gebhart/patrepeval huggingface dataset:
Selective 2′-Hydroxyl Acylation Analyzed by Protection from Exoribonuclease (2020)

Selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) is a powerful approach for characterizing RNA structure and dynamics at single-nucleotide resolution. However, SHAPE technology is limited, sometimes severely, because primer extension detection obscures structural information for ~15 nts at the 5′ end and 40–60 nts at the 3′ end of the RNA. Moreover, detection by primer extension is more complex than the actual structure-selective chemical interrogation step. Here we quantify covalent adducts in RNA directly by adduct-inhibited exoribonuclease degradation. RNA 2′-O-adducts block processivity of a 3′→5′ exoribonuclease, RNase R, to produce fragments that terminate three nucleotides 3′ of the modification site. We analyzed the structure of the native thiamine pyrophosphate (TPP) riboswitch aptamer domain and identified large changes in local nucleotide dynamics and global RNA structure upon ligand binding. In addition to numerous changes that can be attributed to ligand recognition, we identify a single nucleotide bulge register shift, distant from the binding site, that stabilizes the ligand-bound structure. Selective 2′-hydroxyl acylation analyzed by protection from exoribonuclease (RNase-detected SHAPE) should prove broadly useful for facile structural analysis of small non-coding RNAs and for RNAs that have functionally critical structures at their 5′ and 3′ ends.
Analysing Humanly Generated Random Number Sequences: A Pattern-Based Approach (2012)

In a random number generation task, participants are asked to generate a random sequence of numbers, most typically the digits 1 to 9. Such number sequences are not mathematically random, and both extent and type of bias allow one to characterize the brain's "internal random number generator". We assume that certain patterns and their variations will frequently occur in humanly generated random number sequences. Thus, we introduce a pattern-based analysis of random number sequences. Twenty healthy subjects randomly generated two sequences of 300 numbers each. Sequences were analysed to identify the patterns of numbers predominantly used by the subjects and to calculate the frequency of a specific pattern and its variations within the number sequence. This pattern analysis is based on the Damerau-Levenshtein distance, which counts the number of edit operations that are needed to convert one string into another. We built a model that predicts not only the next item in a humanly generated random number sequence based on the item's immediate history, but also the deployment of patterns in another sequence generated by the same subject. When a history of seven items was computed, the mean correct prediction rate rose up to 27% (with an individual maximum of 46%, chance performance of 11%). Furthermore, we assumed that when predicting one subject's sequence, predictions based on statistical information from the same subject should yield a higher success rate than predictions based on statistical information from a different subject. When provided with two sequences from the same subject and one from a different subject, an algorithm identifies the foreign sequence in up to 88% of the cases. In conclusion, the pattern-based analysis using the Levenshtein-Damarau distance is both able to predict humanly generated random number sequences and to identify person-specific information within a humanly generated random number sequence.
Purification of the human apical conjugate export pump MRP2 (1999)

The multidrug resistance protein MRP2 (ABCC2) acts as an ATP-dependent conjugate export pump in apical membranes of polarized cells and confers multidrug resistance. Purified MRP2 is essential for the detailed functional characterization of this member of the family of ATP-binding cassette (ABC) transporter proteins. In human embryonic kidney cells (HEK293), we have permanently expressed MRP2 containing an additional C-terminal (His)6-tag. Immunoblot and immunofluorescence analyses detected the MRP2-(His)6 overexpressing clones. Isolated membrane vesicles from the MRP2-(His)6-expressing cells were active in ATP-dependent transport of the glutathione S-conjugate leukotriene C4 and were photoaffinity-labelled with 8-azido-[alpha-32P]ATP. MRP2-(His)6 was solubilized from membranes of MRP2-(His)6-cells and purified to homogeneity in a three-step procedure using immobilized metal affinity chromatography, desalting, and immunoaffinity chromatography. The identity of the pure MRP2-(His)6 was verified by MS analysis of tryptic peptides. The purified MRP2-(His)6 glycoprotein was reconstituted into proteoliposomes and showed functional activity as ATPase in a protein-dependent manner with a Km for ATP of 2.1 mM and a Vmax of 25 nmol ADP x mg MRP2-1 x min-1. This ATPase activity was substrate-stimulated by oxidized and reduced glutathione and by S-decyl-glutathione. Future studies using pure MRP2 reconstituted in proteoliposomes should allow further insight into the molecular parameters contributing to MRP2 transport function and to define its intracellular partners for transport and multidrug resistance.
A multi-head intradermal electroporation device allows for tailored and increased dose DNA vaccine delivery to the skin (2014)

The identification of an effective and tolerable delivery method is a necessity for the success of DNA vaccines in the clinic. This manuscript describes the development and validation of a multi-headed intradermal electroporation device which would be applicable for delivering multiple DNA vaccine plasmids simultaneously but spatially separated. Reporter gene plasmids expressing green and red fluorescent proteins were used to demonstrate the impact of spatial separation on DNA delivery to increase the number of transfected cells and avoid interference through visible expression patterns. To investigate the impact of plasmid interference on immunogenicity, a disease target was investigated where issues with multi-valent vaccines had been previously described. DNA-based Hantaan and Puumala virus vaccines were delivered separately or as a combination and the effect of multi-valence was determined by appropriate assays. While a negative impact was observed for both antigenic vaccines when delivered together, these effects were mitigated when the vaccine was delivered using the multi-head device. We also demonstrate how the multi-head device facilitates higher dose delivery to the skin resulting in improved immune responses. This new multi-head platform device is an efficient, tolerable and non-invasive method to deliver multiple plasmid DNA constructs simultaneously allowing the tailoring of delivery sites for combination vaccines. Additionally, this device would allow the delivery of multi-plasmid vaccine formulations without risk of impacted immune responses through interference. Such a low-cost, easy to use device platform for the delivery of multi-agent DNA vaccines would have direct applications by the military and healthcare sectors for mass vaccination purposes.
The icon is dead: Long live the icon (1983)

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Sialic acid O-acetylation: From biosynthesis to roles in health and disease (2021)

Sialic acids are nine-carbon sugars that frequently cap glycans at the cell surface in cells of vertebrates as well as cells of certain types of invertebrates and bacteria. The nine-carbon backbone of sialic acids can undergo extensive enzymatic modification in nature and O-acetylation at the C-4/7/8/9 position in particular is widely observed. In recent years, the detection and analysis of O-acetylated sialic acids have advanced, and sialic acid-specific O-acetyltransferases (SOATs) and O-acetylesterases (SIAEs) that add and remove O-acetyl groups, respectively, have been identified and characterized in mammalian cells, invertebrates, bacteria, and viruses. These advances now allow us to draw a more complete picture of the biosynthetic pathway of the diverse O-acetylated sialic acids to drive the generation of genetically and biochemically engineered model cell lines and organisms with altered expression of O-acetylated sialic acids for dissection of their roles in glycoprotein stability, development, and immune recognition, as well as discovery of novel functions. Furthermore, a growing number of studies associate sialic acid O-acetylation with cancer, autoimmunity, and infection, providing rationale for the development of selective probes and inhibitors of SOATs and SIAEs. Here, we discuss the current insights into the biosynthesis and biological functions of O-acetylated sialic acids and review the evidence linking this modification to disease. Furthermore, we discuss emerging strategies for the design, synthesis, and potential application of unnatural O-acetylated sialic acids and inhibitors of SOATs and SIAEs that may enable therapeutic targeting of this versatile sialic acid modification.
Rapid communication: diallelic single-stranded conformational polymorphism detected in the bovine prolactin gene1 (1994)

Journal Article Rapid communication: diallelic single-stranded conformational polymorphism detected in the bovine prolactin gene Get access H. M. Zhang, H. M. Zhang 2Department of Animal Sciences, University of Arizona, Tucson 85721 Search for other works by this author on: Oxford Academic PubMed Google Scholar S. K. DeNise, S. K. DeNise 2Department of Animal Sciences, University of Arizona, Tucson 85721 Search for other works by this author on: Oxford Academic PubMed Google Scholar R. L. Ax R. L. Ax 2Department of Animal Sciences, University of Arizona, Tucson 85721 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Animal Science, Volume 72, Issue 1, January 1994, Page 256, https://doi.org/10.2527/1994.721256x Published: 01 January 1994 Article history Received: 01 September 1993 Accepted: 01 October 1993 Published: 01 January 1994
Nanotechnology's impact on aircraft design and maintenance (2003)

Unique research efforts relating to the development of nanoscale devices to replace standard integrated circuits, and eventually entire electronic systems. Standard integrated circuits (IC) have limitations or restrictions in size, speed, reliability, complexity and finding suitable replacements for discontinued items. Nanoscale device development and understanding has dramatically grown. One of the key properties of quantum physics that quantum computers rely on is the ability of certain atoms or nuclei to work together as quantum bits. These computing devices are a fraction of the size of typical ICs (nanoscale). Nanoscale devices developed using quantum physics principles have unlimited potential to revolutionize the methods and design of fabricated printed circuit cards and complete systems. They can replace an entire PC board or the set of PC boards that comprise a Line Replaceable Unit (LRU). This would be a good and practical jumping-off point to going directly to the complete device, system, or function level. This might include a nanoscale computer (general purpose or flight control), transmitter, GPS receiver, position and/or attitude sensors in either a stand-alone configuration, or combined within conventional devices (e.g., a nanoscale communications suite (xmtr/rcvr, etc.)) encapsulated within the Plexiglas canopy or the control yoke of an F16 rather than behind the instrument panel or maybe the whole comm suite into the pilot's helmet.
Preparation of TiO<sub>2</sub> Fine Particles Supported on Silica Gel as Photocatalyst (1994)

The composite silica gel which supported nanometer-size TiO2 fine particles with platinum was prepared by the sol-gel method in order to obtain a high photocatalytic activity and to discuss the mechanism of photocatalytic hydrogen generation by TiO2 fine particles in aqueous solution.The heat-treated composite gel showed a hydrogen generation rate almost 4 times larger than that of the TiO2 sol in aqueous ethanol solution. However, little hydrogen was generated from pure deionized water.The photocatalytic activity of the composite gel is considered to be affected by both the surface condition and the crystalline phase of TiO2 fine particles when the correlation among the changes with heat treatment in hydrogen generation rate, the amount of photo-generated Ti3+ ions and the structure of composite gel was examined. The superiority of the hydrogen photogeneration rate of the composite gel compared with a TiO2 suspension system is attributed to its controllability of the crystallite size and the crystalline phase of semiconductor fine particles since they remain in a highly dispersive condition during heat treatment.
Artifacts in magnetic resonance imaging from metals (1996)

Metallic biomedical implants, such as aneurysm clips, endoprostheses, and internal orthopedic devices give rise to artifacts in the magnetic resonance image (MRI) of patients. Such artifacts impair the information contained in the image in precisely the region of most interest, namely near the metallic device. Ferromagnetic materials are contraindicated because of the hazards associated with their movement during the MRI procedure. In less-magnetic metals, it has been suggested that the extent of the artifact is related to the magnetic susceptibility of the metal, but no systematic data appear to be available. When the susceptibility is sufficiently small, an additional artifact due to electrical conductivity is observed. We present an initial systematic study of MRI artifacts produced by two low susceptibility metals, titanium (relative permeability μr≊1.0002) and copper (μr≊0.99998), including experimental, theoretical, and computer simulation results.
Abstract C78: Integrin αvβ3 drives stemness in the pregnant and neoplastic mammary gland (2013)

Abstract Carcinoma cell expression of the integrin αvβ3 is associated with enhanced tumorigenicity and metastasis in a diverse array of human tumors. Here, we reveal αvβ3 expression in a subset of CD44+CD24-/low cancer stem cells in human breast tumor biopsies. In fact, αvβ3 is both necessary and sufficient to account for stem-like properties in breast tumor cells, suggesting that αvβ3 may contribute to mammary stem (MaSC)/progenitor cell behavior. While αvβ3 is a luminal progenitor marker in the virgin murine mammary gland, we noted a dramatic, but transient, increase in αvβ3 levels that defined the mammary stem cell pool at mid-pregnancy. Genetic deletion of β3 surprisingly had no effect on luminal progenitor behavior or ductal morphogenesis. In contrast, β3 was specifically required for MaSC clonogenicity and alveologenesis at mid-pregnancy, yet had no influence on MaSCs in the virgin gland. These findings reveal an unexpected role for αvβ3 in driving mammary stemness during pregnancy that may be related to the stem-like properties, and high metastatic potential associated with αvβ3 expression in human breast cancers. Citation Format: Jay Desgrosellier, Jacqueline Lesperance, Laetitia Seguin, David Cheresh. Integrin αvβ3 drives stemness in the pregnant and neoplastic mammary gland. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C78.
Gene markers in brain tumors: What the epileptologist should know (2013)

Gene markers or biomarkers can be used for diagnostic or prognostic purposes for all different types of complex disease, including brain tumors. Prognostic markers can be useful to explain differences not only in overall survival but also in response to treatment and for development of targeted therapies. Multiple genes with specific types of alterations have now been identified that are associated with improved response to chemotherapy and radiotherapy, such as O(6)-methylguanine methyltranferase (MGMT) or loss of chromosomes 1p and/or 19q. Other alterations have been identified that are associated with improved overall survival, such as mutations in isocitrate dehydrogenase 1 (IDH1) and/or isocitrate dehydrogenase 2 (IDH2) or having the glioma CpG island DNA methylator phenotype (G-CIMP). There are many biomarkers that may have relevance in brain tumor-associated epilepsy that do not respond to treatment. Given the rapidly changing landscape of high throughput "omics" technologies, there is significant potential for gaining further knowledge via integration of multiple different types of high genome-wide data. This knowledge can be translated into improved therapies and clinical outcomes for patients with brain tumors.
Discussion on microbial contamination of naval fuels (2009)

Discussion on microbial contamination of naval fuelsArticle Deals with problem of naval fuels' microbial contamination. This problem in Poland is not well known and described, but operational problems encountered very often prove that this is a very serious problem. Examples of laboratory tests performed on real samples are presented as well as possible effects of microbial contamination are discussed. Authors also suggest continuous monitoring of naval fuels as main preventive tool. Article covers following topics:• general information about microorganisms present in naval fuels• conditions necessary for microbial growth, with special attention to conditions encountered on vessels• operational problems resulting from microbial contamination• methods of microorganisms detection and examples of preventive actions.
Pathway and control of sucrose import into initiating cotton fibre cells (2000)

This paper originates from a presentation at the International Conference on Assimilate Transport and Partitioning, Newcastle, NSW, August 1999 Our aim is to unravel the mechanisms controlling fibre cell initiation from the epidermis of cotton ( Gossypium hirsutum L.) ovules. We compared the development of fibres and trichomes in wild type cotton and a fibreless seed ( fls ) mutant, and determined the cellular pathway of sucrose transport into fibre initials on the day of anthesis. Although fibre initiation is inhibited in the fls mutant, leading to the fibreless phenotype, trichome development in other parts of the plant is normal. Confocal imaging analysis revealed that the fluorescent molecule, 5(6)-carboxyfluorescein, which is transported symplastically, moved readily from the integument phloem into initiating fibres. Plasmolysis studies showed that the fibre initials and adjacent non-initiating ovule epidermal cells have similar osmotic potential. Immunolocalisation analysis showed the absence of sucrose transporter proteins in the initiating fibre, but their abundance in the transfer cell precursors at the innermost integument. These results (i) demonstrate that fibre cell initiation is controlled by unique mechanism(s) that differ from that for normal trichome development; (ii) show a symplastic pathway of sucrose import into initiating fibres and strengthen the current opinion that sucrose synthase is likely to be the key enzyme mobilising sucrose into initiating fibres; and (iii) suggest that the initial protrusion of the fibre cells above the ovule surface is largely achieved by increased cell wall extensibility rather than higher turgor as is commonly thought.
HG-03 * A NOVEL MOUSE MODEL OF YOUNG ADULT GLIOBLASTOMA: IN VIVO EXPRESSION OF MUTATED IDH1 (R132H) GENE USING THE SLEEPING BEAUTY TRANSPOSASE SYSTEM (2015)

Glioblastoma Multiforme (GBM) is a malignant primary brain tumor. Genomic analysis of GBMs revealed somatic mutations associated with particular subtypes, which correlate with age at the time of diagnosis. Young adult GBMs include a mutation in Isocitrate Dehydrogenase 1 gene (IDH1-R132H) and mutations in epigenetic regulators, ATRX and H3.3G34, which define an epigenetic and biological subgroup. IDH1-R132H results in gain of an alternative enzymatic function producing the metabolite 2-hydroxglutarate (2HG) and alterations in histone methylation patterns. Animal models are critical to study and understand disease progression and pathogenesis; therefore we developed an in vivo model of young adult GBM through expression of IDH1-R132H, H3.G34 and ATRX knockdown in neonatal mouse brain using the Sleeping Beauty Transposase system. In this model we are studying the effects of these genetic lesions in tumor development and DNA repair mechanisms. The tumors were induced by injection of NRAS and shP53 plasmids in the lateral ventricle of C57BL/6 neonatal mice with or without pKT/IDH1-R132H, Pkt/H3.G34 or PT2/shATRX. Plasmid delivery into stem cells lining the lateral ventricle and tumor progression was monitored by luciferase imaging. The tumors were also used to generate neurospheres for genetic analysis; moribund animals were perfused and analyzed using immunocytochemistry. IDH1-R132H expression increased the levels of H3K27me3 and enhanced median survival of the mice. The groups representing young adult GBM: NRAS/shP53/shATRX/IDH1-R132H and NRAS/shP53/shATRX/H3.G34 also exhibited increased survival compared with the control (NRAS/shP53) and the pediatric (NRAS/shP53/shATRX) groups. Mice developed brain tumors harboring key features of young adult GBMs. We aim to determine the impact of these genetic lesions in median survival, tumor progression and DNA repair mechanisms “in vivo”. Supported by NIH-NINDS grants, the Department of Neurosurgery and Leah's Happy Hearts Foundation to MGC and PRL, and very generous support from Phil F. Jenkins.
Les anti-angiogéniques bientôt en traitement adjuvant ? (2017)

Wu et al. Efficacy of cotargeting angiopoietin-2 and the VEGF pathway in the adjuvant postsurgical setting for early breast, colorectal, and renal cancers. Cancer Research 2016; 76: 6988-7000.
Optimal roughness for minimal adhesion (2007)

Roughness has a significant affect on adhesion. The authors used a single-asperity model to describe a smooth tip in contact with a rough surface and predicted that an optimal size of asperity yields a minimum of adhesion. Experimentally, adhesive forces on silicon wafers with varying roughness were measured using atomic-force-microscopy cantilevers with varying tip radii. It was found that minima do exist, and for all tip radii, the adhesion falls significantly for roughness greater than 1–2nm and drops at higher roughness for larger tips. This work should help minimize stiction in microelectromechanical systems and progress the understanding of nanoscale-contact mechanics.
The Significance of Eccentric and Central Hyperpigmentation, Multifocal Hyper/hypopigmentation, and the Multicomponent Pattern in Melanocytic Lesions Lacking Specific Dermoscopic Features of Melanoma (2008)

Based on our study results and previous prevalence data on these global patterns in benign nevi, we do not believe that lesions with EH or MCP require closer observation than other benign nevi lacking specific dermoscopic features of melanoma.