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Articoli di riviste sul tema "Chron.: 1740"

Autore: Grafiati
Pubblicato: 25 luglio 2024

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1

Duchesne, S., R. Bravina, V. Popov, et al. "Frozen graves of Yakutia, a chronological sequence." VESTNIK ARHEOLOGII, ANTROPOLOGII I ETNOGRAFII, no. 4 (51) (November 27, 2020): 120–30. http://dx.doi.org/10.20874/2071-0437-2020-51-4-11.

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Abstract (sommario):
Distribution, cultural and chronological attribution of frozen graves of Yakutia between the beginning of 17th and end of 19th century. The funerary rites and the artefacts allow to differentiate four chrono-cultural periods (before 1700 AD, from 1700 to 1750 AD, from 1750 to 1800 AD and after 1800 AD) which could be associated with historical events: opening of the trading post of Nertchinsk, expansion of the Kangalasky clan, economic collapse, generalization of Christianization.
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Reuter, Christoph. "Commentary on "An Exploratory Study of Western Orchestration: Patterns through History" by S.H. Chon, D. Huron, & D. DeVlieger." Empirical Musicology Review 12, no. 3-4 (2018): 160. http://dx.doi.org/10.18061/emr.v12i3-4.5992.

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This commentary discusses the exploratory study by Chon, Huron and DeVlieger about the usage and combinations of musical instruments in orchestral works between 1700 and 2000 under the perspective of the evolution of the musical instruments in that time, their acoustical and social aspects as well as recommendations in orchestration treatises of the last 300 years.
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Altun, Yasemin. ""Michelangelo's Seal" in Translation: Élisabeth-Sophie Chéron and the Polemics of Print." Studies in Eighteenth-Century Culture 53, no. 1 (2024): 119–66. http://dx.doi.org/10.1353/sec.2024.a918563.

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Abstract: In 1709, the French painter Élisabeth-Sophie Chéron (1648–1711) designed a print after an engraved carnelian held in Louis XIV's collection and known as "Michelangelo's Seal" for its supposed previous owner. Soon after its 1710 release in Paris, this print prompted a quarrel between Chéron and antiquarian scholars who condemned her unfaithful reproduction of the prized gem, a judgment later reiterated by the connoisseur Pierre-Jean Mariette in his Traité des pierres gravées (1750). While previous studies of "Michelangelo's Seal" have discussed the negative reception encountered by Chéron's print, this essay examines how she formulated the image in the first place. Following recent interest in the role of prints in shaping early modern forms of intermediality, the essay treats the 1709 print as a résumé of Chéron's prior achievements in painting and poetry. I adopt a Benjaminian hermeneutic of translation to analyze the artist's visual strategies and engagement with two of the meanings ascribed to engraved gems in her time: their monumentality as cultural remnants of antiquity and their use as seal-stones. I argue that Chéron tailored her translation of "Michelangelo's Seal" according to her skills and status as an active member of the Royal Academy of Painting and Sculpture since 1672. Moreover, in the process, she subverted not only the intended status of female members of that institution, but also broader, gendered norms of artistic creativity.
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Mejías Trueba, Marta, Maria Dolores Nieto Martín, and Aitana Rodríguez Pérez. "LESS CHRON: a tool for deprescribing in patients with multimorbidity." Journal of Pharmacy Practice and Research 51, no. 2 (2021): 184. http://dx.doi.org/10.1002/jppr.1720.

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Dunham, Kyle C. "A Time to Throw Away Stones: Qohelet’s Enigmatic Reference to Stones as a Hinge for the Themes of War and Peace in the Time Poem." Journal for the Study of the Old Testament 45, no. 3 (2021): 320–35. http://dx.doi.org/10.1177/0309089220950351.

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The time poem in Eccl 3.1–8 reflects a marked structure and progression of themes. These connections suggest that the initial lines of vv. 2, 5, and 8 open their respective stanzas by focusing on a similar theme: war and peace. This thread clarifies the meaning of Qohelet’s enigmatic throwing and gathering stones, activities for which no fewer than nine interpretations have been suggested. While interpreters have favored a reference to sexual intercourse, this view is unlikely. I contend that a preferable solution modifies an earlier interpretation relating the throwing and gathering of stones to acts of wartime and peacetime. The throwing away of stones relates to the demobilization of the military, while the gathering of stones relates to the mobilization for war (1 Sam 17.40; 2 Chron 26.14–15). This interpretation offers a more consistent approach to the themes of war and peace developed in the poem’s stanzas.
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Liu, Jun, Yuguo Du, Yang Liu, Ziyang Zhao, Chao Hu, and Chuanfang Zhao. "Chiron Approach for the Total Synthesis of Brevipolide M." Synlett 33, no. 05 (2022): 478–82. http://dx.doi.org/10.1055/a-1730-9857.

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AbstractAn efficient stereoselective synthesis of brevipolide M was established in 13 linear steps and 17.8% overall yields based on chiron approach. The key steps of our synthesis involved tandem Wittig olefination–tetrahydrofuran cyclization and sequential ring-closing metathesis (RCM)–double-bond migration in one-pot processes.
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CORNÉLISSEN, G., and F. HALBERG. "Toward a 'Chron-Sensus' on Neuroimmunomodulation, with 'Modulation' Operationally and Inferentially Defined." Annals of the New York Academy of Sciences 650, no. 1 Ontogenetic a (1992): 60–67. http://dx.doi.org/10.1111/j.1749-6632.1992.tb49096.x.

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Zsigmond, Zsuzsa, and Áron Süli. "How 'New Horizons' will see the Pluto-Charon system." Journal of Physics: Conference Series 218 (March 1, 2010): 012020. http://dx.doi.org/10.1088/1742-6596/218/1/012020.

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9

Pálfy, J., P. L. Smith, and J. K. Mortensen. "A U-Pb and 40Ar/39Ar time scale for the Jurassic." Canadian Journal of Earth Sciences 37, no. 6 (2000): 923–44. http://dx.doi.org/10.1139/e00-002.

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Published time scales provide discrepant age estimates for Jurassic stage boundaries and carry large uncertainties. The U-Pb or 40Ar/39Ar dating of volcaniclastic rocks with precisely known stratigraphic age is the preferred method to improve the calibration. A radiometric age database consisting of fifty U-Pb and 40Ar/39Ar ages was compiled to construct a revised Jurassic time scale. Accepted ages have a precision of ±5 Ma (2σ) or better and are confined to no more than two adjacent stages. The majority of these calibration points result from integrated bio- and geochronologic dating in the western North American Cordillera and have not been previously used in time scales. Direct dates are available only for the Triassic-Jurassic boundary and the initial boundary of the Crassicosta chron and the Callovian stage. The chronogram method was used to estimate all Early and early Middle Jurassic zone boundaries (attempted here for the first time), late Middle Jurassic substage boundaries, and Late Jurassic stage boundaries. Significant improvement is achieved for the Pliensbachian and Toarcian, where six consecutive zone boundaries are determined. The derived zonal durations are disparate, varying between 0.4 and 1.6 Ma. The latest Jurassic isotopic database remains too sparse, therefore chronogram estimates are improved using interpolation based on magnetochronology. The initial boundaries of Jurassic stages are proposed as follows: Berriasian (Jurassic-Cretaceous): 141.8+2.5&#150 1.8 Ma; Tithonian: 150.5+3.4&#150 2.8 Ma; Kimmeridgian: 154.7+3.8&#150 3.3 Ma; Oxfordian: 156.5+3.1&#150 5.1 Ma; Callovian: 160.4+1.1&#150 0.5 Ma; Bathonian: 166.0+3.8&#150 5.6 Ma; Bajocian: 174.0+1.2&#150 7.9 Ma; Aalenian: 178.0+1.0&#150 1.5 Ma; Toarcian: 183.6+1.7&#150 1.1 Ma; Pliensbachian: 191.5+1.9&#150 4.7 Ma; Sinemurian: 196.5+1.7&#150 5.7 Ma; Hettangian (Triassic-Jurassic): 199.6 ± 0.4 Ma.
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Dolmatov, A. V., P. Yu Gulyaev, and I. V. Milyukova. "Chrono-topographic analysis of the fire focus dynamics in the SHS wave." Journal of Physics: Conference Series 1115 (November 2018): 042024. http://dx.doi.org/10.1088/1742-6596/1115/4/042024.

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Fawaz, Shereen Mohamed, Nahla Belal, Adel ElRefaey, and Mohamed Waleed Fakhr. "A Comparative Study of Homomorphic Encryption Schemes Using Microsoft SEAL." Journal of Physics: Conference Series 2128, no. 1 (2021): 012021. http://dx.doi.org/10.1088/1742-6596/2128/1/012021.

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Abstract Fully homomorphic encryption (FHE) technology is a method of encrypting data that allows arbitrary calculations to be computed. Machine learning (ML) and many other applications are relevant to FHE such as Cloud Computing, Secure Multi-Party, and Data Aggregation. Only the authenticated user has the authority to decrypt the ciphertext and understand its meaning, as encrypted data can be computed and processed to produce an encrypted output. Homomorphic encryption uses arithmetic circuits that focus on addition and multiplication, allowing the user to add and multiply integers while encrypted. This paper discusses the performance of the Brakerski-Fan-Vercauteren scheme (BFV) and Cheon, Kim, Kim, and Song (CKKS) scheme using one of the most important libraries of FHE “Microsoft SEAL”, by applying certain arithmetic operations and observing the time consumed for every function applied in each scheme and the noise budget after every operation. The results obtained show the difference between the two schemes when applying the same operation and the number of sequential operations each can handle.
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De Lataillade, Tristan, Wenchao Yu, Maxime Pallud, and Matteo Capaldo. "SEAHOWL: Partitioned Multiphysics and Multifidelity Modelling of Wind Turbines with Monolithically Coupled Elastodynamics." Journal of Physics: Conference Series 2767, no. 5 (2024): 052051. http://dx.doi.org/10.1088/1742-6596/2767/5/052051.

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Abstract We introduce SEAHOWL (Servo-Elasto-Aero-Hydro Offshore Wind Lab), a novel multiphysics multifidelity simulation framework for large-scale onshore, offshore, and floating wind turbines. For structural dynamics, multibody and finite element problems are coupled monolithically and solved within a single system of equations through Project Chrono, providing high numerical stability and optimal coupling accuracy. Combined with partitioned multiphysics, modularity is at the heart of the framework with various numerical methods and solvers (internal or external) available for each physics. This flexibility allows for the selection a target trade-off between numerical accuracy and computational efficiency on a use-case basis. Simulations showcased here have been selected through the prism of industrial R&D challenges, covering: controller response and loads over the operational wind range, 3P effect for different levels of fidelity for the blades, floating wind turbine response under irregular waves and turbulent wind, and innovative multibody application for 3P fatigue mitigation. SEAHOWL is cross-validated against the reference OpenFAST whole-turbine simulator from NREL, showing overall good agreement while differences between the two frameworks are highlighted.
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Vanderjagt, Arjo. "Dirk van Miert. Illuster Onderwijs: Het Amsterdamse Athenaeum in de Gouden Eeuw, 1632–1704. Hilversum: Uitgeverij Verloren, 2005. 431 pp. index. append. illus. tbls. chron. bibl. €37.50. ISBN: 90-351-2808-7." Renaissance Quarterly 59, no. 2 (2006): 587–88. http://dx.doi.org/10.1353/ren.2008.0340.

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Biswas, D. K., M. Hyodo, Y. Taniguchi, et al. "Magnetostratigraphy of Plio-Pleistocene sediments in a 1700-m core from Osaka Bay, southwestern Japan and short geomagnetic events in the middle Matuyama and early Brunhes chrons." Palaeogeography, Palaeoclimatology, Palaeoecology 148, no. 4 (1999): 233–48. http://dx.doi.org/10.1016/s0031-0182(98)00185-0.

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Park, So-Hee. "The Members Analysis in Namin･Noron Line Seowons in Sangju Region in the 17th and 18th Centuries -Focusing on Donam･Heungam Seowons-." Institute of Korean Cultural Studies Yeungnam University 81 (August 31, 2022): 89–124. http://dx.doi.org/10.15186/ikc.2022.08.31.03.

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Abstract (sommario):
In Sangju, there are Donam and Heungam Seowons, which represented Namin and Noron lines in Yeongnam in the late Joseon era.
 Donam Seowon was established by all the literati classes in Sangju, mainly the followers of Ryu, Seong-ryong and Jeong Gyeong-se in the 17th Century. There were conflicts with the Sarim in Andong and Yean, which had been arising from the process of enshrinement of Ryu, Seong-ryong and Jeong Gyeong-se rather than those derived from the factions, while continuing the relationship with Yeoheon school. These could be confirmed by Shimwonrok, the records of the visitors of the seowon.
 Since then, in 1660, Donam Seowo requested donation to 15 eubs in order to rebuild Myeonryundang which had been demolished by fire.
 When reviewing the regions, Andong and Yean communities were omitted, while the Udo regions were relatively dominated.
 Heungam Seowon was built under protection by the ruling Noron in Sangju in the 18th C entury. T he s ewon was run by s uch the houses of Seong of Changnyeong, Chae of Incheon, and Shin of Pyeongsan, the Noron groups in Sangju and they built Seosan Seowon and Chunguidan, later, uniting their groups. T hey made the c laim when they found that Sangju’s local governor Cho, Jeong-man’s name was deleted in Shimwonrok in Donam Seowon, dominated this seowon, and elected the head from their own faction, having conflicts with Namin. It implies that there were so intense conflicts around Donam Seowon. However, since 1743, Donam Seowon’s head was elected among Namin Line, and then, Ryu, Shim-choon(a great-grand son of Ryu, Jin) who was a famous scholar and a follower of Jeong, Jong-ro at that time, Lee, Kyung-yu(a great-grandson of Lee, Man-bu) and Kang, Se-ryun were inaugurated as the head of the Seowon, enhancing the institution’s reputation.
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Datta, Kunal, Prasanta Kumar Ghosh, Arti Rushi, and Mahendra Shirsat. "Polymeric Nanofibriller Matrix on ITO Substrate for Flexible Chemical Sensing Applications." Journal of Physics: Conference Series 2426, no. 1 (2023): 012047. http://dx.doi.org/10.1088/1742-6596/2426/1/012047.

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Abstract The authors present here a facile electrochemical approach to synthesize Poly(Aniline) nanofibriller matrix on ITO coated PET substrate for development of wearable or embeddable sensors. Electrochemical parameters were optimized for even diametric synthesis and controlled length of Poly (Aniline)) nanofibers. A three – step chrono potentiometric deposition was found to be efficient for the synthesis of the matrix. Precise tuning of galvanic conditions during the synthesis process was highly effective and repetitive towards controlling the nucleation of Poly (Aniline) seeds on the substrate that serves as the basis of nanofibers with presumable diameter range. Charge conduction behaviour of the matrix was studied via Linear Sweep Voltammetry and a semiconducting nature was observed. The synthesized nanofibrillar sensor platforms were subjected to Scanning Electron Microscopy (SEM), UV-VIS Spectroscopy and FTIR spectroscopy for elucidation of morphological and structural aspects. The distribution of nanofibers network throughout the substrate was uniform and dendritic. Flexibility characteristics of the sensors were studied by bending the sensor to different radii and in-situ monitoring of resistance. The synthesized sensor platforms were subjected to NO2 sensing in chemiresistive mode under dynamic conditions to investigate the applicability of the same under real-time applications. Upon exposure to different concentrations of NO2, the devices exhibit a rapid response at concentrations as low as 1 ppm. The betterment in overall sensing behaviour in comparison to conventional thin film type sensors could be attributed to the one-dimensional structure of nanofibers leading to effective diffusion on analyte molecules and low scattering loss during charge transport. These flexible sensors can be interesting for novel mobile applications.
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Borshch, Elena V. "Interior as a Scene in the Depictions of French Illustrators of Racine’s Works in the 18th Century: A Comparative Aspect." Vestnik of Saint Petersburg University. Arts 13, no. 1 (2023): 128–46. http://dx.doi.org/10.21638/spbu15.2023.106.

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French literary illustration of the 18th century is studied from the point of view of depicting an interior as a locale. The problem of the influence of literary and visual sources on the formation of the image of an interior is studied through several series of illustrations for Racine’s Works in 18th century editions. The main sources of comparative research are the illustrations for J. Racine’s Berenice, engraved from drawings by French artists L. Cheron (1723), L.-F. Dubourg (1743), J. de Sève (1760), H.-F. Gravelot (1768), J.-J.-F. Lebarbier (1796). Reading Racine’s Berenice in French and Russian, reading critical works about “Racine’s space” helps to understand the image of locale in the playwright’s version. The events of Racine’s Berenice take place in the confined space of an ancient Roman palace. The author modernizes the locale, using the concepts of the French noble interior of his time — “cabinet”, “apartments”. The description of the scene has a minimum of detail, is contradictory and insufficient for literal depictions. The artists, following the example of the playwright, interpreted the scene in the spirit of modernity, but changed and supplemented the main and secondary details. As a rule, they depicted the reception area of the ceremonial apartments and accurately conveyed the styles of interior decoration (Grand style, Transition style, Neoclassicism, Directory style). The artists explained the episode and the play as a whole by means of compositional tools that had a wide semantic range. Comparison the illustrations among themselves and comparison the book engravings with architectural engravings shows the continuity of the artistic tradition and adherence to the academic rules of working with depiction. The artists repeated the compositions of similar illustrations and quoted the interior design projects of the 17th–18th centuries. The image of a locale in the illustration was directly dependent on visual sources, and not on the text. The method of depicting an interior in the illustrations was based on selective and arbitrary reflection of the text, actualizing the appearance of a locale, using the semantics of details and partial copying of samples.
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Aleksander Maryks, Robert. "Piotr Stolarski. Friars on the Frontier: Catholic Renewal and the Dominican Order in Southeastern Poland, 1594–1648. Catholic Christendom, 1300–1700. Farnham: Ashgate Publishing Limited, 2010. xvi + 266 pp. index. append. map. chron. bibl. $124.95. ISBN: 978–1–4094–0595–5." Renaissance Quarterly 64, no. 3 (2011): 980–81. http://dx.doi.org/10.1086/662917.

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Withington, Phil. "J. T. Smith and M. A. North, eds. St Albans 1650–1700: A Thoroughfare Town and Its People. Hatfield: University of Hertfordshire Press, 2003. xvi + 264 pp. index. append. illus. tbls. map. chron. bibl. $34.95. ISBN: 0-9542189-3-0." Renaissance Quarterly 59, no. 1 (2006): 264–65. http://dx.doi.org/10.1353/ren.2008.0233.

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Maryks, Robert Aleksander. "Natalia Nowakowska. Church, State and Dynasty in Renaissance Poland: The Career of Cardinal Fryderyk Jagiellon (1468–1503). Catholic Christendom, 1300–1700. Aldershot: Ashgate Publishing Company, 2007. xx + 222 pp. index. illus. tbls. map. chron. bibl. $99.95 ISBN: 978-0-7546-5644-9." Renaissance Quarterly 61, no. 2 (2008): 583–84. http://dx.doi.org/10.1353/ren.0.0118.

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Shaw, Christine. "Kenneth Gouwens and Sheryl E. Reiss, eds. The Pontificate of Clement VII: History, Politics, Culture. Catholic Christendom, 1300–1700. Aldershot, UK: Ashgate Publishing, 2005. xxvi + 438 pp. + 58 b/w pls. index. append. illus. tbls. chron. $99.95. ISBN: 0-7546-0680-5." Renaissance Quarterly 59, no. 2 (2006): 493–94. http://dx.doi.org/10.1353/ren.2008.0329.

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Questier, Michael. "Victor Houliston. Catholic Resistance in Elizabethan England: Robert Persons's Jesuit Polemic, 1580–1610. Catholic Christendom, 1300–1700. Co-published with Institutum Historicum Societatis Iesu (Rome). Aldershot: Ashgate Publishing Company, 2007. vii + 212 pp. index. append. illus. chron. bibl. $99.95. ISBN: 978–0–7546–5840–5." Renaissance Quarterly 61, no. 3 (2008): 1014–15. http://dx.doi.org/10.1353/ren.0.0188.

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Cheang, Maggie Chon U., Monisha Dewan, Lucy Kilburn, et al. "Abstract P2-03-07: Multi-parametric algorithm integrating on-treatment Ki67 value and standard clinicopathological variables to predict risk of recurrences for women > 70 years old with early ER+HER2- tumours in POETIC trial." Cancer Research 83, no. 5_Supplement (2023): P2–03–07—P2–03–07. http://dx.doi.org/10.1158/1538-7445.sabcs22-p2-03-07.

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Abstract Background: Prognosis in older patients with breast cancer (BC) is worse compared to younger patients. No robust and specific tool to predict the risk of recurrence (TTR) for women aged 70 and over is likely due to the lack of representation of this group in the data from clinical trials. In the POETIC trial, of estrogen receptor-positive (ER+) and mainly human epidermal growth factor receptor 2 negative (HER2-) BC (88%), peri-operative aromatase inhibitor (POAI) did not improve treatment outcome, but patients with low baseline Ki67 value (Ki67B) or low POAI-induced Ki67 value (Ki67_2wk) had good outcome with standard of care therapy (usually adjuvant endocrine therapy (adjET) with the addition of chemotherapy as clinically indicated). In this study, we sought to develop a multi-parametric algorithm, named Ki67Cal, by integrating Ki67_2wk value with tumour characteristics to predict TTR for patients > 70 years old (yr) with early ER+HER2- BC treated with adjET only. Methods: Within POETIC, 39% (n=1744) of the randomised patients (n = 4480) were >70 years old. There were 813 patients aged > 70yr, with ER+HER2- BC, randomised to POAI treatment and treated with adjET only. A power calculation indicated that 811 such patients were sufficient to develop a prediction model that minimized overfitting, allowed up to 8 predictors, for predicting 5-years TTR with a median follow-up of 5.24 years and an overall event rate per 1000 person-years = 0.027, and provided an anticipated performance in terms of model fit R2 = 0.08 (Riley et al. BMJ 2020). A three-fold cross-validation approach was applied; an optimal list of features was selected in the training set (n = 538, events = 70); the agreement between expected and observed outcomes from the algorithm on the validation set (n = 275, events = 37) was evaluated by calibration plot. Multivariable Ridge Cox Regression model of significant parameters was built on the dataset merging training and validation datasets (n = 813) for precise estimates of the coefficients of parameters. A subset of post-POAI samples (n = 99) was gene expression profiled with Nanostring to allow pseudo-Oncotype, pseudo-EndoPredict, and RUO-Prosigna scores calculated (Buus et al. npj Breast cancer 2021). The risk groups classified by the Ki67Cal and gene-expression assays (GEP) were compared. Results: Within this cohort, the 5-year TTR was 34.5% (C.I. 24.9-47.9) for those with a high Ki67_2wk (>=10%) and 12.3% (C.I. 9.1-16.7) in those with a high Ki67B that was suppressed to Ki672wk < 10%. The significant features were Ki67_2wk, sampling type (core vs. excision) at surgery, and pathological variables (tumour size, grade, and nodal status) for the final Ki67Cal algorithm. Stratifying patients into five groups (quintiles) by Ki67Cal identified 60% of patients with TTR of < 5% at 5yrs, and 20% of patients with TTR of > 30% at 5yrs. As an exploratory analysis, the risk groups by Ki67Cal and GEP were compared (Table 1). To date, these assays are optimized to be used on untreated ER+HER2- samples; there were fairly good agreements between the high-risk group defined by Ki67Cal with pseudo-EndoPredict and RUO-Prosigna respectively, and low-risk groups by Ki67Cal with Prosigna probably because Prosigna scores are driven by proliferation score. Conclusion: The relatively poor outcome of patients >70yrs in POETIC emphasizes the need for prognostic tools that identify patients who may be treated with endocrine therapy alone or conversely should be considered for additional therapy. Ki67Cal provides a simple tool that identified very low-risk and high-risk patients in 80% of patients with ER+HER2- BC. Table 1: Comparison of the risk groups defined by Ki67Cal algorithm with the three commonly used gene-expression assays (pseudo-EndoPredict, pseudo-Oncotype and RUO-Prosigna) applied on the post-peri-operative aromatase inhibitor samples. Citation Format: Maggie Chon U Cheang, Monisha Dewan, Lucy Kilburn, Gabriele Morani, Lila Zabaglo, Kally Sidhu, Holly Tovey, Xixuan Zhu, Chris Holcombe, Anthony Skene, Ian Smith, John Robertson, Alistair Ring, Nicholas Turner, Judith Bliss, Mitch Dowsett. Multi-parametric algorithm integrating on-treatment Ki67 value and standard clinicopathological variables to predict risk of recurrences for women > 70 years old with early ER+HER2- tumours in POETIC trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-07.
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Kaiser, Martin F., Eileen Mary Boyle, Brian A. Walker, et al. "Specific Identification of High Risk Disease Using Molecular Profiling By Mymap (Myeloma MLPA and translocation PCR) of 1,036 Cases." Blood 126, no. 23 (2015): 2981. http://dx.doi.org/10.1182/blood.v126.23.2981.2981.

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Abstract Introduction Identifying molecular high risk myeloma remains a diagnostic challenge. We previously reported co-segregation of >1 adverse lesion [t(4;14), t(14;16), t(14;20), gain(1q), del(17p)] by iFISH to specifically characterise a group of high risk patients (Boyd et al., Leukemia 2012). However, implementation of this approach is difficult using FISH because of its technical limitations. We recently developed and validated a novel high-throughput all-molecular testing strategy against FISH (MyMaP- Myeloma MLPA and translocation PCR; Kaiser MF et al., Leukemia 2013; Boyle EM et al., Gen Chrom Canc 2015). Here, we molecularly characterised 1,036 patients from the NCRI Myeloma XI trial using MyMaP and validated the co-segregation approach. Materials, Methods and Patients Recurrent translocations and copy number changes were assayed for 1,036 patients enrolled in the NCRI Myeloma XI (NCT01554852) trial using CD138+ selected bone marrow myeloma cells taken at diagnosis. The trial included an intensive therapy arm for younger and fitter and a non-intense treatment arm for elderly and frail patients. Analysis was performed using MyMaP, which comprises TC-classification based multiplex qRT-PCR and multiplex ligation-dependent probe amplification (MLPA; MRC Holland). Median follow up for the analysis was 24 months. Results Adverse translocations [t(4;14), t(14;16), t(14;20)] were present in 18.2% of cases, del(17p) in 9.3%, gain(1q) in 34.5% and del(1p32) in 9.4% of cases. All adverse lesions were associated with significantly shorter PFS and OS by univariate analysis (P <0.05 for all). Of the 1,036 analysed cases, 13.5% carried >1 adverse lesion, 33.9% had one isolated adverse lesion and 52.6% had no adverse lesion. Presence of >1, 1 or no adverse lesion was associated with a median PFS of 17.0, 23.9 and 30.6 months (P =3.0x10-9) and OS at 24 months of 67.9%, 75.0% and 86.0% (P =1.8x10-7), respectively. Del(1p) was associated with shorter PFS and OS for the intensive, but not for the non-intensive therapy arm and was independent of the co-segregation model by multivariate analysis regarding OS (P =0.006). We thus included del(1p) as an additional adverse lesion in the model for younger patients. The groups with >1 (19.4% of cases), 1 (31.1%) and no adverse lesions (49.5%) were characterised by median PFS of 19.4, 29.4 and 39.1 months (P =1.2x10-10) and median 24-months survival of 73.8%, 86.4% and 91.5% (P =1.4x10-6), respectively. Hazard Ratio for >1 adverse lesion was 3.0 (95% CI 2.1-4.1) for PFS and 3.8 (95% CI 2.2-6.5) for OS. By multivariate analysis, co-segregation of adverse lesions was independent of ISS for PFS/OS in the entire group of 1,036 cases and in the intensive treatment arm. We integrated adverse lesions and ISS into a combined model defining High Risk (>1 adv les + ISS 2 or 3; 1 adv les + ISS 3) and Low Risk (no adv les + ISS 1 or 2; 1 adv les + ISS 1) and the remainder as Intermediate Risk. The High Risk, Intermediate Risk and Low Risk groups of the total cohort included 11.2%, 41.2% and 41.6% of cases with median PFS of 15.8, 19.8 and 35.2 months (P <2.2x10-16) and median OS at 24 months of 62.9%, 73.7%, and 90.7% (P =4.0x10-14), respectively. Integration of ISS into the model for younger patients resulted in highly specific identification of a High Risk group (15.6% of cases) with HR 3.8 (CI 2.6-5.4) for PFS and 6.2 (CI 3.3-11.6) for OS. Conclusions Co-segregation analysis of adverse genetic lesions is a specific molecular risk stratification tool which has now been validated in two large independent trials including a real-world population of all age groups (UK MRC Myeloma IX; NCRI Myeloma XI; total 1,905 patients). MyMaP is a validated all-molecular analysis approach that makes the otherwise technically challenging assessment of multiple genetic regions by FISH accessible using standard laboratory equipment without bioinformatics requirements. Disclosures Kaiser: BristolMyerSquibb: Consultancy; Chugai: Consultancy; Janssen: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria. Pawlyn:Celgene: Honoraria, Other: Travel support; The Institute of Cancer Research: Employment. Jones:Celgene: Other: Travel support, Research Funding. Savola:MRC Holland: Employment. Owen:Celgene: Honoraria, Research Funding; Janssen: Honoraria. Cook:Celgene: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy; Sanofi: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda Oncology: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau. Gregory:Celgene: Honoraria; Janssen: Honoraria. Davies:Takeda-Milenium: Honoraria; Onyx-Amgen: Honoraria; Celgene: Honoraria; University of Arkansas for Medical Sciences: Employment. Jackson:Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Morgan:Weisman Institute: Honoraria; Takeda-Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment; CancerNet: Honoraria; MMRF: Honoraria.
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Sherborne, Amy L., Dil B. Begum, Amy Price, et al. "Identifying Ultra-High Risk Myeloma By Integrated Molecular Genetic and Gene Expression Profiling." Blood 128, no. 22 (2016): 4407. http://dx.doi.org/10.1182/blood.v128.22.4407.4407.

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Abstract Introduction A significant proportion of myeloma patients relapse early and show short survival with current therapies. Molecular diagnostic tools are needed to identify these high risk patients at diagnosis to stratify treatment and offer the prospect of improving outcomes. Two validated molecular approaches for risk prediction are widely used: 1) molecular genetic risk profiling [e.g. del(17p), t(4;14)] 2) gene expression (GEP) risk profiling, [e.g. EMC92 (Kuiper et al., Leukemia 2012)]. We profiled patients from a large multicentric UK National trial using both approaches for integrated risk stratification. Methods A representative group of 221 newly diagnosed, transplant eligible patients (median age 64 years) treated on the UK NCRI Myeloma XI trial were molecularly profiled. DNA and RNA were extracted from immunomagnetically CD138-sorted bone marrow plasma cells. Molecular genetic profiles, including t(4;14), t(14;16), Del(17p), Gain(1q) were generated using MLPA (MRC Holland) and a TC-classification based qRT-PCR assay (Boyle EM, et al., Gen Chrom Canc 2015, Kaiser MF, et al., Leukemia 2013). GEP risk status as per EMC92 was profiled on a diagnostic Affymetrix platform using the U133plus2.0-based, CE-marked MMprofiler (SkylineDx) which generates a standardised EMC92 risk score, called 'SKY92'. Progression-free (PFS) and overall survival (OS) were measured from initial randomization and median follow-up for the analysed group was 36 months. Statistical analyses were performed using R 3.3.0 and the 'survival' package. Results were confirmed in an independent dataset, MRC Myeloma IX, for which median follow-up was 82.7 months. Results Of the 221 analysed patients, 116 were found to carry an established genetic high risk lesion [t(4;14), t(14;16), del(17p) or gain(1q)]. We and others have recently demonstrated that adverse lesions have an additive effect and that co-occurrence of ≥2 high risk lesions is specifically associated with adverse outcome (Boyd KD et al, Leukemia 2011). 39/221 patients (17.6%) were identified as genetic high risk with ≥2 risk lesions (termed HR2). By GEP, 53/221 patients (24.0%) were identified as SKY92 high risk. Genetic and GEP high risk co-occurred in 22 patients (10.0%), 31 patients (14.0%) were high risk only by GEP and 17 patients (7.7%) by genetics only. SKY92 high risk status was associated with significantly shorter PFS (median 17.1 vs. 34.3 months; P<0.0001; Hazard ratio [HR] 3.2 [95%CI: 2.2-4.7]) and OS (median 36.0 vs. not reached; P<0.0001; HR 3.9 [2.3-6.9]). Genetic risk by HR2 was similarly associated with adverse outcome: median PFS 17.0 vs. 33.6 months; P<0.0001; HR 2.9 [1.9-4.4]), median OS 33.5 vs. not reached; P<0.0001; HR 4.1 [2.3-7.2]). Importantly, by multivariate analysis GEP and genetic high risk status were independently associated with shorter PFS (P<0.001) and OS (P<0.005). We next investigated interactions between genetic and gene expression high risk status. Three groups were defined: 1) Patients with both SKY92 and genetic (HR2) high risk status (n=22), 2) either GEP or genetic high risk (n=48) or 3) absence of GEP or genetic (HR2) high risk status (n=151). Co-occurring GEP and genetic high risk status was associated with very short PFS (median 12.5 vs. 20.0 vs. 38.3 months; P<0.0001) and OS (median 25.6 vs. 47.3 vs. not reached; P<0.0001) [Figure]. When comparing this ultra-high risk group against the remainder of cases (n=199), their risk of progressing and dying early was significantly elevated (PFS HR 4.4 [2.5-6.7]; OS HR 5.9 [3.1-11.0]). We confirmed this finding in 116 transplant-eligible patients from the MRC Myeloma IX trial. Patients carrying both EMC92 and genetic high risk status had a median PFS of 7.8 vs. 25.5 months and median OS of 9.5 vs. 62.1 months (both P<0.0001). Moreover, all patients in this ultra-high risk group progressed within 24 months and died within 48 months. Conclusion We demonstrate, for the first time, that combined genetic and gene expression risk profiling identifies a group of patients with ultra-high risk disease behaviour with high fidelity, using molecular features of the disease. Our results indicate that GEP and genetic high risk profiling identify independently relevant, but inter-related features of high risk disease biology. Integrated genetic and gene expression risk profiling could serve as a valuable tool for risk stratified, innovative treatment approaches in myeloma. Figure Figure. Disclosures Jones: Celgene: Honoraria, Research Funding. Pawlyn:Takeda Oncology: Consultancy; Celgene: Consultancy, Honoraria, Other: Travel Support. Jenner:Amgen: Consultancy, Honoraria, Other: Travel support; Janssen: Consultancy, Honoraria, Other: Travel support, Research Funding; Novartis: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Research Funding. Cook:Glycomimetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Drayson:Abingdon Health: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Davies:Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Morgan:Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Univ of AR for Medical Sciences: Employment; Bristol Meyers: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Jackson:Celgene: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau. Kaiser:Takeda: Consultancy, Other: Travel Support; Amgen: Consultancy, Honoraria; BMS: Consultancy, Other: Travel Support; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Chugai: Consultancy.
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Liu, Jun, Ziyang Zhao, Qingwei Lv, et al. "Stereoselective Total Synthesis of (+)-Brevipolide H from d-Galactal." Synthesis, November 17, 2021. http://dx.doi.org/10.1055/a-1700-3520.

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Abstract (sommario):
AbstractAn efficient and concise synthesis of cytotoxic 5,6-dihydro-α-pyrone (+)-brevipolide H has been accomplished in 12 long linear steps in 8.65% overall yield from readily available chiral synthons, d-galactal and ethyl l-lactate. The features of this synthesis are highly diastereoselective Simmons–Smith cyclopropanation and carbohydrate-based chiron approach to rapid access to key 5,6-dihydro-α-pyrone skeleton.
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27

M, Weckmann, Becker T, Pech M, Koch CE, Oster H, and Kopp MV. "Consecutive Rhinovirus Infection of Epithelial Cells Alters Chrono- Inflammatory Expression Network." Journal of Molecular and Genetic Medicine 11, no. 3 (2017). http://dx.doi.org/10.4172/1747-0862.1000282.

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28

"Joint International Symposium of Congenital Anomalies for The Korea-Japan Basic Scientific Promotion 1–3 October 1999, Doosan Resort Hotel, Chum Chon, Kangwon-do, Korea." Congenital Anomalies 40, no. 1 (2000): 46–48. http://dx.doi.org/10.1111/j.1741-4520.2000.tb00908.x.

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