gebhart/patrepeval huggingface dataset:
The C-terminal ligand-binding domain of Clostridium difficile toxin A (TcdA) abrogates TcdA-specific binding to cells and prevents mouse lethality (2006)

We have investigated the ability of a recombinant protein (REP231), derived from Clostridium difficile toxin A C-terminal domain, to protect against toxin A (TcdA) intoxication in vitro and in vivo. REP231 was cloned, expressed and purified by thyroglobulin affinity chromatography, and demonstrated identical binding properties to TcdA. Immunofluorescence experiments and in vitro cytotoxicity assays using mouse teratocarcinoma cells F9 showed that specific binding of TcdA to F9 cells through its C-terminal domain is essential for producing cytotoxic effects. TcdA binding and cytotoxicity was inhibited by REP231 and a monoclonal antibody directed against the C-terminal domain. Toxin B did not bind to F9 cells and was consequently inactive in cytotoxicity assays. Inhibition studies with lectins and a Le(x)-specific antibody supported earlier findings that a terminal galactose is part of the bound saccharide but excluded Le(x) as a receptor for TcdA. Mice immunised with REP231 were protected against a threefold lethal dose of TcdA. Thus, REP231 appeared to be a suitable candidate to develop an alternative therapeutic agent, which is able to neutralise carbohydrate-mediated TcdA binding and might act as a vaccine.
Pressure-Sensitive Adhesives and Applications (2004)

Pressure-Sensitive Adhesives and Applications, Second Edition explains how pressure-sensitive adhesives (PSAs) work, why they are used, and the technology used to manufacture them. This second edition features the latest developments in the field.Dr. Benedek discusses the factors that affect the rheology and special flow characteristics res
Bioorthogonal labelling of biomolecules: new functional handles and ligation methods (2013)

This review provides a literature overview of bioorthogonal ligation methods for protein modification, which have largely evolved over the last 15 years. Since 1990, various new reactions have been developed that do not involve naturally occurring functional handles. Especially the development of such so-called bioorthogonal ligations has significantly contributed to our ability to selectively modify biomolecules not only in the test tube, but also in living systems.
Reducing Propulsion Airframe Aeroacoustic Interactions with Uniquely Tailored Chevrons: 2. Installed Nozzles (2006)

The flow/acoustic environment surrounding an engine nozzle installed on an airplane, say, under the wing, is asymmetric due to the pylon, the wing and the interaction of the exhaust jet with flaps on the wing. However, the conventional chevrons, which are azimuthally uniform serrations on the nozzle lip, do not exploit the asymmetry due to these propulsion airframe aeroacoustic interactions to reduce jet noise. In this pioneering study we use this non-axisymmetry to our advantage and examine if the total jet-related noise radiated to the ground can be reduced by using different types of azimuthally varying chevrons (AVC) which vary the mixing around the nozzle periphery. Several scale models of the isolated nozzle, representative of high bypass ratio engine nozzles, were made with a pylon and azimuthally varying chevrons on both fan and core nozzles to enhance mixing at the top (near the pylon) with less mixing at the bottom (away from the pylon) or vice versa. Various combinations of fan and core AVC nozzles were systematically tested at typical take-off conditions inside a free jet wind-tunnel and, here, in Part 1 we analyze the acoustics results for the isolated nozzle with a pylon, with installation effects reported in Parts 2 and 3. Several interesting results are discovered: amongst the fan AVCs the top-enhanced mixing T-fan chevron nozzle is quieter in combination with any core AVC nozzle when compared to conventional chevrons; however, the bottom-mixing B-fan chevrons, as well as the core AVC nozzles, by themselves, are noisier. Further, the low-frequency source strengths in the jet plume, obtained via phased microphone arrays, also corroborate the far field sound, and for the T-fan chevrons such sources move further downstream and become weaker than those for baseline or conventional chevron nozzles.
Protein iodination with solid state lactoperoxidase (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein iodination with solid state lactoperoxidaseGary S. David and Ralph A. ReisfeldCite this: Biochemistry 1974, 13, 5, 1014–1021Publication Date (Print):February 1, 1974Publication History Published online1 May 2002Published inissue 1 February 1974https://pubs.acs.org/doi/10.1021/bi00702a028https://doi.org/10.1021/bi00702a028research-articleACS PublicationsRequest reuse permissionsArticle Views247Altmetric-Citations302LEARN 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
Listeriosis in the Pregnant Guinea Pig: a Model of Vertical Transmission (2003)

Feto-placental infections represent a major cause of pregnancy complications, and yet the underlying molecular and cellular mechanisms of vertical transmission are poorly understood. Listeria monocytogenes, a facultative intracellular pathogen, is one of a group of pathogens that are known to cause feto-placental infections in humans and other mammals. The purpose of this study was to evaluate possible mechanisms of vertical transmission of L. monocytogenes. Humans and guinea pigs have a hemochorial placenta, where a single layer of fetally derived trophoblasts separates maternal from fetal circulation. We characterized L. monocytogenes infection of the feto-placental unit in a pregnant guinea pig model and in primary human trophoblasts and trophoblast-derived cell lines. The clinical manifestations of listeriosis in the pregnant guinea pigs and the tropism of L. monocytogenes to the guinea pig placenta resembled those in humans. Trophoblast cell culture systems were permissive for listerial growth and cell-to-cell spread and revealed that L. monocytogenes deficient in internalin A, a virulence factor that mediates invasion of nonphagocytic cells, was 100-fold defective in invasion. However, crossing of the feto-placental barrier in the guinea pig model was independent of internalin A, suggesting a negligible role for internalin-mediated direct invasion of trophoblasts in vivo. Further understanding of vertical transmission of L. monocytogenes will help in designing more effective means of treatment and disease prevention.
Circular RNA: Design Criteria for Optimal Therapeutical Utility (2019)

A growing body of work has shown mRNA-based therapeutics are a promising new potential class of drugs, despite the longstanding belief that RNA was too unstable to be efficiently utilized for such applications. Previous studies have established several RNA modifications (e.g., modified nucleotides, cap analogs, polyadenylation, and codon optimization) that enable production of therapeutic levels of protein. Although the established modifications function, in part, by enhancing the stability of RNA, none does so by providing protection against the large family of exonucleases that are primarily responsible for RNA degradation. Thus, we examined whether exonuclease-resistant, circular RNA (circRNA) could be utilized as a superior alternative to conventional, linear RNA. As there are significant differences between linear and circular RNA there was a need to establish appropriate design criteria specific to circRNA. Therefore, we concentrated our work on three areas of focus, the synthesis, immunity, and translation efficiency specifications of circRNA. Regarding synthesis, we have developed a methodology in which large, circRNAs can be efficiently and reliably generated. We showed that the incorporation of a complement-reverse complement (CRC) motif into circRNA and HPLC-mediated purification respectively improve ligation efficiency and drastically reduce immune activation. Additionally, we have identified optimal regulatory motifs that, when incorporated into circRNA, yield enhanced RNA stability, robust protein translation, and minimal immune stimulation both in vitro and in vivo. Lastly, our proof-of-concept in vivo studies using circRNA encoding erythropoietin (EPO) showed significantly longer protein expression and elevated reticulocyte levels compared to standard, modified linear mRNA. Together, this work offers details regarding the design criteria necessary for circRNA to function well in the therapeutic setting and provides the first in vivo-based evidence for the utility of circRNA as a beneficial modification for enhancing the stability and overall efficacy of mRNA therapeutics.
Direct Interaction of Alzheimer's Disease-related Presenilin 1 with Armadillo Protein p0071 (1999)

Alzheimer's disease-related presenilins are thought to be involved in Notch signaling during embryonic development and/or cellular differentiation. Proteins mediating the cellular functions of the presenilins are still unknown. We utilized the yeast two-hybrid system to identify an interacting armadillo protein, termed p0071, that binds specifically to the hydrophilic loop of presenilin 1. In vivo, the presenilins constitutively undergo proteolytic processing, forming two stable fragments. Here, we show that the C-terminal fragment of presenilin 1 directly binds to p0071. Nine out of 10 armadillo repeats in p0071 are essential for mediating this interaction. Since armadillo proteins, like beta-catenin and APC, are known to participate in cellular signaling, p0071 may function as a mediator of presenilin 1 in signaling events.
Hypoxic regulation of the fetal cerebral circulation (2006)

Fetal cerebrovascular responses to acute hypoxia are fundamentally different from those observed in the adult cerebral circulation. The magnitude of hypoxic vasodilatation in the fetal brain increases with postnatal age although fetal cerebrovascular responses to acute hypoxia can be complicated by age-dependent depressions of blood pressure and ventilation. Acute hypoxia promotes adenosine release, which depresses fetal cerebral oxygen consumption through action of adenosine on neuronal A1 receptors and vasodilatation through activation of A2 receptors on cerebral arteries. The vascular effect of adenosine can account for approximately half the vasodilatation observed in response to hypoxia. Hypoxia-induced release of nitric oxide and opioids can account for much of the adenosine-independent cerebral vasodilatation observed in response to hypoxia in the fetus. Direct effects of hypoxia on cerebral arteries account for the remaining fraction, although the vascular endothelium contributes relatively little to hypoxic vasodilatation in the immature cerebral circulation. In contrast to acute hypoxia, fetal cerebral blood flow tends to normalize during acclimatization to chronic hypoxia even though cardiac output is depressed. However, uncompensated chronic hypoxia in the fetus can produce significant changes in brain structure and function, alteration of respiratory drive and fluid balance, and increased incidence of intracranial hemorrhage and periventricular leukomalacia. At the level of the fetal cerebral arteries, chronic hypoxia increases protein content and depresses norepinephrine release, contractility, and receptor densities associated with contraction but also attenuates endothelial vasodilator capacity and decreases the ability of ATP-sensitive and calcium-sensitive potassium channels to promote vasorelaxation. Overall, fetal cerebrovascular adaptations to chronic hypoxia appear prioritized to conserve energy while preserving basic contractility. Many gaps remain in our understanding of how the effects of acute and chronic hypoxia are mediated in fetal cerebral arteries, but studies of adult cerebral arteries have produced many powerful pharmacological and molecular tools that are simply awaiting application in studies of fetal cerebral artery responses to hypoxia.
Stem Cell-Derived Therapeutic Myelin Repair Requires 7% Cell Replacement (2008)

Embryonic stem cells (ESCs) hold great potential for therapeutic regeneration and repair in many diseases. However, many challenges remain before this can be translated into effective therapy. A principal and significant limit for outcome evaluations of clinical trials is to define the minimal graft population necessary for functional repair. Here we used a preclinical model for quantitative analysis of stem cell grafts, with wild-type ESC grafted into myelin mutant shiverer hosts, to determine minimum graft levels for therapeutic benefit. Using a timed motor function test we identified three groups, including recipients indistinguishable from nongrafted shiverer controls (time [t] = 20.1 +/- 1.1 seconds), mice with marginal improvement (t = 15.7 +/- 1 seconds), and mice with substantial phenotype rescue (t = 5.7 +/- 0.9 seconds). The motor function rescued chimeras also had a considerably extended life span (T(50) > 128 days) relative to both shiverer (T(50) = 108 days) and the nonrescued chimeras. Retrospective genotype analysis identified a strong correlation (r(2) = 0.85) between motor function and ESC-derived chimerism, with > 7% chimerism required for rescue in this murine model of central nervous system myelin pathology. These results establish the minimal levels of engraftment to anticipate therapeutic repair of a cell-autonomous defect by cell transplant therapy.
Antisense oligonucleotides as therapeutic agents (1999)

Antisense oligonucleotides can block the expression of specific target genes involved in the development of human diseases. Therapeutic applications of antisense techniques are currently under investigation in many different fields. The use of antisense molecules to modify gene expression is variable in its efficacy and reliability, raising objections about their use as therapeutic agents. However, preliminary results of several clinical studies demonstrated the safety and to some extent the efficacy of antisense oligodeoxynucleotides (ODNs) in patients with malignant diseases. Clinical response was observed in some patients suffering from ovarian cancer who were treated with antisense targeted against the gene encoding for the protein kinase C-alpha. Some hematological diseases treated with antisense oligos targeted against the bcr/abl and the bcl2 mRNAs have shown promising clinical response. Antisense therapy has been useful in the treatment of cardiovascular disorders such as restenosis after angioplasty, vascular bypass graft occlusion, and transplant coronary vasculopathy. Antisense oligonucleotides also have shown promise as antiviral agents. Several investigators are performing trials with oligonucleotides targeted against the human immunodeficiency virus-1 (HIV-1) and hepatitis viruses. Phosphorothioate ODNs now have reached phase I and II in clinical trials for the treatment of cancer and viral infections, so far demonstrating an acceptable safety and pharmacokinetic profile for continuing their development. The new drug Vitravene, based on a phosphorothioate oligonucleotide designed to inhibit the human cytomegalovirus (CMV), promises that some substantial successes can be reached with the antisense technique.
Small-molecule factor D inhibitors selectively block the alternative pathway of complement in paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (2016)

Paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome are diseases of excess activation of the alternative pathway of complement that are treated with eculizumab, a humanized monoclonal antibody against the terminal complement component C5. Eculizumab must be administered intravenously, and moreover some patients with paroxysmal nocturnal hemoglobinuria on eculizumab have symptomatic extravascular hemolysis, indicating an unmet need for additional therapeutic approaches. We report the activity of two novel small-molecule inhibitors of the alternative pathway component Factor D using <i>in vitro</i> correlates of both paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Both compounds bind human Factor D with high affinity and effectively inhibit its proteolytic activity against purified Factor B in complex with C3b. When tested using the traditional Ham test with cells from paroxysmal nocturnal hemoglobinuria patients, the Factor D inhibitors significantly reduced complement-mediated hemolysis at concentrations as low as 0.01 μM. Additionally the compound ACH-4471 significantly decreased C3 fragment deposition on paroxysmal nocturnal hemoglobinuria erythrocytes, indicating a reduced potential relative to eculizumab for extravascular hemolysis. Using the recently described modified Ham test with serum from patients with atypical hemolytic uremic syndrome, the compounds reduced the alternative pathway-mediated killing of <i>PIGA</i>-null reagent cells, thus establishing their potential utility for this disease of alternative pathway of complement dysregulation and validating the modified Ham test as a system for pre-clinical drug development for atypical hemolytic uremic syndrome. Finally, ACH-4471 blocked alternative pathway activity when administered orally to cynomolgus monkeys. In conclusion, the small-molecule Factor D inhibitors show potential as oral therapeutics for human diseases driven by the alternative pathway of complement, including paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.
Structure and luminescence of BaFBr:Eu2+ and BaFBr:Eu2+, Tb3+ phosphors and thin films (2005)

The inclusion of Tb3+ ions doped into the storage phosphor BaFBr:Eu2+ results in increased purity of the host material as well as an improvement in the linearity of the photostimulated luminescence (PSL) intensity versus the x-ray irradiation dose. Films produced by pulsed laser deposition (PLD) also show similar results, indicating that PLD is a powerful technique for producing high quality, high purity thin films. As a result, the PSL dose response is more linear in the thin films than in the powder samples. The emission intensity of Eu2+ in the phosphors increases with the increasing time of x-ray irradiation while the emission intensity of Tb3+ remains almost constant. This result may be explained by considering the reduction of impurity Eu3+ ions following trapping of the photoexcited electrons. The results demonstrate that these materials are not only potentially useful for medical imaging but also show promise for use in radiation dosimetry.
Mammalian Bax-induced plant cell death can be down-regulated by overexpression of Arabidopsis Bax Inhibitor-1 ( AtBI-1 ) (2001)

We recently isolated the AtBI-1 (Arabidopsis Bax Inhibitor-1) gene, the expression of which suppressed Bax-induced cell death in yeast. To determine whether the same is true in the plant system, transgenic Arabidopsis plants overexpressing Bax protein under a dexamethasone (DEX)-inducible promoter were generated. On DEX treatment, such transgenic plants exhibited marked cell death at the whole-plant level, cell shrinkage, membranous destruction, and other apoptotic phenotypes. Transgenic Bax plants were retransformed with a vector containing the AtBI-1 gene (tagged with green fluorescent protein) under the control of the cauliflower mosaic virus 35S promoter. Plants expressing both Bax and AtBI-1 were able to maintain growth on DEX-treatment by sustaining intracellular integrity. Thus, we present here direct genetic evidence that the plant antiapoptotic protein AtBI-1 is biologically active in suppressing the mammalian Bax action in planta.
Snap-dragging in three dimensions (1990)

A large portion of the user interface in interactive solid modeling systems is devoted to the problem of placing and orienting objects in three dimensions. In particular, many operations must be provided for selecting control points, curves and surfaces, and for translating, rotating and scaling scene components into precise relationships with other scene components. By factoring these operations carefully, it is possible to provide the desired functionality so as to reduce both the size of the user interface and the time that it takes to use it. With snap-dragging, the user takes advantage of three main elements that work together: a general-purpose gravity function, alignment objects that can be created many at a time, and smooth-motion affine transformations. Scene composition is achieved in a single perspective view using a mouse and keyboard. With 19 mouse commands, 15 keyboard commands, 5 menus of numbers, and 1 single-level menu of numerical transformations, this user interface has fewer commands and requires fewer keystrokes than the skitters and jacks technique reported earlier.
Investigation Of Linewidth Uniformity In X-Ray Lithography (1989)

Recently several groups have reported about the production of half micron devices using SOR X-ray lithography /1,2,3/. The device performance was compared to those devices produced by using other lithographic techniques (e.g. electron beam direct writing). However, for future applications it is necessary to fulfill the more stringent subhalf micron design rules. One important challenge is the linewidth control within several nm and the impact on yield, device quality and overlay accuracy.
Discrepancy as a Quality Measure for Sample Distributions (1991)

Discrepancy, a scalar measure of sample point equidistribution, is discussed in the context of Computer Graphics sampling problems. Several sampling strategies and their discrepancy characteristics are examined. The relationship between image error and the discrepancy of the sampling patterns used to generate the image is established. The definition of discrepancy is extended to non-uniform sampling patterns.
Inactivation of Human β-Defensins 2 and 3 by Elastolytic Cathepsins (2003)

beta-Defensins are antimicrobial peptides that contribute to the innate immune responses of eukaryotes. At least three defensins, human beta-defensins 1, 2, and 3 (HBD-1, -2, and -3), are produced by epithelial cells lining the respiratory tract and are active toward Gram-positive (HBD-3) and Gram-negative (HBD-1, -2, and -3) bacteria. It has been postulated that the antimicrobial activity of defensins is compromised by changes in airway surface liquid composition in lungs of patients with cystic fibrosis (CF), therefore contributing to the bacterial colonization of the lung by Pseudomonas and other bacteria in CF. In this report we demonstrate that HBD-2 and HBD-3 are susceptible to degradation and inactivation by the cysteine proteases cathepsins B, L, and S. In addition, we show that all three cathepsins are present and active in CF bronchoalveolar lavage. Incubation of HBD-2 and -3 with CF bronchoalveolar lavage leads to their degradation, which can be completely (HBD-2) or partially (HBD-3) inhibited by a cathepsin inhibitor. These results suggest that beta-defensins are susceptible to degradation and inactivation by host proteases, which may be important in the regulation of beta-defensin activity. In chronic lung diseases associated with infection, overexpression of cathepsins may lead to increased degradation of HBD-2 and -3, thereby favoring bacterial infection and colonization.