gebhart/patrepeval huggingface dataset:
Bipartite regulation of different components of the MHC class I antigen-processing machinery during dendritic cell maturation (2001)

Dendritic cells (DC) are professional antigen-presenting cells (APC) which proceed from immature to a mature stage during their final differentiation. Immature DC are highly effective in terms of antigen uptake and processing, whereas mature DC become potent immunostimulatory cells. Until now, the expression profiles of the major components of the MHC class I antigen-processing machinery (APM) during DC development have not been well characterized. In this study, the mRNA and protein expression levels of the IFN-gamma inducible proteasome subunits, of the proteasome activators PA28, and of key components required for peptide transport and MHC class I-peptide complex assembly have been evaluated in immature and mature stages of human monocyte-derived DC using semiquantitative RT-PCR and Western blot analyses. The IFN-gamma-responsive immunoproteasome subunits LMP2, LMP7 and MECL1 are up-regulated in immature DC, whereas the other components of the MHC class I presentation machinery, such as PA28, TAP, tapasin, and HLA heavy and light chains, were found to be more abundant in mature DC. These findings support the hypothesis that immature DC produced by the differentiation of monocytes in response to IL-4 and granulocyte macrophage colony stimulating factor first increase their capacity to capture antigens and process them into peptides, thereby switching from housekeeping to immunoproteasomes, while mature DC rather up-regulate the components required for peptide translocation and MHC class I-peptide complex formation, and thus specialize in antigen presentation. Our results establish that MHC class I, like MHC class II surface expression, is markedly regulated during DC development and maturation.
Mechanisms and Pathology of Monocrotaline Pulmonary Toxicity (1992)

Monocrotaline (MCT) is an 11-membered macrocyclic pyrrolizidine alkaloid (PA) that causes a pulmonary vascular syndrome in rats characterized by proliferative pulmonary vasculitis, pulmonary hypertension, and cor pulmonale. Current hypotheses of the pathogenesis of MCT-induced pneumotoxicity suggest that MCT is activated to a reactive metabolite(s) in the liver and is then transported by red blood cells (RBCs) to the lung, where it initiates endothelial injury. While several lines of evidence support the requirement of hepatic metabolism for pneumotoxicity, the mechanism and relative importance of RBC transport remain undetermined. The endothelial injury does not appear to be acute cell death but rather a delayed functional alteration that leads to disease of the pulmonary arterial walls by unknown mechanisms. The selectivity of MCT for the lung, as opposed to that of other primarily hepatotoxic PAs, appears likely to be a consequence of the differences in hepatic metabolism and blood kinetics of MCT. A likely candidate for a reactive metabolite of MCT is the dehydrogenation product monocrotaline pyrrole (MCTP). Secondary or phase II metabolism of MCT through glutathione (GSH) conjugation has been characterized recently and appears to represent a detoxification pathway. The role of inflammation in the progression of MCT-induced pulmonary vascular disease is uncertain. Both perivascular inflammation and platelet activation have been proposed as processes contributing to the response of the vascular media. This review presents the experimental evidence supporting these hypotheses and outlines additional questions that arise from them.
Interaction-based simulation (2009)

This thesis presents a technique for producing visual simulations — programs that visualize the execution or behavior of time-varying scenes — from software interactions, first-class structures that moderate the flow of information among software components: The building of programs with software interactions gives rise to Interaction-Based Programming (IBP), a programming methodology that separates the concerns of computation from coordination. Software components compute independently, while software interactions coordinate communications. The integration of IBP with the methods of computer simulation produce Interaction-Based Simulation (IBS), an approach to visual simulation that binds the execution of software interactions to the advancement of time. As tiihe advances, software interactions control the flow of information among components arid the dissemination of temporal information. The utility of IBS is presented in two ways: one, through a logical description of the effect of software interactions on software development and systems created using the approach; and two, through empirical evidence demonstrating the ability of IBS to produce a wide variety of programs that encourage the reuse of software.
DNA sequences of structural genes for Eco RI DNA restriction and modification enzymes. (1981)

We have determined the sequence of a 2210-base pair DNA segment containing genes required for expression of Eco RI DNA restriction and modification phenotypes.Polypeptide sequences encoded within the two longest open reading frames in this region are in agreement with NH2-and COOH-terminal sequences of the two Eco RI enzymes (Rubin, R. A., Modrich, P., and Vanaman, T. C. (
Distinct Uptake Routes of Cell-Penetrating Peptide Conjugates (2008)

Cell-penetrating peptides (CPPs) are a growing family of peptides that have opened a new avenue in drug delivery, allowing various hydrophilic macromolecules to enter cells. In accordance with most other cationic delivery vectors, CPPs seem to rely mostly on endocytosis for internalization. However, due to conflicting results the exact endocytic pathways for CPP uptake have not yet been resolved. Here, we evaluated the ability of seven CPPs, with different chemical properties, to convey peptide nucleic acids (PNAs) inside cells. Assays based on both splice correction, generating biologically active read-out, and on traditional fluorescence measurements were utilized. The same assays were employed to assess different endocytic pathways and the dependence on extracellular heparan sulfates for internalization. Both highly cationic CPPs (M918, penetratin, and Tat) and amphipathic peptides (transportan, TP10, MAP, and pVEC) were investigated in this study. Conjugate uptake relied on endocytosis for all seven peptides but splice-correcting activity varied greatly for the investigated CPPs. The exact endocytic internalization routes were evaluated through the use of well-known endocytosis inhibitors and tracers. In summary, the different chemical properties of CPPs have little correlation with their ability to efficiently deliver splice-correcting PNA. However, conjugates of polycationic and amphipathic peptides appear to utilize different internalization routes.
Aerosol therapy for asthma (2000)

Inhaled drugs play an important role in asthma management. The correct use of an appropriate delivery device is necessary to achieve the desired therapeutic effects of the drug. Currently, chlorofluorocarbon-propelled metered-dose inhalers, with or without spacers, are the most popular aerosol delivery devices. With the planned phase out of the chlorofluorocarbon metered-dose inhalers, the use of other delivery devices is being emphasized. To achieve optimal therapeutic effects, the drug and the delivery device should be considered a "couple". Aerosol delivery devices should provide an adequate "drug dose to the lung", be cost effective, simple to operate, minimize oropharyngeal deposition and systemic side effects, and match the patient's requirements. A new generation of aerosol delivery devices, incorporating the latest advances in aerosol technology, is likely to fulfill many of the goals mentioned above.
Manual for the State-Trait Anxiety Inventory (1970)

The STAI serves as an indicator of two types of anxiety, the state and trait anxiety, and measure the severity of the overall anxiety level.The STAI, which is appropriate for those who have at least a sixth grade reading level, contains four-point Likert items. The instrument is divided into two sections, each having twenty questions. Approximately 15 minutes are required for adults to complete the both STAI. The number on the scale is positively correlated to the anxiety related to in the question.
Paramagnetic, Silicon Quantum Dots for Magnetic Resonance and Two-Photon Imaging of Macrophages (2010)

Quantum dots (QDs) are an attractive platform for building multimodality imaging probes, but the toxicity for typical cadmium QDs limits enthusiasm for their clinical use. Nontoxic, silicon QDs are more promising but tend to require short-wavelength excitations which are subject to tissue scattering and autofluorescence artifacts. Herein, we report the synthesis of paramagnetic, manganese-doped, silicon QDs (Si(Mn) QDs) and demonstrate that they are detectable by both MRI and near-infrared excited, two-photon imaging. The Si(Mn) QDs are coated with dextran sulfate to target them to scavenger receptors on macrophages, a biomarker of vulnerable plaques. TEM images show that isolated QDs have an average core diameter of 4.3 +/- 1.0 nm and the hydrodynamic diameters of coated nanoparticles range from 8.3 to 43 nm measured by dynamic light scattering (DLS). The Si(Mn) QDs have an r(1) relaxivity of 25.50 +/- 1.44 mM(-1) s(-1) and an r(2) relaxivity of 89.01 +/- 3.26 mM(-1) s(-1) (37 degrees C, 1.4 T). They emit strong fluorescence at 441 nm with a quantum yield of 8.1% in water. Cell studies show that the probes specifically accumulate in macrophages by a receptor-mediated process, are nontoxic to mammalian cells, and produce distinct contrast in both T(1)-weighted magnetic resonance and single- or two-photon excitation fluorescence images. These QDs have promising diagnostic potential as high macrophage density is associated with atherosclerotic plaques vulnerable to rupture.
Java-centric distributed computing (1997)

The Java language and platform provide a base for distributed computing that changes several conventional assumptions. In particular, the Java Virtual Machine allows a group of Java-enabled machines to be treated as a homogeneous group rather than a heterogeneous group, despite possible differences in the machine architectures and underlying operating systems. Java also makes it possible to safely and dynamically load code in a running Java process. Together, these features allow a system to invoke methods on remote objects, which can move code associated with language-level objects from the calling process to the process called and vice versa. Combining these qualities with a language-centric design not only significantly simplifies traditional RPC systems, it adds functionality that was previously not possible. We designed Java Remote Method Invocation (RMI) to support pure-Java distributed objects in a seamless manner. RMI allows calls to be made between Java objects in different virtual machines, even on different physical machines.
Androgen replacement for women. (1999)

Further prospective randomized studies of replacement of physiological levels of testosterone in women with androgen deficiency syndrome are needed, using formulations of testosterone available in Canada. The consistency of sexual changes, the associated personal and relationship distress, together with our clinical experience of the gratifying response to physiological replacement, make further studies urgently needed.
Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia (2002)

We examined isolated leukemia B cells of patients with chronic lymphocytic leukemia (CLL) for expression of zeta-associated protein 70 (ZAP-70). CLL B cells that have nonmutated immunoglobulin variable region genes (V genes) expressed levels of ZAP-70 protein that were comparable to those expressed by normal blood T cells. In contrast, CLL B cells that had mutated immunoglobulin variable V genes, or that had low-level expression of CD38, generally did not express detectable amounts of ZAP-70 protein. Leukemia cells from identical twins with CLL were found discordant for expression of ZAP-70, suggesting that B-cell expression of ZAP-70 is not genetically predetermined. Ligation of the B-cell receptor (BCR) complex on CLL cells that expressed ZAP-70 induced significantly greater tyrosine phosphorylation of cytosolic proteins, including p72(Syk), than did similar stimulation of CLL cells that did not express ZAP-70. Also, exceptional cases of CLL cells that expressed mutated immunoglobulin V genes and ZAP-70 also experienced higher levels tyrosine phosphorylation of such cytosolic proteins following BCR ligation. Following BCR ligation, ZAP-70 underwent tyrosine phosphorylation and became associated with surface immunoglobulin and CD79b, arguing for the involvement of ZAP-70 in BCR signaling. These data indicate that expression of ZAP-70 is associated with enhanced signal transduction via the BCR complex, which may contribute to the more aggressive clinical course associated with CLL cells that express nonmutated immunoglobulin receptors.
Regnase-1 degradation is crucial for IL-33– and IL-25–mediated ILC2 activation (2020)

Group 2 innate lymphoid cells (ILC2s) are a critical innate source of type 2 cytokines in allergic inflammation. Although ILC2s are recognized as a critical cell population in the allergic inflammation, the regulatory mechanism(s) of ILC2s are less well understood. Here, we show that Regnase-1, an immune regulatory RNAse that degrades inflammatory mRNAs, negatively regulates ILC2 function and that IκB kinase (IKK) complex-mediated Regnase-1 degradation is essential for IL-33- and IL-25-induced ILC2 activation. ILC2s from Regnase-1AA/AA mice expressing a Regnase-1 S435A/S439A mutant resistant to IKK complex-mediated degradation accumulated Regnase-1 protein in response to IL-33 and IL-25. IL-33- and IL-25-stimulated Regnase-1AA/AA ILC2s showed reduced cell proliferation and type 2 cytokine (IL-5, IL-9, and IL-13) production and increased cell death. In addition, Il2ra and Il1rl1, but not Il5, Il9, or Il13, mRNAs were destabilized in IL-33-stimulated Regnase-1AA/AA ILC2s. In vivo, Regnase-1AA/AA mice showed attenuated acute type 2 pulmonary inflammation induced by the instillation of IL-33, IL-25, or papain. Furthermore, the expulsion of Nippostrongylus brasiliensis was significantly delayed in Regnase-1AA/AA mice. These results demonstrate that IKK complex-mediated Regnase-1 degradation is essential for ILC2-mediated type 2 responses both in vitro and in vivo. Therefore, controlling Regnase-1 degradation is a potential therapeutic target for ILC2-contributed allergic disorders.
Characterization of the Promoter for the Human Long Pentraxin PTX3 (1997)

The "long pentraxins" are an emerging family of genes that have conserved in their carboxy-terminal halves a pentraxin domain homologous to the prototypical acute phase protein pentraxins (C-reactive protein and serum amyloid P component) and acquired novel amino-terminal domains. In this report, a genomic fragment of 1371 nucleotides from the human "long pentraxin" gene PTX3 is characterized as a promoter on tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta exposure in transfected 8387 human fibroblasts by chloramphenicol acetyltransferase and RNase protection assays. In the same cells, the PTX3 promoter does not respond to IL-6 stimulation. Furthermore, IL-1beta and TNFalpha responsiveness is not seen in the Hep 3B hepatoma cell line. The minimal promoter contains one NF-kappaB element which is shown to be necessary for induction and able to bind p50 homodimers and p65 heterodimers but not c-Rel. Mutants in this site lose the ability to bind NF-kappaB proteins and to respond to TNFalpha and IL-1beta in functional assays. Sp1- and AP-1 binding sites lying in proximity to the NF-kappaB site do not seem to play a major role for cytokine responsiveness. Finally, cotransfection experiments with expression vectors validate that the natural promoter contains a functional NF-kappaB site.
Regulatory T Cells in the Control of Host-Microorganism Interactions (2009)

Each microenvironment requires a specific set of regulatory elements that are finely and constantly tuned to maintain local homeostasis. Various populations of regulatory T cells contribute to the maintenance of this equilibrium and establishment of controlled immune responses. In particular, regulatory T cells limit the magnitude of effector responses, which may result in failure to adequately control infection. However, regulatory T cells also help limit collateral tissue damage caused by vigorous antimicrobial immune responses against pathogenic microbes as well as commensals. In this review, we describe various situations in which the balance between regulatory T cells and effector immune functions influence the outcome of host-microorganism coexistence and discuss current hypotheses and points of polemic associated with the origin, target, and antigen specificity of both endogenous and induced regulatory T cells during these interactions.
Molecular Basis of UropathogenicEscherichia coliEvasion of the Innate Immune Response in the Bladder (2008)

In the urinary tract, the innate immune system detects conserved bacterial components and responds to infection by activating the proinflammatory transcription factor NF-kappaB, resulting in cytokine secretion and neutrophil recruitment. Uropathogenic Escherichia coli (UPEC), however, has been shown to evade the host innate immune response by suppressing NF-kappaB activation in urothelial cells, which results in decreased cytokine secretion and increased urothelial apoptosis. To understand the molecular basis of UPEC modulation of inflammation, we performed a genetic screen with UPEC strain NU14 to identify genes which are required for modulation of urothelial cytokine secretion. Disruption of ampG (peptidoglycan permease), waaL (lipopolysaccharide O antigen ligase), or alr (alanine racemase) resulted in increased urothelial interleukin-8 (IL-8) and IL-6 release from urothelial cell cultures. Targeted deletion of these genes also resulted in elevated urothelial cytokine production during UPEC infection. Conditioned media from bacterial cultures of NU14 DeltaampG and NU14 DeltawaaL contained a heat-stable factor(s) which stimulated greater urothelial IL-8 secretion than that in NU14-conditioned medium. In a mouse model of urinary tract infection, NU14 DeltaampG, NU14 DeltawaaL, and NU14 Deltaalr were attenuated compared to wild-type NU14 and showed reduced fitness in competition experiments. Instillation of NU14 DeltaampG or NU14 DeltawaaL increased bladder neutrophil recruitment, indicating that enhanced urothelial cytokine secretion during urinary tract infection results in an altered host response. Thus, UPEC evasion of innate immune detection of bacterial components, such as lipopolysaccharide and peptidoglycan fragments, is likely an important factor in the ability of UPEC to colonize the urinary tract.
Nucleotide sequence of murine ornithine decarboxylase mRNA. (1985)

Ornithine decarboxylase (OrnDCase; L-ornithine carboxy-lyase, EC 4.1.1.17) is the first and rate-limiting enzyme in the biosynthesis of polyamines in mammalian cells. During cell growth the enzyme is regulated by rapid changes in the level of its mRNA and protein. To explore the molecular basis of these changes, we cloned a full-length cDNA copy of the major 2.4-kilobase OrnDCase mRNA from mouse cells and determined its sequence. The cDNA contains 2465 nucleotides derived from OrnDCase mRNA, consisting of a 737-nucleotide-long 5' noncoding segment, a coding segment of 1383 nucleotides terminated by a TAG triplet, and a 342-nucleotide 3' noncoding segment. The encoded protein of 461-amino acid residues has a molecular weight of 51,105 and has a potential site for phosphorylation by casein kinase II. In the unusually long 5' leader sequence, there are four ATG triplets, each of which is followed by an in-phase termination signal; the presence of these upstream ATGs could explain the low in vitro translational activity of OrnDCase mRNA reported earlier. A restriction digest of mouse genomic DNA was probed with a defined OrnDCase coding sequence, revealing a multimembered family of OrnDCase-related genes.
Dialkyltin oxide mediated addition of trimethylsilyl azide to nitriles. A novel preparation of 5-substituted tetrazols (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDialkyltin oxide mediated addition of trimethylsilyl azide to nitriles. A novel preparation of 5-substituted tetrazolsSteven J. Wittenberger and B. Gregory DonnerCite this: J. Org. Chem. 1993, 58, 15, 4139–4141Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://pubs.acs.org/doi/10.1021/jo00067a058https://doi.org/10.1021/jo00067a058research-articleACS PublicationsRequest reuse permissionsArticle Views1919Altmetric-Citations248LEARN 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
Marine Hermit Crab: Shell Selection (1983)

(1983). Marine Hermit Crab: Shell Selection. Science Activities: Vol. 20, No. 4, pp. 24-26.
The Motorola 88110 Superscalar RISC microprocessor (2003)

The Motorola 88110 is a second-generation, single-chip RISC (reduced instruction set computer) microprocessor that uses advanced techniques for exploiting instruction-level parallelism. Superscalar instruction issue, speculative execution, limited dynamic instruction recording and multiple on-chip caches are used to achieve high performance at a cost that makes it ideally suited as a central processor in low-cost personal computers and workstations. The advanced superscalar processor architecture and a high level of circuit integration have been implemented in a high-yield, triple-level metal, CMOS process using 1 mu design rules and requiring under 1.3 million transistors.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>