gebhart/patrepeval huggingface dataset:
In vivo intracardiac optical coherence tomography imaging through percutaneous access: toward image-guided radio-frequency ablation (2011)

Complete catheter-tissue contact and permanent tissue destruction are essential for efficient radio-frequency ablation (RFA) during cardiac arrhythmia treatment. Current methods of monitoring lesion formation are indirect and unreliable. The purpose of this study is to evaluate the feasibility of using optical coherence tomography (OCT) catheter to image endocardial wall in actively beating hearts through percutaneous access. We reported the first in vivo intracardiac OCT imaging through percutaneous access with a thin and flexible OCT catheter. This is a critical step toward image-guided RFA in a clinical setting. A cone-scanning forward-viewing OCT catheter was advanced into beating hearts through percutaneous access in four swine. The OCT catheter was steered by an introducer to touch the endocardial wall. We are able to acquire high quality OCT images in beating hearts, observe the polarization-related artifacts induced by the birefringence of myocardium, and readily evaluate catheter-tissue contact. The observations indicate that OCT could be a promising technique for in vivo guidance of RFA.
Immunocytochemical Localization of the NPY/PYY Y1 Receptor in Enteric Neurons, Endothelial Cells, and Endocrine-like Cells of the Rat Intestinal Tract (1997)

Neuropeptide Y (NPY) and peptide YY (PYY) are structurally related peptides that are considered to mediate inhibitory actions on gastrointestinal motility, secretion, and blood flow. Several receptor subtypes for these peptides have been identified and the Y1, Y2, Y4/PP1, Y5, and Y5/PP2/Y2b receptors have been cloned. In this article we report the immunocytochemical localization of the Y1 receptor to myenteric and submucosal nerve cell bodies, endothelial cells, and scattered endocrine-like cells of rat intestinal tract. Moreover, double immunofluorescence demonstrates that subpopulations of the Y1 receptor-positive nerve cell bodies are immunopositive for NPY, vasoactive intestinal polypeptide, and nitric oxide synthase. In part, such co-localizations were made possible by use of peroxidase-mediated deposition of tyramide, which permitted use of antisera derived from the same species. Our observations suggest the existence of multiple neuronal, endothelial, and endocrine target sites for NPY and PYY and that some of the actions of these regulatory peptides can be mediated by vasoactive intestinal peptide and nitric oxide synthase.
Absence of the amyloid precursor protein gene mutation (APP717: Val->Ile) in 85 cases of early onset Alzheimer's disease. (1993)

Early diagnosis and intravenous immune globulin therapy in paraneo- plastic cerebellar degeneration Effective therapy with intravenous immune globulin (IVIg) has been
Hyperthermic Isolated Limb Perfusion with TNF α and Cisplatin in theTreatment of Osteosarcoma of the Extremities: A Feasibility Study inHealthy Dogs (1999)

Purpose. The feasibility of hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-alpha (TNFalpha ) and cisplatin for the management of osteosarcoma was studied in the canine model.Methods. During seven perfusions in six healthy mongrel dogs (weight 32+/-2 kg) technical aspects of HILP under mild hyperthermia (39- 40) were studied. In five experiments HILP was performed with TNFalpha alone (0.5 mg/l extremity volume), and in two experiments TNFalpha was combined with cisplatin (25 mg/l extremity volume). During the perfusions physiological parameters were monitored and TNFalpha and total cisplatin concentrations were determined.Results. Perfusion conditions (pH, PCO(2) , PO(2), flow and pressure) remained within physiological ranges.Three dogs died within 24 h despite a sublethal systemic concentration of TNFalpha that leaked from the perfusion circuit. Three dogs were terminated; one dog after the second experiment in accordance with Dutch ethical rules; one dog showed an invagination of the small bowel resulting in an ileus; one dog because of necrosis of the perfused limb.Conclusions. This feasibility study in healthy dogs demonstrated that HILP with TNFalpha and cisplatin was associated with a high mortality rate and does not allow us to treat dogs with spontaneous osteosarcoma with TNFalpha and cisplatin HILP. Therefore, an alternative model should be used in the search for the ideal combination of perfusion agents for limb sparing treatment in human osteosarcoma.
Mutation of Arg273 to Leu Alters the Specificity of the Yeast N-Glycan Processing Class I α1,2-Mannosidase (2000)

Class I alpha1,2-mannosidases (glycosyl hydrolase family 47) involved in the processing of N-glycans during glycoprotein maturation have different specificities. Enzymes in the endoplasmic reticulum of yeast and mammalian cells remove a single mannose from Man(9)GlcNAc(2) to form Man(8)GlcNAc(2) isomer B (lacking the alpha1, 2-mannose residue of the middle alpha1, 3-arm), whereas other alpha1,2-mannosidases, including Golgi alpha1,2-mannosidases IA and IB, can convert Man(9)GlcNAc(2) to Man(5)GlcNAc(2). In the present work, it is demonstrated that with a single mutation in its catalytic domain (Arg(273) --> Leu) the yeast endoplasmic reticulum alpha1,2-mannosidase acquires the ability to transform Man(9)GlcNAc to Man(5)GlcNAc. High resolution proton nuclear magnetic resonance analysis of the products shows that the order of removal of mannose from Man(9)GlcNAc is different from that of other alpha1, 2-mannosidases that remove four mannose from Man(9)GlcNAc. These results demonstrate that Arg(273) is in part responsible for the specificity of the endoplasmic reticulum alpha1,2-mannosidase and that small differences in non-conserved amino acids interacting with the oligosaccharide substrate in the active site of class I alpha1, 2-mannosidases are responsible for the different specificities of these enzymes.
Functional polyesters prepared by polymerization of α‐allyl(valerolactone) and its copolymerization with ε‐caprolactone and δ‐valerolactone (2002)

Abstract We report the ring‐opening homopolymerization of α‐allyl(valerolactone), compound 2 , and its copolymerization with ε‐caprolactone and δ‐valerolactone using stannous(II) catalysis. Although the polymerization of substituted δ‐valerolactones has received little attention for the preparation of functional polyesters, we found that compound 2 may be incorporated in controllable amounts into copolymers with other lactones, or simply homopolymerized to give a highly functionalized, novel poly(valerolactone). The presence of the pendant allyl substituent had a substantial impact on the thermal properties of these materials relative to conventional polyesters prepared from lactones, and most of the polymers presented here are liquids at room temperature. Dihydroxylation of the pendant allyl groups gave polyesters with increased hydrophilicity that degraded more or less rapidly depending on their extent of functionality. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1983–1990, 2002
Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas. (1993)

Chromosomal translocations involving chromosome 3, band q27, are among the most common rearrangements in B-cell non-Hodgkin lymphoma. From a bacteriophage lambda library prepared from a lymphoma characterized by a t(3;14)(q27;q32), genomic clones were isolated using a probe from the immunoglobulin heavy chain locus (IGH) joining region. In addition to clones containing an apparently normal IGH rearrangement, others were found to contain one of the translocation breakpoint junctions. Normal chromosome 3 sequences and the reciprocal breakpoint junction were subsequently isolated. DNA probes on each side of the chromosome 3 breakpoint hybridized at high stringency to the DNA of various mammalian species, demonstrating evolutionary conservation. One such probe from the presumptive der(3) chromosome detected an 11-kilobase transcript when hybridized to RNA of B- and T-cell lines. A probe made from partial cDNA clones isolated from a T-cell line hybridized with genomic DNA from both sides of the chromosome 3 breakpoint, indicating that the t(3;14) is associated with a break within the gene on chromosome 3. In situ chromosomal hybridization revealed that the same gene is involved in the t(3;22)(q27;q11). Preliminary nucleotide sequencing shows no identity of the cDNA to gene sequences in available data banks. We propose the name BCL6 (B-cell lymphoma 6) for this gene, since it is likely to play a role in the pathogenesis of certain B-cell lymphomas.
Isolated limb perfusion for an irresectable melanoma recurrence in a Jehovah's witness (2006)

Isolated limb perfusion (ILP) is a treatment option for irresectable melanoma lesions, because with ILP 20-fold higher concentrations of chemotherapy can be achieved locally than is systemically possible and high response rates are subsequently achieved. Jehovah's witnesses do not accept any form of blood transfusion, either autologous or homologous blood or only blood products. The use of an extracorporeal circuit, without the use of any blood products is acceptable for Jehovah's witnesses. The case of a 59-year-old Jehovah's witness with an irresectable melanoma recurrence for which an ILP. Because of adequate blood flow through the perfused limb, the limb did not become acidotic, even though there was a significant drop in the Hb concentration in the limb during the ILP. Isolated limb perfusions without the use of any blood transfusion products are technically possible, but an adequate preoperative hemoglobin concentration is a prerequisite.
Combination of a monoclonal anti‐phosphatidylserine antibody with gemcitabine strongly inhibits the growth and metastasis of orthotopic pancreatic tumors in mice (2005)

Pancreatic cancer continues to have a dismal prognosis and novel therapy is needed. In this study, we evaluate a promising new target for therapy, phosphatidylserine (PS). PS is an anionic phospholipid located normally on the inner leaflet of the plasma membrane in mammalian cells. In the tumor microenvironment, PS becomes externalized on vascular endothelium. The monoclonal antibody 3G4 binds PS and promotes an inflammatory response against tumor blood vessels, resulting in reduction of tumor growth. Mice with orthotopic pancreatic tumors were treated with 3G4, gemcitabine or a combination of both drugs. Tumor burden including pancreas weight and metastatic lesions (liver, lymph node and peritoneal) were reduced 3- to 5-fold by the combination therapy as compared with 1.5- to 2-fold with 3G4 and gemcitabine alone, respectively. Treatment of tumor-bearing animals with the combination therapy increased macrophage infiltration into the tumor mass 10-fold and reduced microvessel density in the tumor by 2.5-fold compared with tumors from untreated animals. Gemcitabine alone and 3G4 alone were less effective than the combination of the 2 agents together. The additive therapeutic effect of both agents appears to be because chemotherapy increases PS exposure on tumor vascular endothelium and amplifies the target for attack by 3G4. In conclusion, 3G4 enhanced the anti-tumor and anti-metastatic activity of gemcitabine without contributing to toxicity.
Enhancement of in vivo immune response by tumor necrosis factor. (1987)

Interleukin 1 (IL-1) has been shown to regulate several immunologic functions. Since tumor necrosis factor (TNF) shares many biologic properties with IL-1, we have investigated here the role of TNF in the modulation of the immune response. We have thus tested low doses of human recombinant TNF-alpha (hu rTNF-alpha) for its capacity to enhance the in vivo antibody responses evaluated at the cellular level in the hemolytic plaque assay. It was found that hu rTNF-alpha, like human IL-1 beta, is able to enhance the immune response to a T cell-dependent antigen (sheep red blood cells). Interestingly, at variance with human recombinant IL-1 beta, hu rTNF-alpha was not able to enhance the in vivo antibody response to a T cell-independent antigen (type III pneumococcal polysaccharide). These results suggest that low levels of TNF may have a role in the modulation of the immune response in vivo and shed new light on the biologic significance of this mediator.
Adaptive transform scheme to reduce PAR of an OFDM signal (2005)

One major drawback in orthogonal frequency division multiplexing (OFDM) system is its high peak-to-average power ratio (PAR). Most of the PAR reduction techniques are based on changing the signal constellation symbols in a frame before evaluating the inverse discrete Fourier transformation (IDFT). A simple way to achieve this change is to use a linear transformation in the form of orthogonal matrix. Hadamard transform of data symbols has recently been proposed to reduced PAR. Motivated by this approach, we investigate the use of Fourier and cosine transforms to reduce the PAR. We also propose an adaptive transform scheme to further reduce the PAR with minimized complexity. This approach reduces the PAR by 4 dB for an OFDM signal with 128 subcarriers. We also compare the performance and the complexity of the proposed scheme with the selected mapping (SLM) technique.
Algorithms for nonnegative matrix and tensor factorizations: a unified view based on block coordinate descent framework (2013)

We review algorithms developed for nonnegative matrix factorization (NMF) and nonnegative tensor factorization (NTF) from a unified view based on the block coordinate descent (BCD) framework. NMF and NTF are low-rank approximation methods for matrices and tensors in which the low-rank factors are constrained to have only nonnegative elements. The nonnegativity constraints have been shown to enable natural interpretations and allow better solutions in numerous applications including text analysis, computer vision, and bioinformatics. However, the computation of NMF and NTF remains challenging and expensive due the constraints. Numerous algorithmic approaches have been proposed to efficiently compute NMF and NTF. The BCD framework in constrained non-linear optimization readily explains the theoretical convergence properties of several efficient NMF and NTF algorithms, which are consistent with experimental observations reported in literature. In addition, we discuss algorithms that do not fit in the BCD framework contrasting them from those based on the BCD framework. With insights acquired from the unified perspective, we also propose efficient algorithms for updating NMF when there is a small change in the reduced dimension or in the data. The effectiveness of the proposed updating algorithms are validated experimentally with synthetic and real-world data sets.
l<inf>1</inf>-optimal robust iterative learning controller design (2008)

In this paper we consider the robust iterative learning control (ILC) design problem for SISO discrete-time linear plants subject to unknown, bounded disturbances. Using the supervector formulation of ILC, we apply a Youla parameterization to pose a MIMO l <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> -optimal control problem. The problem is analyzed for three situations: (1) the case of arbitrary ILC controllers that use current iteration tracking error (CITE), but without explicit integrating action in iteration, (2) the case of arbitrary ILC controllers with CITE and with explicit integrating action in iteration, and (3) the case of ILC controllers without CITE but that force an integral action in iteration. Analysis of these cases shows that the best ILC controller for this problem when using a non-CITE ILC algorithm is a standard Arimoto-style update law, with the learning gain chosen to be the system inverse. Further, such an algorithm will always be worse than a CITE-based algorithm. It is also found that a trade-off exists between asymptotic tracking of reference trajectories and rejection of unknown-bounded disturbances and that ILC does not help alleviate this trade-off. Finally, the analysis reinforces results in the literature noting that for SISO discrete-time linear systems, first-order ILC algorithms can always do as well as higher-order ILC algorithms.
Efficient Conversion of Nitriles to Amides with Basic Hydrogen Peroxide in Dimethyl Sulfoxide (1989)

Nitriles 1 are efficiently transformed into N-unsubstituted amides 2 at 20°C in 5-30 mins in good yield and with high selectivity, using basic 30% hydrogen peroxide in dimethyl sulfoxide.
Towards digital microfluidic circuits: creating, transporting, cutting and merging liquid droplets by electrowetting-based actuation (2003)

This paper reports a breakthrough in our quest for digital microfluidic circuits - full completion of all four fundamental microfluidic operations: (1) creating, (2) transporting, (3) cutting, and (4) merging of liquid droplets, based on electrowetting-on-dielectric (EWOD) actuation. All the operations were achieved with 25 V/sub DC/ lower than EWOD actuation voltages previously reported. We also report conditions to reduce the driving voltage even further and conditions to drive a droplet as fast as 250 mm/s.
Abietadiene Synthase from Grand Fir ( ) cDNA ISOLATION, CHARACTERIZATION, AND BACTERIAL EXPRESSION OF A BIFUNCTIONAL DITERPENE CYCLASE INVOLVED IN RESIN ACID BIOSYNTHESIS (1996)

(-)-Abietic acid, the principal diterpenoid resin acid of the wound-induced oleoresin secreted by grand fir (Abies grandis), is synthesized by the cyclization of geranylgeranyl diphosphate to (-)-abieta-7(8),13(14)-diene, followed by sequential three-step oxidation of the C-18 methyl group of the olefin to a carboxyl function. The enzyme catalyzing the cyclization reaction, abietadiene synthase, was purified from stems of wounded grand fir saplings and was digested with trypsin. Amino acid sequence information from the resulting peptides allowed construction of degenerate oligonucleotide primers, which amplified a 551-base pair fragment from a wound-induced stem cDNA library. This hybridization probe was then utilized to screen the wound-induced stem cDNA library, from which three cDNA clones were isolated that were functionally expressed in Escherichia coli, thereby confirming that a single protein catalyzes the complex, multistep cyclization of geranylgeranyl diphosphate to abietadiene. cDNA isolate Ac22.1, which yielded the highest expressed level of cyclase activity, was 2861 base pairs in length and encoded an 868-amino acid open reading frame that included a putative plastidial transit peptide. Deduced amino acid sequence comparison to other terpene cyclases revealed an amino-terminal region of the abietadiene synthase, which resembles those of enzymes that employ substrate double bond protonation to initiate the carbocationic reaction cascade, and a carboxyl-terminal region of the synthase, which resembles those of enzymes that employ ionization of the substrate allylic diphosphate ester function to initiate the cyclization reaction. This apparent fusion of segments of the two distinct terpenoid cyclase types is consistent with the novel mechanism of the bifunctional abietadiene synthase in catalyzing both protonation-initiated and ionization-initiated cyclization steps.
Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy (2019)

Cardiomyopathy is a leading cause of death for Duchenne muscular dystrophy. Here, we find that the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) can share common ligands but play distinct roles in dystrophic heart and skeletal muscle pathophysiology. Comparisons of their ligand structures indicate that the Δ9,11 modification of the first-in-class drug vamorolone enables it to avoid interaction with a conserved receptor residue (N770/N564), which would otherwise activate transcription factor properties of both receptors. Reporter assays show that vamorolone and eplerenone are MR antagonists, whereas prednisolone is an MR agonist. Macrophages, cardiomyocytes, and CRISPR knockout myoblasts show vamorolone is also a dissociative GR ligand that inhibits inflammation with improved safety over prednisone and GR-specific deflazacort. In mice, hyperaldosteronism activates MR-driven hypertension and kidney phenotypes. We find that genetic dystrophin loss provides a second hit for MR-mediated cardiomyopathy in Duchenne muscular dystrophy model mice, as aldosterone worsens fibrosis, mass and dysfunction phenotypes. Vamorolone successfully prevents MR-activated phenotypes, whereas prednisolone activates negative MR and GR effects. In conclusion, vamorolone targets dual nuclear receptors to treat inflammation and cardiomyopathy with improved safety.
Antibody Humanization Using Monovalent Phage Display (1997)

Antibody humanization often requires the replacement of key residues in the framework regions with corresponding residues from the parent non-human antibody. These changes are in addition to grafting of the antigen-binding loops. Although guided by molecular modeling, assessment of which framework changes are beneficial to antigen binding usually requires the analysis of many different antibody mutants. Here we describe a phage display method for optimizing the framework of humanized antibodies by random mutagenesis of important framework residues. We have applied this method to humanization of the anti-vascular endothelial growth factor murine monoclonal antibody A4.6.1. Affinity panning of a library of humanized A4.6.1 antibody mutants led to the selection of one variant with greater than 125-fold enhanced affinity for antigen relative to the initial humanized antibody with no framework changes. A single additional mutation gave a further 6-fold improvement in binding. The affinity of this variant, 9.3 nM, was only 6-fold weaker than that of a murine/human chimera of A4.6.1. This method provides a general means of rapidly selecting framework mutations that improve the binding of humanized antibodies to their cognate antigens and may prove an attractive alternative to current methods of framework optimization based on cycles of site-directed mutagenesis.
Multiple mechanisms of B cell immunoregulation in man after administration of in vivo corticosteroids. (1984)

Despite the extensive clinical use of corticosteroids (CS) in the treatment of immune-mediated diseases, relatively little is known concerning the effects of CS on B cell function as measured by in vitro assays. The effects of single-dose vs several days of in vivo CS therapy on the spontaneous and mitogen-induced Ig production by human peripheral blood B cells are reported here. Spontaneous Ig production by individual B cells was enhanced by in vivo CS as measured by an in vitro plaque-forming cell (PFC) assay. The same increased response was also observed with a brief in vitro exposure of the B cells to CS, which suggests that a mere brief exposure to an active CS analogue is all that is required to produce the enhanced response. The immunoregulatory effects of in vivo CS on mitogen-induced Ig production are more complex. Pokeweed mitogen-induced PFC responses were suppressed 4 to 5 hr after a single in vivo pharmacologic dose of CS, with complete recovery by 24 hr. In contrast, after a 5-day course of CS, the suppressed PFC response did not recover until 60 hr after the last dose. Moreover, several mechanisms of suppression were operative. Ten hours after completing the 5-day course of CS, there was a relative enrichment in the peripheral blood compartment of lymphocytes bearing the OKT8 suppressor/cytotoxic T cell phenotype that coincided with a depressed PFC response. At 36 hr after the last dose, the T lymphocyte profile returned to normal while B cell function remained suppressed. The complex, multifaceted modulation of the immune response, resulting from redistribution of cell subsets as well as altered cell functions, vary with time-dose parameters of in vivo CS administration. These observations should provide additional insights into the heterogeneity of CS-induced therapeutic effects.