initiated. Sulfonamidopyrrolidinones containing 4-hydroxy- and 4-aminobenzamidines were discovered to be effective inhibitors of fXa. X-ray crystallographic experiments in trypsin and molecular modeling studies suggest that our inhibitors bind by insertion of the 4-hydroxybenzamidine moiety into the S-1 subsite of the fXa active site. Of the P-4 groups examined, the pyridylthienyl sulfonamides were found to confer excellent potency and selectivity especially in combination with 4-hydroxybenzamidine. Compound 20b (RPR130737) was shown to be a potent fXa inhibitor (K(i) = 2 nM) with selectivity against structurally related serine proteinases (>1000 times). Preliminary biological evaluation demonstrates the effectiveness of this inhibitor in common assays of thrombosis in vitro (e.g. activated partial thromboplastin time) and in vivo (e.g. rat FeCl(2)-induced carotid artery thrombosis model).
ChemInform Abstract: SYNTHESES OF ACIDS, DERIVATIVES OF 4‐HYDROXY‐1,5‐NAPHTHYRIDINE (1974)

Abstract Im Hinblick auf die bakterizide Aktivität von Negram (Acidum Nalidixicum), einer 1,8‐Naphthyridin‐3‐carbonsäure, werden für bakteriologische Untersuchungen die 1,5‐Naphthyridincarbonsäuren (V) und (X) synthetisiert.
Herbaspirillum colonization increases growth and nitrogen accumulation in aluminium‐tolerant rice varieties (2002)

• Varieties of rice (Oryza sativa) differing in tolerance to aluminium (Al) were evaluated for their N-fixation ability after inoculation with a gusA-marked strain of Herbaspirillum seropedicae Z67. • Under axenic conditions, by 30 d, inoculation resulted in enhanced nitrogenase activity, d. wt, total N and total C content only in the Al-tolerant varieties, and one (cv. Moroberekan) showed significantly more 15N2 incorporation than an Al-sensitive variety (‘IR45’). There were no differences in the number of the bacteria colonizing the different varieties, but the Al-tolerant ones secreted larger amounts of C in their root exudates, and bacteria colonizing the roots of cv. Moroberekan strongly expressed gusA and NifH proteins. • Under glasshouse conditions, by 30 d, inoculation resulted in increased growth of both cvs IR45 and Moroberekan, but the latter showed significantly greater nitrogenase activity and 15N dilution. In a long-term experiment, by 120 d, cv. Moroberekan showed a significant increase in N content after inoculation. • Herbaspirilla were localized on and within roots and aerial parts of cvs Moroberekan and IR45 under both growth conditions. The role of N fixation in growth promotion of rice by H. seropedicae is discussed in terms of availability of C.
Conserved sequence motifs in the initiator proteins for rolling circle DNA replication encoded by diverse replicons from eubacteria, eucaryotes and archaebacteria (1992)

An amino acid motif was identified that consists of the sequence HisHydrHisHydrHydrHydr (Hydr--bulky hydrophobic residue) and is conserved in two vast classes of proteins, one of which is involved in initiation and termination of rolling circle DNA replication, or RCR (Rep proteins), and the other in mobilization (conjugal transfer) of plasmid DNA (Mob proteins). Based on analogies with metalloenzymes, it is hypothesized that the two conserved His residues in this motif may be involved in metal ion coordination required for the activity of the Rep and Mob proteins. Rep proteins contained two additional conserved motifs, one of which was located upstream, and the other downstream from the 'two His' motif. The C-terminal motif encompassed the Tyr residue(s) forming the covalent link with nicked DNA. Mob proteins were characterized by the opposite orientation of the conserved motifs, with the (putative) DNA-linking Tyr being located near their N-termini. Both Rep and Mob protein classes further split into several distinct families. Although it was not possible to find a motif or pattern that would be unique for the entire Rep or Mob class, unique patterns were derived for large subsets of the proteins of each class. These observations allowed the prediction of the amino acid residues involved in DNA nicking, which is required for the initiation of RCR or conjugal transfer of single-stranded (ss) DNA, in Rep and Mob proteins encoded by a number of replicons of highly diverse size, structure and origin. It is conjectured that recombination has played a major part in the dissemination of genes encoding related Rep or Mob proteins among the replicons exploiting RCR. It is speculated that the eucaryotic small ssDNA replicons encoding proteins with the conserved RCR motifs and replicating via RCR-related mechanisms, such as geminiviruses and parvoviruses, may have evolved from eubacterial replicons.
A Simple and Practical Synthesis of 2-Aminoimidazoles (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Simple and Practical Synthesis of 2-AminoimidazolesThomas L. Little and Stephen E. WebberCite this: J. Org. Chem. 1994, 59, 24, 7299–7305Publication Date (Print):December 1, 1994Publication History Published online1 May 2002Published inissue 1 December 1994https://pubs.acs.org/doi/10.1021/jo00103a021https://doi.org/10.1021/jo00103a021research-articleACS PublicationsRequest reuse permissionsArticle Views4095Altmetric-Citations112LEARN 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