gebhart/patrepeval huggingface dataset:
Identification of benzothiazoles as potential polyglutamine aggregation inhibitors of Huntington's disease by using an automated filter retardation assay (2002)

Preventing the formation of insoluble polyglutamine containing protein aggregates in neurons may represent an attractive therapeutic strategy to ameliorate Huntington's disease (HD). Therefore, the ability to screen for small molecules that suppress the self-assembly of huntingtin would have potential clinical and significant research applications. We have developed an automated filter retardation assay for the rapid identification of chemical compounds that prevent HD exon 1 protein aggregation in vitro. Using this method, a total of 25 benzothiazole derivatives that inhibit huntingtin fibrillogenesis in a dose-dependent manner were discovered from a library of approximately 184,000 small molecules. The results obtained by the filter assay were confirmed by immunoblotting, electron microscopy, and mass spectrometry. Furthermore, cell culture studies revealed that 2-amino-4,7-dimethyl-benzothiazol-6-ol, a chemical compound similar to riluzole, significantly inhibits HD exon 1 aggregation in vivo. These findings may provide the basis for a new therapeutic approach to prevent the accumulation of insoluble protein aggregates in Huntington's disease and related glutamine repeat disorders.
Induced-Stress Analysis of SU-8 Polymer Based Single Mass 3-Axis Piezoresistive MEMS Accelerometer (2019)

This paper presents the induced-stress analysis of an SU-8 polymer based 3-axis piezoresistive MEMS accelerometer having a single proof mass along with proposed fabrication process flow. Polymer accelerometers are simple to fabricate and have better sensitivity because of their lower Young's modulus. It is also easy to integrate any highly sensitive piezoresistive material as a layer to further enhance the performance. In this work, structural design and push-pull mechanism of the beam and its use to achieve the desired results have been explained. Using basic structural analysis, locations of the maximum induced stress are identified. For acceleration of 100 g and 1 g, the proposed design has been investigated for the stress field in the structure and shown the improvement by comparing the performance with two published design presented in the paper. The proposed fabrication process is compatible with several piezoresistive materials such as ZnO nanorods, graphene and carbon nanotubes (CNTs).
Analysis of the Improvement in Accuracy Using Multiple Gyros (2015)

The possibility to improve the accuracy of angular velocity estimate by optimally combining multiple individual micro electromechanical systems (MEMS) gyroscopes is analyzed in this paper. Kalman filter (KF) is used to fuse the numerous measurements into a single improved rate estimate. Based on the virtual gyro idea, a revised approach can give an unbiased estimator regardless of the true angular velocity signal. Numerical simulations are performed to demonstrate the desirable performance, reducing the bias drift and noise.
Generation of Stereochemically Defined Tetrasubstituted Enolborinates by 1,4‐Hydroboration of α,β‐Unsaturated Morpholine Carboxamides with (Diisopinocampheyl)borane (2013)

Methyl hier, Methyl da: Die Titelreaktion mit (Ipc)2BH ergibt tetrasubstituierte Enolborinate, deren Aldolreaktionen mit Aldehyden in außergewöhnlich diastereo- und enantioselektiver Weise zu Produkten mit vollständig kohlenstoffsubstituierten quartären Zentren führen. Durch Änderung des Substitutionsmusters am Amid sind die beiden Diastereomere des α-Methyl-α-ethyl-β-hydroxycarboxamids (1 oder 2) zugänglich. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
New Selective and Potent 5-HT1B/1DAntagonists:  Chemistry and Pharmacological Evaluation ofN-Piperazinylphenyl Biphenylcarboxamides and Biphenylsulfonamides (2000)

A series of new analogues of N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl] 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamide (1; GR127935) as potent and selective 5-HT(1B/1D) antagonists were synthesized and evaluated pharmacologically. Their receptor binding profiles were comparable to that of 1. The 1,3,4-oxadiazole isomer 2 and the 4'-aminocarbonyl and 4'-amidinyl analogues (9 and 10) of 1 had higher affinities at the rat 5-HT(1B) receptor (IC(50) = 0.93, 1. 3, and 0.5 nM, respectively) and calf 5-HT(1D) receptor (IC(50) = 37, 10, and 3 nM, respectively) than did 1 (1.6 and 52 nM for rat 5-HT(1B) and calf 5-HT(1D) receptors, respectively). In the functional in vitro testing of 5-HT(1B/1D) antagonistic properties, 2, 9, 10, 11b (O-demethylated derivative of 2), 13a (O-methylsulfonyl analogue of 2), and 16 (which differs from 2 with a sulfonamide linker) showed more pronounced effects in the K(+)-induced 5-HT release in the cortex of guinea pig than did 1 and 3 (SB224289). Compounds 2, 9, and 10 were equally potent as 1 in rabbit saphenous vein model (pA(2) > 9). A biochemical study of 2 with in vivo microdialysis in the rat brain showed that it is capable of augmenting citalopram (a selective serotonin reuptake inhibitor, SSRI) induced 5-HT release in rat ventral hippocampus, while preventing the decrease in acetylcholine release elicited by citalopram administration. The molecular structure of 2 was determined by single-crystal X-ray analysis. The log P and log D values of these compounds were calculated. This study contributes to the SAR study of N-piperazinylphenyl biphenylcarboxamides as selective and potent 5-HT(1B/1D) antagonists.
Correlating N2 and CH4 Adsorption on Microporous Carbon Using a New Analytical Model (1998)

A new pore size distribution (PSD) model is developed to readily describe PSDs of microporous materials with an analytical expression. Results from this model can be used to calculate the corresponding adsorption isotherm to compare the calculated isotherm to the experimental isotherm. This aspect of the model provides another check on the validity of the model's results. The model is developed on the basis of a 3-D adsorption isotherm equation that is derived from statistical mechanical principles. Least-squares error minimization is used to solve the PSD without any preassumed distribution function. In comparison with several well-accepted analytical methods from the literature, this 3-D model offers a relatively realistic PSD description for select reference materials, including activated-carbon fibers. N2 and CH4 adsorption is correlated using the 3-D model for commercial carbons BPL and AX-21. Predicted CH4 adsorption isotherms at 296 K based on N2 adsorption at 77 K are in reasonable agreement with experimental CH4 isotherms. Use of the model is also described for characterizing PSDs of tire-derived activated carbons and coal-derived activated carbons for air-quality control applications.
Les nanotechnologies peuvent-elles contribuer à traiter les maladies sévères ? (extraits) (2010)

[…] Les nanotechnologies ont fait leur apparition et le monde de l’infiniment petit a révolutionné la manière d’administrer les médicaments. Parce qu’elles sont à une échelle nanométrique (1 nm = 10-9m), les nanotechnologies ne sont pas la simple miniaturisation d’objets plus grands mais elles possèdent des propriétés que l’on ne retrouve qu’à cette échelle de taille. Le domaine du médicament n’échappe pas à cette règle. Jusqu’au début des années 1970, on considérait qu’il n’était pas possibl...
Amniotic Fluid and Bone Marrow Derived Mesenchymal Stem Cells Can be Converted to Smooth Muscle Cells in the Cryo-Injured Rat Bladder and Prevent Compensatory Hypertrophy of Surviving Smooth Muscle Cells (2006)

In this model stem cell transplantation has a limited effect on smooth muscle cell regeneration. Instead it can regulate post-injury bladder remodeling, possibly via a paracrine mechanism.
SOI-CMOS Platform for Monolithically Integrating High-Voltage Driver Circuits with Bulk-Micromachined Actuators (2007)

We present a newly developed technology platform for monolithically integrating high voltage DMOS (Double-diffused Metal Oxide Semiconductor) circuits upwards of 40V with bulk-micromachined actuators (XY-stage) using both the top and the bottom surfaces of an SOI (Silicon-on-Insulator) wafer. Driver circuits were pre-fabricated on an 8-μm-thick SOI wafer by the DMOS processes, after which MEMS electrostatic actuators were integrated into the identical SOI layer as well as the substrate by post-processing using DRIE (Deep Reactive Ion Etching). Thanks to this monolithic integration technique, multi-layered high-aspect-ratio structures were produced.
Abstract C63: Biological characterization of GSK2126458, a novel and potent inhibitor of phosphoinositide 3-kinase and the mammalian target of rapamycin (mTOR) (2009)

Abstract The phosphoinositide 3-kinase (PI3K) pathway is among the most commonly activated pathways in human cancer. The biological role of PI3K in growth and survival of cancer cells and the prevalence of activating mutations in human cancers are well documented and a significant proportion of tumors would be predicted to benefit from inhibition of this pathway. Here we report on the characterization of the pan-PI3K pyridylsulfonamide inhibitor GSK2126458: a very potent (PI3K app Ki = 19 pM), reversible, ATP-competitive inhibitor of wild-type PI3K and the ‘hotspot’ activating mutants of p110 found in human cancer. GSK2126458 demonstrated good selectivity for the PI3K family of enzymes including the mTORC1 and mTORC2 complexes, when evaluated in a large panel of protein kinases. Consistent with potent PI3K enzyme inhibition, GSK2126458 decreased the cellular levels of phosphorylated AKT, p70S6K, PRAS40 and ERK in a concentration and time dependent manner, the IC50 for pAKT in the HCC1954 breast carcinoma cell line was 2 nM. GSK2126458 induced the nuclear translocation of the FOXO3a transcription factor in a concentration dependent manner that mechanistically appeared bimodal. Growth inhibition was time and concentration dependent with a 3 day exposure resulting in a growth IC50 (gIC50) of 9 nM in HCC1954 cells with evidence of cell death. Cell death correlated with induction of caspase 3 and 7 activity suggesting apoptosis was the mechanism of cell death. GSK2126458 had a breadth of activity for potent cell growth inhibition and induction of cell death in a variety of human cancer cells. GSK2126458 demonstrated robust, dose dependent in vivo pharmacodynamic activity as measured by inhibition of phospho-AKT in advanced BT474 breast cancer cell xenograft tumors. Inhibition of AKT phosphorylation was rapid and lasted for several hours after a single oral administration of GSK2126458. Transient increases in plasma insulin and blood glucose were observed. Evaluation of in vivo tumor growth effects of GSK2126458 in xenograft models demonstrated dose dependent tumor growth delay in several models of diverse tumor lineage and tumor regression in a breast cancer xenograft. The biological profile of GSK2126458 supports the clinical advancement of this compound and GSK2126458 has entered Phase I human clinical trials. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C63.
Decoder-Side Motion Vector Refinement in VVC: Algorithm and Hardware Implementation Considerations (2020)

This paper presents an overview of the decoder-side motion vector refinement (DMVR) algorithm in the Versatile Video Coding (VVC) standard. The proposed DMVR algorithm aims to increase the prediction accuracy of the blocks coded in merge mode using the bilateral matching-based refinement method. Compared with previous decoder-side motion vector derivation approaches, the proposed method significantly increases the coding efficiency without signaling additional side information. Furthermore, the hardware implementation considerations of the DMVR design are particularly focused in this study. This paper details and analyzes the novel features of DMVR contributing to the increase in coding efficiency and the reduction in computational complexity and implementation difficulty. Experimental results based on the VVC test model version 8.0 demonstrate that average Bjøntegaard Delta rate savings of 0.80 % and 2.81 % are achieved for the “tool-off” and “tool-on” test configurations, respectively. Moreover, 4 % additional decoding time and negligible additional external memory bandwidth requirements of DMVR based on the common test conditions for VVC are reported.
Blue-box approach to power electronics and machines educational laboratories (2005)

Our approach to laboratory education in power electronics and electric machines is presented. The approach centers upon "blue-box" laboratory components, that aid the student in rapid experiment assembly without disguising important aspects of the hardware. Several example experiments are presented. Schematics and construction techniques for the hardware are publicly available.
<title>Metrics program for assessing diffractive energy imaging system performance</title> (2002)

A standardized metrics program was developed and implemented by Advanced Diagnostics, Inc. (ADI) to quantify Diffractive Energy Imaging (DEI) system performance. DEI is a medical imaging technology which uses primarily diffracted wave information obtained form passing ultrasound energy through the anatomy. The resulting real-time, large field-of-view, high-resolution images are currently undergoing clinical evaluation for detection and management of breast disease. This unique imaging modality required novel modifications to conventional measurement and evaluation tools. Measurement tools were developed and metrics procedures were standardized to ensure measurement accuracy and repeatability during performance testing. The system modulation transfer function, effective size of the field- of-view, spatial resolution across the effective field-of- view, contrast resolution, minimum detection, and field uniformity were quantified. Improved system metrics monitor improvements to DEI image quality and are supported through images of target standards and subjective validation using images of human anatomy.
A Method for the Net Contra-thermodynamic Isomerization of Cyclic Trisubstituted Alkenes (2013)

A simple sequence for the net contra-thermodynamic isomerization of cyclic trisubstituted alkenes is reported consisting of a radical addition of p-chlorothiophenol, followed by oxidation to the sulfoxide and thermal syn-elimination to give the least substituted isomeric cycloalkene.
Synthesis of Tumor-Avid Photosensitizer−Gd(III)DTPA Conjugates: Impact of the Number of Gadolinium Units in T1/T2 Relaxivity, Intracellular localization, and Photosensitizing Efficacy (2010)

To develop novel bifunctional agents for tumor imaging (MR) and photodynamic therapy (PDT), certain tumor-avid photosensitizers derived from chlorophyll-a were conjugated with variable number of Gd(III)aminobenzyl DTPA moieties. All the conjugates containing three or six gadolinium units showed significant T(1) and T(2) relaxivities. However, as a bifunctional agent, the 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) containing 3Gd(III) aminophenyl DTPA was most promising with possible applications in tumor-imaging and PDT. Compared to HPPH, the corresponding 3- and 6Gd(III)aminobenzyl DTPA conjugates exhibited similar electronic absorption characteristics with a slightly decreased intensity of the absorption band at 660 nm. However, compared to HPPH, the excitation of the broad "Soret" band (near 400 nm) of the corresponding 3Gd(III)aminobenzyl-DTPA analogues showed a significant decrease in the fluorescence intensity at 667 nm.
Assessment of pulsatile insulin secretion derived from peripheral plasma C-peptide concentrations by nonparametric stochastic deconvolution (2019)

The characteristics of pulsatile insulin secretion are important determinants of type 2 diabetes pathophysiology, but they are understudied due to the difficulties in measuring pulsatile insulin secretion noninvasively. Deconvolution of either peripheral C-peptide or insulin concentrations offers an appealing alternative to hepatic vein catheterization. However, to do so, there are a series of methodological challenges to overcome. C-peptide has a relatively long half-life and accumulates in the circulation. On the other hand, peripheral insulin concentrations reflect relatively fast clearance and hepatic extraction as it leaves the portal circulation to enter the systemic circulation. We propose a method based on nonparametric stochastic deconvolution of C-peptide concentrations, using individually determined C-peptide kinetics, to overcome these limitations. The use of C-peptide (instead of insulin) concentrations allows estimation of portal (and not post-hepatic) insulin pulses, whereas nonparametric stochastic deconvolution allows evaluation of pulsatile signals without any a priori assumptions of pulse shape and occurrence. The only assumption required is the degree of smoothness of the (unknown) secretion rate. We tested this method first on simulated data and then on 29 nondiabetic subjects studied during euglycemia and hyperglycemia and compared our estimates with the profiles obtained from hepatic vein insulin concentrations. This method produced satisfactory results both in the ability to fit the data and in providing reliable estimates of pulsatile secretion, in agreement with hepatic vein measurements. In conclusion, the proposed method enables reliable and noninvasive measurement of pulsatile insulin secretion. Future studies will be needed to validate this method in people with type 2 diabetes.
Comparison of Different Pulse Modulation Modes for Holmium:Yttrium–Aluminum–Garnet Laser Lithotripsy Ablation in a Benchtop Model (2021)

<b><i>Introduction:</i></b> Manipulation of Holmium:Yttrium-Aluminum-Garnet laser parameters such as pulse energy (PE), frequency, and duration can impact laser lithotripsy ablation efficiency. In 2017, Lumenis introduced Moses™ Technology, which uses pulse modulation to enhance the delivery of energy from fiber to stone as well as to minimize stone retropulsion. Since the introduction of Moses Technology, other companies have brought additional pulse modulation concepts to market. The purpose of this <i>in vitro</i> study is to compare the pulse characteristics and stone ablation efficiency of Lumenis Moses Technology with Quanta's Vapor Tunnel™. <b><i>Materials and Methods:</i></b> Submerged BegoStone phantoms were systematically ablated using either the Lumenis Moses Pulse 120H or the Quanta Litho 100 clinical laser system. Two PEs (0.4 and 1 J), three fiber-stone standoff distances (SDs) (0.5, 1, 2 mm), and all available pulse duration and modulation modes for each laser were tested in combination. Fiber speed was adjusted to scan across the stone surface at either 1 or 10 pulses/mm to form single pulse craters or an ablation trough, respectively. Volumes of single craters and 1 mm trough segments were imaged and quantified using optical coherence tomography. <b><i>Results:</i></b> Ablation volumes decreased with decreasing PE and increasing SD. Statistically significant variability was seen between pulse types (PT) at every tested parameter set. Among pulse modulation modes, Moses Distance (MD) was superior at 0.5 mm in all testing and at 2 mm in trough testing. Vapor Tunnel (VT) was superior in 2 mm single crater testing. All modulated pulses performed similarly at 1 mm. <b><i>Conclusions:</i></b> In this benchtop model of laser lithotripsy, stone ablation was significantly impacted by PT. MD demonstrated superior or noninferior stone ablation at most tested parameters. VT maintained its efficacy the best as SD increased. Future work should focus on the mechanistic differences of these modes relative to other traditional laser pulse modes.
Venous thromboembolic events in the tofacitinib ulcerative colitis clinical development programme (2019)

In this post hoc analysis of patients with UC, during tofacitinib exposure, one patient had DVT and four had PE, all during the OLE study, on predominant dose 10 mg b.d. (83% of overall cohort patients received predominant dose 10 mg b.d.) with venous thromboembolism risk factors. This analysis is limited by small sample size and limited drug exposure; further studies are needed. ClinicalTrials.gov: NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612.
Mobile acoustic sensor system for road edge detection (2006)

In this paper, we propose a novel acoustic sensor network system that can provide road edge detection in order to prevent rollovers. The system can work in "non-cooperative" road scenarios that do not possess any characteristic "cooperative markings," such as white lines, or pavement at the sidewalk.
Electrically tunable efficient broadband long-period fiber grating filter (2003)

Summary form only given. We present a new type of the tunable optical fibre filter based on a metal coated long period grating (LPG) written in a specially-developed fiber containing air regions inside the cladding. The air regions are filled with polymers with high temperature sensitivity resulting in broadband tuning range and high electrical heating efficiency. These new structures are attractive because they are practically insensitive to the variations of the refractive index of the surroundings, and thus can be coated by metal with no measurable changes in the transmission spectrum.
Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation (2018)

Mitochondrial function affects many aspects of cellular physiology, and, most recently, its role in epigenetics has been reported. Mechanistically, how mitochondrial function alters DNA methylation patterns in the nucleus remains ill defined. Using a cell culture model of induced mitochondrial DNA (mtDNA) depletion, in this study we show that progressive mitochondrial dysfunction leads to an early transcriptional and metabolic program centered on the metabolism of various amino acids, including those involved in the methionine cycle. We find that this program also increases DNA methylation, which occurs primarily in the genes that are differentially expressed. Maintenance of mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation in the context of mtDNA loss rescues methionine salvage and polyamine synthesis and prevents changes in DNA methylation and gene expression but does not affect serine/folate metabolism or transsulfuration. This work provides a novel mechanistic link between mitochondrial function and epigenetic regulation of gene expression that involves polyamine and methionine metabolism responding to changes in the tricarboxylic acid (TCA) cycle. Given the implications of these findings, future studies across different physiological contexts and in vivo are warranted.