gebhart/patrepeval huggingface dataset:
Increasing fibrillar amyloidosis is associated with improved cognition and synaptic preservation caused by microglia modulation (2019)

Aim: Immunmodulatory treatment with the PPARγ agonist Pioglitazone shows heterogeneous results in Alzheimer`s disease (AD). We aimed to apply longitudinal in-vivo PET monitoring combined with terminal cognitive assessment to investigate PET as a tool for longitudinal monitoring of treatment effects and to establish efficacy determinants.Methods: PS2APP (TG) mice and C57Bl/6 (WT) mice were randomly stratified in Pioglitazone (N=13 TG, N=8 WT) and placebo treatment (N=10 TG, N=7 WT) at the age of 8 months. Therapy was conducted for 5 months (mo). All mice received amyloid-PET (Aβ-PET) scans (F-18-Florbetaben) at baseline and after 5 mo, to investigate progression of plaque load. TSPO-PET (F-18-GE180) was performed at baseline, after 0.5 mo, 2.5 mo and 5 mo to analyze changes in microglial activation. Forebrain PET signals were assessed for each timepoint. Behavioral testing after the terminal PET scan was followed by molecular validation including immunohistochemical (IHC) and profiling of microglia phenotypes, plaque composition and synaptic density.Results: Pioglitazone treatment resulted in a reduction of -13% (p < 0.001) in the TSPO-PET signal as well as an unexpected increase of Aβ-PET in the treatment group compared to placebo (+16% vs. +13%; p < 0.05; supporting Fig. a) for the entire monitoring period. IHC proved Aβ-PET results and showed more fibrillar plaque load in the treatment group (4.2% vs 2.8%, p < 0.05; Fig. b). Nonetheless, we observed improved cognitive performance (escape latency 3.2 vs. 4.8 seconds, p < 0.05) and attenuated synaptic loss (0.43 vs. 0.38 VGLUT1/µm2, p < 0.001) after treatment. Importantly, we discovered a direct correlation between Aβ-PET increase with TSPO decrease (R=0.62; p < 0.05) and improved cognitive outcome (R=0.39 p < 0.05). IHC revealed, that dense proportions of the Aβ plaque raised during treatment, whereas looser parts of Aβ plaques decreased. Genetic analyses indicated a treatment dependent change in microglial gene signature (Fig. c).Conclusions: Reduction of microglial activation by Pioglitazone anti-inflammatory treatment is associated with increasing fibrillar Aβ. However, this shift of loose to more dense proportions of Aβ plaques is accompanied by improved cognitive performance and attenuated synaptic loss after treatment. This finding has strong implications to Pioglitazone treatment monitoring by Aβ-PET as a signal increase over time could be misinterpreted as a treatment failure. Furthermore, this indicates for the first time that increasing fibrillar amyloidosis can preserve cognition.
Operational Verification of a Pump-Augmented Loop Heat Pipe with Auxiliary Evaporators (2021)

View Video Presentation: https://doi.org/10.2514/6.2021-3156.vid This paper reports initial test data obtained for a simplified ammonia pump-augmented loop heat pipe (PA-LHP), which is more powerful and versatile than regular LHPs. Unlike conventional LHPs, PA-LHPs with pumped auxiliary evaporators can acquire thermal energy from multiple distributed heat sources. Analysis of the test data indicates that the PA-LHP worked in a stable manner under varied heat loads and fluctuations of the cooling air temperature. The standard LHP reservoir-evaporator assembly controlled the system operating temperature and provided capillary pressure potential for the fluid circulation in the LHP flow contour. The mechanical pump added to the liquid return line circulated fluid through the second flow contour with auxiliary flow-through evaporators, as well as through the condenser shared by the two flow contours. These two conjoined flow contours were typically able to operate simultaneously and reach a steady state steady flow conditions by automatically balancing the pressure drops and saturation temperatures for the corresponding components.
Building a distributed full-text index for the Web (2001)

We identify crucial design issues in building a distributed inverted index for a large collection of web pages. We introduce a novel pipelining technique for structuring the core index-building system that substantially reduces the index construction time. We also propose a storage scheme for creating and managing inverted files using an embedded database system. We suggest and compare different strategies for collecting global statistics from distributed inverted indexes. Finally, we present performance results from experiments on a testbed distributed indexing system that we have implemented.
Ro 48-8.071, a new 2,3-oxidosqualene:lanosterol cyclase inhibitor lowering plasma cholesterol in hamsters, squirrel monkeys, and minipigs: comparison to simvastatin (1997)

2,3-Oxidosqualene:lanosterol cyclase (OSC, E.C. 5.4.99.7) represents a unique target for a cholesterol lowering drug. Partial inhibition of OSC should reduce synthesis of lanosterol and subsequent sterols, and also stimulate the production of epoxysterols that repress HMG-CoA reductase expression, generating a synergistic, self-limited negative regulatory loop. Hence, the pharmacological properties of Ro 48-8.071, a new OSC inhibitor, were compared to that of an HMG-CoA reductase inhibitor, simvastatin. Ro 48-8.071 blocked human liver OSC and cholesterol synthesis in HepG2 cells in the nanomolar range; in cells it triggered the production of monooxidosqualene, dioxidosqualene, and epoxycholesterol. It was safe in hamsters, squirrel monkeys and Göttingen minipigs at pharmacologically active doses, lowering LDL approximately 60% in hamsters, and at least 30% in the two other species, being at least as efficacious as safe doses of simvastatin. The latter was hepatotoxic in hamsters at doses > 30 mumol/kg/day limiting its window of efficacy. Hepatic monooxidosqualene increased dose-dependently after treatment with Ro 48-8.071, up to approximately 20 micrograms/g wet liver or less than 1% of hepatic cholesterol, and it was inversely correlated with LDL levels. Ro 48-8.071 did not reduce coenzyme Q10 levels in liver and heart of hamsters, and importantly did not trigger an overexpression of hepatic HMG-CoA reductase, squalene synthase, and OSC itself. In strong contrast, simvastatin stimulated these enzymes dramatically, and reduced coenzyme Q10 levels in liver and heart. Altogether these findings clearly differentiate the OSC inhibitor Ro 48-8.071 from simvastatin, and support the view that OSC is a distinct key component in the regulation of the cholesterol synthesis pathway.
Design of experiments-based stability and control derivative modelling (2008)

This article investigates modelling aircraft non-dimensional aerodynamic-propulsive coefficients by using a design of experiment technique based on a linear parameter variation model. A case study is conducted to estimate the stability and control derivatives from aircraft response behaviour in longitudinal motion. For demonstrating technique feasibility, a non-linear simulator for the F-16 was used to assess the proposed approach. A set of doublet elevator and throttle inputs is initially executed at different locations over the operational flight envelope. Then, the aircraft response is used in identifying the derivative variations with velocity, altitude, aircraft mass, and centre of gravity position. A sequential experiment using a factorial design and augmented face central axial points was employed to model the variation. The validity of the proposed method was evaluated by comparing the estimated and actual variation of the derivatives. The proposed approach is generally applicable for wind tunnel and flight tests.
Principles and practice of emergency medicine (1978)

Resuscitation techniques and tips trauma nontrauma emergencies special populations environmental and toxicology emergencies miscellaneous appendices, normal reference values, useful tables.
P1‐291: Early magnetic resonance imaging results from the addneuromed Alzheimer's disease study (2008)

Multi-centre MRI studies are a key tool for investigating the natural history of mild cognitive impairment and Alzheimer's disease and for testing potential new pharmaceuticals. We present here early results from the first timepoint of the European Union and EFPIA sponsored InnoMed / AddNeuroMed multi-center MRI study of longitudinal changes in Alzheimer's disease (AD). MRI data compatible with the ADNI image acquisition protocol was collected from 85 AD patients, 87 subjects with MCI and 88 controls at six European MRI sites and uploaded to the Loris database system at the Karolinska Institutet, Sweden. The underlying database system was developed at the McGill Brain Imaging Centre, Montreal. Following careful quality control the 3D T1-weighted images were processed using the Civet image processing pipeline to automatically determine whole brain volumes normalized to the intracranial cavity (ICC) and mean cortical thickness measures. Right and left hippocampal volumes were determined by manual delineation by an expert observer and normalized to the ICC. Ninety-six percent of T1-weighted volumes passed the quality control criteria. Whole brain volumes, cortical thickness measures and hippocampal volumes showed significant differences between the Alzheimer's and MCI groups and between the Alzheimer's and control groups. Only hippocampal volumes showed significant difference between the control and MCI groups. The AddNeuroMed study has collected high quality data for 96% of the subjects enrolled across six different sites. Early results show the sensitivity of hippocampal volumes in distinguishing between Alzheimer's disease, mild cognitive impairment and control groups. These results will allow us to refine our strategy for further more detailed analyses.
Autonomous Vehicle Cut-In Algorithm for Lane-Merging Scenarios via Policy-Based Reinforcement Learning Nested Within Finite-State Machine (2022)

Lane-merging scenarios pose highly challenging problems for autonomous vehicles due to conflicts of interest between the human-driven and cutting-in autonomous vehicles. Such conflicts become severe when traffic increases, and cut-in algorithms suffer from a steep trade-off between safety and cut-in performance. In this study, a reinforcement learning (RL)-based cut-in policy network nested within a finite state machine (FSM)—which is a high-level decision maker, is proposed to achieve high cut-in performance without sacrificing safety. This FSM-RL hybrid approach is proposed to obtain 1) a strategic and adjustable algorithm, 2) optimal safety and cut-in performance, and 3) robust and consistent performance. In the high-level decision making algorithm, the FSM provides a framework for four cut-in phases (ready for safe gap selection, gap approach, negotiation, and lane-change execution) and handles the transitions between these phases by calculating the collision risks associated with target vehicles. For the lane-change phase, a policy-based deep-RL approach with a soft actor–critic network is employed to get optimal cut-in performance. The results of simulations show that the proposed FSM-RL cut-in algorithm consistently achieves a high cut-in success rate without sacrificing safety. In particular, as the traffic increases, the cut-in success rate and safety are significantly improved over existing optimized rule-based cut-in algorithms and end-to-end RL algorithm.
Randomized, Double-blind, Placebo-controlled Study of a Multispecies Probiotic Mixture in Nonalcoholic Fatty Liver Disease (2019)

The intestinal microbiota is closely associated with the development of obesity and nonalcoholic fatty liver disease (NAFLD). This study investigated the effects of probiotic treatment on visceral fat area (VFA) and intrahepatic fat (IHF) fraction in NAFLD. Sixty-eight obese NAFLD patients (>5% proton density fat fraction [PDFF] on magnetic resonance imaging [MRI]) were randomized to probiotic and placebo groups for 12 weeks. The probiotic mixture included 6 bacterial species. VFA and IHF were measured using the MRI-PDFF technique. Body weight and total body fat were reduced in the probiotic group but not in the placebo group. The mean IHF fraction was reduced after 12 weeks of treatment in the probiotic group compared to that at baseline (from 16.3 ± 15.0% to 14.1 ± 7.7%, p = 0.032) but was not reduced in the placebo group. The decrease in IHF (mean difference: -2.61%, p = 0.012) was also greater in the probiotic group than in the placebo group. Reduction of triglyceride was greater in the probiotic treatment group than in the placebo group (mean difference: -34.0 mg/dl, p = 0.0033). However, the changes in IHF percentage and triglyceride levels were not different between placebo and control groups after adjusting for changes in body weight. Treatment with probiotics for 12 weeks resulted in significant reduction in IHF and body weight in obese NAFLD patients.
Quantifying Subcellular Localization of Methylene Blue in Cultured Brain Cells (2019)

Subcellular distribution of Methylene blue (MB) in six cultured brain cell lines was investigated. Results demonstrate MB accumulates significantly more in mitochondria of glioblastoma cells relative to normal astrocytes.
[Studies on the alkaloids of Huperzia serrata (Thunb.) Trev]. (1988)

Three alkaloids were isolated from Huperzia serrata (Tunb.) Trev. Two of them were identified as known alkaloids huperzine B(Ⅰ) and N-methyl huperzine B(Ⅲ), respectively. The third alkaloid Ⅱ was found to be a new compound named huperzinine. Its structure was confirmed on the basis of chemical and spectral data (UV, IR, NMR, MS).
Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin (2009)

Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.
A New Synthesis of Triphenodithiazines and Triphenodithiazinequinoes (1983)

Abstract A new class of 6,13-bis(arylamino)triphenodithiazines has been synthesized by condensing chloranil with arylamines followed by the reaction of the resulting 2,5-bis(arylamino)-3,6-dichloro-1,4-benzoquinones with zinc 2-aminobenzenthiolates (4) in the presence of a base in Methyl Cellosolve. On the other hand, the reaction of 2,5-dianilino-3,6-dichloro-1,4-benzoquinone (3a) with 4 in DMF proceeded unexpectedly to give 7,14-dihydro-6,13-triphenodithiazinequinones by eliminating the anilino groups of 3a.
Correction: Corrigendum: Circadian control of bile acid synthesis by a KLF15-Fgf15 axis (2015)

Nature Communications 6: Article number: 7231 (2015); Published: 4 June 2015; Updated: 27 August 2015. The original version of this Article incorrectly named the author Shuxin Han as Sean Han. This has now been corrected in both the PDF and HTML versions of the Article.
Modeling and sensing risky user behavior on mobile devices (2014)

As mobile technology begins to dominate computing, understanding how their use impacts security becomes increasingly important. Fortunately, this challenge is also an opportunity: the rich set of sensors with which most mobile devices are equipped provide a rich contextual dataset, one that should enable mobile user behavior to be modeled well enough to predict when users are likely to act insecurely, and provide cognitively grounded explanations of those behaviors. We will evaluate this hypothesis with a series of experiments designed first to confirm that mobile sensor data can reliably predict user stress, and that users experiencing such stress are more likely to act insecurely.
Biomass Valorization for Fuel and Chemicals Production – A Review (2018)

The transformation of biomass into fuel and chemicals is becoming increasingly popular as a way to mitigate global warming and diversify energy sources. Biomass is a renewable, carbon-neutral resource, and fuels derived from biomass usually burn more cleanly than fossil fuels. It has been estimated that biomass could provide about 25% of global energy requirements. In addition, biomass can also be a source of valuable chemicals, pharmaceuticals and food additives. Several kinds of biomass can be converted to fuel and chemicals. Examples are wood and wood waste, agricultural crops, agricultural waste, litter from animal feedlots, waste from food processing operations and sludge from water treatment plants.Various processes can be used to convert biomass to energy. The biomass can be burned, transformed into a fuel gas through partial combustion, into a biogas through fermentation, into bioalcohol through biochemical processes, into biodiesel, into a bio-oil or into a syngas from which chemicals and fuels can be synthesized. Wood combustion, bioethanol production from either sugarcane or corn, and biodiesel production from oilseeds are currently the most economically significant processes but still need significant improvements. A detailed review of the many processes that can convert biomass into fuels and chemicals shows that no individual process is without drawbacks. As a result, it is recommended that a biorefinery is the best solution to combine and integrate various processes to maximize economic and environmental benefits, while minimizing waste and pollution.
Preparation and Reactions of Di-1,3,5-triazinyl Ethers. I. Preparation of Di-1,3,5-triazinyl Ethers (1978)

Abstract Di-1,3,5-triazinyl ethers have been prepared by the condensation of 2-chloro-1,3,5-triazines with potassium 1,3,5-triazin-2-olate in acetonitrile in the presence of a small amount of cyclic polyether. Di-1,3,5-triazinyl ether was also prepared by the reaction of 2-chloro-1,3,5-triazine with potassium nitrite.
Gallbladder polyp mimicking an obstructive calculus. (1978)

The second documented case of obstructing polyp of the gallbladder-an extremely rare lesion-is presented. Symptoms were indistinguishable from those of acute obstructive cholecystitis. The mechanism of obstruction is hypothesized.
Intrapartum Magnesium Sulfate and the Potential for Cardiopulmonary Drug–Drug Interactions (2014)

Intrapartum administration of drugs that interact with MgSO4 is common and associated with prolonged hospital stays and potentially cardiopulmonary drug-drug interactions. Caution is warranted when prescribing MgSO4 in combination with known interacting medications.
A general process for the development of peptide-based immunoassays for monoclonal antibodies (2010)

Phage-displayed peptide libraries can be a source of highly specific mimetopes for therapeutic mAb. The biotinylated forms of those peptides are compatible with conventional ELISA methods with sensitivities comparable to other assay methods and sufficient for pharmacological studies of those mAb given at high dose. The process outlined here can be applied to any mAb to enable improved pharmacokinetic analysis during the development and clinical use of this class of therapies.
Using phosphoproteomics and next generation sequencing to discover novel therapeutic targets in patient antibodies (2020)

<b>Introduction</b>: The goal of this review is to survey proteomics and next generation sequencing (NGS) approaches to discover phosphopeptide neoantigens that can be used as targets for individualized cancer therapy and diagnostics. Neoantigens are peptides or proteins that can be derived from tumor-specific or viral alterations containing mutated sequences including different post-translational modifications that will not be found in normal human cells. These neoantigens can be highly specific for the individual affected tissue. Mass spectrometry combined with NGS allow identifying autoantibodies specific for neoantigens, including neoantigens that contain phosphorylated moieties. <b>Areas covered</b>: We discuss recognition of neoantigens through the application of phosphoproteomics. We focus on phosphoprotein modifications that can be accurately identified with mass spectrometry and can serve as rarely described targets for immunotherapy and diagnosis in cancer and autoimmune diseases. Identification of these phospho-moiety containing neoantigens gives the possibility to search for corresponding autoantibodies, especially if NGS and mass spectrometry are combined. <b>Expert commentary</b>: Identification of post-translational modifications with mass spectrometry gives possibilities to define modifications that are specific for cancer and autoimmune diseases. This technology develops rapidly, and gives opportunities to select neoantigens that are highly specific for cancer and immune diseases and to sequence autoantibodies involved.
Solid Oxide Fuel Cell Technology Development and its Distributed Generation Market Potential (2020)

Presented by NETL at 2017 Fuel Cell Seminar and Exposition, 11/17
The interaction of software prefetching with ILP processors in shared-memory systems (1997)

Current microprocessors aggressively exploit instruction-level parallelism (ILP) through techniques such as multiple issue, dynamic scheduling, and non-blocking reads. Recent work has shown that memory latency remains a significant performance bottleneck for shared-memory multiprocessor systems built of such processors.This paper provides the first study of the effectiveness of software-controlled non-binding prefetching in shared memory multiprocessors built of state-of-the-art ILP-based processors. We find that software prefetching results in significant reductions in execution time (12% to 31%) for three out of five applications on an ILP system. However, compared to previous-generation system, software prefetching is significantly less effective in reducing the memory stall component of execution time on an ILP system. Consequently, even after adding software prefetching, memory stall time accounts for over 30% of the total execution time in four out of five applications on our ILP system.This paper also investigates the interaction of software prefetching with memory consistency models on ILP-based multiprocessors. In particular, we seek to determine whether software prefetching can equalize the performance of sequential consistency (SC) and release consistency (RC). We find that even with software prefetching, for three out of five applications, RC provides a significant reduction in execution time (15% to 40%) compared to SC.