gebhart/patrepeval huggingface dataset:
Structural and Biophysical Characterization of the 40 kDa PEG−Interferon-α2aand Its Individual Positional Isomers (2005)

The human recombinant Interferon-alpha(2a) (IFNalpha(2a)) is a potent drug (Roferon-A) to treat various types of cancer and viral diseases including Hepatitis B/C infections. To improve the pharmacological properties of the drug, a new pegylated form of IFNalpha(2a) was developed (PEGASYS). This 40 kDa PEG-conjugated IFNalpha(2a) ((40)PEG-IFNalpha(2a)) is obtained by the covalent binding of one 40 kDa branched PEG-polymer to a lysine side chain of IFNalpha(2a). (40)PEG-IFNalpha(2a) is a mixture of mainly six monopegylated positional isomers modified at K31, K134, K131, K121, K164, and K70, respectively. Here we report the detailed structural and biophysical characterization of (40)PEG-IFNalpha(2a) and its positional isomers, in comparison with IFNalpha(2a), using NMR spectroscopy, analytical ultracentrifugation, circular dichroism, fluorescence spectroscopy, and differential scanning calorimetry. Our results show that the three-dimensional structure of IFNalpha(2a) is not modified by the presence of the polymer in all positional isomers constituting (40)PEG-IFNalpha(2a). Regardless of where the PEG-polymer is attached, it adopts a very mobile and flexible random coil conformation, producing a shield for the protein without a permanent coverage of the protein surface. Hydrodynamic data indicate that the protein-attached PEG has a slightly more compact random-coil structure than the free PEG-polymer. Our results also provide evidence of significant structural and physicochemical advantages conferred by the pegylation: increase of the effective hydrodynamic volume and modification of the molecular shape, higher temperature stability, and reduced tendency for aggregation. These results are of tremendous pharmacological interest and benefit as was clinically shown with PEGASYS. This study constitutes a new standard for the characterization of pegylated proteins and enables an important step toward the understanding on a molecular level of the binding of (40)PEG-IFNalpha(2a) and its positional isomers to its cellular receptors.
Friendship characteristics and activity patterns of adolescents with an autism spectrum disorder (2011)

This study compared perceptions of adolescents' friendships between adolescents with an autism spectrum disorder (ASD) and their parents, examined factors associated with friendship qualities, and investigated the adolescents' reports on the activities they did with friends and how activity patterns differed by gender. Ninety-one adolescents with an ASD and their parents completed mail-based surveys during the summer months. Adolescents with an ASD identified more friends than did their parents, but they agreed on the friends' characteristics. About half of the adolescents spent an average of 4 hours per day with friends during the summer months. Male adolescents with an ASD most frequently played video games with friends, whereas females most frequently had conversations with friends. The findings suggest that adolescents with an ASD and their parents identify different peers as the adolescent's friends. The findings also reveal similarities and differences in friendships between adolescents with an ASD and typically developing adolescents.
Optical Computation with Negative Light Intensity with a Plastic Bacteriorhodopsin Film (1997)

The inability to use light intensity to represent negative values limits the potential of optical computing. The protein bacteriorhodopsin, an optically switchable bistable material, was used to represent an image as a local concentration of one of its two states. Light of one wavelength increased this concentration and represented positive intensity, whereas light of a different wavelength decreased the concentration and represented negative intensity. Optical subtraction was demonstrated by performing the mathematical operation of a difference of Gaussians. The electro-optical characteristics of bacteriorhodopsin films portend a variety of practical applications for this system.
OnabotulinumtoxinA Displays Greater Biological Activity Compared to IncobotulinumtoxinA, Demonstrating Non-Interchangeability in Both In Vitro and In Vivo Assays (2020)

Differences in botulinum neurotoxin manufacturing, formulation, and potency evaluation can impact dose and biological activity, which ultimately affect duration of action. The potency of different labeled vials of incobotulinumtoxinA (Xeomin<sup>®</sup>; 50 U, 100 U, or 200 U vials; incobotA) versus onabotulinumtoxinA (BOTOX<sup>®</sup>; 100 U vial; onabotA) were compared on a unit-to-unit basis to assess biological activity using in vitro (light-chain activity high-performance liquid chromatography (LCA-HPLC) and cell-based potency assay (CBPA)) and in vivo (rat compound muscle action potential (cMAP) and mouse digit abduction score (DAS)) assays. Using LCA-HPLC, incobotA units displayed approximately 54% of the protease activity of label-stated equivalent onabotA units. Lower potency, reflected by higher EC<sub>50</sub>, ID<sub>50</sub>, and ED<sub>50</sub> values (pooled mean ± SEM), was displayed by incobotA compared to onabotA in the CBPA (EC<sub>50</sub>: incobotA 7.6 ± 0.7 U/mL; onabotA 5.9 ± 0.5 U/mL), cMAP (ID<sub>50</sub>: incobotA 0.078 ± 0.005 U/rat; onabotA 0.053 ± 0.004 U/rat), and DAS (ED<sub>50</sub>: incobotA 14.2 ± 0.5 U/kg; onabotA 8.7 ± 0.3 U/kg) assays. Lastly, in the DAS assay, onabotA had a longer duration of action compared to incobotA when dosed at label-stated equivalent units. In summary, onabotA consistently displayed greater biological activity than incobotA in two in vitro and two in vivo assays. Differences in the assay results do not support dose interchangeability between the two products.
High power gaas MMIC switches with planar semi-insulated-gate fets (SIGFETs) (2005)

Planar-structured GaAs MMIC switches with Semi-Insulated-Gate FETS (SIGFETs) as the control elements demonstrated 4.8dB higher power handling capability (1dB signal compression) than compatible GaAS MMIC switches with conventional recessed-gate FETs. This improved power performance is chiefly due to the semi-insulated layer under the gate, which allows higher gate breakdown voltages. The semi-insulated layer was fabricated with low energy boron ion implantation in a completely planar,
Double-Hit Diffuse Large B-Cell Lymphoma (2012)

Article Tools ONCOLOGY GRAND ROUNDS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2012.43.5800 Journal of Clinical Oncology - published online before print September 4, 2012 PMID: 22949152 Double-Hit Diffuse Large B-Cell Lymphoma Jonathan W. FriedbergxJonathan W. FriedbergSearch for articles by this author Show More University of Rochester, Rochester, NY https://doi.org/10.1200/JCO.2012.43.5800 First Page Full Text PDF Figures and Tables © 2012 by American Society of Clinical Oncology
Site-Directed RNA Editing in Vivo Can Be Triggered by the Light-Driven Assembly of an Artificial Riboprotein (2015)

Site-directed RNA editing allows for the manipulation of RNA and protein function by reprogramming genetic information at the RNA level. For this we assemble artificial RNA-guided editases and demonstrate their transcript repair activity in cells and in developing embryos of the annelid Platynereis dumerilii. A hallmark of our assembly strategy is the covalent attachment of guideRNA and editing enzyme by applying the SNAP-tag technology, a process that we demonstrate here to be readily triggered by light in vitro, in mammalian cell culture, and also in P. dumerilii. Lacking both sophisticated chemistry and extensive genetic engineering, this technology provides a convenient route for the light-dependent switching of protein isoforms. The presented strategy may also serve as a blue-print for the engineering of addressable machineries that apply tailored nucleic acid analogues to manipulate RNA or DNA site-specifically in living organisms.
GTP cyclohydrolase I gene transfer augments intracellular tetrahydrobiopterin in human endothelial cells: effects on nitric oxide synthase activity, protein levels and dimerisation (2002)

These findings suggest that GTPCH gene transfer is a valid approach to increase BH4 levels in human endothelial cells, and provide new evidence for the relative importance of different mechanisms underlying BH4-mediated eNOS regulation in intact human endothelial cells. Additionally, these observations suggest that GTPCH may be a rational target to augment endothelial BH4 and normalise eNOS activity in endothelial dysfunction states.
Localization and quantification of mRNA for matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in human benign and malignant prostatic tissue (2000)

BACKGROUND The family of matrix metalloproteinases (MMPs) has been shown to be involved in proteolytic degradation of the extracellular matrix, which is an essential step in tumor invasion and metastasis. MMPs are tightly regulated by the levels of active enzymes and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). MMP-2 and its ratio to TIMP-2 have been associated with tumor recurrence and progression in a number of human malignancies. METHODS We examined the relationship between MMP-2 and TIMP-2 mRNA expression in 42 men with malignant (n = 32) and benign (n = 10) prostates using nonisotopic in situ hybridization and Northern blot analysis. RESULTS mRNA for MMP-2 and TIMP-2 was localized to the malignant epithelial cells of both high- and low-grade tumors in the periphery of the glands and in areas of extracapsular involvement, and to the glandular epithelium in the benign prostates. Using Northern blot analysis, the mean MMP-2 to TIMP-2 ratio was approximately one in the benign prostates and low-grade and -stage cancers. The MMP-2 to TIMP-2 ratio increased to 3.3 in the high-grade and 2.8 in the high-stage tumors. CONCLUSIONS The results suggest a close association between MMP-2/TIMP-2 expression and local tumor invasion, with a disruption in expression of the two genes leading to disease progression. Future studies should focus on the activity of these enzymes and on the ratio of enzyme/inhibitor expression, which may become a useful prognostic marker in prostate cancer. Prostate 42:18–25, 2000. © 2000 Wiley-Liss, Inc.
Computer-Assisted Intra-Operative Magnetic Resonance Imaging Monitoring of Interstitial Laser Therapy in the Brain: A Case Report (1998)

Hardware and software for a customized system to use magnetic resonance imaging (MRI) to noninvasively monitor laser-induced interstitial thermal therapy of brain tumors are reported. An open-configuration interventional MRI unit was used to guide optical fiber placement and monitor the deposition of laser energy into the targeted lesion. T1-weighted fast spin echo and gradient echo images were used to monitor the laser tissue interaction. The images were transferred from the MRI scanner to a customized research workstation and were processed intraoperatively. Newly developed software enabled rapid (27-221 ms) availability of calculated images. A case report is given showing images which reveal the laser-tissue interaction. The system design is feasible for on-line monitoring of interstitial laser therapy. © 1998 Society of Photo-Optical Instrumentation Engineers.
What aspects of periods are most bothersome for women reporting heavy menstrual bleeding? Community survey and qualitative study (2007)

Women with heavy periods are bothered by a range of menstrual symptoms and their impact on everyday life. Clinical emphasis should be on clarifying the presenting problem and providing help and advice for this, as well as on excluding serious disease. Sometimes simple approaches, such as help with analgesia, may be all that is required.
Optical Properties of Short Range Ordered Arrays of Nanometer Gold Disks Prepared by Colloidal Lithography (2003)

The optical properties of gold nanodisk arrays prepared by colloidal lithography are studied experimentally. The arrays exhibit short range translational order and weak interparticle interactions. Tunable localized surface plasmon resonances are achieved by varying the diameter of the disks at constant disk height. The macroscopic optical properties are well-described by modeling the gold disks as oblate spheroids in the electrostatic limit. The optical sensing capabilities of the disks are investigated by varying the surrounding refractive index. It is found, in agreement with theory, that more oblate disk shapes have higher sensitivity. This suggests that nanodisks prepared by colloidal lithography are of interest as substrates for optimizing optical biosensing methods at the nanometer scale.
SQUID BIOLUMINESCENCE II. ISOLATION FROM WATASENIA SCINTILLANS AND SYNTHESIS OF 2-(p-HYDROXYBENZYL)-6-(p-HYDROXYPHENYL)-3,7-DIHYDROIMIDAZO[1,2-a]PYRAZIN-3-ONE (1975)

Abstract 2-(p-Hydroxybenzyl)-6-(p-hydroxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin-3-one was isolated from the squid, Watasenia scintillans. Its structure was determined by synthesis. It is considered to be a precursor of hitherto unknown Watasenia luciferin or photoprotein.
Spike-Timing-Dependent Hebbian Plasticity as Temporal Difference Learning (2001)

A spike-timing-dependent Hebbian mechanism governs the plasticity of recurrent excitatory synapses in the neocortex: synapses that are activated a few milliseconds before a postsynaptic spike are potentiated, while those that are activated a few milliseconds after are depressed. We show that such a mechanism can implement a form of temporal difference learning for prediction of input sequences. Using a biophysical model of a cortical neuron, we show that a temporal difference rule used in conjunction with dendritic backpropagating action potentials reproduces the temporally asymmetric window of Hebbian plasticity observed physio-logically. Furthermore, the size and shape of the window vary with the distance of the synapse from the soma. Using a simple example, we show how a spike-timing-based temporal difference learning rule can allow a network of neocortical neurons to predict an input a few milliseconds before the input's expected arrival.
Do corticotropin releasing factor-1 receptors influence colonic transit and bowel function in women with irritable bowel syndrome? (2009)

Corticotropin releasing factor (CRF), a mediator of stress response, alters gastrointestinal (GI) functions. Stress-related changes in colonic motility are blocked by selective CRF(1) receptor antagonists. Our aim was to assess whether modulation of central and peripheral CRF(1) receptors affects colonic transit and bowel function in female patients with diarrhea-predominant irritable bowel syndrome (D-IBS). This randomized, double-blind, placebo-controlled, 2-wk study evaluated the effects of oral pexacerfont (BMS-562086), a selective CRF(1) receptor antagonist, 25 and 100 mg qd, on GI and colonic transit of solids [by validated scintigraphy with primary end point colonic geometric center (GC) at 24 h] and bowel function (by validated daily diaries) in 39 women with D-IBS. The 100-mg dose was comparable to a dose that inhibited colonic motility in stressed rats. Treatment effects were compared by analysis of covariance with baseline colonic transit as covariate. The study had 80% power (alpha = 0.05) to detect clinically meaningful (26%) differences in colonic transit. Thirty-nine of 55 patients fulfilled eligibility criteria (9 screen failures, 5 baseline GC24 outside prespecified range). At baseline, three treatment groups had comparable age, body mass index, and GC 24 h. Significant effects of pexacerfont relative to placebo were not detected on colonic GC24 (P = 0.53), gastric emptying, orocecal transit, ascending colon emptying half-time, and stool frequency, consistency, and ease of passage. No safety issues were identified. We conclude that in women with D-IBS, pexacerfont, 25 or 100 mg qd, does not significantly alter colonic or other regional transit or bowel function. The role of central and peripheral CRF(1) receptors in bowel function in D-IBS requires further study.
Enantioselective biotransformation of pentoxifylline into lisofylline using wine yeast biocatalysis. (2007)

Lisofylline (1-(5-R-hydroxyhexyl)-3,5-dimethylxanthine (LSF)) is a new methylxanthine, a stereospecific isomer which is a metabolite of pentoxifylline (1-(5-oxohexyl)-3,5-dimethylxanthine (PTX)). Alcohol dehydrogenases (E.C. 1.1.X.Y.) are enzymes that catalyze the oxidation and reduction of hydroxyl and carbonyl compounds. They may be employed either as crude or purified enzymes or as components of whole cells. The aim of this study was to explore the stereoselective bioreduction of PTX in the presence of whole cell baker's and wine yeasts, which function as biocatalysts in the production of LSF. The experiments were conducted in water and a number of organic solvents (toluene, hexane, ethyl acetate), and we obtained LSF with different yields and ee values. Our research demonstrated that the highest activity is shown when the KKPU strain is used in an aqueous medium. The biotransformation of PTX into LSF in this case was characterized by high yield and enantioselectivity: 95% and ee = 98%, respectively.
Highly Regioselective [2 + 2 + 2] Cycloaddition of Terminal Alkynes Catalyzed by η6-Arene Complexes of Titanium Supported by Dimethylsilyl-Bridged p-tert-Butyl Calix[4]arene Ligand (2000)

Two new Ti−η6-arene complexes [(DMSC)Ti{η6-1,2,4-C6H3(SiMe3)3}] (6) and [(DMSC)Ti{η6-1,3,5-C6H3But3}] (7) containing 1,2-alternate, Me2Si-bridged p-tert-butylcalix[4]arene (DMSC) ancillary ligand have been synthesized. The solid-state structure of 6 revealed a highly folded arene ligand [with a dihedral angle of 29.7(7)°] and suggests that 6 is better described as a 7-titananorbornadiene species. Both 6 and 7 are efficient catalysts for highly regioselective [2 + 2 + 2] cycloaddition of terminal alkynes to yield 1,2,4-substituted benzenes. Kinetic studies of the catalytic [2 + 2 + 2] cycloaddition of Me3SiC⋮CH revealed first-order dependence on [6] and [Me3SiC⋮CH]; and activation parameters, ΔH⧧ = 14 kcal/mol, and ΔS⧧ = −11 cal/mol K, that are consistent with an associative mechanism. The reaction rate is influenced by the steric requirements of both the alkyne and the η6-arene compound. The high selectivity for 1,2,4-substituted benzene may be understood in terms of the directing influence of the DMSC ligand.
Throughput for packet radio networks with dynamic power levels (1984)

A packet radio network consists of a set of computers whose intercommunication needs are served by mobile radios. In this work, relatively simple models are used to determine attainable throughputs in such networks under a variety of routing scheduling strategies. In particular, we assume uniform traffic requirements between all pairs of nodes and an idealized capture effect. Through the derivation and numerical solution of a differential equation, it is shown that a large network of nodes which are uniformly spaced along a line and which uses slotted-Aloha channel access can attain a throughput of 2.05/e if its transmitters can dynamically adjust their power, as opposed to a 1/e throughput attainable in fixed-power networks.
A Neuron-Silicon Junction: A Retzius Cell of the Leech on an Insulated-Gate Field-Effect Transistor (1991)

An identified neuron of the leech, a Retzius cell, has been attached to the open gate of a p-channel field-effect transistor. Action potentials, spontaneous or stimulated, modulate directly the source-drain current in silicon. The electronic signals match the shape of the action potential. The average voltage on the gate was up to 25 percent of the intracellular voltage change. Occasionally weak signals that resemble the first derivative of the action potential were observed. The junctions can be described by a model that includes capacitive coupling of the plasma membrane and the gate oxide and that accounts for variable resistance of the seal.
A simple and accurate method to measure the threshold voltage of an enhancement-mode MOSFET (1982)

A new, simple method to measure the V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</inf> of an enhancement-mode MOSFET has been developed based on the analytical model of the subthreshold current. V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</inf> is determined to be the gate voltage at which the I <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DS</inf> reaches the constant threshold current, and this method is accurate over a wide range of device dimensions, bias conditions, and operating temperatures.
The application of the linear-quadratic dose-effect equation to fractionated and protracted radiotherapy (1985)

The linear-quadratic (LQ) dose-effect formalism is currently providing new perspectives into the ways in which alterations in the dose per fraction in conventional radiotherapy may be used to bring about improved results with respect to early or late normal tissue reactions. In this paper, using a model initially developed by Roesch, the LQ equations are explored further in terms of dose-rate rather than dose. By the incorporation of one other parameter, mu, which relates to the rate of repair of sub-lethal radiation damage, a more general formalism is obtained. In particular, equations are derived which can be used to examine the relative effectiveness of different treatment regimes, including those involving decaying sources. Such equations are of wider applicability than other LQ derivations which relate only to dose-response relationships. The extended equations, which are fully consistent with the existing LQ method, are also shown to lead directly to other independently established, relationships for protracted irradiation. The nature of the link between high and low dose-rate treatments is discussed, and some worked examples provide indications of how the new equations may be used to assess further the potential clinical benefits of low dose-rate treatments and permanent implants.
Batch fabrication of carbon nanotube bearings (2007)

Relative displacements between the atomically smooth, nested shells in multiwalled carbon nanotubes (MWNTs) can be used as a robust nanoscale motion enabling mechanism. Here, we report on a novel method suited for structuring large arrays of MWNTs into such nanobearings in a parallel fashion. By creating MWNT nanostructures with nearly identical electrical circuit resistance and heat transport conditions, uniform Joule heating across the array is used to simultaneously engineer the shell geometry via electric breakdown. The biasing approach used optimizes process metrics such as yield and cycle-time. We also present the parallel and piecewise shell engineering at different segments of a single nanotube to construct multiple, but independent, high density bearings. We anticipate this method for constructing electromechanical building blocks to be a fundamental unit process for manufacturing future nanoelectromechanical systems (NEMS) with sophisticated architectures and to drive several nanoscale transduction applications such as GHz-oscillators, shuttles, memories, syringes and actuators.