gebhart/patrepeval huggingface dataset:
Abstract #1683: mTOR pathway inhibition via folate receptor specific delivery of the folate-everolimus conjugate EC0565 (2009)

The discovery that expression of the membrane-bound, high affinity folate receptor (FR) occurs in a significant number of human malignancies has led to the development of many folate-targeted therapeutic agents. Studies in FR-positive tumor models have demonstrated remarkable anti-tumor activity of various folate-drug conjugates under conditions that do not appreciably cause toxicity. The ability to chemically link a variety of drugs to folate offers an array of choices for targeting different proteins and biochemical pathways within the FR-positive cell. For example, it is known that aberrations in mTOR pathway signaling can lead to the development and progression of many cancers and inflammatory diseases. Likewise, mTOR inhibitors, such as rapamycin and everolimus, have been studied extensively and have been clinically shown to exhibit immunosuppressive and anti-neoplastic effects. Here, we have investigated the ability of a novel folate-everolimus conjugate, named EC0565, to reduce the levels of phospho-ribosomal protein S6 (p-RPS6, a translation-regulating protein downstream of mTOR) in a panel of cell lines. The results of our studies demonstrated that EC0565 potently inhibited p-RPS6 (EC50 = 8.2 nM) in the high FR-expressing KB cell line; further, the activity of EC0565 was completely blocked at each dose level with a co-incubated excess of a benign folate analog, thus indicating that EC0565\#8217;s activity was FR-specific. We also observed a strong correlation between the level of FR expression and the ability of EC0565 to inhibit p-RPS6. For example, whereas 100 nM EC0565 caused near complete abrogation of p-RPS6 in KB cells, and substantial or measurable activity in IGROV and SKOV3 cell lines, levels of p-RPS6 were unaffected in the FR-negative A549 cell line. Importantly, when A549 cells were treated with untargeted everolimus, p-RPS6 was completely inhibited indicating that lack of activity with EC0565 was not due to lack of base drug activity against A549 cells. Kinetically, EC0565 activity lagged behind that of everolimus (t1/2 = 1.3 h and 0.48 h, respectively), which is in concordance with a FR-mediated, endocytic delivery mechanism. Despite the significant FR-specific activity observed at the molecular level, proliferative activity of KB cells was unaffected by either EC0565 or everolimus in vitro. However, some modest anti-tumor activity (i.e. tumor growth delay) was observed with a 3 \#956;mol/kg qdx5 dosing regimen against the KB xenograft tumor model in nude mice. Collectively, these data demonstrate that EC0565 blocks mTOR pathway activity by a FR-dependent mechanism, and they support further study with other FR-expressing cell/tumor models, especially in those that are proliferation-sensitive towards mTOR inhibition. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1683.
Versatile pharmacological activities of phytochemicals through their effects on nuclear receptors (2018)

Phytochemicals are well-known to exert versatile pharmacological activities, and these activities had been ascribed to their antioxidative activity and ability to interact with membranes. This review focuses on the activities of phytochemicals against nuclear receptors (NRs) and summarizes recent progress in this area, leading to elucidation of the versatile pharmacological activities of phytochemicals. The in vitro modes of action of 94 phytochemicals on 19 NRs and their in vivo modulatory activities in regulating the physiological functions of NRs, as well as the modulatory activities of some phytochemicals against NR signaling networks in the regulation of aquaporins and circadian rhythm, are described. These studies have revealed not only that there are phytochemicals capable of modulating multiple NRs but also that NRs perform their physiological roles in co-operation with other NRs through crosstalk between them as well as working independently. Hence, further efforts are needed to clarify the entire picture of the pharmacological activities of phytochemicals against NRs.
Teechan: Payment Channels Using Trusted Execution Environments (2016)

Blockchain protocols are inherently limited in transaction throughput and latency. Recent efforts to address performance and scale blockchains have focused on off-chain payment channels. While such channels can achieve low latency and high throughput, deploying them securely on top of the Bitcoin blockchain has been difficult, partly because building a secure implementation requires changes to the underlying protocol and the ecosystem. We present Teechan, a full-duplex payment channel framework that exploits trusted execution environments. Teechan can be deployed securely on the existing Bitcoin blockchain without having to modify the protocol. It: (i) achieves a higher transaction throughput and lower transaction latency than prior solutions; (ii) enables unlimited full-duplex payments as long as the balance does not exceed the channel's credit; (iii) requires only a single message to be sent per payment in any direction; and (iv) places at most two transactions on the blockchain under any execution scenario. We have built and deployed the Teechan framework using Intel SGX on the Bitcoin network. Our experiments show that, not counting network latencies, Teechan can achieve 2,480 transactions per second on a single channel, with sub-millisecond latencies.
Organometallic chemistry with buckminsterfullerene. Preparation and properties of an indenyliridium(I) complex (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrganometallic chemistry with buckminsterfullerene. Preparation and properties of an indenyliridium(I) complexRobert S. Koefod, Mark F. Hudgens, and John R. ShapleyCite this: J. Am. Chem. Soc. 1991, 113, 23, 8957–8958Publication Date (Print):November 1, 1991Publication History Published online1 May 2002Published inissue 1 November 1991https://pubs.acs.org/doi/10.1021/ja00023a060https://doi.org/10.1021/ja00023a060research-articleACS PublicationsRequest reuse permissionsArticle Views340Altmetric-Citations93LEARN 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
Use of NDT and Pocket Computers in Pavement Evaluation (1985)

The profile and clearance heights at seven bridges of the New Jersey approach roads to the George Washington Bridge needed upgrading. To do this, nondestructive test (NDT) techniques were carried out on the pavement surfaces to determine the subgrade properties under the existing pavement. The NDT dynamic load and the measured deflection basin were analyzed to calculate the subgrade parameters, the elastic modulus (E) the CBR, and the modulus of reaction (K). The testing and calculation of 100 points, under heavy traffic volume, were completed in four hours. The subgrade parameters were used to design the reconstructed new pavement structure for local environmental conditions and for 20‐yr projected traffic loading.
Dose translation between laboratory animals and human in preclinical and clinical phases of drug development (2018)

Preclinical Research & Development Appropriate translation and determination of the maximum recommended starting dose in human is a vital task in new drug development and research. Allometric scaling is the most frequently used approach for dose extrapolation based on normalization of dose-to-body surface area. Misinterpretation of allometric dose conversion and safety factor application can lead to major problems in calculating maximum recommended safe starting dose in first-in-human clinical trials. Therefore, dose translation always necessitates careful consideration of body surface area, pharmacological, physiological and anatomical factors, pharmacokinetic parameters, metabolic function, receptor, and life span. The concept of estimating the first-in-human dose, interspecies scaling between species and the factors influencing the dose escalation were reviewed. The pros and cons of various approaches to determine first-in-human dose including allometric scaling, pharmacokinetically guided approach, minimal anticipated biological effect level, pharmacokinetic-pharmacodynamic modeling, similar drug approach, and microdosing were explained. The five steps to estimate maximum recommended starting dose for human studies by scaling factor were elaborated. Few examples, illustrating the application of different approaches were also demonstrated along with concerns that may be considered while applying such methods. Furthermore, typical considerations in dose administration, dosing through diet, maximum absorbable dose, blood sampling, and anesthesia in animal species were discussed. In summary, this review may serve as a concise guide for predicting human equivalent dose from animal species for researchers involved in various phases of preclinical and early clinical drug development.
Über die Lichtabsorption verzweigter Polymethinfarbstoffe (1960)

Abstract Tri‐ und Pentamethincyanin‐Farbstoffe, deren Polymethinkette in α‐ bzw. γ(ms)‐Stellung verzweigt ist, unterscheiden sich von den entsprechenden unverzweigten Polymethinfarbstoffen in ihrer Lichtabsorption. Durch Vergleich der Absorptionsmaxima verzweigter und unverzweigter Cyanine läßt sich zeigen, daß die Absorption der verzweigten durch die längstkettigen Polymethinsysteme bedingt ist, die als Grenzformen an ihrer Mesomerie beteiligt sein können. Bei den α‐verzweigten Trimethincyaninen steht die Deutung der Lichtabsorption in guter Übereinstimmung mit den Ergebnissen von F. M. Hamer und Mitarbeitern über die Absorption dreikerniger Polymethine. Die γ‐verzweigten Pentamethincyanine zeigen zwei Maxima ähnlicher Intensität im sichtbaren Gebiet, wenn die Seitenkette endständig zwei elektronensaugende Gruppen trägt und nicht durch sterische Hinderung aus der Ebene der Hauptkette herausgedrängt wird. Die beiden Maxima lassen sich deuten als Überlagerung der Teilabsorptionen des unverzweigten Pentamethincyanins und des Triens, aus denen das verzweigte Cyanin zusammengesetzt erscheint. Die Breite der Absorptionsbande dreikerniger, α‐verzweigter Trimethincyanine spricht für eine unvollständige Ladungsresonanz zwischen den drei Kernen.
[Non-neoplastic central hearing loss--a review]. (1991)

Acquired central auditory disorders not due to a tumour are unusual. The well-known conditions such as hypoxic encephalopathy, erythroblastosis, bacterial meningitis and trauma are reviewed. Recent experimental and clinical studies contribute to progress in the understanding of the pathogenesis and etiology of these conditions. The pattern of presbyacusis and cortical deafness is discussed also. AIDS must be considered as a new cause of acquired central auditory dysfunction.
Are There 10 31 Virus Particles on Earth, or More, or Fewer? (2020)

The number of virus particles on Earth is frequently reported in the scientific literature and in general-interest publications as being on the order of 10<sup>31</sup>, with some confusion about whether this is a high or low estimate. This number is often given without a source, although it should be attributed to a paper by Hendrix et al. published in 1999 (R. W. Hendrix, M. C. Smith, R. N. Burns, M. E. Ford, and G. F. Hatfull, Proc Natl Acad Sci U S A 96:2192-2197, 1999, https://doi.org/10.1073/pnas.96.5.2192). As with any oft-repeated statistic, it is informative to know how it has been derived and whether it should be revised in the light of new evidence. I review the history of the 10<sup>31</sup> estimate and use more recent assessments of the number of bacterial and viral particles in various habitats to conclude that the best estimate of the number of virus particles on Earth ("the Hendrix product") remains close to 10<sup>31</sup> and is unlikely to be either much less or much more than that.
Polarized neutron diffraction and Moessbauer effect study of the magnetic ordering in wustite, FeyO (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolarized neutron diffraction and Moessbauer effect study of the magnetic ordering in wustite, FeyOClive Wilkinson, Anthony K. Cheetham, Gary J. Long, Peter D. Battle, and David A. O. HopeCite this: Inorg. Chem. 1984, 23, 20, 3136–3141Publication Date (Print):September 1, 1984Publication History Published online1 May 2002Published inissue 1 September 1984https://doi.org/10.1021/ic00188a023Request reuse permissionsArticle Views216Altmetric-Citations43LEARN 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 InReddit PDF (761 KB) Get e-Alertsclose Get e-Alerts
Partial Least Square Regression PLS-Regression (2007)

The impact of the findings from the Women's Health Initiative trial of estrogen plus progestin cannot be attributed to any real or imagined conflicts of interest between government, researchers, and journals. Rather, the findings overturned decades of dogma in part promoted by the pharmaceutical industry, and the reaction to these unexpected findings was in direct proportion to their importance in reversing a misguided practice of prescribing the drug for chronic disease prevention. The findings have been widely accepted, as shown by the sustained subsequent reduction in prescriptions. However, conflicts of interest may influence a minority unwilling to accept the findings. The decrease in the use of a drug with an adverse risk profile for prevention of chronic disease is a public good.
Feature Selection for Monotonic Classification (2011)

Monotonic classification is a kind of special task in machine learning and pattern recognition. Monotonicity constraints between features and decision should be taken into account in these tasks. However, most existing techniques are not able to discover and represent the ordinal structures in monotonic datasets. Thus, they are inapplicable to monotonic classification. Feature selection has been proven effective in improving classification performance and avoiding overfitting. To the best of our knowledge, no technique has been specially designed to select features in monotonic classification until now. In this paper, we introduce a function, which is called rank mutual information, to evaluate monotonic consistency between features and decision in monotonic tasks. This function combines the advantages of dominance rough sets in reflecting ordinal structures and mutual information in terms of robustness. Then, rank mutual information is integrated with the search strategy of min-redundancy and max-relevance to compute optimal subsets of features. A collection of numerical experiments are given to show the effectiveness of the proposed technique.
A high-efficiency, single-junction, back-surface GaAs concentrator solar cell: Annual subcontract report, 1 February 1985-30 April 1986 (1987)

The goals of Phase I of this research program were to determine the performance potential and technological feasibility of the Al/sub x/Ga/sub 1-x/As-GaAs back-surface, point-contact concentrator solar cell. The scope of the work required that the goals would be achieved by applying an analytical model, a corresponding computer simulation, and thorough preliminary material growth and cell fabrication. The computer simulation provided realistic, quantitative projections of cell performance. Epitaxial growth and device fabrication demonstrated the technological feasibility of the structure and identified key issues to be resolved in Phase II. Computer modeling results are presented. An optimized cell design and performance characteristics of similar cell designs were investigated. The optimum value of each parameter was obtained by allowing only that parameter to vary over a selected range and then determining the value at maximum efficiency. Simulation results showed that 30% efficiency may be obtained under operational conditions of 10T solar concentration and 300K.
Molecular subtyping of Neisseria meningitidis serogroup B: comparison of five methods (1996)

In order to compare methods for subtyping Neisseria meningitidis serogroup B isolates, 96 isolates obtained from various locations in the United States and northwestern Europe were subtyped by five methods: monoclonal antibody (MAb)-based serotyping and serosubtyping, DNA macrorestriction analysis by pulsed-field gel electrophoresis (PFGE), multilocus enzyme electrophoresis (MEE), ribotyping, and PCR-restriction fragment length polymorphism of the internally transcribed spacer region of the rRNA operon (ITS PCR-RFLP). All N. meningitidis serogroup B isolates were typeable by PFGE, MEE, ribotyping, and ITS PCR-RFLP. Only 44.8% of the isolates were completely typeable (both serotype and serosubtype determination) by MAb-based serotyping and serosubtyping. 60.4% of the isolates could be serotyped but not serosubtyped, and 90.6% of the isolates could be either serotyped or serosubtyped. Simpson's discrimination indices of diversity for the methods were as follows: PFGE, 99.7%; MEE, 99.4%; ribotyping, 98.8%; MAb serotyping, 75.8%; MAb serotyping and/or serosubtyping 97.5%; and ITS PCR-RFLP, 84.2%. The high degree of diversity observed by PFGE, MEE, and ribotyping can be explained by the fact that isolates were collected from different geographic locations at various times. PFGE, MEE, and ribotyping showed greater discriminatory abilities than MAb-based serotyping and serosubtyping or ITS PCR-RFLP.
Uveoscleral outflow following cyclodialysis in the monkey eye using a fluorescent tracer. (1985)

Cyclodialysis was performed in one eye of each of eight cynomolgus monkeys. Two days later, the intraocular pressure was 1.6 +/- 0.7 mmHg in eyes with cyclodialysis and 12.0 +/- 0.7 mmHg in fellow control eyes. 10(-4) M fluorescein-isothiocyanate dextran (70,000 molecular weight) was perfused into the anterior chamber of each eye for 30 min. The eyes were enucleated and dissected into sclera, choroid, retina, iris, and ocular fluid. Samples were homogenized and centrifuged, and the fluorescence of the supernatant was measured. Expressed as equivalent volumes of aqueous, the rate of anterior chamber movement of tracer via uveoscleral pathways was 1.40 +/- 0.17 microliter/min in cyclodialysis eyes and 0.34 +/- 0.10 microliter/min in control eyes. Cyclodialysis results in a fourfold increase in uveoscleral outflow, contributing to the observed hypotony.
Identification and Pharmacological Profile of an Indane Based Series of Ghrelin Receptor Full Agonists (2018)

Cachexia and muscle wasting are very common among patients suffering from cancer, chronic obstructive pulmonary disease, and other chronic diseases. Ghrelin stimulates growth hormone secretion via the ghrelin receptor, which subsequently leads to increase of IGF-1 plasma levels. The activation of the GH/IGF-1 axis leads to an increase of muscle mass and functional capacity. Ghrelin further acts on inflammation, appetite, and adipogenesis and for this reason was considered an important target to address catabolic conditions. We report the synthesis and properties of an indane based series of ghrelin receptor full agonists; they have been shown to generate a sustained increase of IGF-1 levels in dog and have been thoroughly investigated with respect to their functional activity.
Characteristics of the response of the iliac artery to wall shear stress in the anaesthetized pig (2007)

The functional significance of shear stress-induced vasodilatation in large conduit arteries is unclear since changes in the diameter have little effect on the resistance to blood flow. However, changes in diameter have a relatively large effect on wall shear stress which suggests that the function of flow-mediated dilatation is to reduce wall shear stress. The mean and pulsatile components of shear stress vary widely throughout the arterial system and areas of low mean and high amplitude of wall shear stress are prone to the development of atheroma. In this study, using an in vivo model with the ability to control flow rate and amplitude of flow independently, we investigated the characteristics of the response of the iliac artery to variations in both the mean and amplitude of wall shear stress. The results of this study confirm that increases in mean wall shear stress are an important stimulus for the release of nitric oxide by the endothelium as indicated by changes in arterial diameter and show for the first time, in vivo, that increases in the amplitude of the pulsatile component of shear stress have a small but significant inhibitory effect on this response. A negative feedback mechanism was identified whereby increases in shear stress brought about by increases in blood flow are reduced by the release of nitric oxide from the endothelium causing dilatation of the artery, thus decreasing the stimulus to cell adhesion and, through a direct action of nitric oxide, inhibiting the process of cell adhesion. The results also provide an explanation for the uneven distribution of atheroma throughout the arterial system, which is related to the ratio of pulsatile to mean shear stress and consequent variability in the production of NO.
Surfactant-free starch-graphene composite films as simultaneous oxygen and water vapour barriers (2022)

Abstract A single coating formulation for multifunctional composites, such as a gas barrier against both oxygen and water vapour, is the holy grail for the packaging industry. Since the last decade, graphene has been touted as the ideal barrier material in composites due to its morphology and impermeability to all gases. However, this prospect is limited by either poor dispersion of graphene or excess surfactants to aid the dispersion, both leading to shortcuts that allow gas permeation through the composite. Here, we demonstrate a combined gas barrier with starch-graphene composite films made from a single formulation of surfactant-free starch nanoparticle-stabilized graphene dispersion (2.97 mg mL −1 ). Hence, the incorporated graphene reduces the permeability of both the oxygen and the water vapour by over 70% under all the relative humidity conditions tested. Moreover, these films are foldable and electrically conductive (9.5 S m −1 ). Our surfactant-free approach of incorporating graphene into an industrially important biopolymer is highly relevant to the packaging industry, thus offering cost-effective and water-based solution depositions of multifunctional composite films for wide-ranging applications, such as gas barriers in food packaging.