gebhart/patrepeval huggingface dataset:
In vivo terahertz imaging of rat skin burns (2012)

A reflective, pulsed terahertz (THz) imaging system was used to acquire high-resolution (d(10-90)/λ~1.925) images of deep, partial thickness burns in a live rat. The rat's abdomen was burned with a brass brand heated to ~220°C and pressed against the skin with contact pressure for ~10 sec. The burn injury was imaged beneath a Mylar window every 15 to 30 min for up to 7 h. Initial images display an increase in local water concentration of the burned skin as evidenced by a marked increase in THz reflectivity, and this likely correlates to the post-injury inflammatory response. After ~1 h the area of increased reflectivity consolidated to the region of skin that had direct contact with the brand. Additionally, a low reflecting ring of tissue could be observed surrounding the highly reflective burned tissue. We hypothesize that these regions of increased and decreased reflectivity correlate to the zones of coagulation and stasis that are the classic foundation of burn wound histopathology. While further investigations are necessary to confirm this hypothesis, if true, it likely represents the first in vivo THz images of these pathologic zones and may represent a significant step forward in clinical application of THz technology.
Molecular cloning of a human gene (S31) encoding a novel serotonin receptor mediating inhibition of adenylyl cyclase (1992)

We report the molecular cloning of human gene (S31) containing an open reading frame of 1095 nucleotides, which encodes a protein of 365 amino acids. The encoded protein contains seven hydrophobic putative transmembrane domains considered the hallmark of G protein-coupled receptors. The amino acid sequence shows highest homology to receptors for serotonin (5-hydroxytryptamine). Expression of this receptor in murine Ltk- cells conferred upon these cells the ability to respond to serotonin by inhibition of adenylyl cyclase. No response was observed to isoproterenol, epinephrine, histamine, dopamine or melatonin in the transfected cells. We propose that the human gene S31 encodes a novel serotonin receptor.
Electrophysiological Mapping and Histological Examinations of the Swine Atrium with Sustained (≥24 h) Atrial Fibrillation: A Suitable Animal Model for Studying Human Atrial Fibrillation (2003)

Pacing-induced sustained AFib (> or =24 h) in adult pigs is a feasible and efficient animal model with electrophysiological and histological characteristics closely similar to those seen in humans.
Direct costs and health-related resource utilisation in the 6 months after insulin initiation in German patients with type 2 diabetes mellitus in 2006: INSTIGATE study (2008)

Resource utilisation and costs related to diabetes increased in the 6 months following insulin initiation, mainly driven by specialist care resource use, insulin, and blood glucose monitoring. Total direct costs of diabetes care of the patients with a less favourable profile of BMI and HbA(1c) at baseline are higher compared to other patients.
Contrasting chromatin organization of CpG islands and exons in the human genome (2010)

Human promoters containing a CpG island tend to remain nucleosome-free as well as methylation-free. In contrast, exons demonstrate a high degree of methylation and nucleosome occupancy. Exonic DNA methylation seems to function together with exonic nucleosomes and H3K36me3 for the proper splicing of transcripts with different expression levels.
The ligninase of Phanerochaete chrysosporium generates cation radicals from methoxybenzenes. (1985)

The hemoprotein ligninase of Phanerochaete chrysosporium catalyzes, in the presence of H2O2, a variety of seemingly different oxidations in lignin and lignin model compounds. Here we show that the enzyme also catalyzes the oxidation of various methoxybenzenes. ESR spectroscopy shows that the compounds are oxidized to aryl cation radicals. These decompose, evidently by H2O addition. Thus, 1,4-dimethoxybenzene is converted to p-benzoquinone and methanol. We propose a unified mechanism, based on formation of aryl cation radicals, to explain the various reactions catalyzed by the ligninase.
Diverging Divergences: Examining Variants of Jensen Shannon Divergence for Corpus Comparison Tasks (2020)

Jensen-Shannon divergence (JSD) is a distribution similarity measurement widely used in natural language processing. In corpus&#13;\ncomparison tasks, where keywords are extracted to reveal the divergence between different corpora (for example, social media posts&#13;\nfrom proponents of different views on a political issue), two variants of JSD have emerged in the literature. One of these uses a weighting&#13;\nbased on the relative sizes of the corpora being compared. In this paper we argue that this weighting is unnecessary and, in fact, can lead&#13;\nto misleading results. We recommend that this weighted version is not used. We base this recommendation on an analysis of the JSD&#13;\nvariants and experiments showing how they impact corpus comparison results as the relative sizes of the corpora being compared change.
Direct observation of R-loop formation by single RNA-guided Cas9 and Cascade effector complexes (2014)

Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems protect bacteria and archaea from infection by viruses and plasmids. Central to this defense is a ribonucleoprotein complex that produces RNA-guided cleavage of foreign nucleic acids. In DNA-targeting CRISPR-Cas systems, the RNA component of the complex encodes target recognition by forming a site-specific hybrid (R-loop) with its complement (protospacer) on an invading DNA while displacing the noncomplementary strand. Subsequently, the R-loop structure triggers DNA degradation. Although these reactions have been reconstituted, the exact mechanism of R-loop formation has not been fully resolved. Here, we use single-molecule DNA supercoiling to directly observe and quantify the dynamics of torque-dependent R-loop formation and dissociation for both Cascade- and Cas9-based CRISPR-Cas systems. We find that the protospacer adjacent motif (PAM) affects primarily the R-loop association rates, whereas protospacer elements distal to the PAM affect primarily R-loop stability. Furthermore, Cascade has higher torque stability than Cas9 by using a conformational locking step. Our data provide direct evidence for directional R-loop formation, starting from PAM recognition and expanding toward the distal protospacer end. Moreover, we introduce DNA supercoiling as a quantitative tool to explore the sequence requirements and promiscuities of orthogonal CRISPR-Cas systems in rapidly emerging gene-targeting applications.
Vinyl Sulfones as Mechanism-Based Cysteine Protease Inhibitors (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTVinyl Sulfones as Mechanism-Based Cysteine Protease InhibitorsJames T. Palmer, David Rasnick, Jeffrey L. Klaus, and Dieter BrommeCite this: J. Med. Chem. 1995, 38, 17, 3193–3196Publication Date (Print):August 1, 1995Publication History Published online1 May 2002Published inissue 1 August 1995https://pubs.acs.org/doi/10.1021/jm00017a002https://doi.org/10.1021/jm00017a002research-articleACS PublicationsRequest reuse permissionsArticle Views3766Altmetric-Citations410LEARN 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
Nitric Oxide and Peroxynitrite Interactions with Mitochondria (2002)

Nitric oxide (*NO) and peroxynitrite (ONOO-) avidly interact with mitochondrial components, leading to a range of biological responses spanning from the modulation of mitochondrial respiration, mitochondrial dysfunction to the signaling of apoptotic cell death. Physiological levels of *NO primarily interact with cytochrome c oxidase, leading to a competitive and reversible inhibition of mitochondrial oxygen uptake. In turn, this leads to alterations in electrochemical gradients, which affect calcium uptake and may regulate processes such as mitochondrial transition pore (MTP) opening and the release of pro-apoptotic proteins. Large or persistent levels of *NO in mitochondria promote mitochondrial oxidant formation. Peroxynitrite formed either extra- or intra-mitochondrially leads to oxidative damage, most notably at complexes I and II of the electron transport chain, ATPase, aconitase and Mn-superoxide dismutase. Mitochondrial scavenging systems for peroxynitrite and peroxynitrite-derived radicals such as carbonate (CO3*-) and nitrogen dioxide radicals (*NO2) include cytochrome c oxidase, glutathione and ubiquinol and serve to partially attenuate the reactions of these oxidants with critical mitochondrial targets. Detection of nitrated mitochondrial proteins in vivo supports the concept that mitochondria constitute central loci of the toxic effects of excess reactive nitrogen species. In this review we will provide an overview of the biochemical mechanisms by which *NO and ONOO- regulate or alter mitochondrial functions.
ENCODE data at the ENCODE portal (2015)

The Encyclopedia of DNA Elements (ENCODE) Project is in its third phase of creating a comprehensive catalog of functional elements in the human genome. This phase of the project includes an expansion of assays that measure diverse RNA populations, identify proteins that interact with RNA and DNA, probe regions of DNA hypersensitivity, and measure levels of DNA methylation in a wide range of cell and tissue types to identify putative regulatory elements. To date, results for almost 5000 experiments have been released for use by the scientific community. These data are available for searching, visualization and download at the new ENCODE Portal (www.encodeproject.org). The revamped ENCODE Portal provides new ways to browse and search the ENCODE data based on the metadata that describe the assays as well as summaries of the assays that focus on data provenance. In addition, it is a flexible platform that allows integration of genomic data from multiple projects. The portal experience was designed to improve access to ENCODE data by relying on metadata that allow reusability and reproducibility of the experiments.
ISDN reaches the market (1995)

The integrated-services digital network, for 10 years seen only in limited installations, is branching out around the world. The author describes how telephone carriers are now starting to report a big boost in ISDN installations. He details how the surge is the result of an increasing appetite for bandwidth, a broadening suite of ISDN-enabled applications, wider availability of the network's services, and better prices for service and equipment.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Integrative Analysis Reveals Relationships of Genetic and Epigenetic Alterations in Osteosarcoma (2012)

Integrative analysis of genome-wide genetic and epigenetic alterations identified dependencies and relationships between DNA copy number, DNA methylation and mRNA expression in osteosarcomas, contributing to better understanding of osteosarcoma biology.
Induction of strong and persistent MelanA/MART‐1‐specific immune responses by adjuvant dendritic cell‐based vaccination of stage II melanoma patients (2005)

A significant percentage of stage II melanoma patients (tumor thickness>1 mm) remain at risk of tumor recurrence after primary tumor excision. In this study, we used tumor antigen-pulsed dendritic cells as an adjuvant for immunization of these "high-risk" melanoma patients after resection of the primary tumor. A total of 13 patients were included and vaccinated 6 times every 14 days with autologous dendritic cells pulsed with a MelanA/MART-1 peptide in combination with a recall antigen. Antigen-specific immune responses were monitored before, during and up to 1 year after the last vaccination. The majority of patients exhibited increased recall antigen-specific CD4+ T cell responses upon vaccination. MelanA/MART-1-specific CD8+ T cells were expanded in 9/13 patients resulting in increased frequencies of memory cells in these patients. CD8+ T cells acquired the capacity to secrete IFN-gamma, to proliferate in culture in response to the tumor antigen used for vaccination and postvaccine samples contained MelanA/MART-1-specific T cells that recognized also the natural MelanA/MART-1-antigen expressed by tumor cells. Moreover, vaccination induced a long-lived tumor antigen-specific DTH-reactivity in the majority of the patients, detectable even 12 months after the last immunization. These data demonstrate for the first time that vaccination with tumor antigen-pulsed dendritic cells in a clinically adjuvant setting induces strong and persistent antigen-specific T-cell responses in tumor-free stage II melanoma patients, suggesting that tumor protective T cell immunity can be achieved.
From the President (2009)

This history project and indeed all the ASM celebrations happening in 2009 have their origins in the meeting of Council held on the Gold Coast in 2006. It was at that meeting that then President, Julian Rood, had an inkling that our Golden Jubilee was approaching. It is perhaps a reflection of the fact that we can so quickly lose track of the past that no one could definitively name our year of foundation. After subsequent research revealed the significance of 1959, Council quickly agreed that 2009 should be a special year of celebration for us.
Accelerating micro-scale PCR (polymerase chain reactor) for modular lab-on-a-chip system (2005)

The polymerase chain reaction (PCR) is a powerful technique used to exponentially amplify specific DNA sequences of interest through repetitive temperature cycling. The temperatures used in PCR are typically 90°C - 94°C for denaturation, 50°C - 70°C for renaturation, and 70°C - 75°C for extension. The double-stranded helix of nucleotides, carrying the genetic information, is separated during denaturation, reacts with chemical primers during renaturation, and becomes a complete, replica, double-stranded DNA helix structure during extension. The primary drawback of current commercial benchtop PCR machine is its cycle time due to its large thermal capacitance, and micro PCR is under developing using microfabrication technology; smaller and faster in different types of PCR are the primary goal in this study. Continuous flow PCR is one of the primary types of micro PCR and it relies on a continuous flow through three temperature zones to achieve rapid thermal cyclings. To understand its biological performance, an experiment was carried out to study its limiting dynamic performance at different flow velocities from 1 mm/s to 15 mm/s and a thermal and fluidic numerical simulation was realized to give ideas of thermal performance and explain the experimental results. A 5.2 s/cycle for 500 bp and a 9.7 s/cycle for 997 bp were accomplished in this experiment. Thermal management was critical in PCR since the biological performance was primarily dependent on precise temperature control. Liquid crystal is a common tool in investigating thermal performance using its optical properties, which will have different color based on its local temperature. A liquid crystal was realized on renaturation zone of CFPCR chip and post image process was used to help interpret the experimental results. A non-uniform temperature distribution was observed due to the low thermal conductivity of substrate, polycarbonate, and non-uniform temperature supply. Another goal in this research was to develop another type of PCR using different driving mechanism to search other possibilities and compare results with CFPCR. An electrokineitc shuttle PCR was developed and its basic idea was using electrokinetic force to drive DNA fragment through three static temperature zones in a single microchannel. The flow velocities realized in this experiment were 1mm/s to 3mm/s and lower amplification yields were observed. The reasons were unintentional flows such as siphoning flow and hydrodynamic flow, which made the DNA fragment move in a chaotic temperature sequences and result in a lower yield.
Derivatives of (−)-7-Methyl-2-(5-(pyridinyl)pyridin-3-yl)-7-azabicyclo[2.2.1]heptane Are Potential Ligands for Positron Emission Tomography Imaging of Extrathalamic Nicotinic Acetylcholine Receptors (2007)

A series of novel racemic 7-methyl-2-(5-(pyridinyl)pyridin-3-yl)-7-azabicyclo[2.2.1]heptane derivatives with picomolar in vitro binding affinity at nicotinic acetylcholine receptors (nAChRs) were synthesized and their enantiomers were resolved by semipreparative chiral HPLC. The (-)-enantiomers showed substantially greater in vitro inhibition binding affinity than the corresponding (+)-enantiomers. The compounds with best binding affinities have been radiolabeled with positron emitting isotopes 11C and 18F as potential radioligands for positron emission tomography imaging of the nAChR. In vivo enantioselectivity of the radiolabeled (-)-7-methyl-2-(5-(pyridinyl)pyridin-3-yl)-7-azabicyclo[2.2.1]heptane derivatives was observed in biodistribution studies in rodents and baboon. One of the radiolabeled compounds, (-)-7-methyl-2-exo-[3'-(2-[18F]fluoropyridin-5-yl))-5'-pyridinyl]-7-azabicyclo[2.2.1]heptane, exhibited good properties as a first practical PET radioligand for imaging of extrathalamic nAChR in baboon brain and holds promise for further investigation for human studies.
Regulation of human bone marrow-derived osteoprogenitor cells by osteogenic growth factors. (1995)

Human bone marrow contains a distinct cell population that expresses bone proteins and responds to transforming growth factor beta 1 (TGF-beta), but not to hematopoietic growth factors (Long, M. W., J. L. Williams, and K. G. Mann. 1990. J. Clin. Invest. 86:1387-1395). We now report the isolation, characterization, and growth factor responsiveness of these precursors to human osteoblasts and the identification of a human osteoprogenitor cell. Immunological separation of human bone marrow nonadherent low-density (NALD) cells results in a marked enrichment of cells that express osteocalcin, osteonectin, and bone alkaline phosphatase. Flow cytometric analyses show that distinct cell subpopulations exist among these isolated cells. The majority of the bone antigen-positive cells are approximately the size of a lymphocyte, whereas other, less frequent antibody-separated subpopulations consist of osteoblast-like cells and osteoprogenitor cells. In serum-free cultures, TGF-beta stimulates the small, antigen-positive cells to become osteoblast-like, as these cells both increase in size, and express increased levels of osteocalcin and alkaline phosphatase. Antibody-separated cells also contain a separate population of clonal progenitor cells that form colonies of osteoblast-like cells when cultured in serum-free, semi-solid media. Two types of human osteoprogenitor cells are observed: a colony-forming cell (CFC) that generates several hundred bone antigen-positive cells, and a more mature cluster-forming cell that has a lesser proliferative potential and thus generates clusters of 20-50 antigen-positive cells. Osteopoietic colony-forming cells and cluster-forming cells have an obligate but differential requirement for osteogenic growth factors. The CFCs respond to TGF-beta, basic fibroblast growth factor (bFGF), bone morphogenic protein-2 (BMP-2), and 1, 25-dihydroxy vitamin D3 (1,25-OH D3). In contrast to the colony-forming cells, cluster-forming cells are regulated predominantly by 1,25-OH D3 and TGF-beta, but fail to respond to bFGF. We conclude that human bone marrow contains a nonhematogenous, heterogeneous population of bone precursor cells among which exists a population of proliferating osteoprogenitor cells. Further characterization of these bone precursor cell populations should yield important information on their role in osteogenesis in both health and disease.
Evolution of Secondary Metabolite Production: Potential Roles for Antibiotics as Prebiotic Effectors of Catalytic RNA Reactions (2007)

It has been proposed that organic molecules related to known secondary metabolites have existed since the beginning of biochemical evolution and were present in primordial soups. Under primitive earth conditions certain of these molecules may have played roles as effectors in prebiotic reactions, especially those involving catalytic RNA (ribozymes). We demonstrate that a number of antibiotic-related secondary metabolites bind to group I introns and either inhibit splicing reactions or promote the formation of intron oligomers. This is consistent with the functional co-evolution of catalytic RNA and secondary metabolites as antibiotic inhibitors of translation, and supports the notion of an evolutionary relationship between group I introns and ribosomal RNA.
An autocatalytic mechanism of protein nitrosylation (2000)

Nitros(yl)ation is a widespread protein modification that occurs during many physiological and pathological processes. It can alter both the activity and function of a protein. Nitric oxide (( small middle dot)NO) has been implicated in this process, but its mechanism remained uncertain. ( small middle dot)NO is unable to react with nucleophiles under oxygen-free conditions, suggesting that its higher oxides, such as N(2)O(3), were actually nitrosylating agents. However, low concentrations and short lifespans of these species in vivo raise the question of how they could efficiently locate target proteins. Here we demonstrate that at physiological concentrations of ( small middle dot)NO, N(2)O(3) forms inside protein-hydrophobic cores and causes nitrosylation within the protein interior. This mechanism of protein modification has not been characterized, because all previously described mechanisms (e.g., phosphorylation, acetylation, ADP-ribosylation, etc.) occur via attack on a protein by an external modification agent. Oxidation of ( small middle dot)NO to N(2)O(3) is facilitated by micellar catalysis, which is mediated by the hydrophobic phase of proteins. Thus, a target protein seems to be a catalyst of its own nitrosylation. One of the applications of this finding, as we report here, is the design of specific hydrophobic compounds whose cooperation with ( small middle dot)NO and O(2) allows the rapid inactivation of target enzymes to occur.
Transapical aortic valve replacement under real-time magnetic resonance imaging guidance: experimental results with balloon-expandable and self-expanding stents (2010)

SE stents were easier to position and deploy, thus leading to fewer complications during tAVI. Future optimization of SE stent design should improve clinical results.