gebhart/patrepeval huggingface dataset:
Sense- and antisense-mediated gene silencing in tobacco is inhibited by the same viral suppressors and is associated with accumulation of small RNAs (2001)

Antisense-mediated gene silencing (ASGS) and posttranscriptional gene silencing (PTGS) with sense transgenes markedly reduce the steady-state mRNA levels of endogenous genes similar in transcribed sequence. RNase protection assays established that silencing in tobacco plants transformed with plant-defense-related class I sense and antisense chitinase (CHN) transgenes is at the posttranscriptional level. Infection of tobacco plants with cucumber mosaic virus strain FN and a necrotizing strain of potato virus Y, but not with potato virus X, effectively suppressed PTGS and ASGS of both the transgenes and homologous endogenes. This suggests that ASGS and PTGS share components associated with initiation and maintenance of the silent state. Small, ca. 25-nt RNAs (smRNA) of both polarities were associated with PTGS and ASGS in CHN transformants as reported for PTGS in other transgenic plants and for RNA interference in Drosophila. Similar results were obtained with an antisense class I beta-1,3-glucanase transformant showing that viral suppression and smRNAs are a more general feature of ASGS. Several current models hold that diverse signals lead to production of double-stranded RNAs, which are processed to smRNAs that then trigger PTGS. Our results provide direct evidence for mechanistic links between ASGS and PTGS and suggest that ASGS could join a common PTGS pathway at the double-stranded RNA step.
Sequence-Specific Fluorescence Detection of DNA by Polyamide−Thiazole Orange Conjugates (2005)

Fluorescent methods to detect specific double-stranded DNA sequences without the need for denaturation may be useful in the field of genetics. Three hairpin pyrrole-imidazole polyamides 2-4 that target their respective sequences 5'-WGGGWW-3', 5'-WGGCCW-3', and 5'-WGWWCW-3' (W = A or T) were conjugated to thiazole orange dye at the C-termini to examine their fluorescence properties in the presence and absence of match duplex DNA. The conjugates fluoresce weakly in the absence of DNA but showed significant enhancement (>1000-fold) upon the addition of 1 equiv of match DNA and only slight enhancement with the addition of mismatch DNA. The polyamide-dye conjugates bound specific DNA sequences with high affinity (Ka > 10(8) M(-1)) and unwound the DNA duplex through intercalation (unwinding angle, phi, approximately 8 degrees). This new class of polyamides provides a method to specifically detect DNA sequences without denaturation.
Role of macrophage colony-stimulating factor in atherosclerosis: studies of osteopetrotic mice. (1997)

Previous in vitro and in vivo studies have suggested that macrophage colony-stimulating factor (M-CSF) plays a role in atherogenesis. To examine this hypothesis, we have studied atherogenesis in osteopetrotic (op/op) mice, which lack M-CSF due to a structural gene mutation. Atherogenesis was induced either by feeding the mice a high fat, high cholesterol diet or by crossing op mice with apolipoprotein E (apo E) knockout mice to generate mice lacking both M-CSF and apo E. In both the dietary and apo E knockout models, M-CSF deficiency resulted in significantly reduced atherogenesis. For example, in the apo E knockout model, homozygosity for the op mutation totally abolished aortic atherogenesis in male mice and reduced the size of the lesions approximately 97% in female mice. Mice heterozygous for the op mutation also exhibited a significant decrease in lesion size. Among apo E knockout mice, the frequency of atherosclerosis in aortic arch was 0/6 (op/op), 1/15 (op/+), and 12/16 (+/+). The effect of the M-CSF on atherosclerosis did not appear to be mediated by changes in plasma lipoproteins, as the op mice exhibited higher levels of atherogenic lipoprotein particles. The effects of the op mutation on atherogenesis may have resulted from decreased circulating monocytes, reduced tissue macrophages, or diminished arterial M-CSF.
Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells. (1993)

Vascular cell adhesion molecule 1 (VCAM-1) is expressed in both endothelial and epithelial cell types, where it contributes to lymphocyte migration to sites of inflammation. Its expression is regulated by cytokines, in part through two kappa B-like regulatory elements. Because NF-kappa B can be composed of multiple alternative subunits with differential effects on gene expression, the role of different specific NF-kappa B family members subunits in VCAM-1 regulation is unknown. In this report, we define the contribution of different NF-kappa B family members to VCAM-1 gene regulation. We show that both kappa B sites in the VCAM-1 enhancer are required to optimally stimulate gene expression, but the enhancer is differentially regulated by specific combinations of NF-kappa B subunits. At low concentrations, RelA(p65) acted in concert with the approximately 50-kDa product of p105 NF-kappa B, NF-kappa B1(p50), to stimulate transcription, and at high concentrations, RelA(p65) alone stimulated the VCAM-1 promoter. In contrast, NF-kappa B2 inhibited functional activation of the VCAM reporter by p65. Consistent with this finding, an additional binding complex was detected by using recombinant NF-kappa B2(p49)/RelA(p65) with radiolabeled VCAM kappa B site probes. Interestingly, the human immunodeficiency virus enhancer responded differently to stimulation by NF-kappa B subunits, with optimal response to p49(100)/p65. Analysis of NF-kappa B mRNA in human umbilical vein endothelial cells revealed that nfkb1, nfkb2, and relA NF-kappa B but not c-rel were induced by tumor necrosis factor alpha and lipopolysaccharide, which also induce VCAM-1. These data suggest that specific subunits of NF-kappa B regulate VCAM-1 and differentially activate other genes in these cells.
Genome-Wide Identification of Potential Plant E2F Target Genes (2005)

Entry into the S phase of the cell cycle is controlled by E2F transcription factors that induce the transcription of genes required for cell cycle progression and DNA replication. Although the E2F pathway is highly conserved in higher eukaryotes, only a few E2F target genes have been experimentally validated in plants. We have combined microarray analysis and bioinformatics tools to identify plant E2F-responsive genes. Promoter regions of genes that were induced at the transcriptional level in Arabidopsis (Arabidopsis thaliana) seedlings ectopically expressing genes for the E2Fa and DPa transcription factors were searched for the presence of E2F-binding sites, resulting in the identification of 181 putative E2F target genes. In most cases, the E2F-binding element was located close to the transcription start site, but occasionally could also be localized in the 5' untranslated region. Comparison of our results with available microarray data sets from synchronized cell suspensions revealed that the E2F target genes were expressed almost exclusively during G1 and S phases and activated upon reentry of quiescent cells into the cell cycle. To test the robustness of the data for the Arabidopsis E2F target genes, we also searched for the presence of E2F-cis-acting elements in the promoters of the putative orthologous rice (Oryza sativa) genes. Using this approach, we identified 70 potential conserved plant E2F target genes. These genes encode proteins involved in cell cycle regulation, DNA replication, and chromatin dynamics. In addition, we identified several genes for potentially novel S phase regulatory proteins.
Defective inflammatory response in interleukin 6-deficient mice. (1994)

Systemic and localized inflammation elicit a number of host responses which include fever, cachexia, hypoglycemia, and major changes in the concentration of liver plasma proteins. Interleukin 6 (IL-6) is considered an important mediator of the inflammatory response, together with IL-1 and tumor necrosis factor alpha (TNF-alpha). The purpose of this study was to unequivocally determine the role of IL-6 in these phenomena making use of IL-6-deficient mice that we have recently generated by gene targeting. We report here that in the absence of IL-6, mice are unable to mount a normal inflammatory response to localized tissue damage generated by turpentine injection. The induction of acute phase proteins is dramatically reduced, mice do not lose body weight and only suffer from mild anorexia and hypoglycemia. In contrast, when systemic inflammation is elicited through the injection of bacterial lipopolysaccharide (LPS), these parameters are altered to the same extent both in wild-type and IL-6-deficient mice, demonstrating that under these conditions IL-6 function is dispensable. Moreover, we show that LPS-treated IL-6-deficient mice produce three times more TNF-alpha than wild-type controls, suggesting that increased TNF-alpha production might be one of the compensatory mechanisms through which a normal response to LPS is achieved in the absence of IL-6. We also show that corticosterone is normally induced in IL-6-deficient mice, demonstrating that IL-6 is not required for the activation of the hypothalamic-pituitary-adrenal axis. Our results reinforce the idea that different patterns of cytokines are involved in systemic and localized tissue damage, and identify IL-6 as an essential mediator of the inflammatory response to localized inflammation.
Biodegradable Poly(Lactic Acid) and Poly (Lactide-Co-Glycolide) Polymers in Sustained Drug Delivery (1990)

Poly(lactic acid) [PLA] and its co-polymers with glycolic acid [PLCG] have been known for the past 20 years of its biodegradability and histocompatibility. Their physico-chemical and biological properties have been found suitable, in many instances, for sustaining drug release in vivo and in vitro from days to months. A wide variety of drugs ranging from small molecular weight therapeutic agents to peptide hormones, antibiotics, chemotherapeutic drugs have been studied using these biodegradable polymers. Several parenteral and oral dosage forms have been investigated, which includes microcapsules, implants, pseudolatices, nanoparticles, tablets, films as well as occular devices for local delivery of drug into the eye. An attempt have been taken in this paper to review the prospect of using these biodegradable polymers for long term parenteral drug delivery of different classes of drugs.
Picture My Voice : Audio to Visual Speech Synthesis using Artificial Neural Networks (1999)

This paper presents an initial implementation and evaluation of a system that synthesizes visual speech directly from the acoustic waveform. An artifical neural network (ANN) was trained to map the cepstral coefficients of an individual&amp;apos;s natural speech to the control parameters of an animated synthetic talking head. We trained on two data sets; one was a set of 400 words spoken in isolation by a single speaker and the other a subset of extemporaneous speech from 10 different speakers. The system showed learning in both cases. A perceptual evaluation test indicated that the system&amp;apos;s generalization to new words by the same speaker provides significant visible information, but significantly below that given by a text-to-speech algorithm. 1. INTRODUCTION Persons find it hard to communicate when the auditory conditions are poor, e.g. due to noise, limited bandwidth, or hearing-impairment. Under such circumstances, face-to-face communication is preferable. The visual component of speech c...
Spectral Similarity and Difference of Naphthalenetetracarboxylic Dianhydride, Perylenetetracarboxylic Dianhydride, and Their Derivatives (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpectral Similarity and Difference of Naphthalenetetracarboxylic Dianhydride, Perylenetetracarboxylic Dianhydride, and Their DerivativesMasafumi Adachi, Yukichi Murata, and Shinichiro NakamuraCite this: J. Phys. Chem. 1995, 99, 39, 14240–14246Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/j100039a009https://doi.org/10.1021/j100039a009research-articleACS PublicationsRequest reuse permissionsArticle Views917Altmetric-Citations87LEARN 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 options Get e-Alerts
Neuroendocrine Prostate Cancer After Hormonal Therapy: Knowing Is Half the Battle (2014)

Article Tools ONCOLOGY GRAND ROUNDS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2014.57.5100 Journal of Clinical Oncology - published online before print September 15, 2014 PMID: 25225431 Neuroendocrine Prostate Cancer After Hormonal Therapy: Knowing Is Half the Battle Scott T. TagawaxScott T. TagawaSearch for articles by this author Show More Weill Cornell Medical College, New York, NY https://doi.org/10.1200/JCO.2014.57.5100 First Page Full Text PDF Figures and Tables © 2014 by American Society of Clinical Oncology
Ultrathin (&#x223C;2nm) HfO<inf>x</inf> as the fundamental resistive switching element: Thickness scaling limit, stack engineering and 3D integration (2014)

This paper addresses the thickness scaling limit of HfO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</inf> -based RRAM through a combination of theoretical calculations of electron transport and experimental demonstration of 2nm-HfO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</inf> devices. The comparison of 2nm devices with thicker references and bilayer stacks confirm the switching thickness is less than 2nm. The 3D integration of 2nm-HfO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</inf> devices enables much larger array size and leads to superior performances compared to planar devices.
Analogs of (2‘-5‘)oligo(A). Endonuclease activation and inhibition of protein synthesis in intact cells. (1981)

Synthetic analogs of (2'-5')oligo(A) were assayed for endonuclease activation in cell extracts and for inhibition of protein synthesis in intact cells. The analogs are triadenylates: (i) methylated in the terminal 3'-OH; (ii) methylated at all three 3'-OH groups; (iii) with different numbers of phosphate groups at the 5' terminus or with a methylene group between the beta- and gamma-phosphate. Only 5'-phosphorylated monomethylated analogs activate an endonuclease in cell extracts and are powerful inhibitors of protein synthesis in intact cells. The analogs with only one 5'-terminal phosphate may require addition of another phosphate for activity since the kinase inhibitor 2-aminopurine prevents endonuclease activation by this compound but not by the di- and triphosphate-terminated triadenylates. These results suggest that two terminal phosphates and one or two free 3'-OH are required for endonuclease activation and inhibition of protein synthesis. The monomethylated analogs are more active than (2'-5')pppA3 because of their resistance to degradation by cellular enzymes. Accordingly, the monomethylated analogs cause a prolonged inhibition of protein synthesis in human fibroblasts treated with nanomolar concentrations of these compounds.
Seven Strains of Enterovirus D68 Detected in the United States during the 2014 Severe Respiratory Disease Outbreak (2014)

ABSTRACT Clusters of severe respiratory disease in the United States were reported to the CDC beginning in August 2014. Enterovirus D68 (EV-D68) was identified from 83% (30/36) of initial severe cases. Investigations in August and September found severe EV-D68 cases to be widespread across the United States. We report seven EV-D68 genomes from the outbreak.
and denatured protein substrates (2015)

Abstract: An understanding of the binding specfficity of leukocyte integrins is important to determine the range of ligands that interact with these receptors during inflammatory processes. In this study we show that the a4131 integrin can interact with casein and denatured albumin and promote leukocyte adhesion through these interactions. This was demonstrated with the use of blocking antibodies directed to a43j and peptide adhesion competitors containing the a43i binding tripeptide, Leu-Asp-Val (LDV). Consistent with this data, the adhesion is completely divalent cation-dependent and is stimulated by known activators of leukocyte integrin function, namely phorbol ester and the integrm activating antibody, 8A2. It is inter-esting to note that neither bovine a-casein or human albumin contain an LDV site (present in the CS-i site of alternatively spliced fibronectin) or an IDS site (pres-ent in VCAM-1) yet they promote adhesion through this integrin. Furthermore, a413j directly binds to Sepharose columns containing casein, casein frag-ments, or denatured albumin but does not bind col-umns containing native albumin. These data suggest that the binding specfficity for the integrin is con-siderably broader than previously realized. This work has implications for how subsets of leukocytes may interact with damaged proteins during tissue injury and
Human recombinant antibodies specific for hepatitis C virus core and envelope E2 peptides from an immune phage display library (1996)

Hepatitis C virus (HCV) is the aetiological agent responsible for most cases of non-A non-B hepatitis. Hepatitis C is a disease of clinical importance because of its high infection rate in blood donors and its persistence as chronic infections which may lead to cirrhosis and hepatocellular carcinoma in the long term. The variability of the HCV genome has posed difficulties in serological detection and vaccine design. The recent advance in phage technology offers a means of cloning human anti-HCV antibodies of a defined specificity that may have potential therapeutic use. We now report the generation of a phage display library using the V(H) genes of a HCV-infected patient and the V(L) genes of two non-immune individuals. From this library we were able to obtain specific IgG single-chain Fvs (scFvs) that recognize viral core and envelope proteins by selection on synthetic peptides derived from the core sequence PKARRPEGRTWAQPG and the envelope E2 sequence RPIDDFDQGWGPITY. The specificity of the scFvs was demonstrated by their specific reactions with homologous peptides in ELISA and the specific blocking of scFv binding by homologous peptides, in a dose-dependent manner, in inhibition ELISA. The binding of the anticore 4c2 to homologous peptide was blocked by HCV-positive human sera in an antibody-concentration-dependent manner, suggesting that the scFv recognizes a similar if not identical epitope to those of one or more of the polyclonal antibodies present in the sera.
DistAl: An inter-pattern distance-based constructive learning algorithm (1999)

Multi-layer networks of threshold logic units (TLU) offer an attractive framework for the design of pattern classification systems. A new constructive neural network learning algorithm (DistAl) based on inter-pattern distance is introduced. DistAl constructs a single hidden layer of hyperspherical threshold neurons. Each neuron is designed to determine a cluster of training patterns belonging to the same class. The weights and thresholds of the hidden neurons are determined directly by comparing the inter-pattern distances of the training patterns. This offers a significant advantage over other constructive learning algorithms that use an iterative (and often time consuming) weight modification strategy to train individual neurons. The individual clusters (represented by the hidden neurons) are combined by a single output layer of threshold neurons. The speed of DistAl makes it a good candidate for datamining and knowledge acquisition from large datasets. The paper presents results of experiments using several artificial and real-world datasets. The results demonstrate that DistAl compares favorably with other learning algorithms for pattern classification.
859 Inhibition of the kinase activity of hematopoietic progenitor kinase 1 enhances anti-PD-1-induced reinvigoration of human tumor-infiltrating CD8+ T cells (2020)

<h3>Background</h3> Immune checkpoint inhibitors (ICIs) including anti-CTLA-4, anti-PD-1, and anti-PD-L1 have been clinically used for the treatment of various types of cancer. However, ICIs have a limited efficacy, and it is required to develop a strategy to enhance the efficacy of ICIs. Hematopoietic progenitor kinase 1 (HPK1) was recently known to inhibit T cell receptor (TCR) signaling by targeting SLP76 thus suppress T-cell effector functions. <h3>Methods</h3> In the present study, we examined the expression of HPK-1 and SLP76 in tumor-infiltrating lymphocytes (TILs) obtained from renal cell carcinoma tissues, in relation with the expression of PD-1 and other immune checkpoint receptors by performing flow cytometry analysis. In addition, we examined if inhibition of the kinase activity of HPK1 by CMPD0914, that is a potent, selective and orally available HPK1 inhibitor, enhanced effector functions of tumor-infiltrating CD8+ T cells in the presence of anti-PD-1 blocking antibodies. <h3>Results</h3> First, we found that HPK1 and SLP76 are expressed in both CD8+ and CD4+ T cells including Foxp3+ regulatory T cells irrespective of PD-1 expression. Intriguingly, the expression levels of HPK1 and SLP76 were significantly higher in the PD-1bright population compared to the PD-1- or PD-1dim populations. Further characterization revealed that HPK1 and SLP76 were highly expressed in CD8+ T-cell populations expressing TOX, a transcription regulator of T-cell exhaustion, or TCF-1, a transcription factor related to progenitor-like exhausted T cells. In ex vivo functional assays, anti-PD-1 treatment increased the production of IFN-γ and TNF, and the expression of a proliferation marker, Ki-67 among tumor-infiltrating CD8+ T cells. Interestingly, the effects of anti-PD-1 treatment were further enhanced by the combination treatment with CMPD0914. <h3>Conclusions</h3> In summary, we demonstrated that HPK1 and SLP76 are expressed by human tumor-infiltrating T cells, particularly PD-1brightCD8+ T cells, and that anti-PD-1-induced T-cell reinvigoration is significantly enhanced by an HPK1 inhibitor, CMPD0914, rationalizing the combination of anti-PD1/PD-L1 and HPK1 inhibitors for the treatment of cancer.