gebhart/patrepeval huggingface dataset:
Herpesvirus infection enhances cholesterol and cholesteryl ester accumulation in cultured arterial smooth muscle cells. (1981)

In our previous experiments, atherosclerosis similar to that in humans was reproducibly induced in both normocholesterolemic and hypercholesterolemic specific-pathogen-free (SPF) chickens by infection with Marek's disease herpesvirus (MDV). In contrast, uninfected chickens fed either relatively cholesterol-poor or cholesterol-supplemented diets did not develop this arterial disease. In experiments reported here, the hypothesis that infection of arterial smooth muscle cells (SMCs) with MDV would enhance lipid accumulation in these cells was tested. The number of MDV-infected SMCs with lipid stained with oil red O was assessed, and the lipid content of these cells was quantitated chemically by chromatographic and fluorometric analyses. These data were compared to those of uninfected control cells and, in the case of chemical analyses, were also compared to SMCs infected with a second avian herpesvirus, turkey herpesvirus (HVT). Results indicate the following: 1) The percentage of MDV-infected SMCs containing stainable lipid was significantly greater than the percentage of uninfected SMCs; 2) Increased total lipid accumulation was observed in MDV-infected SMC, particularly cholesterol (CH) and cholesteryl esters (CEs), as compared with uninfected or HVT-infected cells; 3) The types of CEs and nonesterified fatty acids (NEFA) accumulating in MDV-infected cells (particularly saturated types of CEs and NEFAs) were significantly different than those in uninfected or HVT-infected SMCs. These qualitative and quantitative differences in lipid content between infected and uninfected SMCs suggest that infection with MDV results in altered intracellular lipid metabolism. Results support the hypothesis that lipid accumulation in arteries of normocholesterolemic chickens may result from MDV infection acting at the cellular level to induce lipid accumulation that resembles that in human atheroarteriosclerosis.
Abrogation of postentry restriction of HIV-1-based lentiviral vector transduction in simian cells (2003)

HIV-1 replication in simian cells is restricted at an early postentry step because of the presence of an inhibitory cellular factor. This block reduces the usefulness of HIV-1-based lentiviral vectors in primate animal models. Here, we demonstrate that substitution of the cyclophilin A (CyPA) binding region in the capsid of an HIV-1-based lentiviral vector (LV) with that of the macrophage tropic HIV-1 Ba-L resulted in a vector that was resistant to the inhibitory effect and efficiently transduced simian cells. Notably, the chimeric gag LV efficiently transduced primary simian hematopoietic progenitor cells, a critical cellular target in gene therapy. The alterations in the CyPA binding region did not affect CyPA incorporation; however, transduction by the gag chimeric LV seemed to be relatively insensitive to cyclosporin A, indicating that it does not require CyPA for early postentry steps. In dual infection experiments, the gag chimeric LV failed to remove the block to transduction of the WT LV, suggesting that the gag chimeric LV did not saturate the inhibitory simian cellular factor. These data suggest that the CyPA binding region of capsid contains a viral determinant involved in the postentry restriction of HIV-1-based lentiviral vectors. Overall, the findings demonstrate that the host range of HIV-1-based LV can be altered by modifications in the packaging construct.
Effects of peptide YY on the human cardiovascular system: reversal of responses to vasoactive intestinal peptide (1992)

Peptide YY (PYY) reverses the increased intestinal secretion stimulated by vasoactive intestinal peptide (VIP) in humans. VIP also dilates blood vessels, so we investigated the effect of PYY on the cardiovascular system. Six volunteers received PYY, 0.4 and 1.2 pmol.kg-1 x min-1 i.v. for 2 h, reproducing plasma levels seen postprandially and during a diarrheal illness, respectively. Cardiac function was assessed by echocardiography. PYY infused at 0.4 pmol.kg-1 x min-1 had no effect on cardiovascular parameters. PYY infused at 1.2 pmol.kg-1 x min-1 caused a fall in both stroke volume from 128 +/- 8 to 110 +/- 8 ml/beat (mean +/- 95 confidence interval, P < 0.01) and cardiac output from 7.2 +/- 0.4 to 6.1 +/- 0.4 l/min (P < 0.01). Effects of infusion of PYY into the brachial artery at doses of 0-16 pmol/min were assessed using venous occlusion plethysmography in six subjects. PYY infusion caused a dose-dependent fall in forearm blood flow. Six subjects received VIP, 5 pmol.kg-1 x min-1 i.v., causing a rise in heart rate from 55 +/- 3 to 70 +/- 3 beats/min and increased cardiac output from 7.3 +/- 1.1 to 13.1 +/- 1.1 l/min. The addition of PYY, 0.4 pmol.kg-1 x min-1 i.v., did not affect the heart rate significantly but decreased the cardiac output to 10.4 +/- 1.1 l/min (P < 0.01). Infusions of PYY into the brachial artery at 5 pmol/min decreased local vasodilation induced by VIP infused at 2 pmol/min at the same site by 40% (P < 0.01), even though this dose of PYY had no significant effect on local blood flow when given alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Reversal of type 1 diabetes by a new MHC II‐peptide chimera: “Single‐epitope‐mediated suppression” to stabilize a polyclonal autoimmune T‐cell process (2010)

Polyclonality of self-reactive CD4(+) T cells is the hallmark of several autoimmune diseases like type 1 diabetes. We have previously reported that a soluble dimeric MHC II-peptide chimera prevents and reverses type 1 diabetes induced by a monoclonal diabetogenic T-cell population in double Tg mice [Casares, S. et al., Nat. Immunol. 2002. 3: 383-391]. Since most of the glutamic acid decarboxylase 65 (GAD65)-specific CD4(+) T cells in the NOD mouse are tolerogenic but unable to function in an autoimmune environment, we have activated a silent, monoclonal T-regulatory cell population (GAD65(217-230)-specific CD4(+) T cells) using a soluble I-A(αβ) (g7)/GAD65(217-230)/Fcγ2a dimer, and measured the effect on the ongoing polyclonal diabetogenic T-cell process. Activated GAD65(217-230)-specific T cells and a fraction of the diabetogenic (B(9-23)-specific) T cells were polarized toward the IL-10-secreting T-regulatory type 1-like function in the pancreas of diabetic NOD mice. More importantly, this led to the reversal of hyperglycemia for more than 2 months post-therapy in 80% of mice in the context of stabilization of pancreatic insulitis and improved insulin secretion by the β cells. These findings argue for the stabilization of a polyclonal self-reactive T-cell process by a single epitope-mediated bystander suppression. Dimeric MHC class II-peptide chimeras-like approach may provide rational grounds for the development of more efficient antigen-specific therapies in type 1 diabetes.
Tumor-activated Prodrugs—A New Approach to Cancer Therapy (2004)

Systemic cytotoxic (antiproliferative) anticancer drugs rely primarily for their therapeutic effect on cytokinetic differences between cancer and normal cells. One approach aimed at improving the selectivity of tumor cell killing by such compounds is the use of less toxic prodrug forms that can be selectively activated in tumor tissue (tumor-activated prodrugs; TAP). There are several mechanisms potentially exploitable for the selective activation of TAP. Some utilize unique aspects of tumor physiology such as selective enzyme expression or hypoxia. Others are based on tumor-specific delivery techniques, including activation of prodrugs by exogenous enzymes delivered to tumor cells via monoclonal antibodies (ADEPT) or generated in tumor cells from DNA constructs containing the corresponding gene (GDEPT). Whichever activating mechanism is used, only a small proportion of the tumor cells are likely to be competent to activate the prodrug. Therefore, TAP need to fully exploit these "activator" cells by being capable of killing activation-incompetent cells as well via a "bystander effect." A wide variety of chemistries have been explored for the selective activation of TAP. Examples are given of the most important-the reduction of quinones, N-oxides, and nitroaromatics by endogenous enzymes or radiation; the cleavage of amides by endogenous peptidases; and hydrolytic metabolism by a variety of exogenous enzymes, including phosphatases, kinases, amidases, and glycosidases.
Induction of specific changes in the surface membrane of myeloid leukemic cells by steroid hormones (1975)

Normal mature macrophages and granulocytes have surface membrane receptors for specific immunoglobulin and immunoglobulin complement, which can be detected by rosette formation with erythrocytes coated with antibody (EA) or with antibody and complement (EAC). There are three types of myeloid leukemia cells, IR-+D-+, IR-+D-minus and IR-minus D-minus. IR-+D-+ cells were induced to form receptors for EAC but not- for EA by the steroid hormones prednisolone, dexamethasone and estradiol. Induction required protein synthesis and was not inhibited by cordycepin or vinblastine. Optimum induction required the continued presence of the hormones. IR-+D-+ cells were also induced by these hormones to migrate in agar, attach to the surface of a Petri dish and form macrophages. IR-+D-minus cells showed a lower inducibility by these hormones and no formation of macrophages. There was no induction of any of these changes with IR-minusD-minus cells. The steroid hormones progesterone, testosterone and cortisone did not induce these changes in any of the leukemic cells and inhibited induction by prednisolone, dexamethasone and estradiol. The results indicate that specific surface membrane changes in myeloid leukemic cells can be induced by certain steroid hormones.
Substantive Due Process and Parental Corporal Punishment: Democracy and the Excluded Child (1995)

This Article questions whether parents have a right to corporally punish their children, and if they do, how this right should be defined. The author argues that parents should not receive the heightened constitutional protection conferred by a fundamental right. She argues that the political process already adequately protects the interests of parents in disciplining their children. To the extent that the political process chooses to permit parents to administer reasonable corporal punishment, this Article proposes a five-part test that courts can use to determine whether an act of corporal punishment fits within that reasonableness standard. This test is more sensitive to the interests of children than are current standards and resolves all doubts in favor of the children.
The design and implementation of a log-structured file system (1992)

This paper presents a new technique for disk storage management called a log-structured file system . A log-structured file system writes all modifications to disk sequentially in a log-like structure, thereby speeding up both file writing and crash recovery. The log is the only structure on disk; it contains indexing information so that files can be read back from the log efficiently. In order to maintain large free areas on disk for fast writing, we divide the log into segments and use a segment cleaner to compress the live information from heavily fragmented segments. We present a series of simulations that demonstrate the efficiency of a simple cleaning policy based on cost and benefit. We have implemented a prototype log-structured file system called Sprite LFS; it outperforms current Unix file systems by an order of magnitude for small-file writes while matching or exceeding Unix performance for reads and large writes. Even when the overhead for cleaning is included, Sprite LFS can use 70% of the disk bandwidth for writing, whereas Unix file systems typically can use only 5–10%.
Antibody Correlates and Predictors of Immunity to Naturally Occurring Influenza in Humans and the Importance of Antibody to the Neuraminidase (2013)

Increasing anti-HA and NA antibody in serum and secretions correlated with reducing pH1N1 influenza virus infection and illness in healthy young adults. Both anti-HA and anti-NA antibody are independent predictors of immunity to influenza; ensuring induction of both by vaccination is desirable.
SEPARATION OF CO2 FROM FLUE GASES BY CARBON-MULTIWALL CARBON NANOTUBE MEMBRANES (2001)

Multiwalled carbon nanotubes (MWNT) were found to be an effective separation media for removing CO{sub 2} from N{sub 2}. The separation mechanism favors the selective condensation of CO{sub 2} from the flowing gas stream. Significant uptakes of CO{sub 2} were measured at 30 C and 150 C over the pressure range 0.5 to 5 bar. No measurable uptake of nitrogen was found for this range of conditions. The mass uptake of CO{sub 2} by MWNT was found to increase with increasing temperature. A packed bed of MWNT completely removed CO{sub 2} from a flowing stream of CO{sub 2}/N{sub 2}, and exhibited rapid uptake kinetics for CO{sub 2}.
Astrocytes are the major intracerebral source of macrophage inflammatory protein‐3α/CCL20 in relapsing experimental autoimmune encephalomyelitis and in vitro (2003)

Macrophage inflammatory protein-3alpha/CCL20 is a recently identified chemokine that binds to CCR6 and acts as a chemoattractant for memory/differentiated T-cells, B-cells, and immature dendritic cells. We have previously reported that CCL20 and CCR6 mRNAs are expressed in the CNS of SJL mice with experimental autoimmune encephalomyelitis (EAE) and that CCL20 is produced by CNS-infiltrating leukocytes at disease onset and, additionally, by intraparenchymal astrocyte-like cells during disease relapses. In this study, we provide further immunohistochemical evidence that astrocytes represent the main CNS source of CCL20 during EAE. Moreover, we show that the proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha, but not interferon-gamma, induce expression of CCL20 mRNA and secretion of CCL20 protein in cultures of mouse brain-derived astrocytes. We also show that supernatants from cytokine-activated astrocytes stimulate the migration of polarized T helper cells and that this effect is partially inhibited by anti-CCL20 antibody. These findings suggest that, through secretion of CCL20, astrocytes could play an important role in orchestrating the recruitment of specific leukocyte subsets to the inflamed CNS and in regulating CNS-targeted immune responses.
Effects of grape seed extract and its ethylacetate/ethanol fraction on blood glucose levels in a model of type 2 diabetes (2009)

The present study observed the effects of grape seed extract (GSE) and its ethylacetate (E) and ethylacetate/ethanol (EE) fractions on blood glucose levels in C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice at 4-12 weeks of age. In the GSE- and EE fraction-treated db/db group, the blood glucose concentration began to be lower than that in the vehicle-treated db/db group at 6 weeks after treatment, while the blood glucose concentration in the E fraction-treated db/db group was similar to that in the vehicle-treated db/db group. The glycosylated hemoglobin (HbA1c) level in the vehicle-treated db/db groups was 9.3%, whereas HbA1c levels in the GSE- and EE fraction-treated db/db group decreased significantly to 5.7% and 6.1%, respectively, at 8 weeks after treatment. However, administration of GSE and its EE fraction did not show any significant effects on body weights and food consumption in db/db mice. These results suggest that GSE and its EE fraction have a potential to decrease the blood glucose and HbA1c level, which is applicable to good healthy foods for reducing blood glucose levels.
Immediate implantation after extraction of a horizontally fractured maxillary lateral incisor. (1991)

When indicated, osseointegrated implant prosthetics may be placed immediately following atraumatic tooth extraction. This article describes the delicate and precise surgical and prosthetic disciplines for an immediate extraction and implant case.
Effects of transforming growth factor- beta on human lymphokine-activated killer cell precursors. Autocrine inhibition of cellular proliferation and differentiation to immune killer cells. (1988)

With subpopulations of human lymphoid cells that were enriched for lymphokine-activated killer (LAK) cell precursors, studies were performed to examine the effects of transforming growth factor-beta (TGF-beta) on their IL-2-dependent growth and differentiation to killer cells. The majority of the LAK precursor cells appeared to reside in nonadherent, non-T, and non-B lymphocyte populations that expressed CD11 and CD16 Ag. These cells were induced to proliferate and become LAK cells by high concentrations of rIL-2 alone in the apparent absence of any prior activation with mitogen or Ag. The partially purified lymphocyte subpopulations generated varying but several-fold greater levels of LAK killing on a per cell basis than did unfractionated lymphocytes. The exogenous addition of TGF-beta to the LAK precursor cultures, markedly inhibited IL-2-stimulated growth as well as the development of LAK activity in a dose-dependent manner. The antimitotic effect of TGF-beta was reversible; inhibition of proliferation could be largely restored by increasing the concentration of IL-2 in culture. In contrast, TGF-beta inhibition of cytotoxicity was relatively independent of the concentration of IL-2. Further, LAK precursors constitutively expressed TGF-beta mRNA and high affinity receptor for TGF-beta. Activation of LAK precursors with IL-2 alone, resulted in a three- to fivefold up-regulation of intracellular TGF-beta mRNA and TGF-beta biologic activity secreted in the culture media. Furthermore, Northern blotting revealed that the resting LAK precursors did not express the Tac-mRNA. Receptor binding studies with 125I-IL-2 suggested the presence of a single class of IL-2R with an apparent Kd of intermediate range (beta-chain of IL-2R) on the unstimulated cells. Stimulation with high concentrations of Il-2 induced Tac-mRNA (both the 3.5- and 1.5-kb transcripts) and resulted in the expression of high affinity IL-2R (Kd approximately 10(-11) M) on these cells. Suppression of IL-2-dependent responses by TGF-beta was accompanied by a selective down-regulation of the 1.5-kb Tac-mRNA as well as by reduction in high affinity IL-2R. The results suggest a negative autocrine control of TGF-beta on IL-2-dependent growth and differentiation of human LAK cells, possibly related to regulate the killer activation function.
Plasma clearance of human extracellular-superoxide dismutase C in rabbits. (1988)

Extracellular-superoxide dismutase (EC-SOD) is heterogenous in the vasculature with regard to heparin affinity and can be separated into three fractions: A, without affinity; B, with weak affinity; and C, with relatively strong heparin affinity. The plasma clearance of intravenously injected 125I-labeled and unlabeled human EC-SOD C was studied in rabbits. About 90% of injected 125I-EC-SOD C was eliminated from the blood within 5-10 min. Injection of heparin after 10 or 20 min led to an immediate release of all sequestered 125I-EC-SOD C back to the blood plasma. Later injections of heparin led to diminished release, although release could still be demonstrated after 72 h. A half-time of approximately 10 h could be calculated for heparin-releasable 125I-EC-SOD C. Unlabeled EC-SOD C, determined as enzymic activity and with ELISA, was likewise sequestered and released to the same degree as 125I-labeled EC-SOD C by heparin as tested at 20 min and 5 h. The immediacy of the heparin-induced release indicates that the sequestered enzyme had been bound to endothelial cell surfaces. The length of the half-time suggests that the putative cell surface binding has a physiological function and is not primarily a step in enzyme degradation. The distribution of sequestered 125I-labeled EC-SOD C to different organs was determined at times between 10 min and 24 h. Of the organs, the liver contained the most 125I-EC-SOD C, followed by kidney, spleen, heart, and lung. At all investigated times, the content in the analyzed organs was nearly as large as the amount that could be promptly released to plasma by intravenous heparin. This indicates that almost all 125I-EC-SOD C in the organs was present on endothelial cell surfaces and was not bound by other tissue cell surfaces, or was present within the cells.
Immunogenicity and efficacy of the novel cancer vaccine based on simian adenovirus and MVA vectors alone and in combination with PD-1 mAb in a mouse model of prostate cancer (2016)

Prostate cancer possesses several characteristics that make it a suitable candidate for immunotherapy; however, prostate cancer vaccines to date demonstrate modest efficacy and low immunogenicity. The goal of the present pre-clinical study was to explore the immunogenic properties and protective efficacy of a novel prostate cancer immunotherapy based on the heterologous prime-boost viral-vectored vaccination platform. The simian adenovirus, ChAdOx1, and modified vaccinia Ankara virus, MVA, encoding a prostate cancer-associated antigen, the six transmembrane epithelial antigen of the prostate 1 (STEAP1), induced strong sustained antigen-specific CD8+ T-cell responses in C57BL/6 and BALB/c male mice. Unexpectedly, the high vaccine immunogenicity translated into relatively low protective efficacy in the murine transplantable and spontaneous models of prostate cancer. A combination of the vaccine with PD-1 blocking antibody significantly improved survival of the animals, with 80 % of mice remaining tumour-free. These results indicate that the ChAdOx1-MVA vaccination regime targeting STEAP1 combined with PD-1 therapy might have high therapeutic potential in the clinic.
Favourable culture conditions for mycelial growth of <i>Hydnum repandum</i>, a medicinal mushroom (2013)

In this study, factors such as pH, temperature, carbon and nitrogen sources that affect mycelial growth of Hydnum repandum, a medicinal mushroom, were investigated. Different inoculum media for vegetative inoculum production were also examined. The best suitable pH for mycelial growth was found to be 5.5. Among constant temperatures, the best mycelial growth was obtained at 20 and 25°C. The mycelial growth drastically decreased at 15°C, and no mycelia were obtained at 30°C. Glucose and mannitol were found to be the most suitable carbon sources. Ca(NO3)2 as a nitrogen source gave the best results for mycelial growth. The poorest mycelial growth was noted in sucrose and xylose as carbon sources and in NH4NO3 and (NH4)2HPO4 as nitrogen sources. Peat and peat: vermiculite mixtures (1:4, 1:6, 1:8 and 1:10, v:v) were the best media to use in producing the vegetative inoculum of H. repandum.
Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth (2009)

Neovascularization in response to tissue injury consists of the dual invasion of blood (hemangiogenesis) and lymphatic (lymphangiogenesis) vessels. We reported recently that 21-nt or longer small interfering RNAs (siRNAs) can suppress hemangiogenesis in mouse models of choroidal neovascularization and dermal wound healing independently of RNA interference by directly activating Toll-like receptor 3 (TLR3), a double-stranded RNA immune receptor, on the cell surface of blood endothelial cells. Here, we show that a 21-nt nontargeted siRNA suppresses both hemangiogenesis and lymphangiogenesis in mouse models of neovascularization induced by corneal sutures or hindlimb ischemia as efficiently as a 21-nt siRNA targeting vascular endothelial growth factor-A. In contrast, a 7-nt nontargeted siRNA, which is too short to activate TLR3, does not block hemangiogenesis or lymphangiogenesis in these models. Exposure to 21-nt siRNA, which we demonstrate is not internalized unless cell-permeating moieties are used, triggers phosphorylation of cell surface TLR3 on lymphatic endothelial cells and induces apoptosis. These findings introduce TLR3 activation as a method of jointly suppressing blood and lymphatic neovascularization and simultaneously raise new concerns about the undesirable effects of siRNAs on both circulatory systems.