gebhart/patrepeval huggingface dataset:
Antibodies that are specific for a single amino acid interchange in a protein epitope use structurally distinct variable regions. (1991)

We have analyzed how the immune system generates antibodies that are specific for analogues of an epitope on the influenza virus hemagglutinin (HA) that differ solely by the presence of Asp or Gly at amino acid 225. Most antibodies induced in response to HA(Asp225) use one of a few closely related variable (V) region structures that are encoded by characteristic VH/Vk gene segment combinations. Remarkably, none of these VH/Vk combinations was induced in response to HA(Gly225). Instead of modifying the HA(Asp225)-specific V regions by junctional variation or somatic mutation to recognize the altered epitope, new VH/Vk combinations were used. The expression of unique VH/Vk combinations appears to confer exquisite specificity to the selection of HA-specific B cells from the pre-immune repertoire.
Synthesis of Calix[4]arene and Porphyrin Tethering Four Chiral Five-Membered Cyclic Carbonates (2002)

Calix[4]arene tethering four chiral five-membered cyclic carbonates 1c was synthesized by O-glycidylation of p-tert-butylcalix[4]arene 1a with (R)-glycidyl tosylate, followed by carbonation with carbon dioxide catalyzed by lithium bromide. Porphyrin tethering chiral five-membered cyclic carbonates 2c was similarly synthesized.
Activation of retinoid receptors RAR alpha and RXR alpha induces differentiation and apoptosis, respectively, in HL-60 cells. (1996)

Induction of granulocytic differentiation in HL-60 myeloid leukemia cells by retinoids is followed by their death via apoptosis. Retinoids are known to mediate their biological effects through at least two distinct types of nuclear receptors, the retinoic acid receptors and retinoid X receptors. We undertook to characterize the potential role of these receptors in inducing differentiation and apoptosis by retinoids. For this, we used a previously described variant of an HL-60 cell line (HL-60R) in which retinoid receptor function has been abrogated due to a trans-dominant negative mutation. Retroviral vector-mediated gene transfer was used to introduce the normal retinoic acid receptor (RAR alpha) or retinoid X receptor (RXR alpha) into HL-60R cells. Our results suggest that ligand-induced activation of RAR alpha is sufficient to induce differentiation in HL-60 cells, whereas activation of RXR alpha can induce direct apoptosis of these cells without their prior commitment to differentiate.
Tutorial on diffuse light transport (2008)

A tutorial introduction to diffuse light transport is presented. The basic analytic equations of time-resolved, steady-state and modulated light transport are introduced. The perturbation method for handling slight heterogeneities in optical properties is outlined. The treatment of boundary conditions such as an air/tissue surface is described. Finite mesh-based numerical methods are introduced to calculate the diffuse light field in complex tissues with arbitrary boundaries. Applications in tissue spectroscopy and imaging illustrate these theoretical and computational tools.
Regionally selective alterations in local cerebral glucose utilization evoked by charybdotoxin, a blocker of central voltage‐activated K+‐channels (2001)

The quantitative [14C]-2-deoxyglucose autoradiographic technique was employed to investigate the effect of charybdotoxin, a blocker of certain voltage-activated K+ channels, on functional activity, as reflected by changes in local rates of cerebral glucose utilization in rat brain. Intracerebroventricular administration of charybdotoxin, at doses below those producing seizure activity, produced a heterogeneous effect on glucose utilization throughout the brain. Out of the 75 brain regions investigated, 24 displayed alterations in glucose utilization. The majority of these changes were observed with the intermediate dose of charybdotoxin administered (12.5 pmol), with the lower (6.25 pmol) and higher (25 pmol) doses of charybdotoxin producing a much more restricted pattern of change in glucose utilization. In brain regions which displayed alterations in glucose at all doses of charybdotoxin administered, no dose dependency in terms of the magnitude of change was observed. The 21 brain regions which displayed altered functional activity after administration of 12.5 pmol charybdotoxin were predominantly limited to the hippocampus, limbic and motor structures. In particular, glucose utilization was altered within three pathways implicated within learning and memory processes, the septohippocampal pathway, Schaffer collaterals within the hippocampus and the Papez circuit. The nigrostriatal pathway also displayed altered local cerebral glucose utilization. These data indicate that charybdotoxin produces alterations in functional activity within selected pathways in the brain. Furthermore the results raise the possibility that manipulation of particular subtypes of Kv1 channels in the hippocampus and related structures may be a means of altering cognitive processes without causing global changes in neural activity throughout the brain.
Bilateral Fetal Mesencephalic Grafting in Two Patients with Parkinsonism Induced by 1-Methyl-4-Phenyl-L,2,3,6-Tetrahydropyridine (MPTP) (1992)

Bilateral implantation of fetal mesencephalic tissue can induce substantial long-term functional improvement in patients with parkinsonism and severe dopamine depletion and is accompanied by increased uptake of fluorodopa by the striatum. The results in these patients resemble those obtained in MPTP-treated primates and suggest that this will be a useful model for the assessment of transplantation therapies in Parkinson's disease.
The Botany Array Resource: e‐Northerns, Expression Angling, and promoter analyses (2005)

The Botany Array Resource provides the means for obtaining and archiving microarray data for Arabidopsis thaliana as well as biologist-friendly tools for viewing and mining both our own and other's data, for example, from the AtGenExpress Consortium. All the data produced are publicly available through the web interface of the database at http://bbc.botany.utoronto.ca. The database has been designed in accordance with the Minimum Information About a Microarray Experiment convention -- all expression data are associated with the corresponding experimental details. The database is searchable and it also provides a set of useful and easy-to-use web-based data-mining tools for researchers with sophisticated yet understandable output graphics. These include Expression Browser for performing 'electronic Northerns', Expression Angler for identifying genes that are co-regulated with a gene of interest, and Promomer for identifying potential cis-elements in the promoters of individual or co-regulated genes.
Function of Oxidative Cross-Linking of Cell Wall Structural Proteins in Plant Disease Resistance. (1994)

Elicitation of soybean cells causes a rapid insolubilization of two cell wall structural proteins, p33 and p100. Likewise, a short elicitation of 30 min rendered cell walls more refractory to enzyme digestion as assayed by the yield of protoplasts released. This effect could be ascribed to protein cross-linking because of its insensitivity to inhibitors of transcription (actinomycin D) and translation (cycloheximide) and its induction by exogenous H2O2. Moreover, the induced loss of protoplasts could be prevented by preincubation with DTT, which also blocks peroxidase-mediated oxidative cross-linking. The operation of protein insolubilization in plant defense was also demonstrated by its occurrence in the incompatible interaction but not in the compatible interaction between soybean and Pseudomonas syringae pv glycinea. Likewise, protein insolubilization was observed in bean during non-host hypersensitive resistance to the tobacco pathogen P. s. pv tabaci mediated by the hypersensitive resistance and pathogenicity (Hrp) gene cluster. Our data strongly suggest that rapid protein insolubilization leads to a strengthened cell wall, and this mechanism functions as a rapid defense in the initial stages of the hypersensitive response prior to deployment of transcription-dependent defenses.
Serenoa repens (Permixon�): A 5?-reductase types I and II inhibitor?new evidence in a coculture model of BPH (1999)

BACKGROUND The aim of this study was to determine the effect of the phytotherapeutic agent, Permixon®, on a novel coculture model of benign prostatic hyperplasia (BPH) in an effort to better understand the mode of action of the drug in vivo. METHODS The effect of Permixon®, at the calculated therapeutic concentration, on the activity of 5α-reductase isoenzymes was evaluated utilizing a pH-specific assay. Prostate-specific antigen (PSA) secretions into the medium were measured in the presence and absence of Permixon® and quantified by an ELISA assay. The morphological patterns before and following Permixon® treatment were also examined by electron microscopy. All results were compared to controls. RESULTS Permixon® at a concentration of 10 μg/ml (calculated plasma concentration in patient receiving recommended therapeutic dosage) was shown to be an effective inhibitor of both 5α-reductase types I and II isoenzymes without influencing the secretion of PSA by the epithelial cells, even after stimulation with testosterone. The morphology of Permixon®-treated cells was found to be markedly different from that of untreated controls. Cells which had been treated with the drug demonstrated extensive accumulation of lipids in the cytoplasm and widespread damage of intracellular membranes, including mitochondrial and nuclear membranes. CONCLUSIONS Permixon® is an effective dual inhibitor of 5α-reductase isoenzyme activities in the prostate. Unlike other 5α-reductase inhibitors, Permixon® induces this effect without interfering with the cells' capacity to secrete PSA, thus permitting the continued use of PSA measurements for prostate cancer screening. Prostate 40:232–241, 1999. © 1999 Wiley-Liss, Inc.
Ligand-dependent luminescence of ultra-small Eu3+-doped NaYF4 nanoparticles (2013)

Pure cubic phase ultra-small α-NaYF<sub>4</sub>:4 % Eu<sup>3+</sup> colloidal nanoparticles were synthesized by thermal decomposition reaction using three various capping ligands, i.e., oleic acid, trioctylphosphine oxide, and hexadecylamine. To expose as many Eu<sup>3+</sup> ions as possible to interactions with the surface-bounded ligands, the nanoparticles were fabricated to have the diameters below 10 nm. The geometrical structure and properties of surface ligands needed for qualitative estimation of their influence on spectroscopic features of the investigated Eu<sup>3+</sup> doped nanoparticles were obtained from DFT quantum-chemical calculations. Significant changes of luminescence spectra shapes and luminescence lifetime values were observed upon changes in the local chemical environment. We show that the ratio <i>R</i> = <sup>5</sup><i>D</i><sub>0</sub> → <sup>7</sup><i>F</i><sub>1</sub>/<sup>5</sup><i>D</i><sub>0</sub> → <sup>7</sup><i>F</i><sub>2</sub> of the intensities of the forced electric dipole (<i>J</i> = 2) and magnetic dipole (<i>J</i> = 1) transitions in the synthesized Eu<sup>3+</sup> doped nanoparticles is highly sensitive to the type of ligand present on the nanoparticle surface. Similarly, <sup>5</sup><i>D</i><sub>0</sub> luminescence lifetimes are found to be sensitive to the refractive index, and also to the dielectric constant of ligands used during the synthesis to coat nanoparticles surface. We argue that the photophysical and electro-optical properties of colloidal Eu<sup>3+</sup> doped inorganic nanoparticles show hyper-sensitive response to the chemical surroundings in the close vicinity of the nanoparticle itself. The behavior of both steady-state luminescence and its kinetics demonstrates the potential suitability of the studied nanoparticles for constructing self-referencing optical nano-sensors.
Characterization of IgG1 Conformation and Conformational Dynamics by Hydrogen/Deuterium Exchange Mass Spectrometry (2009)

Protein function is dictated by protein conformation. For the protein biopharmaceutical industry, therefore, it is important to have analytical tools that can detect changes in protein conformation rapidly, accurately, and with high sensitivity. In this paper we show that hydrogen/deuterium exchange mass spectrometry (H/DX-MS) can play an important role in fulfilling this need within the industry. H/DX-MS was used to assess both global and local conformational behavior of a recombinant monoclonal IgG1 antibody, a major class of biopharmaceuticals. Analysis of exchange into the intact, glycosylated IgG1 (and the Fab and Fc regions thereof) showed that the molecule was folded, highly stable, and highly amenable to analysis by this method using less than a nanomole of material. With improved chromatographic methods, peptide identification algorithms and data-processing steps, the analysis of deuterium levels in peptic peptides produced after labeling was accomplished in 1-2 days. On the basis of peptic peptide data, exchange was localized to specific regions of the antibody. Changes to IgG1 conformation as a result of deglycosylation were determined by comparing exchange into the glycosylated and deglycosylated forms of the antibody. Two regions of the IgG1 (residues 236-253 and 292-308) were found to have altered exchange properties upon deglycosylation. These results are consistent with previous findings concerning the role of glycosylation in the interaction of IgG1 with Fc receptors. Moreover, the data clearly illustrate how H/DX-MS can provide important characterization information on the higher order structure of antibodies and conformational changes that these molecules may experience upon modification.
Haemodynamic responses to exercise, ATP infusion and thigh compression in humans: insight into the role of muscle mechanisms on cardiovascular function (2008)

The muscle pump and muscle vasodilatory mechanism are thought to play important roles in increasing and maintaining muscle perfusion and cardiac output ((.)Q) during exercise, but their actual contributions remain uncertain. To evaluate the role of the skeletal muscle pump and vasodilatation on cardiovascular function during exercise, we determined leg and systemic haemodynamic responses in healthy men during (1) incremental one-legged knee-extensor exercise, (2) step-wise femoral artery ATP infusion at rest, (3) passive exercise (n=10), (4)femoral vein or artery ATP infusion (n=6), and (5) cyclic thigh compressions at rest and during passive and voluntary exercise (n=7). Incremental exercise resulted in progressive increases in leg blood flow (DeltaLBF 7.4 +/- 0.7 l min(-1)), cardiac output (Delta (.)Q 8.7 +/- 0.7 l min(-1)), mean arterial pressure (DeltaMAP 51 +/- 5 mmHg), and leg and systemic oxygen delivery and (.)VO2 . Arterial ATP infusion resulted in similar increases in (.)Q , LBF, and systemic and leg oxygen delivery, but central venous pressure and muscle metabolism remained unchanged and MAP was reduced. In contrast,femoral vein ATP infusion did not alter LBF, (.)Q or MAP. Passive exercise also increased blood flow (DeltaLBF 0.7 +/- 0.1 l min(-1)), yet the increase in muscle and systemic perfusion, unrelated to elevations in aerobic metabolism, accounted only for approximately 5% of peak exercise hyperaemia.Likewise, thigh compressions alone or in combination with passive exercise increased blood flow (DeltaLBF 0.5-0.7 l min(-1)) without altering (.)Q, MAP or (.)VO2. These findings suggest that the skeletal muscle pump is not obligatory for sustaining venous return, central venous pressure,stroke volume and (.)Q or maintaining muscle blood flow during one-legged exercise in humans.Further, its contribution to muscle and systemic peak exercise hyperaemia appears to be minimal in comparison to the effects of muscle vasodilatation.
Bad Is a BH3 Domain-Containing Protein That Forms an Inactivating Dimer with Bcl-X L (1997)

The Bcl-2 related protein Bad is a promoter of apoptosis and has been shown to dimerize with the anti-apoptotic proteins Bcl-2 and Bcl-XL. Overexpression of Bad in murine FL5.12 cells demonstrated that the protein not only could abrogate the protective capacity of coexpressed Bcl-XL but could accelerate the apoptotic response to a death signal when it was expressed in the absence of exogenous Bcl-XL. Using deletion analysis, we have identified the minimal domain in the murine Bad protein that can dimerize with Bcl-xL. A 26-amino-acid peptide within this domain, which showed significant homology to the alpha-helical BH3 domains of related apoptotic proteins like Bak and Bax, was found to be necessary and sufficient to bind Bcl-xL. To determine the role of dimerization in regulating the death-promoting activity of Bad and the death-inhibiting activity of Bcl-xL, mutations within the hydrophobic BH3-binding pocket in Bcl-xL that eliminated the ability of Bcl-xL to form a heterodimer with Bad were tested for the ability to promote cell survival in the presence of Bad. Several of these mutants retained the ability to impart protection against cell death regardless of the level of coexpressed Bad protein. These results suggest that BH3-containing proteins like Bad promote cell death by binding to antiapoptotic members of the Bcl-2 family and thus inhibiting their survival promoting functions.
Topography Of Membrane Proteins (1989)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them (2004)

The basic route and mechanisms for leukocyte migration across the endothelium remain poorly defined. We provide definitive evidence for transcellular (i.e., through individual endothelial cells) diapedesis in vitro and demonstrate that virtually all, both para- and transcellular, diapedesis occurs in the context of a novel "cuplike" transmigratory structure. This endothelial structure was comprised of highly intercellular adhesion molecule-1- and vascular cell adhesion molecule-1-enriched vertical microvilli-like projections that surrounded transmigrating leukocytes and drove redistribution of their integrins into linear tracks oriented parallel to the direction of diapedesis. Disruption of projections was highly correlated with inhibition of transmigration. These findings suggest a novel mechanism, the "transmigratory cup", by which the endothelium provides directional guidance to leukocytes for extravasation.
Quantitation of Promoter Methylation of Multiple Genes in Urine DNA and Bladder Cancer Detection (2006)

Testing a small panel of genes with the quantitative methylation-specific PCR assay in urine sediment DNA is a powerful noninvasive approach for the detection of bladder cancer. Larger independent confirmatory cohorts with longitudinal follow-up will be required in future studies to define the impact of this technology on early detection, prognosis, and disease monitoring before clinical application.
Engineering luciferase enzymes and substrates for novel assay capabilities (2004)

In the development of HTS as a central paradigm of drug discovery, fluorescent reporter molecules have generally been adopted as the favored signal transducer. Nevertheless, luminescence has maintained a prominent position among certain methodologies, most notably genetic reporters. Recently, there has been growing partiality for luminescent assays across a broader range of applications due to their sensitivity, extensive linearity, and robustness to library compounds and complex biological samples. This trend has been fostered by development several new assay designs for diverse targets such as kinases, cytochrome p450's, proteases, apoptosis, and cytotoxicity. This review addresses recent progress made in the use of bioluminescent assays for drug discovery, highlighting new detection capabilities brought about by engineering luciferase enzymes and substrates. In reporter gene applications, modified luciferases have provided greatly improved expression efficiency in mammalian cells, improved responsiveness to changes of transcriptional rate, and increased the magnitude of the reporter response. Highly stabilized luciferase mutants have enabled new assays strategies for high-throughput screening based on detection of ATP and luciferin. Assays based on ATP support rapid analysis of cell metabolism and enzymatic processes coupled to ATP hydrolysis. Although luciferin is found natively only in luminous beetles, coupled assays have been designed using modified forms of luciferin requiring the action of second enzyme to yield luminescence. Due to the very low inherent background and protection of the photon-emitter afforded by the enzyme, bioluminescent assays often outperform the analogous fluorescent assays for analyses performed in multiwell plates.
PeerAccess (2005)

This paper introduces the PeerAccess framework for reasoning about authorization in open distributed systems, and shows how a parameterization of the framework can be used to reason about access to computational resources in a grid environment. The PeerAccess framework supports a declarative description of the behavior of peers that selectively push and/or pull information from certain other peers. PeerAccess local knowledge bases encode the basic knowledge of each peer (e.g., Alice's group memberships), its policies governing the release of each possible piece of information to other peers, and information that guides and limits its search process when trying to obtain particular pieces of information from other peers. PeerAccess proofs of authorization are verifiable and nonrepudiable, and their construction relies only on the local information possessed by peers and their parameterized behavior with respect to query answering, information push/pull, and information release policies (i.e., no omniscient viewpoint is required). We present the PeerAccess language and peer knowledge base structure, the associated formal semantics and proof theory, and examples of the use of PeerAccess in constructing proofs of authorization to access computational resources.
Thermally darkenable photochromic glasses (1975)

Thermally darkenable photochromic (TDPC) glasses have been produced by precipitating copper−doped silver halide crystallites in certain lanthanum borate base glasses. A TDPC glass is characterized by a darkened state which is stable at room temperature but which can be bleached by visible light. The glass will return to the darkened state with the passage of time. The rate of darkening and the color of the darkened state are affected by temperature. These TDPC glasses are further characterized by the vanishing of the darkened color above a certain high temperature and redarkening of the glass below a certain somewhat lower temperature. These temperatures are believed associated with the melting and crystallization of the silver halide particles.