gebhart/patrepeval huggingface dataset:
Functional characterization of a novel NMDA receptor positive allosteric modulator (2017)

The NMDA receptor is a glutamatergic ionotropic receptor key in mediating neuronal plasticity across virtually all synaptic circuits in the brain. An increasing list of neurological disorders have implicated NMDA receptor hypofunction as an integral part of pathogenesis, necessitating the production of NMDA receptor potentiators as therapeutics. To date, most of these attempts have used increased co-agonism at the glycine binding site of NMDA receptors, but this strategy has been plagued by low specificity and efficacy. Specific allosteric modulation of NMDA receptors is an ideal solution, but until recently, no known drugs were capable of doing so. Building off previous work in our lab that discovered a novel family of compounds capable of modulating NMDA receptor activity through its apical N-terminal domain, we identified and characterized a drug candidate, Npam59, predicted to potentiate both GluN2A- and 2B-containing NMDA receptors. Npam59 was shown to potentiate NMDA currents mediated by both subtypes with EC50 in the low-micromolar range. Npam59 also potentiated d-amphetamine-induced dopamine release in the ventral striatum in an NMDA receptor-dependent manner, but had no observable effect when administered alone. Finally, Npam59 potentiated d-amphetamine-induced hyperlocomotion in Sprague-Dawley rats. These results demonstrate that Npam59 can potentiate the function of NMDA receptors, including both GluN2A- and 2B-containing ones, suggesting its potential as a research tool and drug candidate for further development. Npam59 is the first known NMDA receptor allosteric potentiator with specificity for both GluN2A and GluN2B. Its characterization provides the foundation for therapeutic development and novel insights into the interaction of dopamine-glutamate signaling in the ventral striatum.
Delivery of Cytokines by Liposomes. III. Liposome- Encapsulated GM-CSF and TNF-?? Show Improved Pharmacokinetics and Biological Activity and Reduced Toxicity in Mice (1997)

In an attempt to potentiate the therapeutic index of cytokines, recombinant mouse granulocyte/macrophage colony-stimulating factor (GM-CSF) and recombinant human tumor necrosis factor alpha (TNF-alpha) were encapsulated in large (0.3-2.2 microns) multilamellar vesicles composed of various lipids, using several encapsulation methods. Liposomal cytokine activity was tested in vitro and in vivo and was compared with that of the soluble cytokines. The main observations were as follows: (a) The mean encapsulation efficiency, as determined by bioassays, was 49-79%, depending on the formulation, for GM-CSF, and 48% for TNF-alpha; (b) some of the entrapped cytokine preparations displayed high stability at 4 degrees C, with < 30% loss of biologic activity during a 4-month period; (c) release of TNF-alpha, but not of GM-CSF, from the liposomes was required for their biological activity in vitro; (d) plasma half-lives (t1/2 alpha, t1/2 beta) and the area under the curve (AUC) of the entrapped cytokines were 10-20 times greater than those of the soluble cytokines; (e) the toxicity of liposomal TNF-alpha was one-third and one-seventh that of soluble TNF-alpha in normal and tumor-bearing mice, respectively; (f) administration of liposomal GM-CSF (5 x 10(4)-2 x 10(5) U, one to five times) to normal and 5-fluorouracil-treated mice led to a two- to fourfold increase in the absolute number of peritoneal and spleen leukocytes and of GM colony-forming cells in the spleen, as compared with the levels obtained using soluble GM-CSF; and (g) under the experimental conditions used, neither free nor liposomal GM-CSF significantly increased the absolute number of blood leukocytes, although liposomal GM-CSF markedly (threefold) enhanced the level of blood granulocytes. Collectively, these findings suggest that liposome-entrapped GM-CSF and TNF-alpha may be more efficacious immunomodulators than the soluble cytokines.
Effects of Anode Buffer Layers on the Performance of P3HT/C70-PCBM Photovoltaic Devices (2008)

In this paper, we fabricated and compared the photovoltaic properties of two different kinds of PEDOT:PSS buffer layer systems. The first was with the PEDOT:PSS buffer layers of different PEDOT to PSS ratios, 1 to 2.5 for Baytron P and 1 to 6 for Baytron PVP AI4083, respectively. The second system included the buffer layers with the same PEDOT to PSS ratio, but with the changed conductivities by doping with 2, 4, 6, 8, and 10 wt% of glycerol. The power conversion efficiency was governed by the series resistance of the device and the resistivity of the applied PEDOT:PSS films, while the parallel resistance and the diode rectification characteristics are affected by the ratio of PEDOT to PSS on buffer layer.
Supplementary Figure 2 from Vulnerabilities of <i>PTEN</i>–<i>TP53</i>-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition (2023)

&lt;p&gt;PDF - 2951K, Olaparib induces a differing response in vivo depending on the genetic background.&lt;/p&gt;
Syntheses of Pyrethroid Acids (1981)

Abstract In the course of the last decade the chemistry of insecticides was expanded with the discovery of new cyclopropanecarboxylic acid esters of specific structure, far superior in action to the hitherto known insecticides of other substance classes or the natural prototypes from the group of pyrethrum constituents. The discovery quickly precipitated a host of wide‐ranging studies on the synthesis of these compounds. The development of selective methods of synthesizing complicated small rings called for a comprehensive repertoire: thus, synthesis of the compounds on an industrial scale makes use of sigmatropic rearrangement, radical addition, and nucleophilic ring closure with carbanions. These new industrial syntheses have acquired particular topicality because of their use of stereospecific and enantioselective methods.
Liquid metal polymer composites: from printed stretchable circuits to soft actuators (2022)

Abstract Soft polymers embedded with liquid metals like eutectic gallium-indium (EGaIn) exhibit unique combinations of mechanical, electrical, and thermal properties that are not possible with other material systems. For example, a soft silicone elastomer embedded with a percolating network of EGaIn microdroplets can function as a highly soft and elastic conductor that can be stretched to 600% strain without significant change in electrical resistance. Depending on the choice of polymer matrix and EGaIn microstructure, these soft material composites can be engineered to exhibit mechanical and electrical self-healing properties as well as high fracture toughness and resistance to tearing. Moreover, when solid filler particles like silver flakes are added to EGaIn-polymer composites, they can function as printable conductive inks that are fully elastic, non-marking, and non-smearing when cured. In this short review, we present different classes of EGaIn-polymer composites, discuss approaches to materials synthesis and patterning, and compare their properties with other material systems. Additionally, we will review applications of this emerging class of materials in domains ranging from wearable bioelectronics to soft robotics, shape programmable smart materials, as well as energy storage and harvesting devices.
Supplementary Table S2 from Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate (2023)

Supplementary Table S2 from Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate
The constitutive production of the endocannabinoid 2‐arachidonoylglycerol participates in oligodendrocyte differentiation (2010)

Endocannabinoids have recently emerged as instructive cues in the developing central nervous system, and, based on the expression of their receptors, we identified oligodendrocytes as potential targets of these molecules. Here, we show that the enzymes responsible for the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG), diacylglycerol lipase alpha (DAGLα) and beta (DAGLβ), and degradation, monoacylglycerol lipase (MAGL), can be found in oligodendrocytes at different developmental stages. Moreover, cultured oligodendrocyte progenitor cells (OPCs) express DAGLα and β abundantly, resulting in the stronger production of 2-AG than in differentiated oligodendrocytes. The opposite is observed with MAGL. CB1 and CB2 receptor antagonists (SR141716 and AM630) impaired OPC differentiation into mature oligodendrocytes and likewise, inhibiting DAGL activity with RHC-80267 or tetrahydrolipstatin also blocked oligodendrocyte maturation, an effect reversed by the addition of exogenous 2-AG. Likewise, 2-AG synthesis disruption using specific siRNAs against DAGLα and DAGLβ significantly reduced myelin protein expression in vitro, whereas a pharmacological gain-of-function approach by using cannabinoid agonists or MAGL inhibition had the opposite effects. ERK/MAPK pathway is implicated in oligodendrocyte differentiation because PD98059, an inhibitor of MEK1, abrogated oligodendrocyte maturation. The cannabinoid receptor antagonists and RHC-80267 all diminished basal ERK1/2 phosphorylation, effects that were partially reversed by the addition of 2-AG. Overall, our data suggest a novel role of endocannabinoids in oligodendrocyte differentiation such that constitutive release of 2-AG activates cannabinoid receptors in an autocrine/paracrine way in OPCs, stimulating the ERK/MAPK signaling pathway.
Rhenium and iridium (1997)

Re is used together with Ir in a number of metallurgical applications. Ir has been used as coating for Re rocket thrusters and as an oxidation-resistant coating in a number of other applications. The high strength of Re at elevated temperature is combined with the oxidation resistance and high melting point of Ir. The use of the two metals together is advantageous due to absence of stable intermetallic compounds. Both Re and Ir alloying additions improve the ductility of W. The high solubility of Re in Ir is also taken advantage of to produce Ir-based alloys for structural applications. Uses of Re in conjunction with Ir are discussed.
Incremental redundancy to reduce data retention errors in flash-based SSDs (2015)

As the market becomes competitive, SSD manufacturers are making use of multi-bit cell flash memory such as MLC and TLC chips in their SSDs. However, these chips have lower data retention period and endurance than SLC chips. With the reduced data retention period and endurance level, retention errors occur more frequently. One solution for these retention errors is to employ strong ECC to increase error correction strength. However, employing strong ECC may result in waste of resources during the early stages of flash memory lifetime as it has high reliability and data retention errors are rare during this period. The other solution is to employ data scrubbing that periodically refreshes data by reading and then writing the data to new locations after correcting errors through ECC. Though it is a viable solution for the retention error problem, data scrubbing hurts performance and lifetime of SSDs as it incurs extra read and write requests. Targeting data retention errors, we propose incremental redundancy (IR) that incrementally reinforces error correction capabilities when the data retention error rate exceeds a certain threshold. This extends the time before data scrubbing should occur, providing a grace period in which the block may be garbage collected. We develop mathematical analyses that project the lifetime and performance of IR as well as when using conventional data scrubbing. Through mathematical analyses and experiments with both synthetic and real workloads, we compare the lifetime and performance of the two schemes. Results suggest that IR can be a promising solution to overcome data retention errors of contemporary multi-bit cell flash memory. In particular, our study shows that IR can extend the maximum data retention period by 5 to 10 times. Additionally, we show that IR can reduce the write amplification factor by half under real workloads.
The Escort System: A Safety Monitor for People Living with Alzheimer's Disease (2010)

The Escort system monitors residents of assisted living communities and alerts caregivers when they walk aimlessly, or "wander," into potentially dangerous situations. The system could help lead to improved care at reduced cost.
A generic solution for warehousing business process data (2007)

Improving business processes is critical to any corporation. Process improvement requires analysis as its first basic step. Process analysis has many unique challenges: i) companies execute many business processes, and devising ad hoc solutions for each of them is too costly. Hence, generic approaches must be sought; ii) the abstraction level at which processes need to be analyzed is much higher with respect to the information available in the process execution environment; iii) the rapidly increasing need of codeveloping the process analysis and the process automation solution and the scale of the problem makes it hard to cope with frequent changes in the sources of process data. To address these problems, we have developed a process warehousing solution, used by HP and its customers. In this paper we describe the solution, the challenges we had to face, and the lessons we learned in implementing and deploying it.
Kurs und rechnerischer Wert des Bezugsrechts (1999)

Abstract In dieser Arbeit wird für den Zeitraum von Januar 1989 bis Dezember 1995 überprüft, ob am deutschen Kapitalmarkt eine Differenz zwischen dem Kurs und dem rechnerischen Wert des Bezugsrechts statistisch immer noch nachweisbar ist und welche Faktoren diese Differenz beeinflussen. Dazu wird die Arbeit in einen theoretischen und einen empirischen Teil gegliedert. Im theoretischen Teil werden zunächst die verschiedenen Möglichkeiten zur Ermittlung des rechnerischen Bezugsrechtswerts und deren Eignung für die empirische Analyse dargestellt. Es folgt die empirische Untersuchung, in der Hypothesen formuliert und überprüft werden. Die Autoren zeigen ein generelles Underpricing des Bezugsrechts, dessen Höhe von der jeweiligen Ausstattung abhängt.
Advances in Quantum and Molecular Mechanical (QM/MM) Simulations for Organic and Enzymatic Reactions (2009)

Application of combined quantum and molecular mechanical (QM/MM) methods focuses on predicting activation barriers and the structures of stationary points for organic and enzymatic reactions. Characterization of the factors that stabilize transition structures in solution and in enzyme active sites provides a basis for design and optimization of catalysts. Continued technological advances allowed for expansion from prototypical cases to mechanistic studies featuring detailed enzyme and condensed-phase environments with full integration of the QM calculations and configurational sampling. This required improved algorithms featuring fast QM methods, advances in computing changes in free energies including free-energy perturbation (FEP) calculations, and enhanced configurational sampling. In particular, the present Account highlights development of the PDDG/PM3 semi-empirical QM method, computation of multi-dimensional potentials of mean force (PMF), incorporation of on-the-fly QM in Monte Carlo (MC) simulations, and a polynomial quadrature method for efficient modeling of proton-transfer reactions. The utility of this QM/MM/MC/FEP methodology is illustrated for a variety of organic reactions including substitution, decarboxylation, elimination, and pericyclic reactions. A comparison to experimental kinetic results on medium effects has verified the accuracy of the QM/MM approach in the full range of solvents from hydrocarbons to water to ionic liquids. Corresponding results from ab initio and density functional theory (DFT) methods with continuum-based treatments of solvation reveal deficiencies, particularly for protic solvents. Also summarized in this Account are three specific QM/MM applications to biomolecular systems: (1) a recent study that clarified the mechanism for the reaction of 2-pyrone derivatives catalyzed by macrophomate synthase as a tandem Michael-aldol sequence rather than a Diels-Alder reaction, (2) elucidation of the mechanism of action of fatty acid amide hydrolase (FAAH), an unusual Ser-Ser-Lys proteolytic enzyme, and (3) the construction of enzymes for Kemp elimination of 5-nitrobenzisoxazole that highlights the utility of QM/MM in the design of artificial enzymes.
DISNET: a Distributed System NETwork (1984)

This paper describes a Distributed Instrument System NETwork (DISNET) which was implemented within the Department of Chemistry at Cleveland State University.
On the Application of Extended Grounded Slot Electrodes to Reduce Noncirculating Bearing Currents (2022)

Power-electronic-converter-induced motor bearing currents are a widespread problem in the field of electrical drives. Parasitic capacitances between the electrical machine's parts provide a path for leakage currents, which finally harm metallic ball bearings. Remembering that end-windings have a significant contribution in building up stray capacitances, a countermeasure affecting both the lamination stack and end-winding areas is needed. This article focuses on a countermeasure against the noncirculating bearing currents in the cluster of solutions at the motor side. The electrostatic shielding approach, which is a known principle to reduce capacitive couplings, is applied in electrical machines every now and then. In this article, the principle of slot-embedded grounded electrodes is extended to cover also the end-windings. Thus, the electrodes provide a better shaft-to-ground voltage mitigating effect compared to the case where electrodes are applied only in the lamination stack area. The feasibility and effectiveness of such a countermeasure are investigated. Different options in terms of scaling of both the machine size and diameter of the electrodes were analyzed and corresponding conclusions were pointed out.
A721. INTER-SUBJECT INVARIANT SCAPULAR AXES FOR GENERALIZED APPLICATIONS (2018)

Introduction: Classical studies have defined axes from prominent scapular landmarks that have been used to synthesise many applications. The morphology of the scapula is however known to be highly variable between individuals1,2,3. This introduces significant variability on the use of these classical axes for various clinical applications. Also, some of the literatureapplied landmarks were highly dependant on the presence of pathology, thus introducing more variability in the products they parented. This limits accuracy in inter-subject comparisons from such applications. Therefore there is a need to identify and define pathology-insensitive anatomical landmarks that are less variable between individuals than the variability of the overall scapular shape. The aim of this study was to define more scapular axes from clearly identifiable landmarks, analysing these and other classical definitions for the best axis that minimizes variability and is closely related to the scapular clinical frame of reference. Materials and Method: Fourteen different axes of new and classical definitions from clearly identifiable landmarks were quantified by applying medical images of 21 scapulae. The orientations of the quantified axes were calculated. The plane of the blade of the scapula was defined, bounded by the angulus inferior4, the spine/medial border intersection5 and the most inferolateral point of the infra-glenoid tubercle. This was applied to grade the alienation of the quantified axes from the scapular blade. The angular relationships between individual axes of a spcapula were quantified, averaged over the 21 specimens and their standard deviations (SD) applied to grade the sensitivity of each axis to interscapular variations in the others. The volume of data required to define an axis (VDA) was noted for its dependency on pathology. These three criteria were weighted according to relative importance such that axes bearing 10° or more from the blade deviated significantly and were eliminated; insensitivity to scapular morphological variations based on the smallest SD and axes applicability in pathology based on VDA of the remaining axes were graded for the final result. Results: A least square line through the centre of the spine root was the most optimal medio-lateral axis. The normal to the plane formed by the spine root line and a least square line through the centre of the lateral border ridge was the most optimal antero-posterior axis. Conclusion: These body-fixed axes are closely aligned to the cardinal planes6 in the anatomical position and thus are clinically applicable, specimen invariant axes that can be used in generalised and patient-specific kinematics modelling.
Stiff-man syndrome in a woman with breast cancer (1998)

We report a patient who developed stiff-man syndrome, including disabling shoulder subluxation and wrist ankylosis, in association with breast cancer. Immunologic investigations disclosed autoimmunity directed against not only glutamic acid decarboxylase but also amphiphysin, a 128-kd protein located in the presynaptic compartment of neurons. The patient improved after surgery and corticosteroid treatment and has been stable for nearly 4 years on only anti-estrogenics. The triad of stiff-man syndrome, breast cancer, and autoantibodies against amphiphysin identifies a new autoimmune paraneoplastic syndrome of the CNS.
Hole Transport of a Liquid-crystalline Phenylterthiophene Derivative Exhibiting the Nematic Phase at Ambient Temperature (2011)

Abstract A liquid-crystalline phenylterthiophene derivative which exhibits a nematic phase at room temperature has been prepared. The hole mobility in the nematic phase at room temperature reaches 4 × 10−4 cm2 V−1 s−1. This value is two orders of magnitude larger than those of amorphous organic semiconductors and comparable to those in the smectic A or C phases of liquid-crystalline semiconductors.