gebhart/patrepeval huggingface dataset:
Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency (2015)

Patients with mutations of the recombination-activating genes (RAG) present with diverse clinical phenotypes, including severe combined immune deficiency (SCID), autoimmunity, and inflammation. However, the incidence and extent of immune dysregulation in RAG-dependent immunodeficiency have not been studied in detail. Here, we have demonstrated that patients with hypomorphic RAG mutations, especially those with delayed-onset combined immune deficiency and granulomatous/autoimmune manifestations (CID-G/AI), produce a broad spectrum of autoantibodies. Neutralizing anti-IFN-α or anti-IFN-ω antibodies were present at detectable levels in patients with CID-G/AI who had a history of severe viral infections. As this autoantibody profile is not observed in a wide range of other primary immunodeficiencies, we hypothesized that recurrent or chronic viral infections may precipitate or aggravate immune dysregulation in RAG-deficient hosts. We repeatedly challenged Rag1S723C/S723C mice, which serve as a model of leaky SCID, with agonists of the virus-recognizing receptors TLR3/MDA5, TLR7/-8, and TLR9 and found that this treatment elicits autoantibody production. Altogether, our data demonstrate that immune dysregulation is an integral aspect of RAG-associated immunodeficiency and indicate that environmental triggers may modulate the phenotypic expression of autoimmune manifestations.
Effects of interferon on cells, viruses, and the immune system : proceedings of a meeting held at the Gulbenkian Institute of Science, Oeiras, Portugal on September 19-September 21, 1973 (1975)

Effects of interferon on cells, viruses, and the immune system: proceedings of a meeting held at the Gulbenkian Institute of Science, Oeiras, Portugal on September 19-September 21, 1973 , Effects of interferon on cells, viruses, and the immune system: proceedings of a meeting held at the... , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
A 1.3 GHz CMOS VCO with 28% frequency tuning (2003)

A 2 V, 6 mA, 1.3 GHz LC-tank VCO, realized in a digital CMOS process, is presented. The tank is made of a metal-oxide-silicon varactor and a series connection of a bondwire and a spiral inductor. This solution enables one to tune all component variations, while gain is maintained constant within /spl plusmn/20% of the nominal value. The measured phase noise at 600 kHz from 1.3 GHz carrier is -119 dbc/Hz.
Effect of Internal Curing on Characteristics of Self-Compacting Concrete by Using Fine and Coarse Lightweight Aggregates (2017)

Internally cured concrete made with prewetted lightweight aggregates (LWAs) has a risk of segregation because of floating LWAs in the process of vibration. Such risk can be reduced by applying internal curing in self-compacting concrete, because it can avoid vibration or rodding processes. In this study, internally cured self-compacting concretes with fine or coarse LWAs were prepared with a replacement level of 20 and 40% by volume of normal-weight aggregates. A segregation resistance test was performed to quantitatively evaluate the floating of LWAs in self-compacting concrete. The effectiveness of internal curing was evaluated in terms of workability, compressive strength, autogenous shrinkage, and transport properties (i.e., water absorption, water desorption, and chloride resistance). Transport properties were also examined for internally cured mortar, which has identical ingredient proportions to the corresponding concretes used for comparison. The results showed that internal curing is useful in reducing the autogenous shrinkage of self-compacting concrete, and no segregation was observed for the fresh concretes. It was also found that the fine LWAs exhibited a better performance in reducing autogenous shrinkage and improving the transport properties compared with the coarse LWAs. The comparison of water absorption test results between a mortar and its corresponding concrete reveals that an increase in the volume fraction of normal-weight aggregates may decrease the effectiveness of internal curing.
The effect of intravenous immunoglobulin on placental transfer of a platelet‐specific antibody: Anti‐P1<sup>A1</sup> (1991)

The isolated perfused lobule of human placenta was used as an in-vitro model to study the effect of intravenous immunoglobulin (IVGG) on the placental transfer of a human platelet-specific antibody (anti-P1A1). Normal human IgG was shown to transfer from the maternal to the fetal circulation of the placental model after a lag period of 2-3 h. IVGG also transferred across the placenta but only after a longer lag period (3-4 h) than normal human IgG at the same concentration, which suggests that IVGG may contain a factor that inhibits the transfer of its own component IgG. The sensitive Western immunoblotting technique was used to demonstrate progressive transfer of anti-P1A1 antibody to the fetal circulation after a 2-3 h lag period. When IVGG and anti-P1A1 antibody were added simultaneously to the maternal circulation, the transfer of platelet-specific antibody was strongly inhibited by IVGG. The inhibitory effect of IVGG on anti-P1A1 antibody transfer was consistent for three different batches of the same IVGG product (Sandoglobulin). These studies provide the first scientific data to support the use of IVGG to inhibit antiplatelet antibody transfer as part of the antenatal management of neonatal alloimmune thrombocytopenia.
Effect of Auristatin PHE on Microtubule Integrity and Nuclear Localization in <i>Cryptococcus neoformans</i> (2002)

The mechanism of action of the fungicidal peptide auristatin PHE was investigated in Cryptococcus neoformans. Since auristatin PHE causes budding arrest in C. neoformans (T. Woyke, G. R. Pettit, G. Winkelmann, and R. K. Pettit, Antimicrob. Agents Chemother. 45:3580-3584, 2001), microtubule integrity and nuclear localization in auristatin PHE-treated cells were examined. Iterative deconvolution in conjunction with an optimized C. neoformans microtubule immunolabeling procedure enabled detailed visualization of the microtubule cytoskeleton in auristatin PHE-treated C. neoformans. The effect of auristatin PHE on C. neoformans microtubule organization was compared with that of the tubulin-binding agent nocodazole. Both drugs produced complete disruption first of cytoplasmic and then of spindle microtubules in a time- and concentration-dependent manner. Sub-MICs of auristatin PHE caused complete microtubule disruption within 4.5 h, while 1.5 times the nocodazole MIC was required for the same effect. For both drugs, disruption of microtubules was accompanied by blockage of nuclear migration and of nuclear and cellular division, resulting in cells arrested in a uninucleate, large-budded stage. Nocodazole and the linear peptide auristatin PHE are remarkably different in structure and spectrum of activity, yet on the cellular level, they have similar effects.
An Apparently New Virus (Family <i>Paramyxoviridae</i>) Infectious for Pigs, Humans, and Fruit Bats (1998)

We isolated an apparently new virus in the family Paramyxoviridae from stillborn piglets with deformities at a piggery in New South Wales, Australia. In 1997, the pregnancy rate and litter size at the piggery decreased markedly, while the proportion of mummified fetuses increased. We found serologic evidence of infection in pigs at the affected piggery and two associated piggeries, in humans exposed to infected pigs, and in fruit bats. Menangle virus is proposed as a common name for this agent, should further studies confirm that it is a newly recognized virus.
Therapeutic Potential of Ponesimod Alone and in Combination with Dimethyl Fumarate in Experimental Models of Multiple Sclerosis. (2019)

Background: Despite the recent approval of new oral therapies for the treatment of multiple sclerosis (MS), a significant percentage of patients are still not free from disease activity. In view of the complex pathogenesis and the relapsing and progressive nature of MS, combination therapy, a classical approach to treat many chronic diseases, could improve disease control over monotherapy. Ponesimod, a selective and rapidly reversible sphingosine-1-phosphate receptor Type 1 (S1P1) modulator, currently in Phase III clinical trial stage in relapsing MS (RMS), and dimethyl fumarate (DMF) would potentially be an ideal combination due to their differing mechanisms of action and oral administration. Objective: The goal of the study was to evaluate the therapeutic effect of ponesimod monotherapy and investigate the potential additive, or synergistic, activity of ponesimod-DMF combination therapy in experimental autoimmune encephalomyelitis (EAE) animal models of MS. Methods: Efficacy was evaluated in the myelin oligodendrocyte glycoprotein (MOG)-induced EAE model in C57BL/6 mice (ponesimod monotherapy) and in the myelin basic protein (MBP)-induced EAE model in Lewis rats (monotherapies and combination therapy). The principal readout was the clinical score assessing paralysis. Additional readouts, such as histopathology, survival, and disease prevalence, were generated in parallel when applicable. Results: Ponesimod monotherapy in the mouse EAE model showed significant efficacy in both preventative and therapeutic settings. In the rat EAE model, ponesimod demonstrated significant dose-dependent efficacy on clinical scores, while DMF showed only modest activity. Combination therapy synergistically reduced the severity and prevalence of disease. Only the combination treatment of ponesimod and DMF fully suppressed clinical disease activity by the end of the study. Conclusion: The results support the potential therapeutic benefits of combining ponesimod with DMF to improve disease activity control in patients with MS. Additionally, the results suggest that combining ponesimod with other oral agents that have different mechanisms of action might also be therapeutically beneficial to patients with MS.
Synthesis, Characterization, and Application of Vanadium−Salan Complexes in Oxygen Transfer Reactions (2009)

We report the synthesis and characterization of several chiral salen- and salan-type ligands and their vanadium complexes, which are derived from salicylaldehyde or salicylaldehyde derivatives and chiral diamines (1R,2R-diaminocyclohexane, 1S,2S-diaminocyclohexane, and 1S,2S-diphenylethylenediamine). The structures of H(2)sal(R,R-chan)(2+) x 2 Cl(-) x (CH(3))(2)CHOH x H(2)O (1c; H(2)sal(R,R-chan) = N,N'-salicyl-R,R-cyclohexanediaminium), Etvan(S,S-chen) (3c; Etvan(S,S-chen) = N,N'-3-ethoxy-salicylidene-S,S-cyclohexanediiminato), and naph(R,R-chen) (6c; naph(R,R-chen) = N,N'-naphthylidene-R,R-cyclohexanediiminato) were determined by single-crystal X-ray diffraction. The corresponding vanadium(IV) complexes and several other new complexes involving different salicylaldehyde-type precursors were prepared and characterized in the solid state and in solution by spectroscopic techniques: UV-vis, circular dichroism, electron paramagnetic resonance, and (51)V NMR, which provide information on the coordination geometry. The salan complexes oxidize in organic solvents to V(V) species, and this process was also studied using spectroscopic techniques. Single crystals suitable for X-ray diffraction were obtained for [{V(V)O[sal(S,S-dpan)]}(2)(mu-O)] x H(2)O x 2(CH(3))(2)CHOH (14c; sal(S,S-dpan) = N,N'-salicyl-S,S-diphenylethylenediaminato) and [{V(V)O[t-Busal(R,R-chan)]}(2)(mu-O)] x 2 (CH(3))(2)CHOH (15c), both containing an OV(V)(mu-O)V(V)O moiety (V(2)O(3)(4+) core) with tetradentate ligands and one mu-oxo bridge. Both structures are the first examples of dinuclear vanadium complexes involving the V(V)(2)O(3)(4+) core with tetradentate ligands, the configuration of the V(2)O(3) unit being twist-angular. The V-salen and V-salan complexes are tested as catalysts in the oxidation of styrene, cyclohexene, cumene, and methyl phenyl sulfide with H(2)O(2) and t-BuOOH as oxidants. Overall, the V-salan complexes show higher activity and normally better selectivity in alkene oxidation and higher activity and enantioselectivity for sulfoxidation than their parent V-salen complexes, therefore being an advantageous alternative ligand system for oxidation catalysis. The better performance of V-salan complexes probably results from their significantly higher hydrolytic stability. Mechanisms for the alkene oxidation with these newly obtained V-salan compounds are discussed, including the use of DFT for the comparison of several alternative mechanisms for epoxidation.
Alkylation of Some Diacylhydrazines (1959)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlkylation of Some DiacylhydrazinesR Hinman and Richard LandborgCite this: J. Org. Chem. 1959, 24, 5, 724–725Publication Date (Print):May 1, 1959Publication History Published online9 July 2003Published inissue 1 May 1959https://pubs.acs.org/doi/10.1021/jo01087a621https://doi.org/10.1021/jo01087a621research-articleACS PublicationsRequest reuse permissionsArticle Views99Altmetric-Citations6LEARN 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
The Rider on the White Horse (1922)

N a relief from the tomb of the Blessed Albert of Pontida (Fig. 2) which Professor Arthur Kingsley Porter1 found in the sacristy of San Giacomo, Albert's old Cluniac priory, at Pontida, near Bergamo,2 occurs a significant subject, the identification of which is the starting point of this study in iconography. The relief represents St. James Major as the lord of the dead, a rare aspect of his cult except upon the pilgrimage-road to Compostella. Iconographically it is, so far as I know, unique. He is the rider on the white horse of the Fourth Miracle (dated 1080, but written c. 1130), who carried the living and the dead. Professor Porter wished to date the relief shortly after 1095: I am not quite sure for my part that it should not be put later, at any rate after the death of another Piedmontese saint, the Blessed Albert of Vercelli, who had been on the pilgrimage to St. James, who died in the Holy Land in 1214, and who came to be associated with Elijah and the Carmelite order and revered even by Mohammedans. The reason for this later approximation will presently appear. Professor Porter very justly notes the parallel between the relief and the third horseman of the Apocalypse,3 who is painted only in a Spanish series of manuscripts that range from the eighth to the eleventh century or later and exist at Urgell, Madrid, Paris, and elsewhere, and are transcriptions of the Commentary of a Spanish monk Beato of Liebena. The relief belongs absolutely to the Compostellan cycle and is a plastic parallel to The Vision of Thurkill, in which the souls were weighed in the Basilica of the Apostle by St. Michael. Here St. James recombines the two aspects of Horus which were usually split and divided between himself and St. Michael. The three naked souls waiting in a palm tree are the souls expectant in the Paradise of God; on the northernmost door of the Pórtico de la Gloria of Master Matthew they sit in rich leafage. Further, they are equivalent to those souls unborn who sit in trees and sing, and the tree is the date palm in which Carpaccio set his St. Ursula with a row of cherub-heads for the cluster of fruit. This part of the relief seems to be derived directly from sculpture on a capital. The theme belongs, as said, to the pilgrimage—“MIGRAVIT AD ASTRA,” says the epitaph—and goes back ultimately perhaps to Egypt, with which the Spanish connection was always close. The priory of San Giacomo was burned in 1373 and the relics translated to S. Maria Maggiore in Bergamo: but the horseman went too. He rides between two bishops, high in the north porch. Indeed, he stayed permanently on North Italian sepulchral monuments, like that of Bernabo Visconti in Milan and those of the Scaligers in Verona.
Experimentelle Untersuchungen zur Leistungsreserve des linken Ventrikels in den ersten Wochen nach akuter Aortenklappeninsuffizienz (1978)

Bei 12 Schweinen (15 - 24 kg) wurden in Narkose (Urethan-Chloralose) angio- kardiographisch Volumenbestimmungen des linken Ventrikels sowie Druckmessungen vor und in der 1., 2. und 4. Woche nach experimenteller Aortenklappeninsuffizienz durchgeführt (Regurgitationsfraktion 0,6). Zur Beurteilung der linksventrikulären Leistungsreserve bestimmten wir die Änderung der mittleren normalisierten systolischen Austreibungsstromstärke (MNSER) bei Belastung durch Angiotensin- Infusion.
Signalling pathways in bradykinin‐ and nitric oxide‐induced hypotension in the normotensive rat; role of K<sup>+</sup>‐channels (1997)

1. Bradykinin and nitric oxide (NO) are potent hypotensive agents. In the present study, the role of K+-channels in the signalling pathways responsible for their hypotensive action was investigated in normotensive, anaesthetized rats. The rats were treated with ion-channel inhibitors before administration of bradykinin (2.8, 5.6, 28 and 56 nmol kg(-1), i.v.) followed in some of the protocols by nitroprusside (1.1, 3.5, 7, 14, and 28 nmol kg(-1), i.v.). 2. No attenuation of the hypotensive response to bradykinin was detected for inhibitors of the Na-K-Cl-cotransporter (30 micromol kg(-1) furosemide), the ATP-sensitive K+-channel (40 micromol kg(-1) glibenclamide), high conductance Ca2+-activated K+-channel (180 micromol kg(-1) tetraethylammonium, 54 micromol kg(-1) tetrabutylammonium, 35 nmol kg(-1) iberiotoxin, 35 nmol kg(-1) charybdotoxin) or the low conductance Ca2+-activated K+-channel (74 nmol kg(-1) apamin). 3. However, the voltage-sensitive K+-channel (I(A)) inhibitor 4-aminopyridine (4.05-40.5 micromol kg(-1)) induced a concentration-dependent (P<0.0001) attenuation of the hypotensive response (P<0.0001). Bradykinin had no effect on heart rate in anaesthetized rats and this observation was not altered by pretreatment with 4-aminopyridine. 4. 4-Aminopyridine (53 micromol kg(-1)) also significantly attenuated the hypotensive response to nitroprusside (P<0.0003) without altering the heart rate concentration-response curve. Of the two Ca2+-activated K+-channel inhibitors tested on nitroprusside-induced hypotension, tetrabutylammonium induced a slight attenuation (P<0.0101), whereas iberiotoxin had no effect. 5. We therefore concluded that, although the acute hypotensive response to bradykinin in the normotensive rat is not mediated through nitric oxide synthesis, the hypotensive response to both agents was mediated through opening of voltage-sensitive K+-channels (I(A)), resulting in a decrease in peripheral vascular resistance.
Prolactin and Prolactin Receptor Expression in Rat,Small Intestine, Intraepithelial Lymphocytes DuringNeonatal Developmen (2001)

Intraepithelial lymphocytes (IEL) are specialized T cells found between the epithelial cells of the small intestine. Because of their location, IEL are the first lymphocytes to contact intestinal bacteria and food antigens. In the neonate, IEL may be the first cells of the immune system to interact with milk-borne hormones including prolactin (PRL). PRL, an endocrine hormone abundant in breast milk, interacts with cells through surface receptors. PRL has been shown to function as an immunoregulator and may affect the development of the newborn's immune system. To determine if PRL plays a role in IEL development, small intestine IEL from rats of various ages were examined for the presence of surface prolactin receptor (PRL-R) and several lymphoid markers by flow cytometry. Between birth and 96 days of age about 80% of IEL were found to express PRL-R. These same cells also expressed the mRNA for PRL. Additionally, all of the IEL subpopulations examined were found to express PRL-R. Analysis of the normal development of rat IEL revealed an age related increase in total IEL, CD4 positive cells as well as a peak in interleukin-2 receptor (IL-2R) expression at weaning. In summary, the results indicate that IEL express PRL and PRL-R. In addition, an activation marker, IL-2R, changes in expression during neonatal development.
Improvement of Wire Chamber Resolution, Multiple Event Capability, and Other Techniques with Programmed Discharge (1965)

Spark chamber and circuit development for computer-wire chamber systems is described, based on programmed discharges added to an initial high voltage pulse. The basic principle is that the discharge caused by an ionizing particle is converted by an appropriate supply circuit to a secondary discharge, which matches without excessive energy dissipation the requirements of the electronic retrieval system, and does not diffuse beyond its original spatial extent. It is shown that it is possible to record both the x and y coordinates if a single spark without dangerous over-voltage on the detector array, and that one can hold the secondary discharge long enough to act as the sole memory element in the system. This leads to the possibility of retrieving correlated coordinates from multiple events with minimum computer time as well as improved recovery time. This work is described in various intermediate stages with emphasis on our objectives and proposed technological innovations rather than final results. Final results will be published later; it is hoped that this paper will attract suggestions as to which aspects of our work should be pursued immediately, modified, or postponed.
Simulation-Based Airframe Noise Prediction of a Full-Scale, Full Aircraft (2016)

A previously validated computational approach applied to an 18%-scale, semi-span Gulfstream aircraft model was extended to the full-scale, full-span aircraft in the present investigation. The full-scale flap and main landing gear geometries used in the simulations are nearly identical to those flown on the actual aircraft. The lattice Boltzmann solver PowerFLOW® was used to perform time-accurate predictions of the flow field associated with this aircraft. The simulations were performed at a Mach number of 0.2 with the flap deflected 39 deg. and main landing gear deployed (landing configuration). Special attention was paid to the accurate prediction of major sources of flap tip and main landing gear noise. Computed farfield noise spectra for three selected baseline configurations (flap deflected 39 deg. with and without main gear extended, and flap deflected 0 deg. with gear deployed) are presented. The flap brackets are shown to be important contributors to the farfield noise spectra in the mid- to high-frequency range. Simulated farfield noise spectra for the baseline configurations, obtained using a Ffowcs Williams and Hawkings acoustic analogy approach, were found to be in close agreement with acoustic measurements acquired during the 2006 NASA-Gulfstream joint flight test of the same aircraft.