gebhart/patrepeval huggingface dataset:
Selective Aurora Kinase Inhibitors Identified Using a Taxol-Induced Checkpoint Sensitivity Screen (2011)

The members of the Aurora kinase family play critical roles in the regulation of the cell cycle and mitotic spindle assembly and have been intensively investigated as potential targets for a new class of anticancer drugs. We describe a new highly potent and selective class of Aurora kinase inhibitors discovered using a phenotypic cellular screen. Optimized inhibitors display many of the hallmarks of Aurora inhibition including endoreduplication, polyploidy, and loss of cell viability in cancer cells. Structure-activity relationships with respect to kinome-wide selectivity and guided by an Aurora B co-crystal structure resulted in the identification of key selectivity determinants and discovery of a subseries with selectivity toward Aurora A. A direct comparison of biochemical and cellular profiles with respect to published Aurora inhibitors including VX-680, AZD1152, MLN8054, and a pyrimidine-based compound from Genentech demonstrates that compounds 1 and 3 will become valuable additional pharmacological probes of Aurora-dependent functions.
Unsedated In‐office Transgastrostomy Esophagoscopy to Monitor Therapy in Pediatric Esophageal Disease (2017)

Monitoring therapy in esophageal inflammatory disorders such as eosinophilic esophagitis and reflux esophagitis often requires frequent endoscopic evaluation. We recently reported the effective use of unsedated in-office transnasal esophagoscopy that significantly decreased costs and anesthetic exposure associated with pediatric esophagoscopy in eosinophilic esophagitis. Here we report a series of pediatric patients with esophagitis with gastrostomy tubes who underwent unsedated transgastrostomy esophagoscopy (TGE) in an office setting. Nine patients (ages 16 months-21 years) tolerated TGE without significant adverse events. Biopsy specimens were adequate for evaluation. This series confirms that unsedated in-office TGE can be used to successfully obtain mucosal biopsies to monitor esophageal inflammatory conditions in children without the use of sedation.
Detailed investigation of real-time steering entropy sensitivity in calling events (2015)

On-board driver state monitoring is considered one of technologies that could reduce traffic accidents caused by human errors, particularly in cases of higher workload due to driver distraction. An approach to assessing driver workload using a real-time steering entropy (RSE) method has been proposed by the authors. RSE quantifies the nature of a driver's corrective steering with an index of relative entropy (RHp) from information theory. The higher the driver workload, the higher the RHp. In this paper, the RSE method was applied to naturalistic driving database gathered from 18 drivers in the United States under joint research between Virginia Tech Transportation Institute (VTTI) and Nissan Motor. RHp was calculated in off line simulation, and cases where the diver's state indicated higher RHp were reviewed in through using video. The result indicates that the RSE method detected over 80% of the cases within 300 sec from when the handheld call started. There may also be differences in the onset of RHp behavior between calls initiated by the driver (outgoing) and incoming calls.
Electron Beam Melting Technology Improvements (2019)

ORNL and Arcam AB have collaborated to improve and broaden the application and dissemination of electron beam melting (EBM) technology. While EBM is a promising additive manufacturing technology with the potential to revolutionize many industries, several issues prevent its widespread adoption at an industrial scale. In collaboration with Arcam, ORNL researchers have worked to improve the reliability of EBM processes using in-situ monitoring methods and data analytics, developed new scan strategies to allow site-specific microstructure control, and expanded EBM technologies to high-temperature materials. This report details the results of this collaboration.
Boron Trifluoride Induced Reactions of Phenylglycidyl Ethers: A Convenient Synthesis of Enantiopure, Stereodefined Fluorohydrins. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Audio–Only Access to Internet Information in a Car (2000)

In this paper, the authors describe research focusing on the design of an unobtrusive, non-visual browser for e-mail and Internet access that is suitable for automobile drivers. The system is a voice-driven interactive audio-only browser which can describe document structure and speak the contents of the document.
Using three scenarios to explain life expectancy in advanced cancer: attitudes of patients, family members, and other healthcare professionals (2022)

Patients, FMs, and HCPs found it helpful to receive personalized prognostic information formatted as three scenarios for survival. It was feasible, acceptable, and safe to use a web-based resource to do this.
Imaging of intrinsic optical stem cell changes in engineered tissues (2006)

Interactions between stem cells and the surrounding matrix are essential in the development of engineered tissues. Spectroscopic imaging of endogenous sources of optical contrast provides a non-invasive means for monitoring such interactions.
[The present epizootological situation in intensively bred cattle in relation to the morbidity and mortality of calves during their rearing]. (1984)

The rise and mass incidence of intestinal and respiratory infections in calves kept in large herds depend on a joint influence of infective agents and numerous endogenous and exogenous factors, mostly with non-specific action. Therefore, purely medical approach fails to provide efficient prevention. Detailed epizootological analysis is needed for taking actual measures; the analysis should concern potential respiratory and intestinal pathogens and should also cover the persistent infections such as IBR, BVD-MD and others. The immunological profile of herd, very unfavorable with the high culling rate, will improve as a result of the introduction of a purpose-oriented vaccination programme, higher level of colostral nutrition, and separate rearing of calves, isolated from the dams, in calf houses managed by the all-in-all-out system.
Skin Penetration of Fatty Acids from Soap Surfactants in Cleansers Dependent on Foam Bubble Size (2013)

Abstract Skin cleansers exhibiting less irritation are required. Although most skin cleansers are applied to the skin in a foam state, the amount of surfactant penetrating into the skin is measured in the solution state. Due to the fact that surfactant penetration causes skin irritation, liquid chromatography/mass spectrometry was used in this study to investigate, from the viewpoint of surfactant penetration, the correlation between foam characteristics and the condition of skin treated with foam. Results demonstrated that as the concentration of surfactant in water drainage from the foam decreased, the composition of surfactants in water drainage shifted to contain smaller amounts of longer‐chain surfactants, whereas the bubble size of the foam became smaller, notwithstanding any change in compounds. When several bubble sizes of foam were added to the skin, it was confirmed that the amount of surfactant penetrating into the skin depends on the levels in the water drainage. The amount of surfactant penetrating into the skin increased with foam bubble size. It was thought that the surfactant at the gas–liquid interface cannot act freely, and thus surfactants in the water drainage tended to penetrate the skin. These results suggest that along with the type of surfactant, both foam morphology and the actual way in which the foam is produced are also important factors that need to be considered when designing milder cleansers.
Ab initio studies of hydrocarbon peroxyl radicals (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAb initio studies of hydrocarbon peroxyl radicalsBrent H. Besler, Michael D. Sevilla, and Perry MacNeilleCite this: J. Phys. Chem. 1986, 90, 24, 6446–6451Publication Date (Print):November 1, 1986Publication History Published online1 May 2002Published inissue 1 November 1986https://pubs.acs.org/doi/10.1021/j100282a009https://doi.org/10.1021/j100282a009research-articleACS PublicationsRequest reuse permissionsArticle Views78Altmetric-Citations37LEARN 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 options Get e-Alerts
Reverting Immune Suppression to Enhance Cancer Immunotherapy (2020)

Tumors employ strategies to escape immune control. The principle aim of most cancer immunotherapies is to restore effective immune surveillance. Among the different processes regulating immune escape, tumor microenvironment-associated soluble factors, and/or cell surface-bound molecules are mostly responsible for dysfunctional activity of tumor-specific CD8<sup>+</sup>T cells. These dynamic immunosuppressive networks prevent tumor rejection at several levels, limiting also the success of immunotherapies. Nevertheless, the recent clinical development of immune checkpoint inhibitors or of molecules modulating cellular targets and immunosuppressive enzymes highlights the great potential of approaches based on the selective disruption of immunosuppressive networks. Currently, the administration of different categories of immunotherapy in combination regimens is the ultimate modality for impacting the survival of cancer patients. With the advent of immune checkpoint inhibitors, designed to mount an effective antitumor immune response, profound changes occurred in cancer immunotherapy: from a global stimulation of the immune system to a specific targeting of an immune component. This review will specifically highlight the players, the mechanisms limiting an efficient antitumor response and the current immunotherapy modalities tailored to target immune suppressive pathways. We also discuss the ongoing challenges encountered by these strategies and provide suggestions for circumventing hurdles to new immunotherapeutic approaches, including the use of relevant biomarkers in the optimization of immunotherapy regimens and the identification of patients who can benefit from defined immune-based approaches.
Anaerobic carbon monoxide metabolism by Pleomorphomonas carboxyditropha sp. nov., a new mesophilic hydrogenogenic carboxydotroph (2018)

Carbon monoxide (CO)-metabolism and phenotypic and phylogenetic characterization of a novel anaerobic, mesophilic and hydrogenogenic carboxydotroph are reported. Strain SVCO-16 was isolated from anaerobic sludge and grows autotrophically and mixotrophically with CO. The genes cooS and cooF, coding for a CO dehydrogenase complex, and genes similar to hycE2, encoding a CO-induced hydrogenase, were present in its genome. The isolate produces H2 and CO2 from CO, and acetate and formate from organic substrates. Based on the 16S rRNA sequence, it is an Alphaproteobacterium most closely related to the genus Pleomorphomonas (98.9%-99.2% sequence identity). Comparison with other previously characterized Pleomorphomonas showed that P. diazotrophica and P. oryzae do not metabolize CO, and P. diazotrophica does not grow anaerobically with organic substrates. Average nucleotide identity values between strain SVCO-16 and P. diazotrophica, P. oryzae or P. koreensis were 86.66 ± 0.21%. These values are below the boundary to define species (95%-96%). Digital DNA-DNA hybridization estimates between strain SVCO-16 and reference strains were also below the 70% threshold for species delineation: 29.1%-34.5%. Based on the differences in CO metabolism, genome analyses and cellular fatty acid composition, the isolate should be classified into the genus Pleomorphomonas as a representative of a novel species, Pleomorphomonas carboxyditropha. The type strain of Pleomorphomonas carboxyditropha is SVCO-16T (strain deposit numbers, DSM 106132T and TSD-119T).
Association Between Transient Interface Fluid on Intraoperative OCT and Textural Interface Opacity After DSAEK Surgery in the PIONEER Study (2014)

Eyes with TIF on iOCT are more likely to develop TIO in the postoperative period. It is believed that the process of gap closure results in TIO, possibly secondary to precipitated solutes, retained viscoelastic, or lamellar irregularities caused by delayed adhesion or uneven matching of lamellar fibrils.
Optimal design of sampling schedules for studying glucose kinetics with tracers (1989)

Minimum size sampling schedules for estimating glucose kinetic parameters from an impulsive (bolus) tracer injection in normal humans and rats are presented. Glucose kinetics are described by a two-compartment linear model, and reference values of the parameters are estimated from a data base with many samples. The optimal sampling schedule (OSS) is determined in each individual by using a D-optimal criterion and consists of four samples. A population optimal sampling schedule (POSS) applicable to all the individuals of a given population is then determined, and its reliability and efficiency in recovering kinetic parameters (e.g., rate constants, plasma clearance rate, and mean residence time) is assessed. The influence of model and measurement error on OSS is discussed. Moreover, the adoption of an enhanced POSS (EPOSS, 8 samples) is shown to improve accuracy and precision of parameter estimates in a predictable manner. Finally some suggestions are given for obtaining more information from turnover studies using a constant infusion of tracer, with or without a priming pulse of tracer.
The Lab Oddity Prevails: Discovery of Pan‐CDK Inhibitor (R)‐S‐Cyclopropyl‐S‐(4‐{[4‐{[(1R,2R)‐2‐hydroxy‐1‐methylpropyl]oxy}‐5‐(trifluoromethyl)pyrimidin‐2‐yl]amino}phenyl)sulfoximide (BAY 1000394) for the Treatment of Cancer (2013)

Lead optimization of a high-throughput screening hit led to the rapid identification of aminopyrimidine ZK 304709, a multitargeted CDK and VEGF-R inhibitor that displayed a promising preclinical profile. Nevertheless, ZK 304709 failed in phase I studies due to dose-limited absorption and high inter-patient variability, which was attributed to limited aqueous solubility and off-target activity against carbonic anhydrases. Further lead optimization efforts to address the off-target activity profile finally resulted in the introduction of a sulfoximine group, which is still a rather unusual approach in medicinal chemistry. However, the sulfoximine series of compounds quickly revealed very interesting properties, culminating in the identification of the nanomolar pan-CDK inhibitor BAY 1000394, which is currently being investigated in phase I clinical trials.
Abstract B4: Evaluation of VEGFxxxb isoforms as a predictive biomarker for anti-VEGF cancer therapy. (2013)

Abstract Biomarkers are critical tools for measuring efficacy of treatments or predicting which patients are mostly likely to respond to a particular therapy. Recently, the VEGF isoform, VEGF165b, was proposed to be a predictive marker for bevacizumab in metastatic colorectal cancer patients. VEGF165b is an anti-angiogenic splice variant that differs from its pro-angiogenic counterpart, VEGF165, by only six amino acids at the C-terminal end of the protein. Members of the VEGFxxxb isoform family are produced by alternative splicing of the 3’ untranslated region (UTR) to generate exon 8b, instead of the conventional exon 8 which produces exon 8a. The study of VEGF165b in colorectal cancer (Bates et al, Clinical Cancer Research, 2012) reported that patients with low VEGF165b:VEGFtotal ratio had improved PFS following bevacizumab + FOLFOX4 treatment, while individuals with higher VEGF165b:VEGFtotal ratios did not benefit. On the other hand, another recent study (Harris et al, PLoS One, 2012) reported that VEGFxxxb isoforms may be a RT-PCR artifact. In this study, we sought to test the role of VEGF165b in the response to anti-VEGF therapy using preclinical human tumor models, and to evaluate the prevalence of VEGFxxxb isoform in human cancer cells and normal tissues using RNA-Seq, a next generation sequencing (NGS) platform that is independent of RT-PCR. Our results show that xenograft tumors engineered to overexpress VEGF165b had similar growth kinetics, tumor vascular density and were equally sensitive to aflibercept or bevacizumab treatment in humanized VEGF SCID mice compared to their parental counterparts. These results indicate that VEGF165b does not have anti-angiogenic properties, and VEGF165b levels did not correlate with the efficacy of anti-VEGF therapy. Furthermore, although we were able to detect VEGF165b splice variants by NGS profiling in cells engineered to overexpress VEGF165b, no NGS evidence supporting the VEGFxxxb isoforms was found in a panel of 24 human cancer cell lines and 12 different types of human normal tissues. To our knowledge, this is the first report to survey VEGFxxxb isoforms using NGS RNA-seq technology. Overall, these studies suggest that closer inspection of VEGFxxxb isoforms may be required before employing VEGF165b as a predictive biomarker for anti-VEGF therapy. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B4. Citation Format: Wen Zhang, Cristina Abrahams, Ying Huang, Baosheng Li, Asma Parveen, Min Ni, Yi Wei, Yueming Ding, Eric Zhang, Hsin Chieh Lin, Gavin Thurston, Qing Zhang. Evaluation of VEGFxxxb isoforms as a predictive biomarker for anti-VEGF cancer therapy. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B4.
Shedding Light on the Extinction‐Enhancement Duality in Gold Nanostar‐Enhanced Raman Spectroscopy (2014)

Surface-enhanced Raman spectroscopy (SERS) has evolved from an esoteric physical phenomenon to a robust and effective analytical method recently. The need of addressing both the field enhancement and the extinction of nanoparticle suspensions, however, has been underappreciated despite its substantive impact on the sensing performance. A systematic experimental investigation of SERS enhancement and attenuation is performed in suspensions of gold nanostars, which exhibit a markedly different behavior in relation to conventional nanoparticles. The relationship is elucidated between the SERS enhancement and the localized surface plasmon resonance band, and the effect of the concentration of the gold nanostars on the signal propagation is investigated. It is shown that an optimal concentration of gold nanostars exists to maximize the enhancement factor (EF), and the maximum EF occurs when the LSPR band is blue-shifted from the excitation wavelength rather than at the on-resonance position.
Lens design with suppressed first order reflections (2010)

Optical systems with a reflected light condition, e.g. microscopes with reflected light illumination or fundus cameras, need to have weak first order ghosts or even to be completely free from them. Sequential ray tracing can be used to control optical performance and reflections on a ray basis during optimization. This is significantly more efficient in computation time and convergence than the usual approaches with non-sequential ray tracing or reconfigured optical systems to cover all critical ghosts. An ophthalmic lens for a fundus camera was designed with first order reflections stripped out by applying sequential ray tracing. The merit-function only had to be completed under certain conditions guaranteeing the absence of any reflections. No additional reconfiguration of the optical system in the design software was necessary.
New family of tilings of three-dimensional Euclidean space by tetrahedra and octahedra (2011)

It is well known that two regular tetrahedra can be combined with a single regular octahedron to tile (complete fill) three-dimensional Euclidean space . This structure was called the "octet truss" by Buckminster Fuller. It was believed that such a tiling, which is the Delaunay tessellation of the face-centered cubic (fcc) lattice, and its closely related stacking variants, are the only tessellations of that involve two different regular polyhedra. Here we identify and analyze a unique family comprised of a noncountably infinite number of periodic tilings of whose smallest repeat tiling unit consists of one regular octahedron and six smaller regular tetrahedra. We first derive an extreme member of this unique tiling family by showing that the "holes" in the optimal lattice packing of octahedra, obtained by Minkowski over a century ago, are congruent tetrahedra. This tiling has 694 distinct concave (i.e., nonconvex) repeat units, 24 of which possess central symmetry, and hence is distinctly different and combinatorically richer than the fcc tetrahedra-octahedra tiling, which only has two distinct tiling units. Then we construct a one-parameter family of octahedron packings that continuously spans from the fcc to the optimal lattice packing of octahedra. We show that the "holes" in these packings, except for the two extreme cases, are tetrahedra of two sizes, leading to a family of periodic tilings with units composed four small tetrahedra and two large tetrahedra that contact an octahedron. These tilings generally possess 2,068 distinct concave tiling units, 62 of which are centrally symmetric.
Synthesis and in Vitro Evaluation of 5-[18F]Fluoroalkyl Pyrimidine Nucleosides for Molecular Imaging of Herpes Simplex Virus Type 1 Thymidine Kinase Reporter Gene Expression (2008)

Two novel series of 5-fluoroalkyl-2'-deoxyuridines (FPrDU, FBuDU, FPeDU) and 2'-fluoro-2'-deoxy-5-fluoroalkylarabinouridines (FFPrAU, FFBuAU, FFPeAU) that have three, four, or five methylene units (propyl, butyl, or pentyl) at C-5 were prepared and tested as reporter probes for imaging herpes simplex virus type 1 thymidine kinase (HSV1- tk) gene expression. The Negishi coupling methodology was employed in efficiently synthesizing the radiolabeling precursors. All six 5-[(18)F]fluoroalkyl pyrimidines were readily prepared from 3-N-benzoyl-3',5'-di-O-benzoyl-protected 5-O-mesylate precursors in 17-35% radiochemical yield (decay-corrected). In vitro studies highlighted that all six [(18)F]-labeled nucleosides selectively accumulated in cells expressing the HSV1-TK protein and there was negligible uptake in control cells. [(18)F]FPrDU, [(18)F]FBuDU, [(18)F]FPeDU, and [(18)F]FFBuAU had the best uptake profiles. Despite their selective accumulation in HSV1- tk-expressing cells, all 5-fluoroalkyl pyrimidine nucleosides had low-to-negligible cytotoxic activity (CC50 > 1000-1209 microM). Ultimately, the results demonstrated that 5-[(18)F]fluoropropyl, [(18)F]fluorobutyl, and [(18)F]fluoropentyl pyrimidine nucleosides have the potential to be in vivo HSV1-TK PET reporter probes over a dynamic range of reporter gene expression levels.