gebhart/patrepeval huggingface dataset:
The Localization of Antigen in Lymph Node Follicles of Congenitally Athymic Nude Rats (1987)

We have examined the postulated dependence on T cells of follicular retention of antigen by studying antigen retention in the draining lymph nodes of congenitally athymic, nude rats after local injections of horseradish peroxidase (HRP). The lymphoid tissues of these rats contained germinal centres and follicular dendritic cells (FDC) that were ultrastructurally identical to those seen in euthymic rats and expressed the differentiation antigen MRC OX2. Nude rat FDC captured and retained locally injected antigen on their surfaces, but as with euthymic rats, only in the presence of previously injected anti-HRP antibody. This demonstrates that the FDC mature both morphologically and functionally in the absence of a thymus or T cells. However, in contrast to euthymic rats, there was no detectable antigen retention in nude rats that had been actively immunized by repeated intraperitoneal injections with HRP for 3 months. The lower number of germinal centres observed in athymic animals compared with their euthymic littermates could thus be explained by deficient production of specific antibody of the isotype necessary for follicular localization of environmental antigens.
Recursive partitioning as an approach to selection of immune markers for tumor diagnosis. (2003)

This initial study shows that multiple antigen miniarrays can provide accurate and valuable tools for cancer detection and diagnosis. Performance of the miniarrays might be enhanced by other combinations of TAAs appropriately selected for different cancer cohorts.
Rapid loss of intraportally transplanted islets: an overview of pathophysiology and preventive strategies (2007)

Islets isolated from multiple pancreas donors are often necessary to achieve euglycemia in type 1 diabetic patients treated by islet allotransplantation. This increases the burden on the limited pool of donor organs. After infusion into the portal vein, a substantial percentage of islets are lost in the immediate post-transplant period through an inflammatory response termed the instant blood-mediated inflammatory reaction (IBMIR). IBMIR is equally, if not more of a problem after islet xenotransplantation, e.g., using pig islets in non-human primates. Coagulation, platelet aggregation, complement activation, and neutrophil and monocyte infiltration play roles in this reaction. IBMIR is potentially triggered by islet surface molecules, such as tissue factor and collagen residues that are normally not in direct contact with the blood. Also, stress during the islet isolation process results in the expression and production of several inflammatory mediators by the islets themselves. The potential mechanisms involved in this rapid graft loss and treatment options to reduce this loss are reviewed. Preventive strategies for IBMIR can include systemic treatment of the recipient, pre-conditioning of the isolated islets, or, in the case of xenotransplantation, genetic modification of the organ-source pig. Pre-conditioning of islets in culture by exposure to anti-inflammatory agents or by genetic modification harbors fewer risks of systemic complications in the recipient. The future of clinical islet transplantation will, at least in part, depend on the success of efforts made to reduce rapid graft loss, and thus allow islet transplantation to become a more efficient therapy by the use of single donors.
Crystal Structure of Argonaute and Its Implications for RISC Slicer Activity (2004)

Argonaute proteins and small interfering RNAs (siRNAs) are the known signature components of the RNA interference effector complex RNA-induced silencing complex (RISC). However, the identity of "Slicer," the enzyme that cleaves the messenger RNA (mRNA) as directed by the siRNA, has not been resolved. Here, we report the crystal structure of the Argonaute protein from Pyrococcus furiosus at 2.25 angstrom resolution. The structure reveals a crescent-shaped base made up of the amino-terminal, middle, and PIWI domains. The Piwi Argonaute Zwille (PAZ) domain is held above the base by a "stalk"-like region. The PIWI domain (named for the protein piwi) is similar to ribonuclease H, with a conserved active site aspartate-aspartate-glutamate motif, strongly implicating Argonaute as "Slicer." The architecture of the molecule and the placement of the PAZ and PIWI domains define a groove for substrate binding and suggest a mechanism for siRNA-guided mRNA cleavage.
Gene replacement, integration, and amplification at the gdhA locus of Corynebacterium glutamicum (1993)

Gene replacement and integration in a Corynebacterium glutamicum ATCC 21086 derivative were achieved by transformation with a nonreplicative plasmid that contains the C. glutamicum ATCC 17965 gdhA gene modified by the insertion of an aphIII cartridge. We isolated rare derivatives of the integrative transformants that have higher levels of expression of the integrated plasmid genes than the parent. Different types of such amplified clones were distinguished according to their antibiotic resistance levels, enzyme specific activities, and physical structures. All amplified clones share a structural DNA motif confined to the chromosomal gdhA locus: a variable number (up to 10) of tandem copies of a unit that includes the selected gene and one flanking repeat. A given clone contains subpopulations that differ in the number of repeats of this unit.
Relaxation of Energy and Approximate Riemann Solvers for General Pressure Laws in Fluid Dynamics (1998)

We consider the Euler equations for a compressible inviscid fluid with a general pressure law $p(\rho,\varepsilon)$, where $\rho$ represents the density of the fluid and $\varepsilon$ its specific internal energy. We show that it is possible to introduce a relaxation of the nonlinear pressure law introducing an energy decomposition under the form $\varepsilon= \varepsilon _1 + \varepsilon _2.$ The internal energy $\varepsilon _1$ is associated with a (simpler) pressure law $p_1(\rho,\varepsilon_1)$; the energy $\varepsilon _2$ is advected by the flow. These two energies are also subject to a relaxation process and in the limit of an infinite relaxation rate, we recover the initial pressure law p. We show that, under some conditions of subcharacteristic type, for any convex entropy associated with the pressure p, we can find a global convex and uniform entropy for the relaxation system. From our construction, we also deduce the extension to general pressure laws of classical approximate Riemann solvers for polytropic gases, which only use a single call to the pressure law (per mesh point and time step). For the Godunov scheme, we show that this extension satisfies stability, entropy, and accuracy conditions.
Modeling and Velocity Control for a Novel Narrow Vehicle Based on Mobile Wheeled Inverted Pendulum (2012)

Traffic problems such as pollution and congestion are becoming more and more serious in urban areas. A potential solution to these problems is to develop narrow vehicles that occupy less space and have lower emissions. There has been increasing interest in underactuated mechanical systems, i.e., mobile wheeled inverted pendulum (MWIP) models, which are widely used in the field of autonomous robotics and intelligent narrow vehicles. A novel narrow vehicle based on an MWIP and a movable seat, called UW-Car, is investigated in this paper. The dynamic model of the underactuated vehicle system running on flat ground is derived by Lagrange's equation of motion. Based on the dynamic model and terminal sliding mode control method, two terminal sliding mode controllers are designed to control velocity and braking of the UW-Car. The first one is used to control the forward speed to a desired value while keeping the body upright and the seat on some fixed position. The second one is a switching sliding mode controller, composed of three terminal sliding mode controllers that quickly brakes the system according to an optimal braking scheme. All the control algorithms are tested in both Matlab simulation and a UW-Car experiment. The simulation and experimental results demonstrate the efficiency of the model and controllers.
Oxysterols (2002)

Oxysterols are oxygenated derivatives of cholesterol that are intermediates or even end products in cholesterol excretion pathways. Because of their ability to pass cell membranes and the blood-brain barrier at a faster rate than cholesterol itself, they are also important as transport forms of cholesterol. In addition, oxysterols have been ascribed a number of important roles in connection with cholesterol turnover, atherosclerosis, apoptosis, necrosis, inflammation, immunosuppression, and the development of gallstones. According to current concepts, oxysterols are physiological mediators in connection with a number of cholesterol-induced metabolic effects. However, most of the evidence for this is still indirect, and there is a discrepancy between the documented potent effects of oxysterols under in vitro conditions and the studies demonstrating that they are of physiological importance in vivo. Oxysterol-binding proteins, such as liver X receptor-alpha (a nuclear receptor), do have a regulatory role in cholesterol turnover, but the physiological ligand of the protein has not yet been defined with certainty. Recently developed genetically engineered mouse models with markedly reduced or increased concentration of some of the oxysterols have exhibited surprisingly small changes in cholesterol turnover and homeostasis. The present review is a critical evaluation of the literature on oxysterols, in particular, the in vivo evidence for a role of oxysterols as physiological regulators of cholesterol homeostasis and as atherogenic factors.
Investigation of methods for speckle contrast reduction (2010)

Speckle arises when coherent light is reflected from a rough screen and observed by an intensity detector with a finite aperture. Because speckle causes serious image degradation when lasers are used as light sources in e.g. projectors, methods for reducing the speckle contrast need to be developed. Different speckle contrast reduction methods are investigated in this thesis, such as a rotating diffuser and a sinusoidal rotating grating. In addition, speckle simulations with the optical system design software ZEMAX has been explored. A setup consisting of a 4-f imaging system with a rotating diffuser in the Fourier plane was developed in order to decide whether or not it is advantageous to perform speckle reduction in the Fourier plane. Hence, measurement series were performed with the rotating diffuser placed at different positions in the 4-f imaging system for comparison. Measurement series were executed both with an empty object plane and with a lens in it to spread the light in the Fourier plane. Placing a rotating diffuser in the Fourier plane does not appear to be effective for speckle contrast reduction. The last setup investigated was a transmissive spatial light modulator (SLM) placed in the beam path. Sinusoidal rotating gratings created by means of gray levels, to simulate a potential modulator based on a deformable polymer layer, were implemented on the SLM. The gratings were rotated around their centers, and in a spiral in order to reduce the speckle contrast. For the first method the modulator speckle contrast was 34% for N = 18 averaged images, and for the second method it was 31% for N = 36 averaged images, both with a grating period of 4 pixels. Due to the drawbacks of the SLM optimal results were not achieved, but the SLM is useful for a proof-of-concept. Further measurements should be performed for this promising, novel method based on a true sinusoidal grating.
Host-Derived Tumor Endothelial Marker 8 Promotes the Growth of Melanoma (2009)

Tumor endothelial marker 8 (TEM8) was initially identified as a gene overexpressed in the vasculature of human tumors and was subsequently identified as an anthrax toxin receptor. To assess the functional role of TEM8, we disrupted the TEM8 gene in mice by targeted homologous recombination. TEM8(-/-) mice were viable and reached adulthood without defects in physiologic angiogenesis. However, histopathologic analysis revealed an excess of extracellular matrix in several tissues, including the ovaries, uterus, skin, and periodontal ligament of the incisors, the latter resulting in dental dysplasia. When challenged with B16 melanoma, tumor growth was delayed in TEM8(-/-) mice, whereas the growth of other tumors, such as Lewis lung carcinoma, was unaltered. These studies show that host-derived TEM8 promotes the growth of certain tumors and suggest that TEM8 antagonists may have utility in the development of new anticancer therapies.
Functional gold nanoparticles for the storage and controlled release of nitric oxide: applications in biofilm dispersal and intracellular delivery (2014)

Gold nanoparticles (size 10 nm) were designed to store and release nitric oxide (NO), by functionalizing their surfaces with functional polymers modified with NO-donor molecules. Firstly, block copolymer chains consisting of poly(oligoethylene glycol methyl ether methacrylate)-b-poly(vinyl benzyl chloride) (P(OEGMA)-b-PVBC)) were prepared using RAFT polymerization. The chloro-functional groups were then reacted with hexylamine, to introduce secondary amine groups to the copolymer chains. The block copolymers were then grafted onto the surface of gold nanoparticles, exploiting the end-group affinity for gold - attaining grafting densities of 0.6 chain per nm<sup>2</sup>. The secondary amine functional groups were then converted to N-diazeniumdiolate NO donor molecules via exposure to NO gas at high pressure (5 atm). The NO-bearing, gold nanoparticles were characterized using a range of techniques, including transmission electron microscopy, dynamic light scattering (DLS), thermal gravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS). The nanoparticles displayed slow release of the nitric oxide in biological media. Proof of potential utility was then demonstrated in two different application areas: Pseudomonas aeruginosa biofilm dispersal and cancer cell cytotoxicity.
Structural and immunological characterization of Burkholderia pseudomallei O-polysaccharide-flagellin protein conjugates (1996)

The O-polysaccharide moiety of Burkholderia pseudomallei 319a lipopolysaccharide was covalently linked to flagellin protein isolated from the same strain. A glycoconjugate incorporating adipic acid dihydrazide as a spacer molecule elicited high-titer immunoglobulin G responses to both the protein and carbohydrate components of the construct. This immunoglobulin G was capable of protecting diabetic rats from challenge with a heterologous B. pseudomallei strain.
Variant diphtheria toxin-interleukin-3 fusion proteins with increased receptor affinity have enhanced cytotoxicity against acute myeloid leukemia progenitors. (2006)

A fusion protein linking a truncated form of diphtheria toxin (DT(388)) to human interleukin-3 (DT(388)IL3) kills malignant progenitors from some patients with acute myeloid leukemia (AML) while sparing normal progenitors. This study evaluated two variants of DT(388)IL3 with increased affinity for the IL-3 receptor (IL-3R) for their cytotoxicity to AML progenitors and determined the ability of quantitative reverse transcription-PCR assessment of expression of the IL-3R subunits to predict the effectiveness of wild-type DT(388)IL3 and its variants. Both the IL-3 deletion variant (Delta125-133) and the amino acid substitution variant (K116W) showed enhanced toxicity against AML colony-forming cells (AML-CFC; but not normal CFC) compared with wild-type DT(388)IL3 with the K116W variant achieving >90% AML-CFC kill with 17 of 23 patient samples. This variant was also more effective against AML cells engrafting in nonobese diabetic severe combined immunodeficient mice. There was a significant correlation between the expression of the alpha and, particularly, the common beta subunit of the IL-3R on AML blasts detected by quantitative reverse transcription-PCR and AML-CFC kill. Thus, the combined use of IL-3R expression to select patients most likely to respond to DT(388)IL3 and the improved cytotoxicity of the K116W DT(388)IL3 variant against leukemic progenitors may enhance the clinical usefulness of these fusion proteins.
Interaction of Human Nuclear Topoisomerase I with Guanosine Quartet-forming and Guanosine-rich Single-stranded DNA and RNA Oligonucleotides (2002)

Human nuclear DNA topoisomerase I (top1) plays a crucial role in DNA replication, transcription, and chromosome condensation. In this study, we show that intra- and intermolecular guanosine quartets (G-quartets) can inhibit top1-mediated DNA cleavage at a high affinity site. Top1-mediated DNA cleavage was also inhibited by a 16-mer single-stranded oligodeoxynucleotide (ODN) containing a G-rich sequence (G(2)T(2)G(5)TG(2)TG(3)) and by its RNA equivalent, neither of which form G-quartet structures. A comparison of various single-stranded ODN for their ability to inhibit top1-mediated DNA cleavage indicated that G-rich sequences containing repeats of 2 or 3 consecutive guanines interspaced with thymines specifically inhibited top1. We also found that both single-stranded and G-quartet-forming ODNs bind to top1 without being cleaved by the enzyme. These results demonstrate that either DNA or RNA G-rich single-stranded and G-quartet-forming oligonucleotides can bind to top1 and prevent cleavage of duplex DNA.
Human erythroleukemia cell line (HEL) undergoes a drastic macrophage- like shift with TPA (1983)

We investigated the effect of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the human erythroleukemia cell line, HEL, and found that TPA addition (10(-6)-10(-8) M) to HEL cell cultures induces morphological, functional, and biochemical changes in HEL cells that are characteristic for macrophage-like cells. Apart from the drastic changes in morphology, the cells greatly enhance their phagocytic ability and acquire receptors for binding and degradation of chemically modified lipoproteins. At the biochemical level, a newly synthesized 85K glycoprotein is observed, and the cells are unresponsive to inducers of globin synthesis. Comparative observations with K562 cells indicate that TPA inhibits, as in HEL cells, spontaneous and induced globin synthesis, but induces minimal macrophage-like properties in these cells. The results with HEL cells are interpreted to indicate that TPA uncovers a latent monocyte-like phenotype in these cells.
HARK No More (2018)

Experimental preregistration is required for publication in many scientific disciplines and venues. When experimental intentions are preregistered, reviewers and readers can be confident that experimental evidence in support of reported hypotheses is not the result of HARKing, which stands for Hypothesising After the Results are Known. We review the motivation and outcomes of experimental preregistration across a variety of disciplines, as well as previous work commenting on the role of evaluation in HCI research. We then discuss how experimental preregistration could be adapted to the distinctive characteristics of Human-Computer Interaction empirical research, to the betterment of the discipline.
Collagen induced arthritis as an experimental model for rheumatoid arthritis (1989)

The type II collagen (CII) induced arthritis animal model (CIA) provides opportunities to study the nature of autoimmune reactions leading to arthritis and may be used as a model for rheumatoid arthritis (RA). Thus, in similarity with RA, the CIA model, when induced with autologous CII, shows a chronic and progressive disease course. The susceptibility to both RA and CIA are correlated to the expression of certain MHC class II allotype genes. In both diseases are autoantibodies to CII and rheumatoid factors produced. Immunohistopathology of affected joints show in both diseases a dominance of activated macrophages/fibroblasts with a significant infiltration of activated T cells and an infiltration of granulocytes. We do here suggest that both RA and CIA are dependent on a synergy between delayed type hypersensitivity and immune complex mediated inflammatory mechanisms and that CIA provides opportunities for studies of immunospecific reactions leading to arthritis.
T1/ST2 Signaling Establishes It as a Member of an Expanding Interleukin-1 Receptor Family (1996)

Through data base searches, we have discovered new proteins that share homology with the signaling domain of the type I interleukin-1 receptor (IL-1RI): human "randomly sequenced cDNA 786" (rsc786), murine MyD88, and two partial Drosophila open reading frames, MstProx and STSDm2245. Comparisons between these new proteins and known IL-1RI homologous proteins such as Toll, 18-Wheeler, and T1/ST2 revealed six clusters of amino acid similarity. We tested the hypothesis that sequence similarity between the signaling domain of IL-1RI and the three mammalian family members might indicate functional similarity. Chimeric IL-1RI receptors expressing the putative signaling domains of T1/ST2, MyD88, and rsc786 were assayed by three separate IL-1 responsive assays, NF-kappaB, phosphorylation of an epidermal growth factor receptor peptide, and an interleukin 8 promoter-controlled reporter construct, for their ability to transduce an IL-1-stimulated signal. All three assays were positive in response to the T1/ST2 chimera, while the MyD88 and rsc786 chimeras failed to respond. These data indicate that the sequence homology between IL-1RI and T1/ST2 indicates a functional homology as well.
Cloning of a novel kinase (SIK) of the SNF1/AMPK family from high salt diet‐treated rat adrenal1 (1999)

PCR-coupled cDNA subtraction hybridization was adapted to identify the genes expressed in the adrenocortical tissues from high salt diet-treated rat. A novel cDNA clone, termed salt-inducible kinase (SIK), encoding a polypeptide (776 amino acids) with significant similarity to protein serine/ threonine kinases in the SNF1/AMPK family was isolated. An in vitro kinase assay demonstrated that SIK protein had autophosphorylation activity. Northern blot revealed that SIK mRNA levels were markedly augmented by ACTH treatment both in rat adrenal glands and in Y1 cells. SIK may play an important role in the regulation of adrenocortical functions in response to high plasma salt and ACTH stimulation.