gebhart/patrepeval huggingface dataset:
Adenosine Receptor Ligands-Recent Developments Part I. Agonists (2000)

Developments in the field of adenosine receptor (AR) agonists of the past years are presented and discussed. Four different AR subtypes, A(1), A(2A), A(2B), and A(3), have been cloned from different species including the human receptors. Recombinant ARs expressed in permanent mammalian cell lines have found wide application in the screening of new ligands. Considerable differences are observed among data from different laboratories, using recombinant receptors for the assays. Reevaluation of compounds at all four receptor subtypes has shown that agonists that were believed to be selective for either A(1) or A(2A) ARs may be potent A(3) agonists and thus, non-selective. Potent and selective agonists for two of the AR subtypes, A(1) and A(3), have been developed. Truly selective A(2A) AR agonists, however, are presently not available. Potent or selective A(2B) agonists are still lacking. Since the treatment with AR agonists may lead to fast desensitization of the receptors, partial agonists, and indirect AR agonists, such as adenosine kinase inhibitors, or allosteric enhancers of adenosine binding, are being developed as site- and event-specific agents.
Decreased expression of ABCD4 and BG1 genes early in the pathogenesis of X-linked adrenoleukodystrophy (2005)

Childhood cerebral adrenoleukodystrophy (CCER), adrenomyeloneuropathy (AMN) and AMN with cerebral demyelination (AMN-C) are the main phenotypic variants of X-linked adrenoleukodystrophy (ALD). It is caused by mutations in the ABCD1 gene encoding a half-size peroxisomal transporter that has to dimerize to become functional. The biochemical hallmark of ALD is the accumulation of very-long-chain fatty acids (VLCFA) in plasma and tissues. However, there is no correlation between the ALD phenotype and the ABCD1 gene mutations or the accumulation of VLCFA in plasma and fibroblast from ALD patients. The absence of genotype-phenotype correlation suggests the existence of modifier genes. To elucidate the mechanisms underlying the phenotypic variability of ALD, we studied the expression of ABCD1, three other peroxisomal transporter genes of the same family (ABCD2, ABCD3 and ABCD4) and two VLCFA synthetase genes (VLCS and BG1) involved in VLCFA metabolism, as well as the VLCFA concentrations in the normal white matter (WM) from ALD patients with CCER, AMN-C and AMN phenotypes. This study shows that: (1) ABCD1 gene mutations leading to truncated ALD protein are unlikely to cause variation in the ALD phenotype; (2) accumulation of saturated VLCFA in normal-appearing WM correlates with ALD phenotype and (3) expression of the ABCD4 and BG1, but not of the ABCD2, ABCD3 and VLCS genes, tends to be correlated with the severity of the disease, acting early in the pathogenesis of ALD.
In vitro transformation of immature hematopoietic cells by the P210 BCR/ABL oncogene product of the Philadelphia chromosome. (1987)

The Philadelphia chromosome [t(9;22)-(q34;q11)] is the cytogenetic hallmark of human chronic myelogenous leukemia. RNA splicing joins sequences from a gene on chromosome 22 (BCR) across the translocation breakpoint to a portion of the ABL oncogene from chromosome 9, resulting in a chimeric protein (P210) that is an active tyrosine kinase. Although strongly correlated with this specific human neoplasm, and implicated as an oncogene by analogy to the gene product of the Abelson murine leukemia virus, the P210 gene had not been tested directly for oncogenic potential in hematopoietic cells. We have used a retroviral gene-transfer system to express P210 in mouse bone marrow cells. When infected bone marrow is plated under conditions for long-term culture of cells of the B-lymphoid lineage, cells expressing high amounts of P210 tyrosine kinase dominate the culture and rapidly lead to clonal outgrowths of immature lymphoid cells. Expression of P210 is growth-stimulatory but not sufficient for full oncogenic behavior. Some clonal lines progress toward a fully malignant phenotype as judged by increased cloning efficiency in agar suspension and frequency and rapidity of tumor induction in syngeneic mice. Such in vitro systems should be useful in evaluating the sequential and perhaps synergistic involvement of the P210 gene and other oncogenes as models for the progressive changes observed in human chronic myelogenous leukemia.
Resonant grating structures: Theory, design, and applications (1998)

Thesis (Ph. D.)--University of Rochester. Institute of Optics, 1998.
Singlet Exciton Fission for Solar Cell Applications: Energy Aspects of Interchromophore Coupling (2009)

Singlet exciton fission, a process that converts one singlet exciton to a pair of triplet excitons, has the potential to enhance the efficiency of both bulk heterojunction and dye-sensitized solar cells and is understood in crystals but not well understood in molecules. Previous studies have identified promising building blocks for singlet fission in molecular systems, but little work has investigated how these individual chromophores should be combined to maximize triplet yield. We consider the effects of chemically connecting two chromophores to create a coupled chromophore pair and compute how various structural choices alter the thermodynamic and kinetic parameters likely to control singlet fission yield. We use density functional theory to compute the electron transfer matrix element and the thermodynamics of fission for several promising chromophore pairs and find a trade-off between the desire to maximize this element and the desire to keep the singlet fission process exoergic. We identify promising molecular systems for singlet fission and suggest future experiments.
Applying cognitive walkthroughs to more complex user interfaces (1992)

The Cognitive Walkthrough methodology was developed in an effort to bring cognitive theory closer to practice; to enhance the design and evaluation of use interfaces in industrial settings. For the first time, small teams of professional developers have used this method to critique three complex software systems. In this paper we report evidence about how the methodology worked for these evaluations. We focus on five core issues: (1) task selection, coverage, and evaluation, (2) the process of doing a Cognitive Walkthrough, (3) requisite knowlege for the evaluators, (4) group walkthroughs, and (5) the interpretation of results. Our findings show that many variables can affect the success of the technique; we believe that if the Cognitive Walkthrough is ultimately to be successful in industrial settings, the method must be refined and augmented in a variety of ways.
Amino Acid Neurotransmitters and New Approaches to Anticonvulsant Drug Action (1984)

Amino acids provide the most universal and important inhibitory (gamma-aminobutyric acid (GABA), glycine) and excitatory (glutamate, aspartate, cysteic acid, cysteine sulphinic acid) neurotransmitters in the brain. An anticonvulsant action may be produced (1) by enhancing inhibitory (GABAergic) processes, and (2) by diminishing excitatory transmission. Possible pharmacological mechanisms for enhancing GABA-mediated inhibition include (1) GABA agonist action, (2) GABA prodrugs, (3) drugs facilitating GABA release from terminals, (4) inhibition of GABA-transaminase, (5) allosteric enhancement of the efficacy of GABA at the receptor complex, (6) direction action on the chloride ionophore, and (7) inhibition of GABA reuptake. Examples of these approaches include the use of irreversible GABA-transaminase inhibitors, such as gamma-vinyl GABA, and the development of anticonvulsant beta-carbolines that interact with the "benzodiazepine receptor." Pharmacological mechanisms for diminishing excitatory transmission include (1) enzyme inhibitors that decrease the maximal rate of synthesis of glutamate or aspartate, (2) drugs that decrease the synaptic release of glutamate or aspartate, and (3) drugs that block the post-synaptic action of excitatory amino acids. Compounds that selectively antagonise excitation due to dicarboxylic amino acids have recently been developed. Those that selectively block excitation produced by N-methyl-D-aspartate (and aspartate) have proved to be potent anticonvulsants in many animal models of epilepsy. This provides a novel approach to the design of anticonvulsant drugs.
A new perspective on concepts of asthma severity and control (2008)

Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control. "Asthma control" refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and lung function decline). The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control, i.e. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patient's phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.
Platelet-Derived Growth Factor Receptor Association with Na+/H+ Exchanger Regulatory Factor Potentiates Receptor Activity (2000)

Platelet-derived growth factor (PDGF) is a potent mitogen for many cell types. The PDGF receptor (PDGFR) is a receptor tyrosine kinase that mediates the mitogenic effects of PDGF by binding to and/or phosphorylating a variety of intracellular signaling proteins upon PDGF-induced receptor dimerization. We show here that the Na(+)/H(+) exchanger regulatory factor (NHERF; also known as EBP50), a protein not previously known to interact with the PDGFR, binds to the PDGFR carboxyl terminus (PDGFR-CT) with high affinity via a PDZ (PSD-95/Dlg/Z0-1 homology) domain-mediated interaction and potentiates PDGFR autophosphorylation and extracellular signal-regulated kinase (ERK) activation in cells. A point-mutated version of the PDGFR, with the terminal leucine changed to alanine (L1106A), cannot bind NHERF in vitro and is markedly impaired relative to the wild-type receptor with regard to PDGF-induced autophosphorylation and activation of ERK in cells. NHERF potentiation of PDGFR signaling depends on the capacity of NHERF to oligomerize. NHERF oligomerizes in vitro when bound with PDGFR-CT, and a truncated version of the first NHERF PDZ domain that can bind PDGFR-CT but which does not oligomerize reduces PDGFR tyrosine kinase activity when transiently overexpressed in cells. PDGFR activity in cells can also be regulated in a NHERF-dependent fashion by stimulation of the beta(2)-adrenergic receptor, a known cellular binding partner for NHERF. These findings reveal that NHERF can directly bind to the PDGFR and potentiate PDGFR activity, thus elucidating both a novel mechanism by which PDGFR activity can be regulated and a new cellular role for the PDZ domain-containing adapter protein NHERF.
Human KGF is FGF-Related with Properties of a Paracrine Effector of Epithelial Cell Growth (1989)

Keratinocyte growth factor (KGF) is a human mitogen that is specific for epithelial cells. The complementary DNA sequence of KGF demonstrates that it is a member of the fibroblast growth factor family. The KGF transcript was present in stromal cells derived from epithelial tissues. By comparison with the expression of other epithelial cell mitogens, only KGF, among known human growth factors, has the properties of a stromal mediator of epithelial cell proliferation.
Rabbit Articular Cartilage Defects Treated With Autologous Cultured Chondrocytes (1996)

Adult New Zealand rabbits were used to transplant autologously harvested and in vitro cultured chondrocytes into patellar chondral lesions that had been made previously and were 3 mm in diameter, extending down to the calcified zone. Healing of the defects was assessed by gross examination, light microscope, and histological-histochemical scoring at 8, 12, and 52 weeks. Chondrocyte transplantation significantly increased the amount of newly formed repair tissue compared to the found in control knees in which the lesion was solely covered by a periosteal flap. In another experiment, carbon fiber pads seeded with chondrocytes were used as scaffolds, and repair significantly increased at both 12 and 52 weeks compared to knees in which scaffolds without chondrocytes were implanted. The histologic quality scores of the repair tissue were significantly better in all knees in which defects were treated with chondrocytes compared to knees treated with periosteum alone and better at 52 weeks compared to knees in which defects were treated with carbon scaffolds seeded with chondrocytes. The repair tissue, however, tended to incomplete the bonding to adjacent cartilage. This study shows that isolated autologous articular chondrocytes that have been expanded for 2 weeks in vitro can stimulate the healing phase of chondral lesions. A gradual maturation of the hyalinelike repair with a more pronounced columnarization was noted as late as 1 year after surgery.
A power re-use technique for improved efficiency of outphasing microwave power amplifiers (1999)

An improved power re-use technique is introduced for application to outphased microwave power amplifiers. The technique allows a significant portion of the wasted out-of-phase components of the signal to be returned to the power supply, resulting in substantial improvements in overall power-amplifier efficiency. A peak re-use RF-to-DC efficiency of 63% was obtained at 1.96 GHz.
A manufacturable complementary GaAs process (2002)

A self-aligned complementary GaAs heterostructure FET process has been established for low power, high-speed digital circuits. The devices are fabricated on four-inch MBE epitaxial wafers consisting of AlGaAs/InGaAs epilayers grown on LEC GaAs substrates. The process uses twelve lithographic steps including two levels of interconnect metal. Typical transconductances of 250 mS/mm and 60 mS/mm are achieved on 1/spl times/10 /spl mu/m N-channel and P-channel devices, respectively. Twenty-three stage unloaded complementary ring oscillators consisting of 1/spl times/10 /spl mu/m N- and P-FETs show propagation delay of 190 ps and speed-power product of 7.5 fJ or 0.35 /spl mu/W/MHz.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Versatile synthesis of sulphamate esters by phase-transfer methods (1982)

The syntheses of sulphamate esters of the general types R1R2NSO3R3, RNHSO3R3, and H2NSO3R3, where R3 may be aliphatic or aromatic, have been achieved in good yield by reaction of the appropriate sulphamoyl chlorides with alcohols and phenols under mild phase-transfer conditions. The present methods have led to generally higher yields, and to shorter reaction times and lower reaction temperatures than were hitherto found necessary. The prior preparation of the alkoxide has also been obviated. Some esters have been rearranged to the isomeric betaines.
Ubiquicidin, a novel murine microbicidal protein present in the cytosolic fraction of macrophages (1999)

Previously we have identified and characterized three murine microbicidal proteins purified from the granule fraction of cells from the murine macrophage cell line RAW264.7. During these studies evidence was obtained for the presence of an additional antimicrobial protein in the cytosolic fraction of RAW264.7 cells that had been activated with interferon-gamma (IFN-gamma). In this study we have purified this protein, designated ubiquicidin, to apparent homogeneity and demonstrated that it is a cationic, small (Mr 6654) protein. Ubiquicidin displayed marked antimicrobial activity against Listeria monocytogenes and Salmonella typhimurium. Using a gel overlay procedure evidence was obtained that the protein also displays activity against Escherichia coli, Staphylococcus aureus, and an avirulent strain of Yersinia enterocolitica. Aminoterminal amino acid sequencing and mass spectrometry analysis of purified ubiquicidin indicated that it is most likely identical to the ribosomal protein S30. This protein is produced by posttranslational processing of the Fau protein, a 133-amino-acid fusion protein consisting of S30 linked to an unusual peptide with significant homology to ubiquitin. The fau gene has been reported to be expressed in a variety of tissues in humans and various animal species. The presence of ubiquicidin in the cytosol of macrophages may serve to restrict the intracellular growth of microorganisms. In addition, because macrophage disintegration will likely lead to release of ubiquicidin into the extracellular environment, it may contribute to host defense after macrophage death.
Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. (2000)

Several types of epidermal growth factor receptor (EGFR) gene mutations have been reported in glioblastomas, and in nearly all cases the alterations have been reported in tumors with EGFR amplification. The objectives of this study were to determine the frequency and diversity of EGFR mutations in glioblastomas and to determine whether gene mutation is inevitably associated with increased EGFR gene dosage. To accomplish these aims, we sequenced cDNA products representing the entire EGFR coding region in 44 glioblastomas, half of which had EGFR amplification. Coding sequence alterations were identified in 17 of the tumors, and each of these cases had amplified EGFR. No mutations were identified in the 22 tumors without EGFR amplification. An additional 26 glioblastomas with EGFR amplification were then examined to establish more reliable frequencies for each type of mutation identified in the tumors for which the entire gene was sequenced. Transcripts associated with the most common mutation lacked coding sequence for amino acids 6-273 (67%). This mutation has been described extensively in the literature. Transcripts encoding receptors that would truncate at amino acid 958 and transcripts encoding receptors that would lack amino acids 521-603 were the next most common types of alteration. Each of these were observed in 15% of the tumors with EGFR amplification. Other mutations were observed at lower frequencies, but among these were three cases with missense mutations. Sixteen of the 48 tumors with EGFR amplification showed multiple types of EGFR mutations (33%), and in one case it was determined that multiple alterations had occurred in the same transcript. In total, these data are consistent with EGFR mutation being exclusively and frequently associated with EGFR amplification. Furthermore, the determination of multiple EGFR mutations within individual tumors suggests that glioblastomas with EGFR amplification have the capacity to produce a variety of functionally distinct EGFRs.
Size-dependent two-photon excitation spectroscopy of CdSe nanocrystals (1996)

Two-photon excitation spectra of highly monodisperse colloidal CdSe nanocrystals with sizes ranging from 22 to 43 \AA{} are compared to one-photon excitation data and to a spherically confined effective-mass model. The main experimental features are well described by this model. However, the first one-photon and two-photon transitions appear indistinguishable, though the model predicts a 20-meV splitting. This discrepancy may reflect the sensitivity of the band-edge structure to deviations from the assumed spherical symmetry. \textcopyright{} 1996 The American Physical Society.
Clusterin regulates vascular smooth muscle cell nodule formation and migration (2001)

Vascular smooth muscle cells (VSMC) are the principal cellular component of the blood vessel wall where they exist in a differentiated state to maintain vascular tone. However, VSMC are not terminally differentiated and can be induced to dediffentiate, proliferate, and migrate. In fact, smooth muscle cell migration from the vascular wall into the lumen of the vessel is a central feature of occlusive vascular pathologies including atherosclerosis and intimal hyperplasia. In vitro, in the presence of an extracellular matrix, cultured vascular smooth muscle cells can migrate and invade the underlying gelatinous matrix, form multicellular nodular aggregations, and secrete the glycoprotein clusterin. Nodular cultures appear to mimic some of the properties of differentiated VSMC, in vivo. Here, to test the hypothesis that clusterin functions to modulate the formation of VSMC nodules and to facilitate cell migration a clusterin negative VSMC clone, SM-CLU13AS (Moulson and Millis, 1999, J Cell Physiol 180:355), was transiently transfected with plasmid pRcCMVCLU that contains the full-length porcine clusterin cDNA sequence under control of the CMV promoter. The transiently transfected VSMC culture expressed and secreted clusterin and formed nodules. To determine if clusterin regulates VSMC migration we used modified Boyden chamber assays. Clusterin, at 10 microg/ml, clearly promotes VSMC migration. In addition, a 15 amino acid synthetic peptide, representing amino acids 118-132 [KQTCMKFYARVCRSG] of the mature clusterin polypeptide, inhibits VSMC attachment to gelatinous substrate. Finally, clusterin appears to have a role in regulating endogenous clusterin expression in the clusterin negative clone. These results clearly establish that clusterin has functional role in VSMC nodule formation and support the conclusion that clusterin is a critical component of smooth muscle cell phenotypic modulation.
Australian consumer payment behaviour and preferences (2011)

Based on a 2010 study of consumer payment patterns, this paper examines how payment methods, including cash, are currently being used in Australia and how that use has changed over time. It also provides qualitative evidence of consumers' preferences regarding different payment methods and highlights some potential areas for improvement in the payments system, as perceived by consumers.
Phenotypic and functional change of cytokine-activated neutrophils: inflammatory neutrophils are heterogeneous and enhance adaptive immune responses (2001)

Polymorphonuclear leukocytes (PMN) are the most abundant leukocytes, comprising about two-thirds of peripheral blood leukocytes, and play major roles in innate immunity. In addition, PMN play critical roles in the development of adaptive immunity. Recently, defensins and other peptides pre-stored in PMN granules were shown to attract monocytes, dendritic cells, and T cells, leading to the hypothesis that the release of PMN granular peptides may link innate and adaptive immunity. During the past several years, we have focused on an alternative hypothesis that activated PMN further differentiate and acquire new phenotypes and functions that enable them to link the two responses. To test our hypothesis, we have taken local and global approaches and have shown several key findings that support the hypothesis. The findings include the requirement for priming PMN by cytokines to induce the delayed expression of MCP-1/CCL2, a signal for mononuclear cells, and the expression of new cell-surface markers by such cytokine-activated PMN. In the present manuscript, we focus on the phenotypic and functional changes that occur during PMN activation with selected cytokines. The results of our study indicate that inflammatory PMN are heterogeneous and play roles in not only innate but also adaptive immunity in response to stimuli released in injured tissues.