gebhart/patrepeval huggingface dataset:
Airway Epithelial Cells Produce B Cell-Activating Factor of TNF Family by an IFN-β-Dependent Mechanism (2006)

Activation of B cells in the airways is now believed to be of great importance in immunity to pathogens, and it participates in the pathogenesis of airway diseases. However, little is known about the mechanisms of local activation of B cells in airway mucosa. We investigated the expression of members of the B cell-activating TNF superfamily (B cell-activating factor of TNF family (BAFF) and a proliferation-inducing ligand (APRIL)) in resting and TLR ligand-treated BEAS-2B cells and primary human bronchial epithelial cells (PBEC). In unstimulated cells, expression of BAFF and APRIL was minimal. However, BAFF mRNA was significantly up-regulated by TLR3 ligand (dsRNA), but not by other TLR ligands, in both BEAS-2B cells (376-fold) and PBEC (224-fold). APRIL mRNA was up-regulated by dsRNA in PBEC (7-fold), but not in BEAS-2B cells. Membrane-bound BAFF protein was detectable after stimulation with dsRNA. Soluble BAFF protein was also induced by dsRNA (> 200 pg/ml). The biological activity of the epithelial cell-produced BAFF was verified using a B cell survival assay. BAFF was also strongly induced by IFN-beta, a cytokine induced by dsRNA. Induction of BAFF by dsRNA was dependent upon protein synthesis and IFN-alphabeta receptor-JAK-STAT signaling, as indicated by studies with cycloheximide, the JAK inhibitor I, and small interfering RNA against STAT1 and IFN-alphabeta receptor 2. These results suggest that BAFF is induced by dsRNA in airway epithelial cells and that the response results via an autocrine pathway involving IFN-beta. The production of BAFF and APRIL by epithelial cells may contribute to local accumulation, activation, class switch recombination, and Ig synthesis by B cells in the airways.
Expression of vascular endothelial growth factor family members in head and neck squamous cell carcinoma correlates with lymph node metastasis (2001)

Up-regulation of VEGF-A (two isoforms) and VEGF-C and down-regulation of VEGF-D have been common features in HNSCC. Thus VEGF-A and VEGF-C appeared to play a vital role in the metastatic process of HNSCC.
Clinical Experience of Ketogenic Diet on Children with Refractory Epilepsy (1999)

Thirteen children with refractory epilepsy received a ketogenic diet (medium chain triglyceride oil diet) as an alternative therapy since September 1997. Their seizure patterns included (1) generalized tonic-clonic seizures, (2) myoclonic seizures, (3) generalized tonic+atonic seizures, (4) complex partial seizures, (5) generalized clonic+atonic+myoclonic seizures, (6) head nodding+myoclonic+gelastic seizures, and (7) generalized tonic-clonic + myoclonic + atonic seizures. Major concerns emphasized on the efficacy and side effects of the diet. Clinical observation one month after the diet revealed that 53.8% of the patients had a＞75% reduction in seizure frequency and 76.9% of the patients had a＞50% reduction in seizure frequency. Six patients had some degrees of improvement in cognitive function and! or school performances. The most common side effects were body weight loss (n=6) and diarrhea (n=5). Others included bad temper (n=1), abdominal cramps (n=2), nausea (n=2), bad body smell (n=1), and renal stones (n=1). Even after discontinuation of the diet, 61.5% of patients still had a＞50% reduction in seizure frequency. We concluded that the ketogenic diet deserves a trial in children with refractory epilepsy.
The peroxisome proliferator–activated receptor γ agonist pioglitazone reduces the development of cartilage lesions in an experimental dog model of osteoarthritis: In vivo protective effects mediated through the inhibition of key signaling and catabolic pathways (2007)

These results indicate the efficacy of pioglitazone in reducing cartilage lesions in vivo. The results also provide new and interesting insights into a therapeutic intervention for OA in which PPARgamma activation can inhibit major signaling pathways of inflammation and reduce the synthesis of cartilage catabolic factors responsible for articular cartilage degradation.
Solution-Phase Parallel Synthesis of an N-Alkylated Dihydropteridinone Library from Fluorous Amino Acids (2004)

Parallel synthesis of an N-alkylated dihydropteridinone library has been accomplished in five steps starting from two displacement reactions of 4,6-dichloro-5-nitropyrimidine, first with fluorous amino acids, then with secondary amines. The hydrogenation of the nitro group followed by microwave-assisted cyclization gave the dihydropteridinones. Further diversification was achieved by the reaction of dihydropteridinones with benzyl halides to afford mono-N-alkylated products. All the reaction intermediates and final products were purified by SPE or precipitation without the need to perform chromatography.
The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. (1981)

In a previous publication the author and his co-workers demonstrated that atherosclerotic lesion development in the aorta of hypercholesterolemic pigs was preceded by intimal penetration of blood-borne mononuclear cells, and that medial smooth muscle cells were not involved in the formation of early fatty lesions in this model. The current study shows that aortic arch lesions do not progress beyond the fatty cell lesion stage for up to 30 weeks of a moderate cholesterol/lard diet, although they become more extensive in area. Mononuclear cells were found adherent to the endothelium, in endothelial junctions, and in the intima during this period, and were ultrastructurally identified as monocytes by the presence of peroxidase-positive granules (peroxisomes) in their cytoplasm. In addition, lesion areas with nonspecific esterase activity correlated well with Sudan IV staining. Intimal monocytes and altered intimal monocytes with an enlarged cytoplasm and containing a few lipid droplets were both shown to be phagocytic by their uptake of ferritin, which had penetrated the intima after intravenous injection. Circulating monocytes and those adherent to the endothelial surface did not contain ferritin in these animals. The results indicate that blood mononuclear cells associated with lesion formation in this model are, in fact, monocytes, which subsequently undergo transformation into macrophage foam cells in fatty streak lesions. The absence of medial cell involvement indicates that monocytes are the major foam cell precursor in these lesions.
Interstate Highway Road-Killed Animals: A Data Source for Biologists (1978)

Analysis of road-killed animals reported by service crews of state road departments could serve as a data source for long-term information on animal populations. Typical data analyzed for a 7-year period for Interstate-80 (1-80) in Nebraska indicated that monthly highs of road-killed animals occurred in May and October. For the nine species analyzed, high frequen- cies of road-kills apparently were associated with breeding activities and dispersal. Carrion or roadside vegetation also might attract wildlife to roads and increase their vulnerability to highway mortality. Road-killed animals were not significantly correlated with average daily traffic (ADT) on an annual or monthly basis (r = 0.07, P > 0.5 and r = 0.25, 0.5 > P > 0.4, respectively). Annual road-killed animals were significantly correlated (r = 0.92, 0.01 > P > 0.001) with average vehi- cle speed (AVS). Annual road-killed pheasants (Phasianus colchicus), as well as April road-killed pheasants were significantly correlated (P < 0.01) with spring rural mail carrier surveys of pheas- ants. Road-kill data may supplement or substitute for existing wildlife census methods, supply information on interactions of two species' populations (e.g., predator-prey) and identify game- crossing areas that might reduce waste of wildlife resources and wildlife-caused vehicle acci- dents.
Effect of human beta (s)-globin chains on cellular properties of red cells from beta-thalassemic mice. (1988)

The transgenic mouse system provides an in vivo setting in which to examine the effects on mouse red cells of hemoglobin genes that have been genetically introduced into the animals' genome. In this report, we have analyzed the cellular properties of red cells from homozygous beta-thalassemic mice (Hbbth-1/Hbbth-1), homozygous beta-thalassemic transgenic mice containing a human beta-sickle (beta(s)) gene (Hbb(th-1)/Hbb(th-1) + beta(s)), and normal animals. The presence of human beta(s)-globin chains in red cells from the Hbbth-1/Hbb(th-1) + beta(s) transgenic animals was noted to have a significant effect on cellular deformability and density distribution, as well as on the degree of anemia in these animals. We conclude from these studies that red cell deformability and density distribution is a sensitive means for assessing at the cellular level the effects of globin genes genetically introduced into whole organisms. In addition, these studies suggest that small decreases in the amount of excess alpha-globin chains can significantly ameliorate the severity of anemia in the beta-thalassemic mouse.
Studies on the role of the 2'-5'-oligoadenylate synthetase-RNase L pathway in beta interferon-mediated inhibition of encephalomyocarditis virus replication (1988)

Interferons inhibit the replication of vesicular stomatitis virus (VSV), but not of encephalomyocarditis virus (EMCV), in mouse JLSV-11 cells. We report the isolation of clonal derivatives from this cell line in which the replication of both viruses is impaired by interferons. These clones were selected from the parental line by virtue of their rescue by interferon treatment from the cytopathic effects of EMCV infection. In one such clone, RK8, the replication of VSV and EMCV and the production of resident murine leukemia virus were inhibited by interferon. On the other hand, in clone RK6, which was isolated without any selection, the replication of VSV, but not of EMCV, was impaired by interferons. The levels of 2'-5'-oligoadenylate synthetase mRNA and enzyme activity were similarly elevated upon interferon treatment in the two clones. However, the level of RNase L, as determined by binding and cross-linking of a radiolabeled 2'-5'-oligoadenylate derivative, was much lower in RK6 cells than in RK8 cells. In accord with this observation, the introduction of 2'-5'-oligoadenylates into cells inhibited protein synthesis much less strongly in RK6 cells than in RK8 cells. These results are consistent with the notion that the 2'-5'-oligoadenylate-dependent RNase L may be a mediator of the inhibition of EMCV replication by interferons.
Transit of pharmaceutical dosage forms through the small intestine. (1986)

The gastrointestinal transit of pharmaceutical dosage forms has been measured in 201 studies in normal subjects using gamma scintigraphy. Solutions, small pellets, and single units (matrix tablets and osmotic pumps) were administered with different amounts of food in the stomach, ranging from fasted state to heavy breakfast. Gastric emptying was affected by the nature of the dosage form and the presence of food in the stomach. Solutions and pellets were emptied even when the stomach was in the digestive mode, while single units were retained for long periods of time, depending on the size of the meal. In contrast, measured intestinal transit times were independent of the dosage form and fed state. The small intestinal transit time of about three hours (mean +/- 1 h SEM) has implications for the design of dosage forms for the sustained release of drugs in specific positions in the gastrointestinal tract.
Thin-Film Schottky Barrier Photodetector Models (2010)

Phenomenological models for the internal quantum efficiency of Schottky barrier photodetectors suitable for the detection of optical radiation below the bandgap energy of the semiconductor are presented and discussed. The detection mechanism is internal photoemission from the metal film into the semiconductor substrate. Three detector configurations are considered: the first consists of a thick metal film on a semiconductor substrate forming a single Schottky barrier; the second consists of a thin metal film on a semiconductor substrate also forming a single Schottky barrier; and the third consists of a thin metal film buried in semiconductor and forming two Schottky barriers (one along each metal-semiconductor interface). In the three cases, illumination through the semiconductor substrate is assumed. The two thin-film configurations provide enhanced internal quantum efficiencies due to multiple hot carrier reflections within the metal film, with the double-barrier case providing the greatest enhancement due to emission over two barriers. The models proposed are based on assessing the emission probability of hot carriers as a function of their energy, taking into account multiple reflections within the metal film and energy losses due to internal scattering (e.g., with phonons and cold carriers). The thin-film single-barrier model was tested via comparisons with responsivity measurements reported in the literature for PtSi/p-Si and Pd <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Si/p-Si detectors.
Activation of canonical Wnt/β‐catenin signaling stimulates proliferation in neuromasts in the zebrafish posterior lateral line (2013)

These data suggest that Wnt/β-catenin signaling is both necessary and sufficient for the control of proliferation of lateral line progenitors during development, ongoing growth of the neuromasts, and hair cell regeneration.
CD4+T-Cell Effectors Inhibit Epstein-Barr Virus-Induced B-Cell Proliferation (2001)

In immunodeficient hosts, Epstein-Barr virus (EBV) often induces extensive B-cell lymphoproliferative disease and lymphoma. Without effective in vitro immune surveillance, B cells infected by the virus readily form immortalized cell lines. In the regression assay, memory T cells inhibit the formation of foci of EBV-transformed B cells that follows recent in vitro infection by EBV. No one has yet addressed which T cell regulates the early proliferative phase of B cells newly infected by EBV. Using new quantitative methods, we analyzed T-cell surveillance of EBV-mediated B-cell proliferation. We found that CD4+ T cells play a significant role in limiting proliferation of newly infected, activated CD23+ B cells. In the absence of T cells, EBV-infected CD23+ B cells divided rapidly during the first 3 weeks after infection. Removal of CD4+ but not CD8+ T cells also abrogated immune control. Purified CD4+ T cells eliminated outgrowth when added to EBV-infected B cells. Thus, unlike the killing of EBV-infected lymphoblastoid cell lines, in which CD8+ cytolytic T cells play an essential role, prevention of early-phase EBV-induced B-cell proliferation requires CD4+ effector T cells.
The immune response in autism: a new frontier for autism research (2006)

Autism spectrum disorders (ASD) are part of a broad spectrum of neurodevelopmental disorders known as pervasive developmental disorders, which occur in childhood. They are characterized by impairments in social interaction, verbal and nonverbal communication and the presence of restricted and repetitive stereotyped behaviors. At the present time, the etiology of ASD is largely unknown, but genetic, environmental, immunological, and neurological factors are thought to play a role in the development of ASD. Recently, increasing research has focused on the connections between the immune system and the nervous system, including its possible role in the development of ASD. These neuroimmune interactions begin early during embryogenesis and persist throughout an individual's lifetime, with successful neurodevelopment contingent upon a normal balanced immune response. Immune aberrations consistent with a dysregulated immune response, which so far, have been reported in autistic children, include abnormal or skewed T helper cell type 1 (T(H)1)/T(H)2 cytokine profiles, decreased lymphocyte numbers, decreased T cell mitogen response, and the imbalance of serum immunoglobulin levels. In addition, autism has been linked with autoimmunity and an association with immune-based genes including human leukocyte antigen (HLA)-DRB1 and complement C4 alleles described. There is potential that such aberrant immune activity during vulnerable and critical periods of neurodevelopment could participate in the generation of neurological dysfunction characteristic of ASD. This review will examine the status of the research linking the immune response with ASD.
The Impact of Carrier Flow Rate and Infusion Set Dead-Volume on the Dynamics of Intravenous Drug Delivery (2005)

The dynamics of IV drug delivery resulting from drug infusions connected to main-line crystalloid carriers can be complex and depend on infusion set dead-volume, drug flow rate, and carrier flow rate. While the concept of dead-volume is intuitive, a lack of appreciation of the interaction with the carrier and drug flow rates can lead to unintended clinical effects resulting from large variations in the delivery rate of potent drugs. We derived mathematical models to quantify these interactions. Experimental simulation with methylene blue infusions tested these predictions. The models predict a lag in response time to changes in carrier or drug flow, which is proportional to the dead-volume and inversely related to the total flow rate. Increasing the carrier rate provides an acute drug bolus. Temporary reduction or cessation of carrier flow decreases the rate of drug delivery, potentially for prolonged periods. Furthermore, a drug bolus results from restoration of the carrier flow. The method of connecting an infusion to a carrier and the use history affects the dynamics of drug delivery. Thus, although complex, the impact of infusion set architecture and changes in carrier and drug flow rates are predictable. These quantitative studies may help optimize the safe use of IV drug infusion systems.
Early detection and treatment of skin cancer. (2000)

The incidence of skin cancer is increasing by epidemic proportions. Basal cell cancer remains the most common skin neoplasm, and simple excision is generally curative. Squamous cell cancers may be preceded by actinic keratoses-premalignant lesions that are treated with cryotherapy, excision, curettage or topical 5-fluorouracil. While squamous cell carcinoma is usually easily cured with local excision, it may invade deeper structures and metastasize. Aggressive local growth and metastasis are common features of malignant melanoma, which accounts for 75 percent of all deaths associated with skin cancer. Early detection greatly improves the prognosis of patients with malignant melanoma. The differential diagnosis of pigmented lesions is challenging, although the ABCD and seven-point checklists are helpful in determining which pigmented lesions require excision. Sun exposure remains the most important risk factor for all skin neoplasms. Thus, patients should be taught basic "safe sun" measures: sun avoidance during peak ultraviolet-B hours; proper use of sunscreen and protective clothing; and avoidance of suntanning.
Control of Recombination Events During Lymphocyte Differentiation: Heavy Chain Variable Region Gene Assembly and Heavy Chain Class Switchinga (1988)

Our recent studies have focused on the organization of immunoglobulin genes in mice and humans and the mechanism and control of the recombination events that are involved in their assembly and expression. This report describes our progress in this area with particular focus on elucidating factors that influence the generation of the antibody repertoire in normal and diseased states. We present a detailed analysis of the organization of the human VH locus, studies that help to elucidate the nature of the recombination defect in mice with severe combined immunodeficiency, and studies of transgenic mice that focus on the mechanism that regulates tissue-specific variable region gene assembly. In addition, we also characterize mechanisms that control the heavy chain class-switch process. Although the latter process apparently involve a recombination system distinct from that involved in variable region assembly, we find that the two recombination events appear to be controlled by similar mechanisms.
A potent adjuvant effect of CD40 antibody attached to antigen (2003)

There is great potential for novel vaccines based on recombinant proteins and synthetic peptides. Unfortunately these antigens often lack the immunogenicity of whole, killed pathogens used in traditional vaccines. Thus there is strong interest in the identification of immunological adjuvants with low reactogenicity, but high potency, to enhance immune responses and realize the potential of these new vaccine strategies. CD40 antibodies have been shown to have adjuvant effects when administered at very high doses. These large doses are impractical and induce a cascade of cytokine release giving rise to septic shock-like symptoms, as well as splenomegaly and polyclonal antibody production. We show here that a very small amount of CD40 antibody can exhibit potent adjuvant effects when attached to soluble antigen. The lack of detectable systemic effects indicates that this method may be a powerful and practical means of enhancing the efficacy of recombinant vaccines.
High frequency oscillatory flows in a slightly rarefied gas according to the Boltzmann–BGK equation (2013)

Abstract The Boltzmann equation provides a rigorous theoretical framework to study dilute gas flows at arbitrary degrees of rarefaction. Asymptotic methods have been applied to steady flows, enabling the development of analytical formulae. For unsteady (oscillatory) flows, two important limits have been studied: (i) at low oscillation frequency and small mean free path, slip models have been derived; and (ii) at high oscillation frequency and large mean free path, the leading-order dynamics are free-molecular. In this article, the complementary case of small mean free path and high oscillation frequency is examined in detail. All walls are solid and of arbitrary smooth shape. We perform a matched asymptotic expansion of the unsteady linearized Boltzmann–BGK equation in the small parameter $\nu / \omega $ , where $\nu $ is the collision frequency of gas particles and $\omega $ is the characteristic oscillation frequency of the flow. Critically, an algebraic expression is derived for the perturbed mass distribution function throughout the bulk of the gas away from any walls, at all orders in the frequency ratio $\nu / \omega $ . This is supplemented by a boundary layer correction defined by a set of first-order differential equations. This system is solved explicitly and in complete generality. We thus provide analytical expressions up to first order in the frequency ratio, for the density, temperature, mean velocity and stress tensor of the gas, in terms of the temperature and mean velocity of the wall, and the applied body force. In stark contrast to other asymptotic regimes, these explicit formulae eliminate the need to solve a differential equation for a body of arbitrary geometry. To illustrate the utility of these results, we study the oscillatory thermal creep problem for which we find a tangential boundary layer flow arises at first order in the frequency ratio.
Three-dimensional microfabrication with two-photon-absorbed photopolymerization (1997)

We propose a method for three-dimensional microfabrication with photopolymerization stimulated by two-photon absorption with a pulsed infrared laser. An experimental system for the microfabrication has been developed with a Ti:sapphire laser whose oscillating wavelength and pulse width are 790 nm and 200 fs, respectively. The usefulness of the proposed method has been verified by fabrication of several kinds of microstructure by use of a resin consisting of photoinitiators, urethane acrylate monomers, and urethane acrylate oligomers.