gebhart/patrepeval huggingface dataset:
Endogenous TOM20 Proximity Labeling: A Swiss-Knife for the Study of Mitochondrial Proteins in Human Cells (2023)

Biotin-based proximity labeling approaches, such as BioID, have demonstrated their use for the study of mitochondria proteomes in living cells. The use of genetically engineered BioID cell lines enables the detailed characterization of poorly characterized processes such as mitochondrial co-translational import. In this process, translation is coupled to the translocation of the mitochondrial proteins, alleviating the energy cost typically associated with the post-translational import relying on chaperone systems. However, the mechanisms are still unclear with only few actors identified but none that have been described in mammals yet. We thus profiled the TOM20 proxisome using BioID, assuming that some of the identified proteins could be molecular actors of the co-translational import in human cells. The obtained results showed a high enrichment of RNA binding proteins close to the TOM complex. However, for the few selected candidates, we could not demonstrate a role in the mitochondrial co-translational import process. Nonetheless, we were able to demonstrate additional uses of our BioID cell line. Indeed, the experimental approach used in this study is thus proposed for the identification of mitochondrial co-translational import effectors and for the monitoring of protein entry inside mitochondria with a potential application in the prediction of mitochondrial protein half-life.
P3‐295: Pharmacokinetic and pharmacodynamic analysis of the gamma‐secretase modulator (GSM) EVP‐0015962 (2010)

Gamma (γ)-secretase has been characterized as the enzyme responsible for the Aβ C-terminal cleavage, which results in the production of Aβ peptides of various lengths including Aβx-40 (> 80%) and Aβx-42 (˜10%). The latter amyloidogenic Aβ42 is deposited early in the course of Alzheimer's disease (AD) and also readily forms soluble and potent neurotoxic oligomers. In early onset AD, a greater proportion of Aβ42 is formed, strongly implicating it as central to the disease etiology. Selective inhibition of this form of Aβ without the affecting other γ-secretase substrates may represent a disease modifying approach for the treatment of AD, as represented by the novel γ-secretase modulator EVP-0015962. - In-vitro characterization of EVP-0015962, carried out in transfected human cells and in normal rat primary cortical neurons, has shown potent reduction of Aβ42 with a concomitant increase in Aβ38 while total levels of Aβ remain essentially unchanged. These modulatory effects have also been observed in cell extracts enriched for γ-secretase activity and do not inhibit signaling via, e.g., the Notch pathway. In-vivo proof of principle in normal rodents (C57/Bl6 mice and Sprague-Dawley rats) demonstrates that a single orally administered dose of EVP-0015962 will exert the modulatory effect on γ-secretase activity, significantly reducing Aβ42 with a concomitant increase in Aβ38 while maintaining total Aβ at a constant level. These overall effects are qualitatively consistent between brain, CSF, and plasma although the exact magnitude of the effect may differ between the compartments. A full pharmacokinetic- pharmacodynamic (PK-PD) time-course profile has been generated for brain, CSF, and plasma, demonstrating a simple relationship between drug exposure and the Aβ effects. However, analysis suggests a difference in the timing of the appearance of Aβ38 and the reduction of Aβ42 in CSF which may ultimately have significant implications for target engagement/biomarker measurements in clinical trials. Overall, our characterization of the GSM, EVP-0015962, continues to support it's clinical development as a potentially disease modifying agent for the treatment of AD, aimed at the selective reduction of the neurotoxic Aβ42.
Volatilization Behavior of Supported Au Nanoparticle Arrays under H₂ at High Temperature (2020)

The fabrication and experimental study of model Au nanoparticle arrays (nanodots) were used to allow a direct comparison of reactive evaporation at elevated temperatures and nonambient H₂-containing gas atmospheres with theoretical models. Strong temperature and H₂-concentration dependencies were confirmed as expected, and the observed dependence in particle diameter with time was effectively described using a reactive evaporation and gas phase diffusion based quantitative model. Deviations from model expectations for a monolithic film of Au due to nanoparticulate structure were effectively captured by accounting for both (1) the reduced effective surface area of Au on the substrate surface and (2) the enhanced partial vapor pressure of Au-containing species in the vapor phase due to surface energy effects. The approach described here is broadly applicable to the quantitative study of stability in noble and precious metal nanoparticles and thin films for sensing and catalytic applications in harsh environmental conditions.
Enhanced Catalytic Four-Electron Dioxygen (O2) and Two-Electron Hydrogen Peroxide (H2O2) Reduction with a Copper(II) Complex Possessing a Pendant Ligand Pivalamido Group (2013)

A copper complex, [(PV-tmpa)Cu(II)](ClO4)2 (1) [PV-tmpa = bis(pyrid-2-ylmethyl){[6-(pivalamido)pyrid-2-yl]methyl}amine], acts as a more efficient catalyst for the four-electron reduction of O2 by decamethylferrocene (Fc*) in the presence of trifluoroacetic acid (CF3COOH) in acetone as compared with the corresponding copper complex without a pivalamido group, [(tmpa)Cu(II)](ClO4)2 (2) (tmpa = tris(2-pyridylmethyl)amine). The rate constant (k(obs)) of formation of decamethylferrocenium ion (Fc*(+)) in the catalytic four-electron reduction of O2 by Fc* in the presence of a large excess CF3COOH and O2 obeyed first-order kinetics. The k(obs) value was proportional to the concentration of catalyst 1 or 2, whereas the k(obs) value remained constant irrespective of the concentration of CF3COOH or O2. This indicates that electron transfer from Fc* to 1 or 2 is the rate-determining step in the catalytic cycle of the four-electron reduction of O2 by Fc* in the presence of CF3COOH. The second-order catalytic rate constant (k(cat)) for 1 is 4 times larger than the corresponding value determined for 2. With the pivalamido group in 1 compared to 2, the Cu(II)/Cu(I) potentials are -0.23 and -0.05 V vs SCE, respectively. However, during catalytic turnover, the CF3COO(-) anion present readily binds to 2 shifting the resulting complex's redox potential to -0.35 V. The pivalamido group in 1 is found to inhibit anion binding. The overall effect is to make 1 easier to reduce (relative to 2) during catalysis, accounting for the relative k(cat) values observed. 1 is also an excellent catalyst for the two-electron two-proton reduction of H2O2 to water and is also more efficient than is 2. For both complexes, reaction rates are greater than for the overall four-electron O2-reduction to water, an important asset in the design of catalysts for the latter.
A Symbolic System Synthesis Approach for Hard Real-Time Systems Based on Coordinated SMT-Solving (2015)

We propose an SMT-based system synthesis approach where the logic solver performs static binding and routing while the background theory solver computes global time-triggered schedules. In contrast to previous work, we assign additional time to the logic solver in order to refine the binding and routing such that the background theory solver is more likely to find a feasible schedule within a reasonable amount of time. We show by experiments that this coordination of the two solvers results in a considerable reduction of the overall synthesis time.
GUIDELINES FOR PLACEMENT OF LONGITUDINAL BARRIERS ON SLOPES. VOLUME III: GUIDELINES. FINAL REPORT (1984)

This research was undertaken to investigate longitudinal barrier impact performance when placed on nonlevel terrain. Tasks performed in this study included: a determination of typical conditions for which longitudinal barriers are placed on nonlevel terrain; an evaluation of the impact behavior of widely used barrier systems when placed on nonlevel terrain; and the development of guidelines for selection and placement of barriers on nonlevel terrain. This volume, 3rd of 3, describes the development and application of guidelines for placement of longitudinal barriers on nonlevel terrain. Data from full-scale crash tests were used to develop containment criteria for four widely used roadside barrier systems. This containment criteria and HVOSM simulations were then employed to develop barrier placement guidelines. Guidelines are presented for each of three different performance standards and are given in the form of 75 figures.
Nucleate Boiling Enhancements on Porous Graphite and Microporous and Macro–Finned Copper Surfaces (2011)

Enhancements in nucleate boiling heat removal with dielectric liquids, by increasing either the bubbles nucleation sites density and/or the wetted surface area, are desirable for immersion cooling of high-power computer chips. This article presents the results of recent investigations of nucleate boiling enhancement of FC-72, HFE-7100, and PF-5060 dielectric liquids on porous graphite, copper microporous surfaces, and copper surfaces with square corner pins, 3 mm × 3 mm in cross-section and 2, 3, and 5 mm tall. All surfaces have a footprint measuring 10 × 10 mm. These investigations examined the effects of liquid subcooling up to 30 K and surface inclination, from upward-facing to downward-facing, on nucleate boiling heat transfer coefficient and critical heat flux. Natural convection of dielectric liquids for cooling chips while in the stand-by mode, at a surface average heat flux <20 kW/m2, is also investigated for the different surfaces.
Microstructural influence of the thermal behavior of arc deposited TiAlN coatings with high aluminum content (2020)

The influence of the microstructure on the thermal behavior of cathodic arc deposited TiAlN coatings was studied as a function of isothermal annealing. Two compositionally similar but structurally different coatings were compared, a Ti0·34Al0·66N0.96 coating with a fine-grain structure consisting of a mixture of cubic (c) and hexagonal (h) phases, and a Ti0·40Al0·60N0.94 coating with a coarse-grain structure of cubic phase. By in situ wide-angle synchrotron x-ray scattering, spinodal decomposition was confirmed in both coatings. The increased amount of internal interfaces lowered the decomposition temperature by 50 °C for the dual-phase coating. During the subsequent isothermal anneal at 1000 °C, a transformation from c-AlN to h-AlN took place in both coatings. After 50 min of isothermal annealing, atom probe tomography detected small amounts of Al (∼2 at.%) in the c-TiN rich domains and small amounts of Ti (∼1 at.%) in the h-AlN rich domains of the coarse-grained single-phase Ti0·40Al0·60N0.94 coating. Similarly, at the same conditions, the fine-grained dual-phase Ti0·34Al0·66N0.96 coating exhibits a higher Al content (∼5 at.%) in the c-TiN rich domains and higher Ti content (∼15 at.%) in the h-AlN rich domains. The study shows that the thermal stability of TiAlN is affected by the microstructure and that it can be used to tune the reaction pathway of decomposition favorably.
Interference with Tissue Factor Prolongs Intrahepatic Islet Allograft Survival in a Nonhuman Primate Marginal Mass Model (2007)

These data suggest that pretreatment of islets and the recipient with anti-TF may limit the effects of IBMIR, thereby enhancing islet engraftment and survival.
CREATING INTERACTIVE DATA DASHBOARDS TO INFORM WIDENING ACCESS POLICY AND PRACTICE DECISION MAKING AT ULSTER UNIVERSITY (2022)

CREATING INTERACTIVE DATA DASHBOARDS TO INFORM WIDENING ACCESS POLICY AND PRACTICE DECISION MAKING AT ULSTER UNIVERSITY
Chemical exchange effects in the NMR spectra of rotating solids (1986)

We present a theoretical analysis based on Floquet theory describing the effect of intermediate rate exchange on line shapes in magic angle sample spinning (MASS) spectra. As a test case, 13C spectra were obtained of dimethyl sulfone (DMS) from 25–55 °C. DMS exhibits an axially symmetric powder pattern at 25 °C which becomes asymmetric due to 180° flips about the twofold axis bisecting the CH3–S–CH3 angle. As the temperature is increased, the principal effect on the MASS spectrum is a pronounced broadening of both the center and sidebands. Calculated spectra fit the experimental spectra well and provide information on the rate constants and the activation energy for the exchange process. These results extend the line shape methods successfully used to study molecular motion in static samples to include high resolution MASS.
Test algorithms for double-buffered random access and pointer-addressed memories (1993)

Test algorithms for static double-buffered RAMs and pointer-addressed memories (PAMs) are presented. The reasons why test algorithms for single-buffered memories are inadequate to test double-buffered memories (DBMs) are discussed. To obtain a realistic fault model, the authors perform an inductive fault analysis on the DBM cells. They also show that the address generation method imposes different requirements on the test algorithms.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Analysis of Angular V-Cycle Multigrid Formulation for Three-Dimensional Discrete Ordinates Shielding Problems (2001)

New angular multigrid formulations have been developed, including the Simplified Angular Multigrid (SAM), Nested Iteration (NI), and V-Cycle schemes, which are compatible with the parallel environment and the adaptive differencing strategy of the PENTRAN three-dimensional parallel S{sub N} code. Through use of the Fourier analysis method for an infinite, homogeneous medium, the effectiveness of the V-Cycle scheme was investigated for different problem parameters including scattering ratio, spatial differencing weights, quadrature order, and mesh size. The theoretical analysis revealed that the V-Cycle scheme is effective for a large range of scattering ratios and is insensitive to mesh size. The effectiveness of the new schemes was also investigated for practical shielding applications such as the Kobayashi benchmark problem and the boiling water reactor core shroud problem.
Acceleration perceived with dynamic visual noise (1984)

The velocity of apparent movement induced by a dynamic visual noise (DVN) version of the Pulfrich effect increases during tracking of the perceived moving textured plane, giving rise to a percept of visual acceleration. Recorded eye movements show consistent acceleration, with a maximum velocity ten times greater than that estimated during fixation of a stationary point superimposed upon the DVN. This gradual increase may be due to continual updating by the efferent copy of the oculomotor control signal that closes a positive-feedback loop. The component of the perceived velocity induced by the DVN is, however, independent of eye velocity, and thus the oculomotor unity negative-feedback control loop is functionally opened.
Some controllability properties of bilinear delay-differential systems (1975)

Bilinear delay-differential systems appear frequently in applications. We present here controllability properties of such systems and in particular we derive criteria for local accessibility, and a "bang-bang" theorem.
Peer-to-Peer Sharing Spurs Scientific Innovation (2009)

The peer-to-peer renegades notwithstanding, open sharing of data among scientists must be the rule rather than the exception in the biomedical arena.
ChemInform Abstract: Methyl Jasmonate: A Short Synthesis of Naturally Occurring Methyl Jasmonate and Its Unnatural Enantiomer via Enantiodivergent Alkylation of Cyclopent‐2‐ene‐1,3‐diol Derivatives by Palladium(0)‐Induced Reactions. (1990)

Abstract Palladium‐catalyzed alkylation of the cyclopentenediol derivative (I) is a useful method for enantiodivergent functionalization resulting in both enantiomeric series (III) and (XII) of chiral building blocks.
Novel benzimidazole inhibitors of botulinum neurotoxin/A display enzyme and cell-based potency (2011)

Botulinum Neurotoxins (BoNTs) are used therapeutically and in cosmetics, providing potential for bioterrorist activity, thus driving the search for small-molecule BoNT inhibitors. This report describes a 70,000-compound screen for inhibition of BoNT/A using a FRET assay to detect proteolysis of a peptide substrate. Hits were confirmed, followed by evaluation to determine compound specificity. Inhibitors fell into three main chemical classes, and on the basis of potency and specificity of inhibition, the activities of two chemotypes were examined further. Compounds exhibited specificity for BoNT/A LC inhibition with respect to other metalloproteases and displayed activity in a neuronal assay for botulinum intoxication.
Reliability of hybrid III-V on Si distributed feedback lasers (2012)

This work reports a reliability study on fabricated hybrid Si distributed feedback lasers with a quarter-wave shifted cavity design. The influence on reliability of a superlattice between the lasing region and the bonded interface is investigated. Aging tests on DFB laser diodes on the hybrid Si platform have been conducted. The diodes with a superlattice showed no significant degradation in threshold current after 5000 hrs of aging even at 70 °C. 50% degradation in threshold current of some diodes at 70°C is estimated to take ~40000 hrs.
Determination of Volumes of Fluid in the Mouth by Fluoride Dilution (1992)

A dilution technique, with fluoride as a marker, has been developed to measure the volume of saliva and other fluids in the mouth. Immediately after swallowing, a small amount of fluoride solution is placed in the mouth, mixed with the oral fluids, and expelled from the mouth. The fluoride concentration of the expelled oral fluid is measured and the volume of fluid in the mouth at the time of spitting calculated from the fluoride dilution. Mean values of 0.75 +/- (SD) 0.28 ml for males and 0.72 +/- (SD) 0.16 ml for females were recorded. The accuracy of the volume determination is about +/- 0.10 ml in vivo. This technique has provided a convenient and rapid means of determining saliva volumes. It could also be used to determine rates of secretion and may prove useful in the clinic for assessing a patient's salivary competence.
ChemInform Abstract: Application of the Allylic Diazene Rearrangement: Synthesis of the Enediyne‐Bridged Tricyclic Core of Dynemicin A. (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Simulation of the charge transport across grain boundaries in p-type SrTiO3 ceramics under dc load: Debye relaxation and dc bias dependence of long-term conductivity (2002)

A mathematical-physical model to describe the charge transport across grain boundaries in p-type SrTiO3 ceramics in the low-temperature regime for arbitrary dc voltage steps has been developed. The finite element model structure consists of a one-dimensional cross section through a ceramic scenario. Mathematical formulation comprises a coupled system of continuity equations (utilizing Maxwell-Boltzmann transport equations) and Poisson’s equation, with the appropriate boundary conditions for a potentiostatic simulation approach. The edges of the model are assumed to be blocking for ionic transport, and penetrable for electronic transport. The model was implemented exploiting routines from the numerical class library DIFFPACK™. After an initial electrostatic simulation a dc bias voltage step is applied. The evolution of the spatial profiles of electric potential, defect concentrations, space-charge density, and electric conductivity, and the current response are calculated. The results for the ceramic model structure confirm the experimentally observed Debye relaxation, and the characteristic dependence of long-term conductivity on the dc bias after space-charge polarization, before the onset of resistance degradation.
Ferroptosis Regulation by the NGLY1/NFE2L1 Pathway (2022)

Cells are equipped with various mechanisms to maintain cell viability upon exposure to stress. The Cap ‘n’ Collar (CNC) family includes five vertebrate stress‐responsive transcription factors. The CNC member nuclear factor erythroid 2 like 2 (NFE2L2) is considered the master regulator of the cellular oxidative stress response. Fellow CNC member nuclear erythroid 2 like 1 (NFE2L1) is better known for its role in responding to proteasome dysfunction. We hypothesized that NFE2L1 also responds to oxidative stress. We demonstrate that genetic disruption of NFE2L1 sensitizes cancer cells to death by a non‐apoptotic, oxidative form of cell death termed ferroptosis. We also show that genetic disruption of N‐glycanase 1 (NGLY1), which catalyzes NFE2L1 deglycosylation and sequence editing, sensitizes cancer cells to ferroptosis through an NFE2L1‐dependent mechanism. Expression of a sequence‐edited NFE2L1 mutant, which mimics NGLY1‐processed NFE2L1, rescues cellular resistance to ferroptosis in NFE2L1 gene‐disrupted cells. Finally, we provide evidence that the ferroptosis protection conferred by NFE2L1 is mediated by the expression of glutathione peroxidase 4 (GPX4). All together, our results highlight the role of NFE2L1 in ferroptosis resistance and implicate NFE2L1 and NGLY1 as potential targets for cancer therapy.
Data-Driven Human-Robot Interaction Without Velocity Measurement Using Off-Policy Reinforcement Learning (2021)

In this paper, we present a novel data-driven design method for the human-robot interaction (HRI) system, where a given task is achieved by cooperation between the human and the robot. The presented HRI controller design is a two-level control design approach consisting of a task-oriented performance optimization design and a plant-oriented impedance controller design. The task-oriented design minimizes the human effort and guarantees the perfect task tracking in the outer-loop, while the plant-oriented achieves the desired impedance from the human to the robot manipulator end-effector in the inner-loop. Data-driven reinforcement learning techniques are used for performance optimization in the outer-loop to assign the optimal impedance parameters. In the inner-loop, a velocity-free filter is designed to avoid the requirement of end-effector velocity measurement. On this basis, an adaptive controller is designed to achieve the desired impedance of the robot manipulator in the task space. The simulation and experiment of a robot manipulator are conducted to verify the efficacy of the presented HRI design framework.
A Story of Two Streams: Reinforcement Learning Models from Human Behavior and Neuropsychiatry (2020)

Drawing an inspiration from behavioral studies of human decision making, we propose here a more general and flexible parametric framework for reinforcement learning that extends standard Q-learning to a two-stream model for processing positive and negative rewards, and allows to incorporate a wide range of reward-processing biases -- an important component of human decision making which can help us better understand a wide spectrum of multi-agent interactions in complex real-world socioeconomic systems, as well as various neuropsychiatric conditions associated with disruptions in normal reward processing. From the computational perspective, we observe that the proposed Split-QL model and its clinically inspired variants consistently outperform standard Q-Learning and SARSA methods, as well as recently proposed Double Q-Learning approaches, on simulated tasks with particular reward distributions, a real-world dataset capturing human decision-making in gambling tasks, and the PacMan game in a lifelong learning setting across different reward stationarities.