gebhart/patrepeval huggingface dataset:
Spinal A 3 adenosine receptor activation acutely restores morphine antinociception in opioid tolerant male rats (2021)

Opioids are potent analgesics, but their pain-relieving effects diminish with repeated use. The reduction in analgesic potency is a hallmark of opioid analgesic tolerance, which hampers opioid pain therapy. In the central nervous system, opioid analgesia is critically modulated by adenosine, a purine nucleoside implicated in the beneficial and detrimental actions of opioid medications. Here, we focus on the A<sub>3</sub> adenosine receptor (A<sub>3</sub> AR) in opioid analgesic tolerance. Intrathecal administration of the A<sub>3</sub> AR agonist MRS5698 with daily systemic morphine in male rats attenuated the reduction in morphine antinociception over 7 days. In rats with established morphine tolerance, intrathecal MRS5698 partially restored the antinociceptive effects of morphine. However, when MRS5698 was discontinued, these animals displayed a reduced antinociceptive response to morphine. Our results suggest that MRS5698 acutely and transiently potentiates morphine antinociception in tolerant rats. By contrast, in morphine-naïve rats MRS5698 treatment did not impact thermal nociceptive threshold or affect antinociceptive response to a single injection of morphine. Furthermore, we found that morphine-induced adenosine release in cerebrospinal fluid was blunted in tolerant animals, but total spinal A<sub>3</sub> AR expression was not affected. Collectively, our findings indicate that spinal A<sub>3</sub> AR activation acutely potentiates morphine antinociception in the opioid tolerant state.
ChemInform Abstract: Synthesis and anti‐Pneumocystis carinii Pneumonia Activity of Novel Dicationic Dibenzothiophenes and Orally Active Prodrugs. (2000)

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.
Effect of tumor infiltrating lymphocytes (TILs) and stromal CD68 on trastuzumab (T) benefit in early stage HER2 positive breast cancer (BC). (2015)

556 Background: The presence of high TILs has been implicated as a predictor of pathologic complete response (pCR) and decreased recurrence rates in BC patients. However, there is conflicting data for the benefit of T in the adjuvant setting for HER2 positive (HER2+) BC patients with high TILs. In addition, greater numbers of CD68 (+) cells (macrophage marker) in tumor stroma has been shown to be an independent prognosticator for reduced BC specific survival. Methods: Core biopsies from52 Her2+ BC patients treated with neoadjuvant (NAT) chemotherapy with or without T were identified. Two pathologists independently quantified stromal TILs and CD68 ratio (inside the TILs population) using Hematoxylin/Eosin and immunohistochemistry respectively. The association of TILs and CD68 with pCR rates was determined by Mann-Whitney U, Chi-square or Fisher’s exact test. Prognostic significance of TILs and CD68 ratio on pCR rates, disease free survival and overall survival (OS) was assessed by Kaplan-Meier analysis and log-rank test. Results: The median age and follow up for the cohort were 52 and 2.8 years, respectively. In the NAT setting, 40 patients received conventional chemotherapy and T (77%) and 12 patients were treated with chemotherapy alone (23%). Overall the pCR rate in the studied population was 40%. Eight patients (15%) had high levels of TILs ( ≥ 60%) and 20 patients (38%) had low CD68 ratio ( ≤ 60%). A high percentage of TILs was significantly correlated to low CD68 ratio (p < 0.0001). High levels of TILs and low CD68 ratio were each associated with greater pCR rates for the cohort of patients who received NAT T, respectively (p = 0.05, p = 0.03). Furthermore, pCR was predictive of better OS (p = 0.02) for the patients treated with NAT T. However, these associations were no longer significant when we performed the analysis on the whole population (p = 0.09, p = 0.32). Conclusions: Our results show that high levels of TILs are associated with low CD68 ratio, and both are predictors of pCR in patients with HER2+ BC receiving NAT T. Importantly, pCR as determined by CD68 and TILs translated into an OS benefit. TILs and CD68 ratio represent potential prognostic and predictive markers in patients with HER2+ BC.
Precision Assembly of Complex Cellular Microenvironments using Holographic Optical Tweezers (2015)

The accurate study of cellular microenvironments is limited by the lack of technologies that can manipulate cells in 3D at a sufficiently small length scale. The ability to build and manipulate multicellular microscopic structures will facilitate a more detailed understanding of cellular function in fields such as developmental and stem cell biology. We present a holographic optical tweezers based technology to accurately generate bespoke cellular micro-architectures. Using embryonic stem cells, 3D structures of varying geometries were created and stabilized using hydrogels and cell-cell adhesion methods. Control of chemical microenvironments was achieved by the temporal release of specific factors from polymer microparticles positioned within these constructs. Complex co-culture micro-environmental analogues were also generated to reproduce structures found within adult stem cell niches. The application of holographic optical tweezers-based micromanipulation will enable novel insights into biological microenvironments by allowing researchers to form complex architectures with sub-micron precision of cells, matrices and molecules.
Trends in digital game-based learning in the mobile era: a systematic review of journal publications from 2007 to 2016 (2018)

The application of mobile learning and the use of game-based instructional strategies have been demonstrated as promoting students' learning performances and motivation. Over the past decade, many researchers and educators have integrated mobile technology and the features of gaming into their instructional designs; however, there has been little systematic review of the applications and trends in mobile technology-supported gaming. In the present study, related international journal publications from 2007 to 2016 were reviewed by searching the WOS database. The aim of this literature review was to highlight the research domain and issues of promoting game-based learning in future mobile technology. Based on this review, trends in mobile game-based learning are proposed from various aspects, such as the adoption of mobile technologies, gaming types, application domains, learning strategies, research issues, research methods, and participants. Accordingly, several suggestions are given for future studies.
Simulation of Fumigant Transport and Volatilization from Tarped Broadcast Applications (2013)

We evaluated the ability of the HYDRUS 2D/3D model to simulate chloropicrin (CP) and 1,3‐dichloropropene (13D) fate, transport, and volatilization. Three fields with similar soil conditions were broadcast fumigated under a totally impermeable film (TIF). One field was used to calibrate HYDRUS by adjusting fumigant degradation rates, soil sorption coefficients, and TIF tarp resistance factors. In comparisons of simulated and measured soil gas concentrations, soil temperature, soil water contents, and inverse‐modeled estimates of fumigant volatilization flux, the model accurately simulated the basic individual processes of fumigant partitioning and degradation, heat transport, and soil water dynamics in the calibration field. Subsequent flux simulations of the remaining two fields were performed using only measured, independently estimated or calibrated inputs with no further adjustments. The magnitudes of simulated cumulative fluxes and both pre‐ and post‐tarpcut discrete flux densities were within the estimated range of uncertainty (factor of ∼2) of conventional inverse‐modeled field‐based flux estimates. However, the timing of maximum discrete flux densities was delayed by 1 to 2 d relative to inverse‐modeled estimates. While HYDRUS provided reasonably accurate flux estimates, it was also evident that parameterization, particularly for TIF tarp permeability properties, generally requires field‐based calibration because of a lack of representative field effective permeability data.
Manipulating volatile emission in tobacco leaves by expressingAspergillus nigerβ‐glucosidase in different subcellular compartments (2004)

Expression of the Aspergillus nigerbeta-glucosidase gene, BGL1, in Nicotiana tabacum plants (cv. Xanthi) had a profound effect on the volatile emissions of intact and crushed leaves. BGL1 was expressed under the control of the cauliflower mosaic virus (CaMV) 35S promoter and targeted to the cytoplasm, cell wall, lytic vacuole (LV), chloroplast or endoplasmic reticulum (ER). Subcellular localization was confirmed by gold immunolabelling, followed by transmission electron microscopy (TEM). Significant beta-glucosidase activity was observed in transgenic plants expressing BGL1 in the cell wall, LV and ER. Compared with controls, all intact transgenic leaves were found to emit increased levels of 2-ethylhexanol, as determined by gas chromatography-mass spectrometry (GC-MS) analysis of the headspace volatiles. Plants expressing BGL1 in the cell wall (Tcw) emitted more trans-caryophyllene than did non-transgenic controls, whereas plants expressing BGL1 in the ER (Ter) and LV (Tvc) emitted more cembrene than did non-transgenic controls. Volatiles released from crushed transgenic leaves and collected with solid-phase microextraction (SPME) polydimethylsiloxane fibre were distinctly enhanced. Significant increases in linalool, nerol, furanoid cis-linalool oxide, 4-methyl-1-pentanol, 6-methyl-hept-5-en-2-ol and 2-ethylhexanol were detected in transgenic plants when compared with wild-type controls. 3-Hydroxyl-beta-ionone levels were increased in crushed Tcw and Ter leaves, but were undetectable in Tvc leaves. The addition of glucoimidazole, a beta-glucosidase inhibitor, abolished the increased emission of these volatiles. These results indicate that the expression of a fungal beta-glucosidase gene in different subcellular compartments has the potential to affect the emission of plant volatiles, and thereby to modify plant-environment communication and aroma of agricultural products.
A multi-omics dataset for the analysis of Frontotemporal Dementia genetic subtypes (2020)

Abstract Understanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Systematic studies on human post-mortem brain tissue of patients with genetic subtypes of FTD are currently lacking. The Risk and Modyfing Factors of Frontotemporal Dementia (RiMod-FTD) consortium therefore has generated a multi-omics dataset for genetic subtypes of FTD to identify common and distinct molecular mechanisms disturbed in disease. Here, we present multi-omics datasets generated from the frontal lobe of post-mortem human brain tissue from patients with mutations in MAPT, GRN and C9orf72 and healthy controls. This data resource consists of four datasets generated with different technologies to capture the transcriptome by RNA-seq, and small RNA-seq, and supplemented this date with CAGE-seq, and methylation profiling. We show concrete examples on how to use the resulting data and confirm current knowledge about FTD and identify new processes for further investigation. This extensive multi-omics dataset holds great value to reveal new research avenues for this devastating disease.
Orthogonal Design of Experiments for Optimization of Lipid Nanoparticles for mRNA Engineering of CAR T Cells (2021)

Viral engineered chimeric antigen receptor (CAR) T cell therapies are potent, targeted cancer immunotherapies, but their permanent CAR expression can lead to severe adverse effects. Nonviral messenger RNA (mRNA) CAR T cells are being explored to overcome these drawbacks, but electroporation, the most common T cell transfection method, is limited by cytotoxicity. As a potentially safer nonviral delivery strategy, here, sequential libraries of ionizable lipid nanoparticle (LNP) formulations with varied excipient compositions were screened in comparison to a standard formulation for improved mRNA delivery to T cells with low cytotoxicity, revealing B10 as the top formulation with a 3-fold increase in mRNA delivery. When compared to electroporation in primary human T cells, B10 LNPs induced comparable CAR expression with reduced cytotoxicity while demonstrating potent cancer cell killing. These results demonstrate the impact of excipient optimization on LNP performance and support B10 LNPs as a potent mRNA delivery platform for T cell engineering.
Production of a Monoclonal Antibody Specific for the Major Outer Membrane Protein of Campylobacter jejuni and Characterization of the Epitope (2007)

Campylobacter species are important enteric pathogens causing disease in humans and animals. There is a lack of a good immunological test that can be used routinely to separate Campylobacter jejuni from other Campylobacter species. We produced monoclonal antibodies (MAbs) directed against the major outer membrane protein (MOMP) of C. jejuni using recombinant MOMP as the antigen. One MAb, designated MAb5C4 and of the immunoglobulin G1 isotype, was found to be potentially specific for C. jejuni. Dot blots demonstrated that MAb5C4 reacted with all 29 isolates of C. jejuni tested but did not react with 2 C. jejuni isolates, 26 other Campylobacter spp. isolates, and 19 non-Campylobacter isolates. Western blotting showed that MAb5C4 bound to a single protein band approximately 43 kDa in size, corresponding to the expected size of C. jejuni MOMP. The detection limit of MAb5C4 in a dot blot assay was determined to be about 5 x 10(3) bacteria. The epitope on the MOMP was mapped to a region six amino acids in length with the sequence 216GGQFNP221, which is 97% conserved among C. jejuni strains but divergent in other Campylobacter spp.; a GenBank search indicated that 95% of C. jejuni isolates will be able to be detected from non-Campylobacter spp. based on the highly specific and conserved region of the GGQFNP polypeptide. The epitope is predicted to be located in a region that is exposed to the periplasm. MAb5C4 is a potentially specific and sensitive MAb that can be used for the specific detection and identification of C. jejuni.
Amplified octave-spanning supercontinuum from chalcogenide waveguides for second-harmonic generation (2017)

Octave-spanning supercontinuum is generated in chalcogenide, Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">23</sub> Sb <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">7</sub> S <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">70</sub> , waveguides pumped at 1550 nm. The 2μm side is subsequently amplified in a Thulium-doped fiber amplifier and utilized for second-harmonic generation (SHG). The generated signal has 55 dB of signal-to-noise ratio.
Investigation of the Effects of Pipe Wall Roughness and Pipe Diameter on the Decompression Wave Speed in Natural Gas Pipelines (2012)

The shock tube experimental results have shown clearly that the decompression wave was slowed down in a pipe with a rough inner surface relative to that in a smooth pipe under comparable conditions. In the present paper a one-dimensional dynamic simulation model, named EPDECOM, was developed to investigate the effects of pipe wall roughness and pipe diameter on the decompression wave speed. Comparison with experimental results showed that the inclusion of frictional effects led to a better prediction than that of the widely used model implemented in GASDECOM. EPDECOM simulation results showed that the effect of roughness on the decompression wave speed is significant for pipe diameters less than 250 mm. However the decompression wave speed is nearly independent of the roughness for diameters above 250 mm as the frictional effect becomes negligible at such diameters.
Contact Resistance in Flat Thin Films (2009)

MEMS-fabricated electrical contacts are commonly used in MEMS relays.These electrical contacts can be as simple as two flat surfaces coming into contact [1].Modeling their contact force/resistance relationship can be difficult because much of the theory on contact resistance was developed for macro-scale contacts [2], and contact properties for MEMS-scale contacts do not always agree with those predicted by this theory [3].One contribution to this disagreement is that when the dimensions of the contact thickness are on the order of the a-spot dimensions, the spreading resistance is affected [4].In order to determine the relationship between contact force and resistance for a wide range of parameters, we have developed a two-coupon test system which allows the properties of these contacts to be empirically determined.The design of the two-coupon system allows for the rapid fabrication of multiple contact materials and geometries.The two-coupon system was used to test the contact resistance properties of sputtered and electroplated Au films in thicknesses of 0.1 μm, 0.3 μm, and 0.5 μm.Contact force was measured using a custom flexural force gauge and the 4-point contact resistance was measured using an integrated Kelvin Structure [5].The results are compared to traditional Holm theory to determine the effects of film thickness on spreading resistance.
Noble metal catalysts and processes for reforming of methane and other hydrocarbons (2023)

Processes for converting methane and/or other hydrocarbons to synthesis gas (i.e., a gaseous mixture comprising H<sub>2</sub> and CO) are disclosed, in which at least a portion of the hydrocarbon(s) is reacted with CO<sub>2</sub>. At least a second portion of the methane may be reacted with H<sub>2</sub>O (steam), thereby improving overall thermodynamics of the process, in terms of reducing endothermicity (ΔH) and the required energy input, compared to “pure” dry reforming in which no H2O is present. Catalysts for such processes advantageously possess high activity and thereby can achieve significant levels of methane conversion at temperatures below those used conventionally under comparable conditions. These catalysts also exhibit high sulfur tolerance, in addition to reduced rates of carbon (coke) formation, even in the processing (reforming) of heavier (e.g., naphtha boiling-range or jet fuel boiling-range) hydrocarbons. The robustness of the catalyst translates to high operating stability. A representative catalyst comprises 1 wt-% Pt and 1 wt-% Rh as noble metals, on a cerium oxide support.
Xanthan Gum Effects on Solubility and Emulsification Properties of Soy Protein Isolate (1997)

ABSTRACT The effect of xanthan gum (XG) on solubility and emulsifying properties of soy protein isolate (SPI) was evaluated. The solubility of SPI was increased by addition of XG (p &lt; 0.05). The emulsifying activity of SPI‐XG was 4 times higher than that of SPI or XG alone (p &lt; 0.05) and similar to that of bovine serum albumin (BSA) (P &gt; 0.05). The emulsifying stability of SPI‐XG dispersions was respectively 3 and 2 times higher than that of SPI and BSA (p &lt; 0.05). The solubility and emulsifying properties of SPI‐XG dispersions were stable over a wide range of pH (3.0 to 9.0), ionic strength (0.1 to 1.0M NaCl), and heat (85°C, 1 hr).
PEGylated Nanoscale Metal–Organic Frameworks for Targeted Cancer Imaging and Drug Delivery (2021)

Nanoscale metal-organic frameworks (nMOFs) are a unique type of hybrid materials, which are broadly applicable as cargo delivery systems. However, the relatively low material stability and insufficient cancer cell interacting capacity have limited nMOFs' applications in cancer theranostics. Herein, a zirconium-based nMOF UiO-66-N<sub>3</sub> was synthesized, and its surface was covalently functionalized with alkyne-containing polyethylene glycol (PEG) via the azide-alkyne click chemistry. After that, F3 peptide was attached for targeting of cancer cells (the material was denoted as UiO-66-PEG-F3). Doxorubicin (DOX) served as a therapeutic drug and a fluorescent label in this study, and it was transported into UiO-66-PEG conjugates with sufficient drug loading efficiency. pH-responsive release of DOX from UiO-66 conjugates was witnessed. The structural integrity of UiO-66-N<sub>3</sub> was maintained post the surface modification process. Flow cytometry and confocal fluorescence microscopy revealed that DOX/UiO-66-PEG-F3 had stronger accumulation in MDA-MB-231 cells (nucleolin<sup>+</sup>) compared with DOX/UiO-66-PEG. In order to track the pharmacokinetic behavior (organ distribution profile) <i>in vivo</i>, the positron-emitting zirconium-89 (<sup>89</sup>Zr) was incorporated into UiO-66-N<sub>3</sub>. Similar PEGylation and F3 peptide conjugation resulted in the formation of <sup>89</sup>Zr-UiO-66-PEG-F3. Serial positron emission tomography (PET) imaging demonstrated that the preferential accumulation of <sup>89</sup>Zr-UiO-66-PEG-F3 in MDA-MB-231 tumors, and their liver clearance was faster than PEGylated UiO-66 using noncovalent methods. Thus, the PEGylated nMOFs using covalent strategies may find broad application in future cancer theranostics.
Tenth topical meeting on the technology of fusion energy: Proceedings (1992)

This report contains papers on the following topics in fusion: alternate concepts and applications; plasma-facing components; magnetics; materials and tritium; safety, recycling and waste management; and blanket shield and neutronics. These paper have been processed separately elsewhere. (LSP).
Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis (2015)

Screening of a fragment library for PDE10A inhibitors identified a low molecular weight pyrimidine hit with PDE10A Ki of 8700 nM and LE of 0.59. Initial optimization by catalog followed by iterative parallel synthesis guided by X-ray cocrystal structures resulted in rapid potency improvements with minimal loss of ligand efficiency. Compound 15 h, with PDE10A Ki of 8.2 pM, LE of 0.49, and >5000-fold selectivity over other PDEs, fully attenuates MK-801-induced hyperlocomotor activity after ip dosing.