gebhart/patrepeval huggingface dataset:
Chirality and its importance in drug development: a synthetic chemist's perspective (1991)

Conference Article| April 01 1991 Chirality and its importance in drug development: a synthetic chemist's perspective Stanley M. Roberts Stanley M. Roberts 1Department of Chemistry, University of Exeter, Exeter EX4 4QD, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1991) 19 (2): 446–453. https://doi.org/10.1042/bst0190446 Article history Received: December 07 1990 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation Stanley M. Roberts; Chirality and its importance in drug development: a synthetic chemist's perspective. Biochem Soc Trans 1 April 1991; 19 (2): 446–453. doi: https://doi.org/10.1042/bst0190446 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: DIBAL, di-isobutylaluminium hydride, LDA, lithium di-isopropylamide, PGF2α, prostaglandin F2α This content is only available as a PDF. © 1991 Biochemical Society1991 Article PDF first page preview Close Modal You do not currently have access to this content.
Occludin as a possible determinant of tight junction permeability in endothelial cells (1997)

Endothelial cells provide a crucial interface between blood and tissue environments. Free diffusion of substances across endothelia is prevented by the endothelial tight junction, the permeability of which varies enormously depending on tissue. Endothelial cells of the blood-brain barrier possess tight junctions of severely limited permeability, whereas those of non-neural tissue are considerably leakier, but the molecular basis for this difference is not clear. Occludin is a major transmembrane protein localizing at the tight junction. In this study, we show, by immunocytochemistry, that occludin is present at high levels and is distributed continuously at cell-cell contacts in brain endothelial cells. In contrast, endothelial cells of non-neural tissue have a much lower expression of occludin, which is distributed in a discontinuous fashion at cell-cell contacts. The apparent differences in occludin expression levels were directly confirmed by immunoblotting. The differences in occludin protein were reflected at the message level, suggesting transcriptional regulation of expression. We also show that occludin expression is developmentally regulated, being low in rat brain endothelial cells at postnatal day 8 but clearly detectable at post-natal day 70. Our data indicate that regulation of occludin expression may be a crucial determinant of the tight junction permeability properties of endothelial cells in different tissues.
On Optimality Criteria for V2G Charging Strategies (2012)

There is a growing interest in treating EVs not only as controllable loads, but also as storage systems, which are able to reduce stresses on the grid during peak times by injecting power back, also known as Vehicle to Grid (V2G). In this paper, we formulate the problem of returning electrical load to the grid as an optimisation problem whose goal is to minimise the costs of drawing energy from the vehicles, while maintaining the effect of energy return on the environment below a safety level.
Nebringen, Münsingen und Monte Bibele – zum archäologischen und bioarchäometrischen Nachweis von Mobilität im 4./3. Jahrhundert v. Chr (2022)

Die Gräberfelder Nebringen (Lkr. Böblingen/D), Münsingen-Rain (Kt. Bern/CH) und Monte Bibele (prov. Bologna/I) sind wichtige Fundorte im Kern- und Expansionsraum der Latènekultur, die sich im 4./3. Jahrhundert v. Chr. über die Alpen bis nach Norditalien ausweitete. Einige Grabfunde geben Hinweise auf Mobilität unter den Bestatteten. Dieses Phänomen wird in den Ergebnissen einer Strontiumisotopenanalyse teilweise widergespiegelt. Ortswechsel konnten für einzelne Individuen oder kleinere Personengruppen nachgewiesen werden – die Bewegung großer Bevölkerungsteile, wie sie uns von den antiken Autoren als keltische Wanderungen überliefert ist, wird hingegen nicht bestätigt.
Exploring the energy landscape of resistive switching in antiferromagnetic Sr(3)Ir(2)O(7) (2018)

We study the resistive switching triggered by an applied electrical bias in antiferromagnetic Mott insulator Sr(3)Ir(2)O(7). The switching was previously associated with an electric-field driven structural transition. Here we use time-resolved measurements of the switching to probe the energy barrier associated with the transition. We quantify the changes in the energy barrier height with respect to the applied bias and find a linear decrease of the barrier with increasing bias. Our observations support the potential of antiferromagnetic transition metal oxides for spintronic applications.
Data from Dominant-Negative Histone H3 Lysine 27 Mutant Derepresses Silenced Tumor Suppressor Genes and Reverses the Drug-Resistant Phenotype in Cancer Cells (2023)

&lt;div&gt;Abstract&lt;p&gt;Histone modifications and DNA methylation are epigenetic phenomena that play a critical role in many neoplastic processes, including silencing of tumor suppressor genes. One such histone modification, particularly at H3 and H4, is methylation at specific lysine (K) residues. Whereas histone methylation of H3-K9 has been linked to DNA methylation and aberrant gene silencing in cancer cells, no such studies of H3-K27 have been reported. Here, we generated a stable cell line overexpressing a dominant-negative point mutant, H3-K27R, to examine the role of that specific lysine in ovarian cancer. Expression of this construct resulted in loss of methylation at H3-K27, global reduction of DNA methylation, and increased expression of tumor suppressor genes. One of the affected genes, &lt;i&gt;RASSF1&lt;/i&gt;, was shown to be a direct target of H3-K27 methylation–mediated silencing. By increasing DNA-platinum adduct formation, indicating increased access of the drug to target DNA sequences, removal of H3-K27 methylation resensitized drug-resistant ovarian cancer cells to the chemotherapeutic agent cisplatin. This increased platinum-DNA access was likely due to relaxation of condensed chromatin. Our results show that overexpression of mutant H3-K27 in mammalian cells represents a novel tool for studying epigenetic mechanisms and the Histone Code Hypothesis in human cancer. Such findings show the significance of H3-K27 methylation as a promising target for epigenetic-based cancer therapies. (Cancer Res 2006; 66(11): 5582-91)&lt;/p&gt;&lt;/div&gt;
Open-Loop Prediction in H.264/AVC for High Definition Sequences (2007)

H.264/AVC is the newest, state-of-the-art, video compression standard. It leads to substantial performance improvement compared to other existing standards. However, like other video standards, it is a hybrid predictive-transform coder. In this paper we propose a more efficient approach to implement the prediction stage. The idea is to employ original data rather than reconstructed ones to perform prediction tests before choosing the best mode. The residue, however, is evaluated using previously decoded data to avoid drifting. Results show that, for high definition sequences, the quality loss is negligible. We are, thus, able to parallelize the intra and inter-prediction parts, which are the most time consuming operations in H.264/AVC.
Demonstration of SDN Based Optical Network Virtualization and Multidomain Service Orchestration (2014)

This paper describes a demonstration of SDN-based optical transport network virtualization and orchestration. Two scenarios are demonstrated: a dynamic setup of optical connectivity services inside a single domain as well as a multidomain service orchestration over a shared optical infrastructure using the architecture defined in the STRAUSS project.
Loss of isoprenylation significantly reduces IgE mediated mast cell activation (2022)

Abstract Allergic disease is the 6th leading cause of chronic illness in the US and accounts for billions of dollars in healthcare costs annually. Mast cells are tissue resident innate immune cells linked to allergic disease and activated by IgE and other ligands. Upon activation they release histamine, cytokines, chemokines, proteases, and lipid mediators evoking allergic symptoms. New ways of targeting mast cells could greatly benefit allergic disease therapy. Previous findings showed repurposing of statin drugs, such as Fluvastatin, reduced allergic symptoms in vitro and in vivo. We found that Fluvastatin suppresses IgE-mediated mast cell activation by inhibiting isoprenylation of proteins. However, statin effects were dependent on genetic background. To avert genetic background dependency, we tested the hypothesis that a dual farnesyl and geranylgeranyl transferase inhibitor (FGTI 2734) would suppress allergic disease withoutgenetic background limitations. We show that FGTI 2734 reduced IgE-mediated degranulation and cytokine production by bone marrow derived mast cells from multiple genetic backgrounds. Similarly, FGTI 2734 also suppressed IgE-mediated anaphylaxis on multiple genetic backgrounds. These in vivo effects extended to an allergic asthma model, in which FGTI 2734 inhibited pulmonary inflammation. Finally, we show that FGTI-2734 can significantly reduce IgE-induced cytokine production from human skin mast cells. These data show that dual farnesyl and geranylgeranyl transferase inhibitors may be an effective therapeutic treatment for mast cell-associated diseases. Supported by NIH (1RO1AI101153)
The Phylogenetically-Related Pattern Recognition Receptors EFR and XA21 Recruit Similar Immune Signaling Components in Monocots and Dicots (2015)

During plant immunity, surface-localized pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs). The transfer of PRRs between plant species is a promising strategy for engineering broad-spectrum disease resistance. Thus, there is a great interest in understanding the mechanisms of PRR-mediated resistance across different plant species. Two well-characterized plant PRRs are the leucine-rich repeat receptor kinases (LRR-RKs) EFR and XA21 from Arabidopsis thaliana (Arabidopsis) and rice, respectively. Interestingly, despite being evolutionary distant, EFR and XA21 are phylogenetically closely related and are both members of the sub-family XII of LRR-RKs that contains numerous potential PRRs. Here, we compared the ability of these related PRRs to engage immune signaling across the monocots-dicots taxonomic divide. Using chimera between Arabidopsis EFR and rice XA21, we show that the kinase domain of the rice XA21 is functional in triggering elf18-induced signaling and quantitative immunity to the bacteria Pseudomonas syringae pv. tomato (Pto) DC3000 and Agrobacterium tumefaciens in Arabidopsis. Furthermore, the EFR:XA21 chimera associates dynamically in a ligand-dependent manner with known components of the EFR complex. Conversely, EFR associates with Arabidopsis orthologues of rice XA21-interacting proteins, which appear to be involved in EFR-mediated signaling and immunity in Arabidopsis. Our work indicates the overall functional conservation of immune components acting downstream of distinct LRR-RK-type PRRs between monocots and dicots.
Solutions to Problems Inherent in Spoken-language Translation: The ATR-MATRIX Approach (1999)

ATR has built a multi-language speech translation system called ATR-MATRIX. It consists of a spoken-language translation subsystem, which is the focus of this paper, together with a highly accurate speech recognition subsystem and a high-definition speech synthesis subsystem. This paper gives a road map of solutions to the problems inherent in spoken-language translation. Spokenlanguage translation systems need to tackle difficult problems such as ungrammaticality, contextual phenomena, speech recognition errors, and the high-speeds required for real-time use. We have made great strides towards solving these problems in recent years. Our approach mainly uses an example-based translation model called TDMT. We have added the use of extralinguistic information, a decision tree learning mechanism, and methods dealing with recognition errors. 1 Introduction ATR began its study of speech translation in the mideighties and has developed a multi-language speech translatio...
WLAN oriented optimization of process bus in IEC 61850-based substation communication network (2015)

The communication standard IEC 61850 which is defined for information exchange in smart grids, has been increasingly used for Substation Automation Systems (SAS). Current mainstream communication technologies such as switched Ethernet and TCP/IP have been adopted for the communications networking. However, with the growing amount of IEDs in one collision domain, a risk of violation of transmission time requirement increases. This raises a concern for optimization of IEC 61850 based substation communication network. The industrial wireless LAN technologies are gaining interest power utility sector, especially for less critical smart distribution network applications. This paper proposes methods of software simulation for performance evaluation of communications network in power substations. This method enables to test the performance of process bus only using Sampled Value (SV) and obtains a maximum number of WLAN IEDs in one collision domain subject to various conditions.
The CCR5 and CXCR4 Coreceptors Are Both Used by Human Immunodeficiency Virus Type 1 Primary Isolates from Subtype C (2003)

Human immunodeficiency virus type 1 (HIV-1) subtype C viruses with different coreceptor usage profiles were isolated from 29 South African patients with advanced AIDS. All 24 R5 isolates were inhibited by the CCR5-specific agents, PRO 140 and RANTES, while the two X4 viruses and the three R5X4 viruses were sensitive to the CXCR4-specific inhibitor, AMD3100. The five X4 or R5X4 viruses were all able to replicate in peripheral blood mononuclear cells that did not express CCR5. When tested using coreceptor-transfected cell lines, one R5 virus was also able to use CXCR6, and another R5X4 virus could use CCR3, BOB/GPR15, and CXCR6. The R5X4 and X4 viruses contained more-diverse V3 loop sequences, with a higher overall positive charge, than the R5 viruses. Hence, some HIV-1 subtype C viruses are able to use CCR5, CXCR4, or both CXCR4 and CCR5 for entry, and they are sensitive to specific inhibitors of entry via these coreceptors. These observations are relevant to understanding the rapid spread of HIV-1 subtype C in the developing world and to the design of intervention and treatment strategies.
Lithium Mechanics: Roles of Strain Rate and Temperature and Implications for Lithium Metal Batteries (2019)

The lack of a reliable rechargeable lithium metal (Li-metal) anode is a critical bottleneck for next-generation batteries. The unique mechanical properties of lithium influence the dynamic evolution of Li-metal anodes during cycling. While recent models have aimed at understanding the coupled electrochemical-mechanical behavior of Li-metal anodes, there is a lack of rigorous experimental data on the bulk mechanical properties of Li. This work provides comprehensive mechanical measurements of Li using a combination of digital-image correlation and tensile testing in inert gas environments. The deformation of Li was measured over a wide range of strain rates and temperatures, and it was fitted to a power-law creep model. Strain hardening was only observed at high strain rates and low temperatures, and creep was the dominant deformation mechanism over a wide range of battery-relevant conditions. To contextualize the role of creep on Li-metal anode behavior, examples are discussed for solid-state batteries, "dead" Li, and protective coatings on Li anodes. This work suggests new research directions and can be used to inform future electrochemical-mechanical models of Li-metal anodes.
Table S1 from JQ1 Induces DNA Damage and Apoptosis, and Inhibits Tumor Growth in a Patient-Derived Xenograft Model of Cholangiocarcinoma (2023)

&lt;p&gt;Time course of increase in tumor volume in mice treated with vehicle (VC) or JQ1.&lt;/p&gt;
Crystallization of hollow mesoporous silica nanoparticles (2015)

International audience
Abstract 1404: A red-shifted fluorescent substrate for aldehyde dehydrogenase, AldeRed 588-A, for labeling viable ALDH-positive cells (2015)

Abstract Normal and cancer stem cells can be isolated based upon the enzymatic activity of aldehyde dehydrogenase I (ALDH1), a detoxifying enzyme responsible for oxidation of hazardous aldehyde byproducts. ALDH1 has been used to isolate cancer stem cells of various human malignancies including bladder, breast, cervical, colon, head and neck, liver, lung, pancreas, prostate and ovary. Currently, the ALDEFLUORTM assay which uses a fluorescent substrate is the only commercially available reagent for ALDH detection. The substrate used in this assay primarily emits in the green region of the electromagnetic spectrum (512nm). For researchers with valuable cell and transgenic animal models in which the target gene of interest has been tagged with eGFP, ALDEFLUOR therefore cannot be used. Selection of cells positive for aldehyde dehydrogenase (ALDH) activity from a green fluorescent background is thus difficult with existing reagents. We now describe a red-shifted fluorescent substrate for ALDH, AldeRed 588-A, that provides additional flexibility for utilizing ALDH as a marker for stem cell and cancer stem cell isolation. The activity of AldRed 588-A was compared with the ALDEFLUOR reagent and demonstrated similar ability to fractionate ALDHpos cells in a number of cell lines tested. Citation Format: Vi Chu, Konstantin Taganov, D Ramesh, Nick Asbrock, Martin Pomper. A red-shifted fluorescent substrate for aldehyde dehydrogenase, AldeRed 588-A, for labeling viable ALDH-positive cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1404. doi:10.1158/1538-7445.AM2015-1404
Linking Pharmacology to Clinical Reports: Cyclobenzaprine and Its Possible Association With Serotonin Syndrome (2011)

The link between cyclobenzaprine (Flexeril) administration and serotonin syndrome (SS) is subject to debate. Establishing such a connection is difficult because of the limited number of case reports available and the almost complete ignorance of its preclinical pharmacology. In this context, evidence is provided here that cyclobenzaprine blocks the serotonin and norepinephrine transporters and binds to another set of five serotonin receptors. SS should be considered when indicative signs occur in the context of cyclobenzaprine use.
Visualization of the Delivery and Release of Small RNAs Using Genetic Code Expansion and Unnatural RNA-Binding Proteins (2018)

Endogenously expressed noncoding RNAs are regulators of mRNA translation and affect diverse biological pathways spanning embryogenesis to cholesterol and fatty acid metabolism. Recently, microRNAs have become an important therapeutic target with strategies that employ oligonucleotides as both mimics and inhibitors of target microRNAs, successfully altering gene expression and cellular pathways in relevant contexts. However, delivery of these exogenous effectors remains a major challenge. Here, we present a method for evaluating noncoding RNA delivery using the viral suppressor of RNA silencing (VSRS) protein p19, optimized for cellular delivery of small RNAs. Using genetic code expansion technology, p-azidophenylalanine (AzF) was incorporated into a recombinant p19 protein and used to develop a fluorescence resonance energy transfer (FRET) sensor. AzF was used to attach FRET acceptor moieties using bioorthogonal chemistry. We show that this strategy not only gives rise to FRET signals that report on small RNA binding, but also allows for fluorescence quenching as well, convenient for measuring RNA release. We demonstrate the successful use of a modified version of the probe to track the delivery and release of small RNAs into mammalian cells. The results provide a basis for a further development of vehicles for small RNA delivery and release for intervening in noncoding RNA biology.
Draft Genome Sequences of Actinobacillus pleuropneumoniae Serotypes 2 and 6 (2010)

Actinobacillus pleuropneumoniae is a bacterial pathogen that causes highly contagious respiratory infection in pigs and has a serious impact on the production economy and animal welfare. As clear differences in virulence between serotypes have been observed, the genetic basis should be investigated at the genomic level. Here, we present the draft genome sequences of the A. pleuropneumoniae serotypes 2 (strain 4226) and 6 (strain Femo).
4343 Development of System Verification Plant for Advanced Humid Air Turbine (2006)

The Advanced Humid Air Turbine system improves the gas turbine thermal efficiency by using high-humidity air without needing a high firing temperature and pressure ratio. The following gas turbine elemental technologies concerning humidity air have been developed to realize the AHAT system: compressor, recuperator, turbine blade cooling, and combustor. A system verification plant that consists of a gas turbine generator (two-stage radial compressor with pressure ratio 8, two-stage axial turbine, single-can combustor), recuperator, humidification tower, water recovery system, and other components will be completed in a few months. The validation and performance test begin in October 2006. The expected performance is: rated output 3.6MW, efficiency 43% (LHV), and NO_x emissions less than 10ppm at 16% O2 from 50% to 100% load.
Cystometric Changes in Pressure-guided Acute Distension Rat Model of the Underactive Bladder™ (2009)

Acute bladder distension results in pressure ischemia, subsequent reperfusion injury, and ultimately damage to the detrusor. We hypothesize that changes in pressure may be a key factor to damage resulting from over-distension and developed a pressure-guided distension model to evaluate cystometric changes. Three groups of adult female Sprague Dawley rats (250 g) were used: a sham distended control group, a 3-day (3D) and 7-day (7D) follow-up group after pressure-guided distension. Under pentobarbital anesthesia, the urethra was clamped and saline was infused (0.04 mL/min) under continuous intravesical pressure monitoring. After reaching 120 cmH2O pressure, infusion was stopped and clamping was maintained for 30 minutes. For sham distension, all procedures except the saline infusion were done. There were no bladder ruptures during distension. Distension volumes needed to achieve the fixed pressure were variable (1.68–2.90 mL), but mean distension volumes were similar between the 3D and 7D groups (2.1 ± 0.1 mL vs. 2.2 ± 0.3 mL). After distension, maximal cystometric capacity and residual urine volume were increased at both time points. Voiding efficiencies were decreased significantly in both the 3D and 7D groups (p < 0.05) compared to controls. Maximal vesical pressure and bladder compliance showed no change before and after distension Our pressure-guided distension model exhibits cystometric characteristics of bladder decompensation. This model for the underactive bladder™ (UAB) may prove useful to further the development of targeted UAB™ treatments.