gebhart/patrepeval huggingface dataset:
Enantiomers of 1-ethyl-7-[3-[(ethylamino)methyl]-1-pyrrolidinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid: preparation and biological activity (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnantiomers of 1-ethyl-7-[3-[(ethylamino)methyl]-1-pyrrolidinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid: preparation and biological activityTownley P. Culbertson, John M. Domagala, Jeffery B. Nichols, Stephen Priebe, and Richard W. SkeeanCite this: J. Med. Chem. 1987, 30, 10, 1711–1715Publication Date (Print):October 1, 1987Publication History Published online1 May 2002Published inissue 1 October 1987https://pubs.acs.org/doi/10.1021/jm00393a004https://doi.org/10.1021/jm00393a004research-articleACS PublicationsRequest reuse permissionsArticle Views812Altmetric-Citations28LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Interaction of C-1027 Chromophore with d(GTATAC)2:  A Binding Model Based on NMR Experiments (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationInteraction of C-1027 Chromophore with d(GTATAC)2: A Binding Model Based on NMR ExperimentsYasushi Okuno, Takashi Iwashita, Toshio Otani, and Yukio SugiuraView Author Information Institute for Chemical Research, Kyoto University Uji, Kyoto 611, Japan Suntory Institute for Bioorganic Research Wakayamadai, Shimamoto-cho Mishima-gun, Osaka 618, Japan Tokushima Research Center, Taiho Pharmaceutical Co., Ltd. Kawauchi-cho, Tokushima 771-01, Japan Cite this: J. Am. Chem. Soc. 1996, 118, 19, 4729–4730Publication Date (Web):May 15, 1996Publication History Received22 January 1996Published online15 May 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja9602051https://doi.org/10.1021/ja9602051rapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views114Altmetric-Citations7LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Chromophores,Genetics,Intercalation,Nucleic acid structure,Oligomers Get e-Alerts
Research Resource: Real-Time Analysis of Somatostatin and Dopamine Receptor Signaling in Pituitary Cells Using a Fluorescence-Based Membrane Potential Assay (2016)

Stable somatostatin analogues and dopamine receptor agonists are the mainstay for the pharmacological treatment of functional pituitary adenomas; however, only a few cellular assays have been developed to detect receptor activation of novel compounds without disrupting cells to obtain the second messenger content. Here, we adapted a novel fluorescence-based membrane potential assay to characterize receptor signaling in a time-dependent manner. This minimally invasive technique provides a robust and reliable read-out for ligand-induced receptor activation in permanent and primary pituitary cells. The mouse corticotropic cell line AtT-20 endogenously expresses both the somatostatin receptors 2 (sst2) and 5 (sst5). Exposure of wild-type AtT-20 cells to the sst2- and sst5-selective agonists BIM-23120 and BIM-23268, respectively, promoted a pertussis toxin- and tertiapin-Q-sensitive reduction in fluorescent signal intensity, which is indicative of activation of G protein-coupled inwardly rectifying potassium (GIRK) channels. After heterologous expression, sst1, sst3, and sst4 receptors also coupled to GIRK channels in AtT-20 cells. Similar activation of GIRK channels by dopamine required overexpression of dopamine D2 receptors (D2Rs). Interestingly, the presence of D2Rs in AtT-20 cells strongly facilitated GIRK channel activation elicited by the sst2-D2 chimeric ligand BIM-23A760, suggesting a synergistic action of sst2 and D2Rs. Furthermore, stable somatostatin analogues produced strong responses in primary pituitary cultures from wild-type mice; however, in cultures from sst2 receptor-deficient mice, only pasireotide and somatoprim, but not octreotide, induced a reduction in fluorescent signal intensity, suggesting that octreotide mediates its pharmacological action primarily via the sst2 receptor.
Metabotropic glutamate receptor signaling is required for NMDA receptor-dependent ocular dominance plasticity and LTD in visual cortex (2015)

A feature of early postnatal neocortical development is a transient peak in signaling via metabotropic glutamate receptor 5 (mGluR5). In visual cortex, this change coincides with increased sensitivity of excitatory synapses to monocular deprivation (MD). However, loss of visual responsiveness after MD occurs via mechanisms revealed by the study of long-term depression (LTD) of synaptic transmission, which in layer 4 is induced by acute activation of NMDA receptors (NMDARs) rather than mGluR5. Here we report that chronic postnatal down-regulation of mGluR5 signaling produces coordinated impairments in both NMDAR-dependent LTD in vitro and ocular dominance plasticity in vivo. The data suggest that ongoing mGluR5 signaling during a critical period of postnatal development establishes the biochemical conditions that are permissive for activity-dependent sculpting of excitatory synapses via the mechanism of NMDAR-dependent LTD.
A Cognitive Sub-Nyquist MIMO Radar Prototype (2019)

We present a cognitive prototype that demonstrates a colocated, frequency-division-multiplexed, multiple-input multiple-output (MIMO) radar, which implements both temporal and spatial sub-Nyquist sampling. The signal is sampled and recovered via the Xampling framework. Cognition is due to the fact that the transmitter adapts its signal spectrum by emitting only those subbands that the receiver samples and processes. Real-time experiments demonstrate sub-Nyquist MIMO recovery of target scenes with 87.5% spatio-temporal bandwidth reduction and signal-to-noise-ratio of -10 dB.
Microbiological Safety and Antibiogram Analysisof Selected Food Products Obtainedin the Marketplace of Peshawar and Mardan,KPK, Pakistan (2019)

Foodborne diseases are very frequent and can easily transmit from contaminated food and food handlers. Among the foodborne pathogens, strains of Staphylococcus aureus, Bacillus cereus, Listeria monocytogen and Clostridium are very important because of its presence in a wide range of foodstuffs. A total of 520 food samples were collected at Peshawar (50%) and Mardan (50%), Khyber Pakhtunkhwa, Pakistan, from April 2016 to March 2017. Isolates were cultured and discriminated by Gram stain, followed by biochemical identification, disk diffusion assay was performed using antibacterial and antifungal agents. Out of 520, only 122 (23.46%) samples were positive for various types of bacterial and fungal pathogens. Gram-positive bacteria was the predominant (70.49%) followed by fungal pathogens (26.23%) and Gram-negative bacterial pathogens (3.27%) among the total positive samples. Prominent bacterial samples were Staphylococcus aureus, Bacillus spp.,
Faculty Opinions recommendation of Effect of nanoparticle conjugation on gene silencing by RNA interference. (2010)

RNA interference (RNAi) is a cellular process whereby the silencing of a particular gene is mediated by short RNAs (siRNAs). Although siRNAs have great therapeutic potential, cellular delivery has been a challenge. Nanoparticle-siRNA conjugates have emerged as potential delivery vehicles; however, reports describing the effects of nanoparticle conjugation on RISC incorporation and subsequent gene silencing have been mixed. In this report, we have systematically evaluated the effect of siRNA coupling strategies using a model nanoparticle system with varying conjugation schemes. We show that the accessibility of the siRNA linked to the nanoparticle and the lability of the cross-linker are critical for efficient gene knockdown. PMID: 20518524 Funding information This work was supported by: Howard Hughes Medical Institute, United States NCI NIH HHS, United States Grant ID: U54-CA119349 NCI NIH HHS, United States Grant ID: U54-CA119335 NCI NIH HHS, United States Grant ID: R01-CA133404 NCI NIH HHS, United States Grant ID: R01-CA124427 NCI NIH HHS, United States Grant ID: P30-CA14051 NCI NIH HHS, United States Grant ID: P01-CA42063 More Less keyboard_arrow_down
RNAi-mediated rheostat for dynamic control of AAV-delivered transgenes (2022)

ABSTRACT Adeno-associated virus (AAV)-based gene therapy could be facilitated by the development of molecular switches to control the magnitude and timing of expression of therapeutic transgenes. RNA interference (RNAi)-based approaches hold unique potential as a clinically proven modality to pharmacologically regulate AAV gene dosage in a sequence-specific manner. We present a generalizable RNAi-based rheostat wherein AAV transgene expression is silenced using the clinically validated modality of chemically modified short interfering RNA (siRNA) conjugates or vectorized co-expression of short hairpin RNA (shRNA). For transgene induction, we employ REVERSIR technology, a synthetic high-affinity oligonucleotide complementary to the siRNA or shRNA guide strand to reverse RNAi activity and rapidly recover transgene expression. For potential clinical development, we report potent and specific siRNA sequences that may allow selective regulation of transgenes while minimizing unintended off-target effects. Our results establish a conceptual framework for RNAi-based regulatory switches with potential for infrequent dosing in clinical settings to dynamically modulate expression of virally-delivered gene therapies.
Methyl quantum tunneling in ionic liquid [DMIm][TFSI] facilitated by Bis(trifluoromethane)sulfonimide lithium salt (2018)

We probe, for the first time, quantum tunneling in the methyl groups of the ionic liquid [DMIm][TFSI] facilitated by the presence of Bis(trifluoromethane)sulfonimide lithium salt. The observation of tunneling is made possible by crystallization, rather than vitrification, of [DMIm][TFSI] at low temperature. Neutron scattering measurements detect quantum tunneling excitations at ~27 μeV at temperatures below 30 K in the presence of LiTFSI at a concentration of 1 mol/kg, but not in salt-free [DMIm][TFSI]. This indicates that the methyl rotational potential barrier is reduced by the presence of LiTFSI, thus bringing the tunneling excitations into the measurable range. The salt-induced reduction of the rotational barrier is corroborated by quasi-elastic scattering data associated with stochastic re-orientation of methyl groups measured between 40 and 60 K.
C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction (2018)

Alpha-synuclein is known to bind to small unilamellar vesicles (SUVs) via its N terminus, which forms an amphipathic alpha-helix upon membrane interaction. Here we show that calcium binds to the C terminus of alpha-synuclein, therewith increasing its lipid-binding capacity. Using CEST-NMR, we reveal that alpha-synuclein interacts with isolated synaptic vesicles with two regions, the N terminus, already known from studies on SUVs, and additionally via its C terminus, which is regulated by the binding of calcium. Indeed, dSTORM on synaptosomes shows that calcium mediates the localization of alpha-synuclein at the pre-synaptic terminal, and an imbalance in calcium or alpha-synuclein can cause synaptic vesicle clustering, as seen ex vivo and in vitro. This study provides a new view on the binding of alpha-synuclein to synaptic vesicles, which might also affect our understanding of synucleinopathies.
Comprehensive Nano-Mechanical and Tribological Characterization of Hair (2007)

This paper presents test procedures and results of tribological and mechanical characterization of hair, treated with various shampoo and conditioners. They allow for a comprehensive functional comparison of hair care products.
High-temperature stable fiber Bragg gratings with ultra strong cladding modes written using the phase mask technique and an infrared femtosecond laser: erratum (2020)

In this erratum, we correct the mistakes in Eqs. (2) and (2a) in Opt. Lett.45, 443 (2020).OPLEDP0146-959210.1364/OL.381111.
Abstract 15865: Novel, Highly Selective Direct Thrombin Inhibitors: Efficacy, Safety, and Tolerability Studies (2016)

Patients with atrial fibrillation and venous thromboembolism require anticoagulation prophylaxis/treatment. Direct oral anticoagulants (DOACs) offer certain advantages over warfarin and heparins, b...
Three-dimensional Optical Microscopy of Biological Specimens (1986)

The ability to analyze biological specimens in three dimensions represents one of the major achievements of modern structural biology. For all but the simplest repeating structures, three-dimensional analysis is a crucial prerequisite for understanding complex biological assemblies. Near atomic resolution analysis of of crystalline proteins, nucleic acids, and viruses by X-ray crystallography approaches the routine. The current frontier focuses on the three dimensional analysis of non-crystalline, non-symmetric biological structures of cellular dimension. Electron microscope tomography and three dimensional optical microscopy are perhaps the most powerful methods for these studies.
Simpson, Semmelweis, and Transformational Change (2005)

The first anesthetic for childbirth and the first recognition of the importance of hand hygiene in obstetrics coincidentally occurred within 5 months of one another in 1847. More than 150 years later, one would have thought that these milestone events would have been fully integrated into practice. However, individuals resist transformational change, which is defined as a fundamental alteration in their beliefs, attitude, and behavior, even when they are confronted with incontrovertible facts. This resistance to change may explain why, in 2005, a large percentage of health care providers still do not practice acceptable hand hygiene, and the pain of childbirth continues to be extolled by some as a necessary part of womanhood, just as pharmacologic pain relief is discouraged.
A validated bioanalytical HPLC method for pharmacokinetic evaluation of 2‐deoxyglucose in human plasma (2011)

2-Deoxyglucose (2-DG), an analog of glucose, is widely used to interfere with glycolysis in tumor cells and studied as a therapeutic approach in clinical trials. To evaluate the pharmacokinetics of 2-DG, we describe the development and validation of a sensitive HPLC fluorescent method for the quantitation of 2-DG in plasma. Plasma samples were deproteinized with methanol and the supernatant was dried at 45°C. The residues were dissolved in methanolic sodium acetate-boric acid solution. 2-DG and other monosaccharides were derivatized to 2-aminobenzoic acid derivatives in a single step in the presence of sodium cyanoborohydride at 80°C for 45 min. The analytes were separated on a YMC ODS C₁₈ reversed-phase column using gradient elution. The excitation and emission wavelengths were set at 360 and 425 nm. The 2-DG calibration curves were linear over the range of 0.63-300 µg/mL with a limit of detection of 0.5 µg/mL. The assay provided satisfactory intra-day and inter-day precision with RSD less than 9.8%, and the accuracy ranged from 86.8 to 110.0%. The HPLC method is reproducible and suitable for the quantitation of 2-DG in plasma. The method was successfully applied to characterize the pharmacokinetics profile of 2-DG in patients with advanced solid tumors.
Ventilation design of tour buses for safety, security, and a highly efficient virus elimination (2022)

Measures to prevent the spread of COVID-19 are critical across the globe. Although a tour bus can carry many people at once, the small closed space is crowded with many people for long periods. Therefore, there is an increased risk of infection on tour buses. The air outlet of an air conditioner is designed to prioritize heating and cooling over ventilation. The aim of this study was to improve the ventilation performance of tour buses. To this end, a large-scale ventilation simulation was carried out using a supercomputer. The results are as follows: (1) when the overall ventilation air flow rate was fixed, it was necessary to intensively install new outlets in the upper rear part of the tour bus for rapid ventilation and (2) the ventilation efficiency was higher when a small number of high-output outlets were installed in the stead of a large number of low-output outlets. The reason for more effective ventilation was to create a large airflow in the tour bus. We proposed the design of a highly efficient ventilation system in a current bus space and elucidated the appropriate layout of ventilation outlets and the optimal protocol for opening windows.
Low-Cost High-Energy Potassium Cathode (2017)

Potassium has as rich an abundance as sodium in the earth, but the development of a K-ion battery is lagging behind because of the higher mass and larger ionic size of K+ than that of Li+ and Na+, which makes it difficult to identify a high-voltage and high-capacity intercalation cathode host. Here we propose a cyanoperovskite KxMnFe(CN)6 (0 ≤ x ≤ 2) as a potassium cathode: high-spin MnIII/MnII and low-spin FeIII/FeII couples have similar energies and exhibit two close plateaus centered at 3.6 V; two active K+ per formula unit enable a theoretical specific capacity of 156 mAh g–1; Mn and Fe are the two most-desired transition metals for electrodes because they are cheap and environmental friendly. As a powder prepared by an inexpensive precipitation method, the cathode delivers a specific capacity of 142 mAh g–1. The observed voltage, capacity, and its low cost make it competitive in large-scale electricity storage applications.
Minimum register instruction sequence problem: revisiting optimal code generation for DAGs (2002)

We revisit the optimal code generation or evaluation order determination problem-the problem of generating an instruction sequence from a data dependence graph (DDG). In particular, we are interested in generating an instruction sequence S that is optimal in terms of the number of registers used by the sequence S. We call this MRIS (Minimum Register Instruction Sequence) problem. We developed an efficient heuristic solution for the MRIS problem based on the notion of instruction lineage. This solution facilitates the sharing of registers among instructions within a lineage and across lineages by exploiting the structure of a DDG. We implemented our solution on a production compiler and measured the reduction in the number of (spill) loads and (Spill) stores and the wall-clock execution time for the SPEC95 floating point benchmark suite. On average our method reduced the number of loads and stores by 11.5% and 15.9%, respectively, and decreased the total execution time by 2.5%.
Serial Scanning and Registration of High Resolution Quantitative Computed Tomography Volume Scans for the Determination of Local Bone Density Changes (1996)

Progress in development of the methods required to study bone remodeling as a function of time is reported. The following topics are presented: 'A New Methodology for Registration Accuracy Evaluation', 'Registration of Serial Skeletal Images for Accurately Measuring Changes in Bone Density', and 'Precise and Accurate Gold Standard for Multimodality and Serial Registration Method Evaluations.'
Assessment of Photosensitizer Dosimetry and Tissue Damage Assay for Photodynamic Therapy in Advanced‐stage Tumors¶ (2004)

ABSTRACT Photodynamic therapy (PDT) efficacy is a complex function of tissue sensitivity, photosensitizer (PS) uptake, tissue oxygen concentration, delivered light dose and some other parameters. To better understand the mechanisms and optimization of PDT treatment, we assessed two techniques for quantifying tissue PS concentration and two methods for quantifying pathological tumor damage. The two methods used to determine tissue PS concentration kinetic were in vivo fluorescence probe and ex vivo chemical extraction. Both methods show that the highest tumor to normal tissue PS uptake ratio appears 4 h after PS administration. Two different histopathologic techniques were used to quantify tumor and normal tissue damage. A planimetry assessment of regional tumor necrosis demonstrated a linear relationship with increasing light dose. However, in large murine tumors this finding was complicated by the presence of significant spontaneous necrosis. A second method (densitometry) assessed cell death by nuclear size and density. With some exceptions the densitometry method generally supported the planimetry results. Although the densitometry method is potentially more accurate, it has greater potential subjectivity. Finally, our research suggests that the tools or methods we are studying for quantifying PS levels and tissue damage are necessary for the understanding of PDT effect and therapeutic ratio in experimental in vivo tumor research.
Co-Secretion of Two Distinct Kappa Light Chains by the Mu-9 Hybridoma (1999)

Mu-9 is a monoclonal antibody (MAb) specific for the CSAp antigen (Ag) expressed by colorectal cancers. By using variable (V)-region-specific primers, the respective VH and VL sequences of Mu-9 were polymerase chain reaction (PCR)-amplified. However, chimeric Ab (cMu-9-1) constructed from these PCR-amplified V sequences failed to bind the CSAp Ag. Although the light chain of murine Mu-9 was not glycosylated, that of cMu-9-1 was found to be O-glycosylated, as confirmed by reducing SDS-PAGE analyses, glycoprotein blotting and O-linked specific deglycosylation studies. Removal of O-linked oligosaccharides either by enzymatic digestion or by blocking O-glycosylation with a specific inhibitor did not restore the immunoreactivity of cMu-9-1, indicating that light chain O-glycosylation was not the cause for lack of immunoreactivity. We reported earlier that screening of a Mu-9 cDNA library uncovered the presence of an additional light chain sequence that was later proven to be the authentic light chain of Mu-9. Analyses of the cDNA sequence encoding the nonimmunoreactive light chain, however, revealed no defects that would preclude the sequence from being translated and secreted by the murine hybridoma. By adapting the Mu-9 hybridoma culture to serum-free conditions, we confirmed the secretion of low levels of O-glycosylated light chain. The biological significance of the O-glycosylation as well as the cosecretion of both light chains with respect to allelic exclusion are discussed.