gebhart/patrepeval huggingface dataset:
HAMSTER-TO-RAT HEART AND LIVER XENOTRANSPLANTATION WITH FK506 PLUS ANTIPROLIFERATIVE DRUGS (1993)

Heterotopic hamster hearts transplanted to unmodified LEW rats underwent humoral rejection in 3 days. Survival was prolonged to a median of 4 days with 2 mg/kg/day FK506. As monotherapy, 15 mg/kg/day cyclophosphamide greatly prolonged graft survival--far more than could be accomplished with RS-61443, brequinar (BQR), mizoribine, methotrexate, or deoxyspergualin. However, when FK506 treatment, which was ineffective alone, was combined with a short induction course (14 or 30 days) of subtherapeutic BQR, RS-61443, or cyclophosphamide, routine survival of heart xenografts was possible for as long as the daily FK506 was continued. In addition, a single large dose of 80 mg/kg cyclophosphamide 10 days preoperatively allowed routine cardiac xenograft survival under FK506. The ability of these antimetabolites to unmask the therapeutic potential of FK506 correlated, although imperfectly, with the prevention of rises of preformed heterospecific cytotoxic antibodies immediately postoperatively. As an adjunct to FK506, azathioprine was of marginal value, whereas mizoribine, methotrexate, and deoxyspergualin (DSPG) were of intermediate efficacy. After orthotopic hepatic xenotransplantation, the perioperative survival of the liver with its well-known resistance to antibodies was less dependent than the heart on the antimetabolite component of the combined drug therapy, but the unsatisfactory results with monotherapy of FK506, BQR, RS-61443, or cyclophosphamide were changed to routine success by combining continuous FK506 with a short course of any of the other drugs. Thus, by breaking down the antibody barrier to xenotransplantation with these so-called antiproliferative drugs, it has been possible with FK506 to transplant heart and liver xenografts with consistent long-term survival of healthy recipients.
Three‐Dimensional Electrogram Mapping Improves Ablation of Left‐Sided Accessory Pathways (1992)

Conventional electrogram mapping techniques for localization of accessory pathways during radiofrequency ablation procedures are time consuming and often inaccurate. We hypothesized that a computer generated, three-dimensional electrogram of retrograde atrial activation created from signal-averaged sequential endocardial bipolar electrograms (collected from the atrial aspect of the mitral annulus using a single transseptal catheter and then time aligned to a known myocardial activation reference) would improve left-sided accessory pathway atrial insertion site identification and increase ablation efficiency. Ablation efficiency was defined by procedure time, fluoroscopy time, duration of radiofrequency energy required to achieve initial accessory pathway block, cumulative ablation energy per procedure, and number of radiofrequency energy applications. Patients with single left-sided accessory atrioventricular connections were studied. Standard mapping results in 31 patients (group A) were compared to a three-dimensional electrogram approach used in 26 patients (group B). Three-dimensional electrogram mapping reduced procedure time (group A 3.8 +/- 1.6 vs group B 2.8 +/- 0.9 hours, P < 0.004), fluoroscopy time (group A 45.3 +/- 35.0 vs group B 25.1 +/- 10.5 min, P < 0.02), time to accessory pathway block (group A 2.6 +/- 1.5 vs group B 1.2 +/- 0.5 sec, P < 0.002), cumulative radiofrequency energy (group A 2126 +/- 2207 vs group B 636 +/- 586 joules, P < 0.0008), and radiofrequency energy applications (group A 5.0 +/- 4.4 vs group B 1.7 +/- 1.2, P < 0.0002). We conclude that three-dimensional electrogram mapping improves left-sided accessory pathway atrial insertion localization, reduces ablation procedure time and radiation exposure, and improves ablation efficiency.
Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-activating Polypeptide Inhibit Interleukin-12 Transcription by Regulating Nuclear Factor κB and Ets Activation (1999)

The vasoactive intestinal peptide (VIP) and the structurally related neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) act as "macrophage-deactivating factors". We showed previously that VIP and PACAP inhibit the production of macrophage-derived tumor necrosis factor-alpha, interleukin (IL)-6, nitric oxide, and IL-12. This study examines the molecular mechanisms involved in the VIP/PACAP inhibition of IL-12 production. VIP and PACAP inhibit IL-12 (p40) gene expression by affecting both NF-kappaB binding and the composition of the Ets-2 binding complex. Both neuropeptides prevent the activation-induced nuclear translocation of the NF-kappaB components p65 and c-Rel by inhibiting the reduction in cytoplasmic IkappaBalpha. Moreover, VIP and PACAP inhibit the synthesis of the interferon responsive factor-1. The decrease in nuclear interferon responsive factor-1 and c-Rel results in alterations of the Ets-2-binding complex. Two transduction pathways, a cAMP-dependent and a cAMP-independent pathway, are involved in the inhibition of IL-12 gene expression and appear to differentially regulate the transcriptional factors involved. Because IL-12 participates in T cell activation and cytolytic T lymphocyte activity and promotes the differentiation of T helper cells into the Th1 subset, the understanding of the mechanisms that affect IL-12 production in normal and pathological conditions could contribute to immune response-based therapies or vaccine designs.
Red Light-Excitable Oxygen Sensing Materials Based on Platinum(II) and Palladium(II) Benzoporphyrins (2008)

New optical oxygen-sensing materials make use of highly luminescent NIR platinum(II) and palladium(II) complexes with benzoporphyrins. Bulk optodes based on polystyrene and sensing nanobeads based on poly(styrene-block-vinylpyrrolidone) and polysulfone are prepared and characterized. The versatility of the new materials is demonstrated. The features include excellent compatibility with most common excitation sources, high brightness, and suitability for subcutaneous oxygen monitoring.
The sequence of the mu transmembrane segment determines the tissue specificity of the transport of immunoglobulin M to the cell surface. (1990)

Membrane IgM is expressed on the surface of B lymphocytes. It is not transported to the surface of transfected plasmacytoma or COS cells. Here, we show that mutation of four hydrophilic amino acids in the microm transmembrane is sufficient to overcome the intracellular retention of membrane IgM in non-B cells. This suggests that the B cell-specific IgM-associated proteins that have been postulated to assist the transport of membrane IgM to the cell surface (3) act either by forming a hydrophobic sheath that surrounds the microm transmembrane segment or by displacing an interaction with this segment that would otherwise cause retention. Experiments with a CD8/mu hybrid H chain indicate that the proteins that assist the transport of membrane IgM to the B cell surface at most need the mu CH4 and transmembrane/cytoplasmic portion for interaction.
Inhibition of Transglutaminase 2, a Novel Target for Pulmonary Fibrosis, by Two Small Electrophilic Molecules (2013)

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive fibrotic destruction of normal lung architecture. Due to a lack of effective treatment options, new treatment approaches are needed. We previously identified transglutaminase (TG)2, a multifunctional protein expressed by human lung fibroblasts (HLFs), as a positive driver of fibrosis. TG2 catalyzes crosslinking of extracellular matrix proteins, enhances cell binding to fibronectin and integrin, and promotes fibronectin expression. We investigated whether the small electrophilic molecules 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) and 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2) inhibit the expression and profibrotic functions of TG2. CDDO and 15d-PGJ2 reduced expression of TG2 mRNA and protein in primary HLFs from control donors and donors with IPF. CDDO and 15d-PGJ2 also decreased the in vitro profibrotic effector functions of HLFs including collagen gel contraction and cell migration. The decrease in TG2 expression did not occur through activation of the peroxisome proliferator activated receptor γ or generation of reactive oxidative species. CDDO and 15d-PGJ2 inhibited the extracellular signal-regulated kinase pathway, resulting in the suppression of TG2 expression. This is the first study to show that small electrophilic compounds inhibit the expression and profibrotic effector functions of TG2, a key promoter of fibrosis. These studies identify new and important antifibrotic activities of these two small molecules, which could lead to new treatments for fibrotic lung disease.
Thrombin binding to GPIbα induces integrin αIIbβ3 dependent platelet adhesion to fibrin in ex vivo flowing whole blood (2004)

We have investigated the role of the thrombin/GPIbalpha interaction in the adhesion of platelets to fibrin in a whole blood ex vivo perfusion model at a shear rate of 280 s(-1). Blood was perfused through parallel-plate chambers containing coverslips coated with cells expressing tissue factor, leading to the generation of thrombin and thus, deposition of fibrin onto the exposed cells. Adhesion of platelets to fibrin and thrombus growth were analyzed. Interestingly, when GPIbalpha was removed from the platelet surface by action of mocarhagin, platelet adhesion on fibrin was inhibited. Furthermore, a monoclonal antibody, VM16d, directed against the thrombin binding site on GPIbalpha also inhibited platelet adhesion on fibrin, showing the importance of the thrombin/GPIbalpha interaction.We then looked at the involvement of alphaIIbbeta3 and showed that platelet adhesion and thrombus growth on fibrin were inhibited by the dodecapeptide, whereas lamifiban only inhibited the growth of the platelet thrombus. These results indicated that binding of thrombin to GPIbalpha induced an intracellular signaling leading to the interaction of the platelet integrin alphaIIbbeta3 with the fibrin-dodecapeptide sequence.
Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement (2008)

At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the United Kingdom issues related to potentially malignant disorders of the oral cavity were discussed by an expert group. The consensus views of the Working Group are presented in a series of papers. In this report, we review the oral epithelial dysplasia classification systems. The three classification schemes [oral epithelial dysplasia scoring system, squamous intraepithelial neoplasia and Ljubljana classification] were presented and the Working Group recommended epithelial dysplasia grading for routine use. Although most oral pathologists possibly recognize and accept the criteria for grading epithelial dysplasia, firstly based on architectural features and then of cytology, there is great variability in their interpretation of the presence, degree and significance of the individual criteria. Several studies have shown great interexaminer and intraexaminer variability in the assessment of the presence or absence and the grade of oral epithelial dysplasia. The Working Group considered the two class classification (no/questionable/ mild - low risk; moderate or severe - implying high risk) and was of the view that reducing the number of choices from 3 to 2 may increase the likelihood of agreement between pathologists. The utility of this need to be tested in future studies. The variables that are likely to affect oral epithelial dysplasia scoring were discussed and are outlined here; these need to be researched in longitudinal studies to explore the biological significance of a low-risk or high-risk dysplasia.
Survivability Analysis of Next-Generation Passive Optical Networks and Fiber-Wireless Access Networks (2011)

Passive optical networks (PONs) are currently evolving into next-generation PONs (NG-PONs) which aim at achieving higher data rates, wavelength channel counts, number of optical network units (ONUs), and extended coverage compared to their conventional counterparts. Due to the increased number of stages and ONUs, NG-PONs face significant challenges to provide the same level of survivability like conventional PONs without exceeding the budget constraints of cost-sensitive access networks. Toward this end, partial optical protection, in combination with interconnecting a subset of ONUs through a wireless mesh network (WMN) front-end, are promising solutions to render NG-PONs survivable in a cost-effective manner. In this paper, we present a probabilistic analysis of the survivability of NG-PONs and hybrid fiber-wireless (FiWi) access networks, taking both optical and wireless protection into account. In addition, we propose different selection schemes to wirelessly upgrade a subset of ONUs, and investigate their performance for a wide range of fiber link failure scenarios and different NG-PON topologies.
Tree-structured speaker clustering for fast speaker adaptation (2002)

The paper proposes a tree-structured speaker clustering algorithm and discusses its application to fast speaker adaptation. By tracing the clustering tree from top to bottom, adaptation is performed step-by-step from global to local individuality of speech. This adaptation method employs successive branch selection in the speaker clustering tree rather than parameter training and hence achieves fast adaptation using only a small amount of training data. This speaker adaptation method was applied to a hidden Markov network (HMnet) and evaluated in Japanese phoneme and phrase recognition experiments, in which it significantly outperformed speaker-independent recognition methods. In the phrase recognition experiments, the method reduced the error rate by 26.6% using three phrase utterances (approximately 2.7 seconds).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Design-Oriented Analysis and Performance Evaluation of Buck PFC Front End (2009)

In universal-line ac/dc converters that require power factor correction (PFC), maintaining a high efficiency across the entire line and load ranges poses a major challenge. Typically, a boost PFC front end exhibits 1%-3% lower efficiency at 100-V line compared to that at 230-V line. It is shown in this paper that a buck PFC front end with an output voltage in the 80-V range can maintain a high efficiency across the entire line and load ranges. A thorough analysis of the buck PFC converter operation and performance along with design optimization guidelines are presented. Experimental results obtained on a 90-W notebook adapter are provided. A loss analysis based on SIMPLIS and PSPICE simulations is also included. Major factors that contribute to the improved efficiency of the buck PFC versus the boost PFC are briefly explained.
DNA Adducts in Biomonitoring (1995)

Application of methods to the measurement of DNA adducts in occupational and environmental studies was surveyed. The methods included the 32P-postlabeling assay, immunoassay, mass spectrometry, and synchronous fluorescence spectroscopy. Methods for detecting excreted urinary RNA and DNA adducts were also discussed. When the techniques have been applied in occupational settings with complex exposures, identification and quantitation of the adduct levels have not been possible. At present emphasis is being placed on the determination of specific adduct levels. This can often be achieved by adding a purification step before the determination of adducts. Inasmuch as humans differ in their metabolic capacity, it has become feasible to determine adducts in humans who are polymorphic in their xenobiotic metabolism.
Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells (2015)

Breast cancer metastasizes to bone, visceral organs, and/or brain depending on the subtype, which may involve activation of a host organ-specific signaling network in metastatic cells. To test this possibility, we determined gene expression patterns in MDA-MB-231 cells and its mammary fat pad tumor (TMD-231), lung-metastasis (LMD-231), bone-metastasis (BMD-231), adrenal-metastasis (ADMD-231) and brain-metastasis (231-BR) variants. When gene expression between metastases was compared, 231-BR cells showed the highest gene expression difference followed by ADMD-231, LMD-231, and BMD-231 cells. Neuronal transmembrane proteins SLITRK2, TMEM47, and LYPD1 were specifically overexpressed in 231-BR cells. Pathway-analyses revealed activation of signaling networks that would enable cancer cells to adapt to organs of metastasis such as drug detoxification/oxidative stress response/semaphorin neuronal pathway in 231-BR, Notch/orphan nuclear receptor signals involved in steroidogenesis in ADMD-231, acute phase response in LMD-231, and cytokine/hematopoietic stem cell signaling in BMD-231 cells. Only NF-κB signaling pathway activation was common to all except BMD-231 cells. We confirmed NF-κB activation in 231-BR and in a brain metastatic variant of 4T1 cells (4T1-BR). Dimethylaminoparthenolide inhibited NF-κB activity, LYPD1 expression, and proliferation of 231-BR and 4T1-BR cells. Thus, transcriptome change enabling adaptation to host organs is likely one of the mechanisms associated with organ-specific metastasis and could potentially be targeted therapeutically.
A 30-b integrated logarithmic number system processor (1991)

The authors describe an integrated processor that performs addition and subtraction of 30-b numbers in the logarithmic number system (LNS). This processor offers 5-MOPS performance in 3- mu m CMOS technology, and is implemented in a two-chip set comprising 170 K transistors. Two techniques are used to achieve this precision in a moderate circuit area. Linear approximation of the LNS arithmetic functions using logarithmic arithmetic is shown to be simple due to the particular functions involved. A segmented approach to linear approximation minimizes the amount of table space required. Subsequent nonlinear compression of each lookup table leads to a further reduction in table size. The result is that a factor of 285 reduction in table size is achieved, compared to previous techniques. The circuit area of the implementation is minimized by optimizing the table parameters, using a computer program that accurately models ROM area. The implementation is highly pipelined, and produces one result per clock cycle using a ten-stage pipeline.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Innate immune response of bronchial epithelial cells to infection with influenza (130.7) (2009)

Abstract Bronchial epithelial cells are the natural human host for influenza infection but knowledge about the innate immune response is limited. Study objectives; characterise the innate immune response of bronchial epithelial cells to infection with human influenza A virus and relate this to virus replication. Methods; Influenza H3N2, A/Wellington/2004 (H3N2) was cultured and titred using plaque assays on Manine Darby Kidney Cells. Primary bronchial epithelial cells (PBECs) were obtained by bronchoscopy and cultured. Their response was compared to an epithelial cell line, Calu 3. Innate immune response was measured by the induction of mRNA by real time PCR for RIG-I, MDA-5, TLR-3, PKR, interferon (IFN)-β. Protein expression was then measured by western blot in cell lysate or supernatant. Results; H3N2 replicated to significantly higher titres in Calu 3 cells 2.8x106 PFU/ml compared to PBECs 789 PFU/ml (p&amp;lt;0.001). Following infection there was greater than 20 fold induction of RIG-I mRNA in both cells, strong protein expression in PBECs by 24hr, only faint expression in Calu3. A thousand fold induction in MDA-5 mRNA was seen in PBECs at 48hr less than 20 fold in Calu3. Induction of IFN-β mRNA by 24hr and protein release in the supernatant was seen in both cells by 6hr. Conclusions; H3N2 replicates less well in PBECs and this is associated with more vigorous induction of RIG-I during early infection and later induction of MDA-5 mRNA.
Countering Abuse of Name-Based Authentication (1994)

Authentication for access control procedures is usually based on the identity of participating entities. In some communications systems, identities are partially or wholly resolved using hostnames or machine addresses in the underlying protocol suite. Access control lists and revocation lists are often defined on the basis of hostnames, whereby the communication subsystem at runtime utilizes machine addresses. After communications between two machines are established, hosts identify each other by their protocol addresses. To map this address to a high--level name, which can then be compared with access control or revocation lists to grant or deny access, a resolution process is initiated. The abstraction from protocol addresses to high--level hostnames is necessary to hide details of heterogeneous communication subsystems, and of dynamic network configurations from the application layer where a uniform, high--level naming scheme is desired. If cryptographic capabilities are used that ...
Spontaneous immortalization of mouse liver sinusoidal endothelial cells (2015)

The spontaneous immortalization of cells in vitro is a rare event requiring genomic instability, such as alterations in chromosomes and mutations in genes. In the present study, we report a spontaneously immortalized liver sinusoidal endothelial cell (LSEC) line generated from mouse liver. These immortalized LSECs showed typical LSEC characteristics with the structure of transcellular fenestrations, the expression of von Willebrand factor (VWF) and the ability to uptake DiI-acetylated-low density lipoprotein (DiI-Ac-LDL). However, these immortalized LSECs lost the ability to form capillary-like structures, and showed clonal and multilayer growth without contact inhibition. Moreover, their proliferation rate increased with the increase in the number of passages. In addition, these cells obained the expression of CD31 and desmin, and showed an upregulation of p53 protein expression; however, their karyotype was normal, and they could not form colonies in soft agar or tumors in SCID mice. In conclusion, in the present study, we successfully established a spontaneously immortalized LSEC line.
Activity regulates the levels of acetylcholine receptor alpha-subunit mRNA in cultured chicken myotubes. (1985)

In vitro blocking the spontaneous activity of primary cultures of chicken embryo myotubes with tetrodotoxin increases approximately equal to 2-fold their content in surface acetylcholine receptor. To investigate this effect at the level of gene expression, chicken genomic DNA sequences coding for the acetylcholine receptor alpha subunit were isolated and characterized. They were shown to belong to a single-copy, polymorphic gene with at least two alleles in the chicken strain utilized. Probes derived from these genomic clones were used to quantitate levels of alpha-subunit mRNA. In culture, a 2-day exposure to tetrodotoxin increased these mRNA levels up to 13-fold, a value similar to that observed after denervation of chick leg muscle (approximately equal to 17-fold). Actin mRNA levels varied little in any of these experiments. These results support the notion that membrane electrical activity affects acetylcholine receptor expression by regulating the accumulation of the corresponding mRNAs.
Higher-order suppressed phase zone plates (1985)

A new phase zone plate with suppressed higher-order flux is proposed and optimum design calculations are made for Al. While the first-order collecting efficiency is equal to that of conventional Fresnel zone plates (∼10%), the ratio of the higher-order flux energy to the first-order energy can be suppressed to &lt;10−3–10−6 in the 300–600-Å wavelength range.