gebhart/patrepeval huggingface dataset:
PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice (2011)

Stimulatory and inhibitory co-receptors play fundamental roles in the regulation of the immune system. We describe a new mouse model of spontaneous autoimmune disease. Activation-induced cytidine deaminase-linked autoimmunity (aida) mice harbor a loss-of-function mutation in the gene encoding lymphocyte activation gene 3 (LAG-3), an inhibitory co-receptor. Although LAG-3 deficiency alone did not induce autoimmunity in nonautoimmune-prone mouse strains, it induced lethal myocarditis in BALB/c mice deficient for the gene encoding the inhibitory co-receptor programmed cell death 1 (PD-1). In addition, LAG-3 deficiency alone accelerated type 1 diabetes mellitus in nonobese diabetic mice. These results demonstrate that LAG-3 acts synergistically with PD-1 and/or other immunoregulatory genes to prevent autoimmunity in mice.
Secreted Klotho Attenuates Inflammation-Associated Aortic Valve Fibrosis in Senescence-Accelerated Mice P1 (2018)

Senescence-accelerated mice P1 (SAMP1) is an aging model characterized by shortened lifespan and early signs of senescence. Klotho is an aging-suppressor gene. The purpose of this study is to investigate whether in vivo expression of secreted klotho (<i>Skl</i>) gene attenuates aortic valve fibrosis in SAMP1 mice. SAMP1 mice and age-matched (AKR/J) control mice were used. SAMP1 mice developed obvious fibrosis in aortic valves, namely fibrotic aortic valve disease. Serum level of Skl was decreased drastically in SAMP1 mice. Expression of MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule 1), F4/80, and CD68 was increased in aortic valves of SAMP1 mice, indicating inflammation. An increase in expression of α-smooth muscle actin (myofibroblast marker), transforming growth factorβ-1, and scleraxis (a transcription factor of collagen synthesis) was also found in aortic valves of SAMP1 mice, suggesting that accelerated aging is associated with myofibroblast transition and collagen gene activation. We constructed adeno-associated virus 2 carrying mouse Skl cDNA for in vivo expression of Skl. <i>Skl</i> gene delivery effectively increased serum Skl of SAMP1 mice to the control level. <i>Skl</i> gene delivery inhibited inflammation and myofibroblastic transition in aortic valves and attenuated fibrotic aortic valve disease in SAMP1 mice. It is concluded that senescence-related fibrotic aortic valve disease in SAMP1 mice is associated with a decrease in serum klotho leading to inflammation, including macrophage infiltration and transforming growth factorβ-1/scleraxis-driven myofibroblast differentiation in aortic valves. Restoration of serum Skl levels by adeno-associated virus 2 carrying mouse Skl cDNA effectively suppresses inflammation and myofibroblastic transition and attenuates aortic valve fibrosis. Skl may be a potential therapeutic target for fibrotic aortic valve disease.
Importance Sampling for Bootstrap Confidence Intervals (1988)

Abstract The use of importance-sampling methods to substantially reduce the amount of resampling necessary for the construction of nonparametric bootstrap confidence intervals is investigated. The classical importance-sampling method of Hammersley and Handscomb (1964) is modified to apply to the estimation of quantiles. Based on this method, a resampling procedure is introduced that recenters the bootstrap distribution of a robust estimator of location to produce estimated confidence limits that are much more accurate (for a given amount of resampling) than those obtained by the usual bootstrap method (Efron 1982). The required recentering is accomplished with a suitable “exponential tilting” similar to that used in another connection by Field and Hampel (1982). This importance-sampling procedure is used to produce bootstrap confidence intervals for location based on a class of estimators that includes symmetric M estimators. These interval estimates are asymptotically optimal in a certain sense. Simulation results for 95% confidence intervals based on a particular robust one-step (from the median) M estimator and its studentized version are presented for sample size 20 for the normal and the normal/uniform (slash) distributions. Studentization is accomplished by dividing the location estimator by the sample analog of its asymptotic standard deviation. The importance-sampling results obtained for bootstrap replication sizes 10, 20, and 40 are compared with the standard bootstrap confidence-interval method based on 400 replications. The simulation size for each case is 10,000. These results suggest that the bootstrap replication size may be reduced by as much as a factor of 10 or more when importance sampling is used. The proposed confidence-interval procedures provide alternatives to those given by Gross (1976), Davison and Hinkley (1986), and DiCiccio and Tibshirani (1987). It seems likely that the general approach proposed in this article could be useful in a variety of other confidence-interval estimation problems.
Cell culture of human colon adenomas and carcinomas. (1987)

Cell lines were established from colon adenomas, including tubular and villous polyps, primary adenocarcinomas, and metastases arising in patients with colon adenocarcinomas. The protocol for cultivating these diverse tissues includes primary cultivation of tissue explants on a type I collagen gel followed by nonenzymatic subculture of the epithelial outgrowth. All early passages were accomplished using low subculture ratios. Cultured cells elaborate morphological structures which are similar to features present in the tissues from which they were cultivated. Specifically, all structural features of colon epithelial cells were identified, including junction formation, prominent microvilli, and mucin secretion, in several cell lines. Five cell lines cultured from colonic neoplasms at different stages of cancer progression were selected for detailed characterization. Cells grown from two tubular polyps had normal human karyotypes. Cells from a villous polyp and all adenocarcinomas were aneuploid with stable marker chromosomes. The established cell lines exhibit distinct phenotypes based on growth characteristics in vitro and in athymic mice; and it is suggested that these cell lines represent useful models for studying the evolution of colon cancer from a benign to an aggressive cell type.
Dynamic magnetic resonance imaging of tumor perfusion (2004)

This work presents approaches and biomedical challenges of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI using small molecular weight gadolinium chelates enables noninvasive imaging characterization of tissue vascularity. Depending on the technique used, data reflecting tissue perfusion (blood flow, blood volume, mean transit time), microvessel permeability surface area product, and extracellular leakage space can be obtained. Insights into these physiological processes can be obtained from inspection of kinetic enhancement curves or by the application of complex compartmental modeling techniques. Potential clinical applications include screening for malignant disease, lesion characterization, monitoring lesion response to treatment, and assessment of residual disease. Newer applications include prognostication, pharmacodynamic assessments of antivascular anticancer drugs, and predicting efficacy of treatment. For dynamic MRI to enter into widespread clinical practice, it will be necessary to develop standardized approaches to measurement and robust analysis approaches. These include the need for commercial equipment manufacturers to provide robust methods for rapidly measuring time-varying change in T1 relaxation rates, incorporation of arterial input function into kinetic modeling processes, robust analysis software that allows input from a variety of MRI devices, and validated statistical tools for the evaluation of heterogeneity.
Stress relaxation in the lamellar copolymer mesophase (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStress relaxation in the lamellar copolymer mesophaseT. A. Witten, L. Leibler, and P. A. PincusCite this: Macromolecules 1990, 23, 3, 824–829Publication Date (Print):February 1, 1990Publication History Published online1 May 2002Published inissue 1 February 1990https://pubs.acs.org/doi/10.1021/ma00205a022https://doi.org/10.1021/ma00205a022research-articleACS PublicationsRequest reuse permissionsArticle Views762Altmetric-Citations186LEARN 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
Hydrogen peroxide stimulates the synthesis of platelet-activating factor by endothelium and induces endothelial cell-dependent neutrophil adhesion. (1988)

Oxidant-induced damage to the intima of pulmonary and systemic vessels is thought to be an important mechanism of injury in a variety of syndromes of vascular damage. Hydrogen peroxide (H2O2) is an active oxygen metabolite that may induce intimal injury by cytolytic attack or by inducing biochemical and functional alterations in the endothelial cells (EC); however, mechanisms involved in noncytolytic perturbation of EC are largely unknown. We found that H2O2 stimulated the synthesis of platelet-activating factor (PAF) by primary cultures of bovine pulmonary artery endothelium (BPAEC) and by human umbilical vein endothelium (HUVEC). In each cell type the incorporation of [3H]acetate into [3H-acetyl]PAF was concentration- and time-dependent and was temporally dissociated from severe plasma membrane disruption and cytolytic cell injury; the newly synthesized PAF remained associated with the EC. H2O2 caused permeabilization of EC to 45Ca2+ and an increase in intracellular Ca2+, suggesting that a transmembrane Ca2+ flux is the signal that initiates PAF synthesis. H2O2 also induced the endothelial cell-dependent adhesion of neutrophils to HUVEC monolayers. This response was rapid, with an onset within minutes and a subsequent time course that paralleled the time course of PAF accumulation, and was dependent on extracellular Ca2+ but not on de novo protein synthesis. These studies demonstrate that H2O2 can induce two rapid activation responses of endothelium, PAF synthesis and EC-dependent neutrophil adhesion, events that may be important in physiologic and pathologic inflammation.
10 Gbit/s directly modulated, high temperature-stabilityexternal fibre grating laser for dense WDM networks (1999)

The authors report on the performance of a 1.55 µm, single frequency semiconductor external fibre grating laser with high temperature stability. The laser shows low static and dynamic chirp when directly modulated at rates up to 10 Gbit/s.
Degradability of Polymers for Implantable Biomedical Devices (2009)

Many key components of implantable medical devices are made from polymeric materials. The functions of these materials include structural support, electrical insulation, protection of other materials from the environment of the body, and biocompatibility, as well as other things such as delivery of a therapeutic drug. In such roles, the stability and integrity of the polymer, over what can be a very long period of time, is very important. For most of these functions, stability over time is desired, but in other cases, the opposite-the degradation and disappearance of the polymer over time is required. In either case, it is important to understand both the chemistry that can lead to the degradation of polymers as well as the kinetics that controls these reactions. Hydrolysis and oxidation are the two classes of reactions that lead to the breaking down of polymers. Both are discussed in detail in the context of the environmental factors that impact the utility of various polymers for medical device applications. Understanding the chemistry and kinetics allows prediction of stability as well as explanations for observations such as porosity and the unexpected behavior of polymeric composite materials in some situations. In the last part, physical degradation such interfacial delamination in composites is discussed.
Microfabricated V-Groove Power Inductors for High-Current Low-Voltage Fast-Transient DC-DC Converters (2006)

Microfabricated thin-film inductors for high-frequency DC-DC power conversion at high currents and low voltages with fast transient response have been fabricated and tested. Inductors with a Co-Zr-O thin-film core and a copper conductor have been fabricated in a silicon substrate. Prototype inductors have been characterized and applied in a 3.3-V-to-1.1-V, 8-A, 5-MHz DC-DC converter and have been shown to exhibit efficiency of up to 89% and power density up to 96 W/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2 </sup> of substrate area. The inductors discussed in this paper emerge as strong candidates for high-efficiency, high-power-density DC-DC converters for advanced digital systems such as microprocessors wherein the fast transient response of the microfabricated inductors can result in significant reduction in the converter's output capacitance
Metabolic Syndrome Accompanied by Hypercholesterolemia Is Strongly Associated With Proinflammatory State and Impairment of Fibrinolysis in Patients With Type 2 Diabetes (2005)

LDL cholesterol is a main determinant of plasma TAFI in patients with type 2 diabetes. Coexistence of MS and HC synergistically accelerates inflammation and impairment of fibrinolysis via elevated concentrations of both TAFI and PAI-1, which inhibit fibrinolysis.
Synthesis and Antiallergy Activity of (1,3,4)Thiadiazolo(3,2-a)-1,2,3-triazolo(4,5-d)pyrimidin-9(3H)-one Derivatives. I. (1992)

A series of 6-substituted [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one derivatives 4a--z were synthesized from 5-substituted 1,3,4-thiadiazol-2-amines 5 by the following consecutive reactions: pyrimidine ring closure with bis(2,4,6-trichlorophenyl) malonate, nitration, chlorination, amination, hydrogenation and diazotization. The structure of 4 was confirmed by an alternate synthesis of 4, involving reaction of 5-substituted 2-azido-1,3,4-thiadiazole 13 with ethyl cyanoacetate, followed by the Dimroth rearrangement and ring closure. The antiallergic activities (anti-passive peritoneal anaphylaxis, anti-passive cutaneous anaphylaxis and anti-slow reacting substance of anaphylaxis activities) of the products were evaluated.
Involvement of Sphingosine 1-Phosphate in Nerve Growth Factor-Mediated Neuronal Survival and Differentiation (1997)

Sphingolipid metabolites, such as ceramide and sphingosine-1-phosphate (SPP), are emerging as a new class of second messengers involved in cellular proliferation, differentiation, and apoptosis. Nerve growth factor (NGF), a neurotrophic factor for pheochromocytoma PC12 cells, induced a biphasic increase in the activity of sphingosine kinase, the enzyme that catalyzes the formation of SPP. This activation was blocked by K252a, an inhibitor of tyrosine kinase A (trkA). A rapid 1.7-fold increase was followed by a marked prolonged increase reaching a maximum of fourfold to fivefold stimulation with a concomitant increase in SPP levels and a corresponding decrease in endogenous sphingosine levels. Levels of ceramide, the precursor of sphingosine, were only slightly decreased by NGF in serum-containing medium. However, NGF decreased the elevation of ceramide induced by serum withdrawal. Treatment of PC12 cells with SPP did not induce neurite outgrowth or neurofilament expression, yet it enhanced neurofilament expression elicited by suboptimal doses of NGF. Moreover, SPP also protected PC12 cells from apoptosis induced by serum withdrawal. To further substantiate a role for SPP in the cytoprotective actions of NGF, we found that N, N-dimethylsphingosine, a competitive inhibitor of sphingosine kinase, also induced apoptosis and interfered with the survival effect of NGF. These effects were counteracted by exogenous SPP. Moreover, other structurally related compounds, such as dihydrosphingosine 1-phosphate and lysophosphatidic acid, had no significant protective effects. Our results suggest that activation of sphingosine kinase and subsequent formation of SPP may play an important role in the differentiation and survival effects induced by NGF.
Silica-based planar lightwave circuits: passive and thermally active devices (2000)

Silica-based planar lightwave circuits (PLCs) are playing key roles in both optical dense wavelength-division multiplexing networks and optical access networks. This paper provides an outline of PLC technology focusing on passive devices such as arrayed waveguide grating multiplexers.
Characterization of Oilseed Lipids from “DHA-Producing Camelina sativa”: A New Transformed Land Plant Containing Long-Chain Omega-3 Oils (2014)

New and sustainable sources of long-chain (LC, ≥C₂₀) omega-3 oils containing DHA (docosahexaenoic acid, 22:6ω3) are required to meet increasing demands. The lipid content of the oilseed of a novel transgenic, DHA-producing land plant, Camelina sativa, containing microalgal genes able to produce LC omega-3 oils, contained 36% lipid by weight with triacylglycerols (TAG) as the major lipid class in hexane extracts (96% of total lipid). Subsequent chloroform-methanol (CM) extraction recovered further lipid (~50% polar lipid, comprising glycolipids and phospholipids) and residual TAG. The main phospholipid species were phosphatidyl choline and phosphatidyl ethanolamine. The % DHA was: 6.8% (of total fatty acids) in the TAG-rich hexane extract and 4.2% in the polar lipid-rich CM extract. The relative level of ALA (α-linolenic acid, 18:3ω3) in DHA-camelina seed was higher than the control. Major sterols in both DHA- and control camelina seeds were: sitosterol, campesterol, cholesterol, brassicasterol and isofucosterol. C₁₆-C₂₂ fatty alcohols, including iso-branched and odd-chain alcohols were present, including high levels of iso-17:0, 17:0 and 19:0. Other alcohols present were: 16:0, iso-18:0, 18:0 and 18:1 and the proportions varied between the hexane and CM extracts. These iso-branched odd-chain fatty alcohols, to our knowledge, have not been previously reported. These components may be derived from wax esters, or free fatty alcohols.
Induction of Adaptive Anti-HER2/neu Immune Responses in a Phase 1B/2 Trial of 2B1 Bispecific Murine Monoclonal Antibody in Metastatic Breast Cancer (E3194): A Trial Coordinated by the Eastern Cooperative Oncology Group (2007)

2B1 is a bispecific murine monoclonal antibody that binds to the extracellular domains of HER2/neu and FcgammaRIII. 2B1 efficiently promotes the lysis of tumor cells overexpressing HER2/neu by natural killer cells and mononuclear phagocytes that express the FcgammaRIII A isoform. Here, we report the results of E3194, a phase 1B/2 trial conducted by the Eastern Cooperative Oncology Group that employed 2B1 therapy in 20 women with metastatic breast cancer. The median age was 51 years. All but 1 patient had received prior chemotherapy. After the first dose, 3 of the initial 8 patients experienced dose-limiting toxicities that required dose-reduction. The nature of these dose-limiting toxicities resulted in a reduced dose from 2.5 mg/m/d to 1 mg/m/d in the remaining 12 patients. Objective antitumor responses were not seen. However, 2B1 therapy induced adaptive immune responses to both intracellular and extracellular domains of HER2/neu. Even though 2B1 antibody therapy did not show activity in metastatic breast cancer at the current administered doses, the ability of this antibody to induce detectable immune responses against an important tumor antigen has implications for understanding the mechanisms by which antibodies that mediate antibody-directed cellular cytotoxicity may exert their clinical antitumor effects.
Improved Efficiency Narrow-Band Acoustooptic Tunable Reflector using Fibre Bragg Grating (1997)

All-fibre versions of bulk devices are very attractive in fibre systems where low insertion loss is always desirable. We have greatly improved the performance of a recently reported [1] Bragg-grating-based acousto-optic superiattice modulator (AOSLM) by reducing the fibre diameter by HF etching. This improves the overlap of acoustic and optical power, resulting in modulator efficiencies as high as 90%. The modulator produces narrow-band amplitude-adjustable reflections that can be tuned over several nm, which is attractive for WDM and laser applications. In the device, an extensional acoustic wave is launched along a fibre Bragg grating. The ensuing superiattice modulation causes additional bands of reflection to appear on both sides of the Bragg condition. The device works by coupling together the forward and backward propagating Bloch modes in the grating (a principle first proposed in 1986 [2,3]) and operates in reflection mode . This differentiates the AOSLM from all previously reported acousto-optic fibre devices, which all rely on intermodal coupling, examples being LP 01 to LP 11 coupling in dual-mode [4] and twin-core [5] fibres, four-port null-couplers [6], polarisation mode couplers in Hi-Bi fibre [7] and guided-to-cladding mode coupling in standard telecom fibre [8]. In all these devices the intermodal beat length L B = λ /( n 1 – n 2 ) at optical wavelength λ between two modes with phase indices n 1 , and n 2 is matched by the acoustic wavelength v s / f s where v s and f s are the acoustic phase velocity and frequency.
Brucella abortus strain 2308 putative glucose and galactose transporter gene: cloning and characterization (1997)

The gene for the putative transporter for glucose and galactose from Brucella abortus strain 2308 was isolated by functional complementation of Escherichia coli strains lacking either glucose or galactose transport systems. The same two plasmid clones were isolated from each screen. These clones restored glucose and galactose transport to the respective E. coli strains. The sequence of the 1806 bp overlap between these two plasmids was determined. A 1242 bp ORF whose disruption eliminated complementation of both E. coli strains showed 36% identity with the E. coli fucP gene encoding a fucose transporter. These two transporters are members of the major facilitator superfamily, in which they represent a previously undescribed family. In addition, an incomplete gene similar to E. coli hisG was found. One of the plasmids complemented E. coli hisG mutants.
Measurement of a Broadband Negative Index with Space-Coiling Acoustic Metamaterials (2013)

We report the experimental demonstration of a broadband negative refractive index obtained in a labyrinthine acoustic metamaterial structure. Two different approaches were employed to prove the metamaterial negative index nature: one-dimensional extractions of effective parameters from reflection and transmission measurements and two-dimensional prism-based measurements that convincingly show the transmission angle corresponding to negative refraction. The transmission angles observed in the latter case also agree very well with the refractive index obtained in the one-dimensional measurements and numerical simulations. We expect this labyrinthine metamaterial to become the unit cell of choice for practical acoustic metamaterial devices that require broadband and significantly negative indices of refraction.