gebhart/patrepeval huggingface dataset:
Enhancement of long‐range EEG coherence by synchronous bifocal transcranial magnetic stimulation (2008)

Interregional coupling of distant brain regions can be measured by electroencephalographic (EEG) coherence reflecting the spatial-temporal correlation between two oscillatory signals. It has been suggested that this coherence in activity is a signature of functional integration of multimodal neuronal networks. Repetitive transcranial magnetic stimulation (rTMS) is a well-established technique for non-invasive cortical stimulation. Its modulating effects outlast the train of stimulation and affect behavior. In the present study, we tested the hypothesis that cortico-cortical coherence between distant brain areas can be selectively enhanced by synchronous bifocal rTMS. Cortico-cortical coherence was assessed in 16 healthy human subjects before and after three trains of synchronous high-frequency (10 Hz) rTMS to the left primary motor cortex and the visual cortex at the occipital pole simultaneously. Stimulation of the left M1 alone served as the control condition. Coherence and spectral power were measured between these areas on the stimulated and the homologue contralateral side. Synchronous bifocal rTMS induced an increase of interregional coupling in the alpha and lower beta band on the stimulated side without effects on spectral power. These data indicate that synchronous bifocal rTMS is a feasible technique for selective modulation of interregional EEG coherence. Furthermore, they raise the hypothesis that interventional enhancement of long-range coherence may effectively modulate interregional integration with behavioral consequences.
Blood-Brain Barrier Molecular Trojan Horse Enables Imaging of Brain Uptake of Radioiodinated Recombinant Protein in the Rhesus Monkey (2013)

Recombinant proteins are large molecule drugs that do not cross the blood-brain barrier (BBB). However, BBB-penetration of protein therapeutics is enabled by re-engineering the recombinant protein as IgG fusion proteins. The IgG domain is a monoclonal antibody (mAb) against an endogenous BBB receptor-mediated transport system, such as the human insulin receptor (HIR), and acts as a molecular Trojan horse to ferry the fused protein across the BBB. In the present study, a recombinant lysosomal enzyme, iduronate 2-sulfatase (IDS), is fused to the HIRMAb, and BBB penetration of the IDS alone vs the HIRMAb-IDS fusion protein is compared in the Rhesus monkey. Recombinant IDS and the HIRMAb-IDS fusion protein were radiolabeled with indirect iodination with the [(125)I]-Bolton-Hunter reagent and with direct iodination with Iodogen/[(125)I]-idodine. IDS and the HIRMAb-IDS fusion protein have comparable plasma pharmacokinetics and uptake by peripheral organs. IDS does not cross the BBB. The HIRMAb-IDS fusion protein crosses the BBB and the brain uptake is 1% of injected dose/brain. Brain imaging shows HIRMAb-IDS penetration to all parts of brain, and immunoprecipitation of brain radioactivity shows intact fusion protein in brain. The use of BBB molecular Trojan horses enables brain imaging of recombinant proteins that are re-engineered for BBB transport.
Surface pole figures by reflection high-energy electron diffraction (2006)

The authors demonstrated that it is possible to construct a reflection high-energy electron diffraction (RHEED) pole figure of a polycrystalline film by recording multiple RHEED patterns as they rotate the substrate around the surface normal. Since electrons have limited penetration depth, the pole figure constructed is a surface pole figure. It is in contrast with the conventional x-ray pole figure which gives an average texture information of the entire film. Surface texture change, particularly the evolution of multiple preferred orientations, in polycrystalline Ru films grown by oblique angle vapor deposition has been observed using this RHEED surface pole figure technique.
Protective Effect of Erythropoietin and Its Carbamylated Derivative in Experimental Cisplatin Peripheral Neurotoxicity (2006)

These results widen the spectrum of possible use of erythropoietin and carbamylated erythropoietin as neuroprotectant drugs, strongly supporting their effectiveness.
Pomegranate Juice Does Not Impair Clearance of Oral or Intravenous Midazolam, a Probe for Cytochrome P450‐3A Activity: Comparison With Grapefruit Juice (2007)

The effect of pomegranate juice (PJ) or grapefruit juice (GFJ) on CYP3A activity was studied in vitro and in healthy human volunteers. In human liver microsomes, the mean 50% inhibitory concentrations (IC(50)) for PJ and GFJ versus CYP3A (triazolam alpha-hydroxylation) were 0.61% and 0.55%, (v/v) respectively, without preincubation of inhibitor with microsomes. After preincubation, the IC(50) for PJ increased to 0.97% (P < .05), whereas the IC(50) for GFJ decreased to 0.41% (P < .05), suggesting mechanism-based inhibition by GFJ but not PJ. Pretreatment of volunteer subjects (n = 13) with PJ (8 oz) did not alter the elimination half-life, volume of distribution, or clearance of intravenous midazolam (2 mg). Administration of PJ also did not affect C(max), total area under the curve (AUC), or clearance of oral midazolam (6 mg). However, GFJ (8 oz) increased midazolam C(max) and AUC by a factor of 1.3 and 1.5, respectively, and reduced oral clearance to 72% of control values. Thus, PJ does not alter clearance of intravenous or oral midazolam, whereas GFJ impairs clearance and elevates plasma levels of oral midazolam.
Transgenic expression of epidermal growth factor and keratinocyte growth factor in beta-cells results in substantial morphological changes (1999)

The upregulation of a limited number of growth factors in our interferon-gamma transgenic model for regeneration within the pancreas lead us to propose that these factors are important during pancreatic regeneration. In this study, we have assessed the influence of two growth factors within the pancreas, epidermal growth factor (EGF) and keratinocyte growth factor (KGF), by ectopically expressing these proteins under the control of the human insulin promoter in transgenic mice. This beta-cell-targeted expression of either EGF or KGF resulted in significant morphological changes, including cellular proliferation and disorganized islet growth. Intercrossing the individual Ins-EGF and Ins-KGF transgenic mice resulted in more profound changes in pancreatic morphology including proliferation of pancreatic cells and extensive intra-islet fibrosis. Insulin-producing beta-cells were found in some of the ducts of older Ins-EGF and Ins-EGFxKGF transgenic mice, and amylase-producing cells were observed within the islet structures of the double transgenic mice. These data suggest that both EGF and KGF are capable of affecting pancreatic differentiation and growth, and that co-expression of these molecules in islets has a more substantial impact on the pancreas than does expression of either growth factor alone.
A Collaborative Enterprise for Multi-Stakeholder Participation in the Advancement of Quantitative Imaging (2011)

Medical imaging has seen substantial and rapid technical advances during the past decade, including advances in image acquisition devices, processing and analysis software, and agents to enhance specificity. Traditionally, medical imaging has defined anatomy, but increasingly newer, more advanced, imaging technologies provide biochemical and physiologic information based on both static and dynamic modalities. These advanced technologies are important not only for detecting disease but for characterizing and assessing change of disease with time or therapy. Because of the rapidity of these advances, research to determine the utility of quantitative imaging in either clinical research or clinical practice has not had time to mature. Methods to appropriately develop, assess, regulate, and reimburse must be established for these advanced technologies. Efficient and methodical processes that meet the needs of stakeholders in the biomedical research community, therapeutics developers, and health care delivery enterprises will ultimately benefit individual patients. To help address this, the authors formed a collaborative program-the Quantitative Imaging Biomarker Alliance. This program draws from the very successful precedent set by the Integrating the Healthcare Enterprise effort but is adapted to the needs of imaging science. Strategic guidance supporting the development, qualification, and deployment of quantitative imaging biomarkers will lead to improved standardization of imaging tests, proof of imaging test performance, and greater use of imaging to predict the biologic behavior of tissue and monitor therapy response. These, in turn, confer value to corporate stakeholders, providing incentives to bring new and innovative products to market.
1002. Immune Responses to AAV and to Factor IX in a Phase I Study of AAV-Mediated, Liver-Directed Gene Transfer for Hemophilia B (2004)

Katherine High,1,2,3 Catherine Manno,1,2 Denise Sabatino,1 Sylvia Hutchison,4 Michael Dake,4 Mahmood Razavi,4 Robin Kaye,1 Valder Aruda,1,2 Roland Herzog,1,2 Pradip Rustagi,4 John Rasko,5 Keith Hoots,6 Phillip Blatt,7 Jurg Sommer,8 Margaret Ragni,9 Margareth Ozelo,10 Barbara Konkle,2 Ruth Lessard,8 Alvin Luk,8 Bertil Glader,4 Glenn Pierce,8 Linda Couto,8 Mark Kay.4
Fabrication of patterned DNA surfaces (1996)

Two photolithographic methods are described for the formation of patterned single or multiple DNA species on SiO2 substrates. In the first approach, substrates are treated with a photochemically labile organosilane monolayer film. Irradiation of these surfaces with patterned deep UV (193 nm) light results in patterned chemically reactive groups which are then reacted with heterobifunctional crosslinking molecules. Covalent attachment of modified synthetic DNA oligomers to the crosslinker results in stable DNA patterns. Alternatively, a photoresist is spin-coated over a silane film which had been previously modified with the heterobifunctional crosslinker. Upon patterned irradiation and subsequent development, the underlying crosslinker-modified layer is revealed, and is then reacted with a chemically modified DNA. Feature dimensions to 1 micron are observed when a single fluorescent DNA is attached to the surface. By performing sequential exposures, we have successfully immobilized two distinguishable DNA oligomers on a single surface. Synthetic DNA immobilized in this manner retains the ability to hybridize to its complementary strand, suggesting that these approaches may find utility in the development of miniaturized DNA-based biosensors.
Color center lasers passively mode locked by quantum wells (1989)

Using multiple-quantum-well (MQW) saturable absorbers, a NaCl color center was passively mode locked to produce 275-fs transform-limited, pedestal-free pulses with a peak power as high as 3.7 kW. The pulses are tunable from lambda =1.59 to 1.7 mu m by choosing MQWs with different bandgaps. The output pulses from the laser were shortened to 25 fs using the technique of soliton compression in a fiber. The steady-state operation of the laser requires the combination of a fast saturable absorber and gain saturation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Pharmacologically active plant metabolites as survival strategy products. (2003)

The fact that plant organisms produce chemical substances that are able to positively or negatively interfere with the processes which regulate human life has been common knowledge since ancient times. One of the numerous possible examples in the infusion of Conium maculatum, better known as Hemlock, a plant belonging to the family umbelliferae, used by the ancient Egyptians to cure skin diseases. The current official pharmacopoeia includes various chemical substances produced by secondary plant metabolisms. For example, the immunosuppressive drugs used to prevent organ transplant rejection and the majority of antibiotics are metabolites produced by fungal organisms, pilocarpin, digitalis, strophantus, salicylic acid and curare are examples of plant organism metabolites. For this reason, there has been an increase in research into plants, based on information on their medicinal use in the areas where they grow. The study of plants in relation to local culture and traditions is known as "ethnobotany". Careful study of the behaviour of sick animals has also led to the discovery of medicinal plants. The study of this subject is known as "zoopharmacognosy". The aim of this article is to discuss the fact that "ad hoc" production of such chemical substances, defined as "secondary metabolites", is one of the modes in which plant organisms respond to unfavourable environmental stimuli, such as an attack by predatory phytophagous animals or an excessive number of plant individuals, even of the same species, in a terrain. In the latter case, the plant organisms produce toxic substances, called "allelopathic" which limit the growth of other individuals. "Secondary metabolites" are produced by metabolic systems that are shunts of the primary systems which, when required, may be activated from the beginning, or increased to the detriment of others. The study of the manner in which such substances are produced is the subject of a new branch of learning called "ecological biochemistry".
Biomarkers of cytokine release syndrome and neurotoxicity related to CAR-T cell therapy (2018)

Severe cytokine release syndrome (CRS) and neurotoxicity following chimeric antigen receptor T cell (CAR-T) therapy can be life-threatening in some cases, and management of those toxicities is still a great challenge for physicians. Researchers hope to understand the pathophysiology of CRS and neurotoxicity, and identify predictive biomarkers that can forecast those toxicities in advance. Some risk factors for severe CRS and/or neurotoxicity including patient and treatment characteristics have been identified in multiple clinical trials of CAR-T cell therapy. Moreover, several groups have identified some predictive biomarkers that are able to determine beforehand which patients may suffer severe CRS and/or neurotoxicity during CAR-T cell therapy, facilitating testing of early intervention strategies for those toxicities. However, further studies are needed to better understand the biology and related risk factors for CRS and/or neurotoxicity, and determine if those identified predictors can be extrapolated to other series. Herein, we review the pathophysiology of CRS and neurotoxicity, and summarize the progress of predictive biomarkers to improve CAR-T cell therapy in cancer.
On the Mechanism of Palladium-Catalyzed Aromatic C−H Oxidation (2010)

The mechanism of Pd-catalyzed aromatic C-H oxidation chemistry continues to be vigorously discussed. Historically, Pd(II)/Pd(IV) catalysis cycles have been proposed. Herein, we present a detailed study of Pd(OAc)(2)-catalyzed aromatic C-H chlorination and propose dinuclear Pd(III) complexes as intermediates. We have identified a succinate-bridged dinuclear Pd(II) complex, which self-assembles during catalysis, as the catalyst resting state. In situ monitoring of catalysis has revealed that chlorination proceeds with turnover-limiting oxidation of a dinuclear resting state, and that acetate ions, liberated during the formation of the catalyst resting state, catalyze the bimetallic oxidation. Informed by reaction kinetics analysis, relevant dinuclear Pd(III) complexes have been prepared and observed to undergo selective C-Cl reductive elimination. Based on the combination of kinetic data obtained during catalysis and explicit structural information of relevant intermediates, we propose a Pd(II)(2)/Pd(III)(2) catalysis cycle for Pd(OAc)(2)-catalyzed aromatic C-H chlorination.
Feedback Linearization of RF Power Amplifiers (2004)

Improving the performance of the power amplifier is the most pressing problem facing designers of modern radio-frequency (RF) transceivers. Linearity and power efficiency of the transmit path are of utmost importance, and the power amplifier has proven to be the bottleneck for both. High linearity enables transmission at the highest data rates for a given channel bandwidth, and power efficiency prolongs battery lifetime in portable units and reduces heat dissipation in high-power transmitters. Cartesian feedback is a power amplifier linearization technique that acts to soften the tradeoff between power efficiency and linearity in power amplifiers. Despite its compelling, fundamental advantages, the technique has not enjoyed widespread acceptance because of certain implementation difficulties. Feedback Linearization of RF Power Amplifiers introduces new techniques for overcoming the challenges faced by the designer of a Cartesian feedback system. The theory of the new techniques are described and analyzed in detail. The book culminates with the results of the first known fully integrated Cartesian feedback power amplifier system, whose design was enabled by the techniques described. Feedback Linearization of RF Power Amplifiers is a valuable reference work for engineers in the telecommunications industry, industry researchers, academic researchers
Demonstration of quantum error correction using linear optics (2005)

We describe a laboratory demonstration of a quantum error correction procedure that can correct intrinsic measurement errors in linear-optics quantum gates. The procedure involves a two-qubit encoding and fast feed-forward-controlled single-qubit operations. In our demonstration the qubits were represented by the polarization states of two single-photons from a parametric down-conversion source, and the real-time feed-forward control was implemented using an electro-optic device triggered by the output of single-photon detectors.
Substrate Hydrolysis by Matrix Metalloproteinase-9* (2001)

The catalytic clefts of all matrix metalloproteinases (MMPs) have a similar architecture, raising questions about the redundancy in substrate recognition across the protein family. In the present study, an unbiased phage display strategy was applied to define the substrate recognition profile of MMP-9. Three groups of substrates were identified, each occupying a distinct set of subsites within the catalytic pocket. The most prevalent motif contains the sequence Pro-X-X-Hy-(Ser/Thr) at P(3) through P(2'). This sequence is similar to the MMP cleavage sites within the collagens and is homologous to substrates the have been selected for other MMPs. Despite this similarity, most of the substrates identified here are selective for MMP-9 over MMP-7 and MMP-13. This observation indicates that substrate selectivity is conferred by key subsite interactions at positions other than P(3) and P(1'). This study shows that MMP-9 has a unique preference for Arg at both P(2) and P(1), and a preference for Ser/Thr at P(2'). Substrates containing the consensus MMP-9 recognition motif were used to query the protein data bases. A surprisingly limited list of putative physiologic substrates was identified. The functional implications of these proteins lead to testable hypotheses regarding physiologic substrates for MMP-9.
Histone Tails: Ideal Motifs for Probing Epigenetics through Chemical Biology Approaches (2010)

Post-translational modifications (PTMs) on histone proteins have emerged as a central theme in the regulation of gene expression and other chromatin-associated processes. The discovery that certain protein domains can recognize acetylated and methylated lysine residues of histones has spurred efforts to uncover and characterize histone PTM-binding proteins. In this task, chromatin biology has strongly benefited from synthetic approaches stemming from chemical biology. Peptide-based techniques have been instrumental in identifying histone mark-binding proteins and analyzing their binding specificities. To explore how histone PTMs carry out their function in the context of chromatin, reconstituted systems based on recombinant histones carrying defined modifications are increasingly being used. They constitute promising tools to analyze mechanistic aspects of histone PTMs, including their role in transcription and their transmission in replication. In this review, we present strategies that have been used successfully to investigate the role of histone modifications, concepts that have emerged from their application, and their potential to contribute to current developments in the field.
Effect of Surfactants on Wetting of Super-Hydrophobic Surfaces (2004)

The effect of surfactants on wetting behavior of super-hydrophobic surfaces was investigated. Super-hydrophobic surfaces were prepared of alkylketene dimer (AKD) by casting the AKD melt in a specially designed mold. Time-dependent studies were carried out, using the axisymmetric drop shape analysis method for contact angle measurement of pure water on AKD surfaces. The results show that both advancing and receding contact angles of water on the AKD surfaces increase over time (∼3 days) and reach the values of about 164 and 147°, respectively. The increase of contact angles is due to the development of a prickly structure on the surface (verified by scanning electron microscopy), which is responsible for its super-hydrophobicity. Aqueous solutions of sodium acetate, sodium dodecyl sulfate, hexadecyltrimethylammonium bromide, and n-decanoyl-n-methylglucamine were used to investigate the wetting of AKD surfaces. Advancing and receding contact angles for various concentrations of different surfactant solutions were measured. The contact angle results were compared to those of a number of pure liquids with surface tensions similar to those of surfactant solutions. It was found that although the surface tensions of pure liquids and surfactant solutions at high concentrations are similar, the contact angles are very different. Furthermore, the usual behavior of super-hydrophobic surfaces that turn super-hydrophilic when the intrinsic contact angle of liquid on a smooth surface (of identical material) is below 90° was not observed in the presence of surfactants. The difference in the results for pure liquids and surfactant solutions is explained using an adsorption hypothesis.
Probing Single Molecule Dynamics (1994)

The room temperature dynamics of single sulforhodamine 101 molecules dispersed on a glass surface are investigated on two different time scales with near-field optics. On the 10(-2)- to 10(2)-second time scale, intensity fluctuations in the emission from single molecules are examined with polarization measurements, providing insight into their spectroscopic properties. On the nanosecond time scale, the fluorescence lifetimes of single molecules are measured, and their excited-state energy transfer to the aluminum coating of the near-field probe is characterized. A movie of the time-resolved emission demonstrates the feasibility of fluorescence lifetime imaging with single molecule sensitivity, picosecond temporal resolution, and a spatial resolving power beyond the diffraction limit.