gebhart/patrepeval huggingface dataset:
Microtubule dynamics in nerve cells: analysis using microinjection of biotinylated tubulin into PC12 cells. (1988)

To study microtubule (MT) dynamics in nerve cells, we microinjected biotin-labeled tubulin into the cell body of chemically fused and differentiated PC12 cells and performed the immunofluorescence or immunogold procedure using an anti-biotin antibody followed by secondary antibodies coupled to fluorescent dye or colloidal gold. Incorporation of labeled subunits into the cytoskeleton of neurites was observed within minutes after microinjection. Serial electron microscopic reconstruction revealed that existing MTs in PC12 neurites incorporated labeled subunits mainly at their distal ends and the elongation rate of labeled segments was estimated to be less than 0.3 micron/min. Overall organization of MTs in the nerve cells was different from that in undifferentiated cells such as fibroblasts. Namely, we have not identified any MT-organizing centers from which labeled MTs are emanating in the cell bodies of the injected cells. Stereo electron microscopy revealed that some fully labeled segments seemed to start in the close vicinity of electron dense material within the neurites. This suggests new nucleation off some structures in the neurites. We have also studied the overall pattern of the incorporation of labeled subunits which extended progressively from the proximal part of the neurites toward their tips. To characterize the mechanism of tubulin incorporation, we have measured mean density of gold labeling per unit length of labeled segments at different parts of the neurites. The results indicate access of free tubulin subunits into the neurites and local incorporation into the neurite cytoskeleton. Our results lead to the conclusion that MTs are not static polymers but dynamic structures that continue to elongate even within the differentiated nerve cell processes.
Synthesis of Unsymmetrical Biaryls by Palladium-Catalyzed Cross Coupling Reactions of Arenes with Tetrabutylammonium Triphenyldifluorosilicate, a Hypervalent Silicon Reagent (1999)

Palladium-catalyzed cross coupling of arenes with tetrabutylammonium triphenyldifluorosilicate, a hypervalent silicon reagent, to give unsymmetrical biaryls is reported. The Pd(0)-catalyzed process proceeds in good yield with aryl iodides, most aryl triflates, and electron-deficient aryl bromides.
The Morphology of the Specialized Atrioventricular Junctional Area: The Evolution of Understanding (2002)

Although knowledge of its existence has barely exceeded one century, the anatomic pathway for conduction of the cardiac impulse from atria to ventricles has been the source of much controversy, controversy that continues to the present day. This article describes how attention to the original descriptions, along with adherence for sensible definitions for the histological distinction of conduction tissues, could have defused many of these disagreements. One of the problems with the initial descriptions was that they were written in German. Even this is no longer a problem, since the major text devoted to the topic has recently been translated into English, and is now available for all to study. This key work was the monograph produced by Sunao Tawara, a Japanese pathologist who studied in the first decade of the 20th century in the laboratory of Ludwig Aschoff. Tawara showed that the atrial impulse was conducted to the ventricular myocardium by a solitary pathway of specialized myocardium. He likened this pathway to a tree, with its roots in the base of the atrial septum, and its branches straddling the crest of the muscular ventricular septum. Significantly, he showed that the pathway became insulated as it crossed from atrial to ventricular musculatures, and suggested that the point at which the muscle became engulfed in fibrous tissue should be taken as the boundary between the "knoten," or atrioventricular node, and the penetrating bundle described earlier by Wilhelm His. The authors' findings are entirely compatible with the account given by Tawara. Like Tawara, they recognize atrial transitional cells, a compact node, the penetrating bundle, and the ventricular conduction pathways as the segments of the conduction axis which can be considered to represent the specialized atrioventricular junction.
Length and structural effect of signal peptides derived from<i>Bacillus subtilis</i>α-amylase on secretion of<i>Escherichja coli</i>β-lactamase in B.<i>subtilis</i>cells (1984)

The precursor of Bacillus subtilis alpha-amylase contains an NH2-terminal extension of 41 amino acid residues as the signal sequence. The E. coli beta-lactamase structural gene was fused with the DNA for the promoter and signal sequence regions. Activity of beta-lactamase was expressed and more than 95% of the activity was secreted into the culture medium. DNA fragments coding for short signal sequences 28, 31, and 33 amino acids from the initiator Met were prepared and fused with the beta-lactamase structural gene. The sequences of 31 and 33 amino acid residues with Ala COOH-terminal amino acid were able to secrete active beta-lactamase from B. subtilis cells. However beta-lactamase was not secreted into the culture medium by the shorter signal sequence of 28 amino acid residues, which was not cleaved. Molecular weight analysis of the extracellular and cell-bound beta-lactamase suggested that the signal peptide of B. subtilis alpha-amylase was the first 31 amino acids from the initiator Met. The significance of these results was discussed in relation to the predicted secondary structure of the signal sequences.
A real-time fluorescence method for enzymatic characterization of specialized human DNA polymerases (2009)

Specialized DNA polymerases are involved in DNA synthesis during base-excision repair and translesion synthesis across a wide range of chemically modified DNA templates. Notable features of these enzymes include low catalytic efficiency, low processivity and low fidelity. Traditionally, in vitro studies of these enzymes have utilized radiolabeled substrates and gel electrophoretic separation of products. We have developed a simple homogeneous fluorescence-based method to study the enzymology of specialized DNA polymerases in real time. The method is based on fluorescent reporter strand displacement from a tripartite substrate containing a quencher-labeled template strand, an unlabeled primer and a fluorophore-labeled reporter. With this method, we could follow the activity of human DNA polymerases beta, eta, iota and kappa under different reaction conditions, and we investigated incorporation of the aberrant nucleotide, 8-oxodGTP, as well as bypass of an abasic site or 8-oxoG DNA template lesion in different configurations. Lastly, we demonstrate that the method can be used for small molecule inhibitor discovery and characterization in highly miniaturized settings, and we report the first nanomolar inhibitors of Y-family DNA polymerases iota and eta. The fluorogenic method presented here should facilitate mechanistic and inhibitor investigations of these polymerases and is also applicable to the study of highly processive replicative polymerases.
Scanning mutagenesis of the putative transmembrane segments of K <sub>ir</sub> 2.1, an inward rectifier potassium channel (1997)

Structural models of inward rectifier K+ channels incorporate four identical or homologous subunits, each of which has two hydrophobic segments (M1 and M2) which are predicted to span the membrane as alpha helices. Since hydrophobic interactions between proteins and membrane lipids are thought to be generally of a nonspecific nature, we attempted to identify lipid-contacting residues in Kir2.1 as those which tolerate mutation to tryptophan, which has a large hydrophobic side chain. Tolerated mutations were defined as those which produced measurable inwardly rectifying currents in Xenopus oocytes. To distinguish between water-accessible positions and positions adjacent to membrane lipids or within the protein interior we also mutated residues in M1 and M2 individually to aspartate, since an amino acid with a charged side chain should not be tolerated at lipid-facing or interior positions, due to the energy cost of burying a charge in a hydrophobic environment. Surprisingly, 17 out of 20 and 17 out of 22 non-tryptophan residues in M1 and M2, respectively, tolerated being mutated to tryptophan. Moreover, aspartate was tolerated at 15 out of 22 and 15 out of 21 non-aspartate M1 and M2 positions respectively. Periodicity in the pattern of tolerated vs. nontolerated mutations consistent with alpha helices or beta strands did not emerge convincingly from these data. We consider the possibility that parts of M1 and M2 may be in contact with water.
Applicability of the Access Node Control Mechanism to Broadband Networks Based on Passive Optical Networks (PONs) (2013)

The purpose of this document is to provide applicability of the Access
Node Control Mechanism to broadband access based on Passive Optical
Networks (PONs). The need for an Access Node Control Mechanism between
a Network Access Server (NAS) and an Access Node Complex, composed of
a combination of Optical Line Termination (OLT) and Optical Network
Termination (ONT) elements, is described in a multi-service reference
architecture in order to perform QoS-related, service-related, and
subscriber-related operations. The Access Node Control Mechanism is
also extended for interaction between components of the Access Node
Complex (OLT and ONT). The Access Node Control Mechanism will ensure
that the transmission of information between the NAS and Access Node
Complex (ANX) and between the OLT and ONT within an ANX does not need
to go through distinct element managers but rather uses direct device-
to-device communication and stays on net. This allows for performing
access-link-related operations within those network elements to meet
performance objectives.
Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. (2001)

Some previous studies have reported an improved prognosis in sporadic colon cancers with microsatellite instability, whereas others have not. In addition, relatively few of those reporting an improved prognosis controlled for tumor stage or were population-based. Therefore, we evaluated the relationship between microsatellite instability and prognosis, tumor stage, and other clinical variables in a population-based study of 1026 individuals. Microsatellite instability was determined by the noncoding mononucleotide repeat BAT-26 and the coding mononucleotide repeat in transforming growth factor-beta receptor type II. Significant relationships were seen between microsatellite instability and proximal tumor location, female gender, young and old age at diagnosis, poor histological differentiation, and low tumor stage (P < 0.01). There was a significant relationship between microsatellite instability and improved prognosis, even after adjusting for stage, with a reduction in the risk of death attributable to colon cancer of approximately 60%. Most of this risk reduction occurred in individuals with American Joint Committee on Cancer stage III tumors, although transforming growth factor-beta receptor type II mutations were associated with a significant reduction in colon cancer death in tumors with distant metastases. We conclude that microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level.
MEC-17 Deficiency Leads to Reduced α-Tubulin Acetylation and Impaired Migration of Cortical Neurons (2012)

Neuronal migration is a fundamental process during the development of the cerebral cortex and is regulated by cytoskeletal components. Microtubule dynamics can be modulated by posttranslational modifications to tubulin subunits. Acetylation of α-tubulin at lysine 40 is important in regulating microtubule properties, and this process is controlled by acetyltransferase and deacetylase. MEC-17 is a newly discovered α-tubulin acetyltransferase that has been found to play a major role in the acetylation of α-tubulin in different species in vivo. However, the physiological function of MEC-17 during neural development is largely unknown. Here, we report that MEC-17 is critical for the migration of cortical neurons in the rat. MEC-17 was strongly expressed in the cerebral cortex during development. MEC-17 deficiency caused migratory defects in the cortical projection neurons and interneurons, and perturbed the transition of projection neurons from the multipolar stage to the unipolar/bipolar stage in the intermediate zone of the cortex. Furthermore, knockdown of α-tubulin deacetylase HDAC6 or overexpression of tubulin(K40Q) to mimic acetylated α-tubulin could reduce the migratory and morphological defects caused by MEC-17 deficiency in cortical projection neurons. Thus, MEC-17, which regulates the acetylation of α-tubulin, appears to control the migration and morphological transition of cortical neurons. This finding reveals the importance of MEC-17 and α-tubulin acetylation in cortical development.
Size-Dependent Enhancement of Electrocatalytic Performance in Relatively Defect-Free, Processed Ultrathin Platinum Nanowires (2010)

We report on the synthesis, characterization, and electrocatalytic performance of ultrathin Pt nanowires with a diameter of less than 2 nm. An acid-wash protocol was employed in order to yield highly exfoliated, crystalline nanowires with a diameter of 1.3 +/- 0.4 nm. The electrocatalytic activity of these nanowires toward the oxygen reduction reaction was studied in relation to the activity of both supported and unsupported Pt nanoparticles as well as with previously synthesized Pt nanotubes. Our ultrathin, acid-treated, unsupported nanowires displayed an electrochemical surface area activity of 1.45 mA/cm(2), which was nearly 4 times greater than that of analogous, unsupported platinum nanotubes and 7 times greater than that of commercial supported platinum nanoparticles.
Characterization of the surface structure of CH3 and CF3 terminated <i>n</i>-alkanethiol monolayers self assembled on Au{111} (1998)

Surface elemental and structural characterization of hexadecanethiol and heptadecanethiol (C16 and C17 for short) and 16,16,16-trifluorohexadecanethiol (FC16) self-assembled monolayers (SAMs) on a Au{111} surface have been obtained from time-of-flight scattering and recoiling spectrometry. The clean Au surface was also characterized in order to identify the azimuthal orientation of the SAMs with respect to the substrate. Classical ion trajectory simulations were used to relate the experimental scattering and recoiling data to the surface structure. The scattered and recoiled atoms originate from the outermost five–six atomic layers, and azimuthal anisotropy was observed in the measurements. The results provide a model for the SAMs in which the alkyl chains chemisorb with the S atoms situated above the face-centered-cubic (fcc) threefold sites of the Au{111} surface to form a continuous film with a (√3×√3)R30° structure that fully covers the Au surface. The orientation of the molecular axis azimuth of the SAMs relative to the Au azimuthal directions was determined. The data indicate that the molecular chains have specific tilt and twist angles relative to the Au surface and six coexisting domains resulting from the six equivalent tilt directions of the molecular axis. Dramatic changes in the anisotropic patterns of the ion scattering azimuthal scans from the surfaces of the SAMs with different terminations were observed. These phenomena result from the different tilt angles of the CH3 and CF3 groups. The data are consistent with free rotation of both the CH3 and CF3 groups. The C16 SAM exhibited the best azimuthal features and was more resistant to radiation damage from the incident Ar+ scattering beam than the other films. Due to the tilt angle of the SAMs, an “ion’s eye view” of the structure, i.e., the positions of the atomic cores as experienced by the incoming keV ions, reveals a regular array of sloping cavities within each unit cell.
Instability in Half-Bridge Circuits Switched With Wide Band-Gap Transistors (2013)

Wide band-gap (WBG) field-effect devices are known to provide a system-level performance benefit compared to silicon devices when integrated into power electronics applications. However, the near-ideal features of these switching devices can also introduce unexpected behavior in practical systems due to the presence of parasitic elements. The occurrence of self-sustained oscillation is one such behavior that has not received adequate study in the literature. This paper provides an analytical treatment of this phenomenon by casting the switching circuit as an unintentional negative resistance oscillator. This treatment utilizes an established procedure from the oscillator design literature and applies it to the problem of power circuit oscillation. A simulation study is provided to identify the sensitivity of the model to various parameters, and the predictive value of the model is confirmed by experiment involving two exemplary WBG devices: a SiC vertical-channel JFET and a SiC lateral-channel MOSFET. The results of this study suggest that susceptibility to self-sustained oscillation is correlated to the available power density of the device relative to the parasitic elements in the circuit, for which wide band-gap devices, to include SiC and GaN transistors, are in a class approaching that of the radio frequency domain.
Cyclodextrins and the emergence of sugammadex (2009)

Residual paralysis, with its subsequent postoperative pulmonary sequelae, is one of the major complications of anaesthesia, and was recognised shortly after the introduction of neuromuscular blocking drugs into routine clinical practice. Although its incidence decreased with the introduction of intermediate duration drugs, and further diminished with routine neuromuscular monitoring and reversal with cholinesterase inhibitors, residual paralysis still remained a problem. In the search for alternatives to stop the effect of neuromuscular blocking drugs and to match their duration of action to clinical need, chelation of the non-depolarising neuromuscular blocking drugs was considered. It was recognised that cyclodextrins could encapsulate steroidal molecules and thereby inactivate the aminosteroidal neuromuscular blocking drugs. In order to improve the binding of rocuronium to the cyclodextrin and to increase the compound's water solubility, the molecule was modified. This led to the development of sugammadex (Org 25969), a modified gamma-cyclodextrin. The modification of the molecule and the initial in vitro studies that led to in vivo and later human studies of this conceptually new drug for anaesthesia are described.
An All-Digital Unified Clock Frequency and Switched-Capacitor Voltage Regulator for Variation Tolerance in a Sub-Threshold ARM Cortex M0 Processor (2018)

An all-digital switched-capacitor (SC) based clock frequency (Felk) and supply voltage (V dd) regulator unifies Fclk and Vdd generation into a single control loop to reduce the V dd margin for variations in a sub-threshold ARM Cortex M0 processor. This fully-integrated unified clock and power (Uni-CaP) architecture allows continuous Vdd scalability without a low-dropout (LDO) regulator. Measurements from a 65nm test chip demonstrate a 16% Vdd reduction (94% Vdd margin recovery) and a 3.2× increase in Fclk operating range.
YEATS domain proteins: a diverse family with many links to chromatin modification and transcriptionThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB’s 51st Annual Meeting – Epigenetics and Chromatin Dynamics, and has undergone the Journal’s usual peer review process. (2009)

Chromatin modifications play crucial roles in various biological processes. An increasing number of conserved protein domains, often found in multisubunit protein complexes, are involved in establishing and recognizing different chromatin modifications. The YEATS domain is one of these domains, and its role in chromatin modifications and transcription is just beginning to be appreciated. The YEATS domain family of proteins, conserved from yeast to human, contains over 100 members in more than 70 eukaryotic species. Yaf9, Taf14, and Sas5 are the only YEATS domain proteins in Saccharomyces cerevisiae. Human YEATS domain family members, such as GAS41, ENL, and AF9, have a strong link to cancer. GAS41 is amplified in glioblastomas and astrocytomas; ENL and AF9 are among the most frequent translocation partners of the mixed lineage leukemia (MLL) gene. This review will focus on the best characterized YEATS proteins, discuss their diverse roles, and reflect potential functions of the YEATS domain.
A 300 MHz 16 b BiCMOS video signal processor (1993)

A 300-MHz, 16-b video signal parallel-pipelined processor (VSP3) that features a vector parallel-pipelined architecture, 300-MHz arithmetic units, a 146-kb, 3-ns SRAM (static random-access memory), a PLL (phase-locked loop) and pass-transistor-type BiNMOS circuits is described. The block diagram of the VSP3 is presented, a timing of the parallel-pipelined vector processing is shown, and the H.261 coding algorithm is described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Preclinical Characterization of GLS4, an Inhibitor of Hepatitis B Virus Core Particle Assembly (2013)

Hepatitis B virus (HBV)-associated chronic liver diseases are treated with nucleoside analogs that target the virus polymerase. While these analogs are potent, drugs are needed to target other virus-encoded gene products to better block the virus replication cycle and chronic liver disease. This work further characterized GLS4 and compared it to the related BAY 41-4109, both of which trigger aberrant HBV core particle assembly, where the virus replication cycle occurs. This was done in HepAD38 cells, which replicate HBV to high levels. In vitro, GLS4 was significantly less toxic for primary human hepatocytes (P < 0.01 up to 100 μM), inhibited virus accumulation in the supernantant of HepAD38 cells (P < 0.02 up to 100 nM), inhibited HBV replicative forms in the liver with a significantly lower 50% effective concentration (EC50) (P < 0.02), and more strongly inhibited core gene expression (P < 0.001 at 100 to 200 nM) compared to BAY 41-4109. In vivo characterization was performed in nude mice inoculated with HepAD38 cells, which grew out as tumors, resulting in viremia. Treatment of mice with GLS4 and BAY 41-4109 showed strong and sustained suppression of virus DNA to about the same extents both during and after treatment. Both drugs reduced the levels of intracellular core antigen in the tumors. Alanine aminotransferase levels were normal. Tumor and total body weights were not affected by treatment. Thus, GLS4 was as potent as the prototype, BAY 41-4109, and was superior to lamivudine, in that there was little virus relapse after the end of treatment and no indication of toxicity.
Double negative regulatory T cells in transplantation and autoimmunity: recent progress and future directions (2012)

T lymphocytes bearing the αβ T cell receptor (TCR) but lacking CD4, CD8, and markers of natural killer (NK) cell differentiation are known as 'double-negative' (DN) T cells and have been described in both humans and rodent models. We and others have shown that DN T cells can act as regulatory T cells (Tregs) that are able to prevent allograft rejection, graft-versus-host disease, and autoimmune diabetes. In the last few years, new data have revealed evidence of DN Treg function in vivo in rodents and humans. Moreover, significant advances have been made in the mechanisms by which DN Tregs target antigen-specific T cells. One major limitation of the field is the lack of a specific marker that can be used to distinguish truly regulatory DN T cells (DN Tregs) from non-regulatory ones, and this is the central challenge in the coming years. Here, we review recent progress on the role of DN Tregs in transplantation and autoimmunity, and their mechanisms of action. We also provide some perspectives on how DN Tregs compare with Foxp3(+) Tregs.