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1

Kusza, S., L. Flori, Y. Gao, A. Teillaud, R. Hu, G. Lemonnier, Z. Bősze, E. Bourneuf, S. Vincent-Naulleau, and C. Rogel-Gaillard. "Transcription specificity of the class Ib genes SLA-6, SLA-7 and SLA-8 of the swine major histocompatibility complex and comparison with class Ia genes." Animal Genetics 42, no. 5 (February 1, 2011): 510–20. http://dx.doi.org/10.1111/j.1365-2052.2010.02170.x.

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2

Stalmaszczyk, Piotr. "LANGUAGE AND THE LEXICON: AN INTRODUCTION. David Singleton. Oxford: Oxford University Press, 2000. Pp. xii + 244. $65.00 cloth, $19.95 paper." Studies in Second Language Acquisition 25, no. 3 (August 4, 2003): 460. http://dx.doi.org/10.1017/s0272263103220192.

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David Singleton observes in the opening lines of Language and the lexicon that “almost everything in language is related in some way or other to words” (p. 1). There is little wonder, therefore, that the lexicon has been at the center of linguistic research and controversies for a long time. Organized into 10 chapters, this book offers a concise overview of major topics in contemporary research. The first chapter provides necessary background information and an overview of the volume. The remaining nine chapters cover a wide range of issues relevant to the lexicon, lexicology, and lexicography. Chapter 2 looks at the lexicon-syntax interface and introduces some contemporary approaches to linguistics and to the lexicon in particular. Chapter 3 presents basic aspects of morphology and word formation, whereas chapter 4 deals with “lexical partnerships,” especially collocations, and rudimentary information on language corpora. Chapter 5 turns to lexical semantics and problems involved in analyzing meaning, and chapter 6 briefly investigates the relations between words, sounds, signs, and writing systems. Chapters 7 and 8 focus on different dimensions of lexical change. Chapter 7 tackles the social, regional, and situational aspects of lexical variation, and chapter 8 describes lexical change, historical processes, language contact, and lexical engineering. Chapter 9 explores the mental lexicon and models of lexical processing. This chapter includes a disappointingly short section on the lexicon in SLA. Finally, the last chapter surveys key concepts and developments in lexicography.
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3

Ardiyanto, Asep, and Pamuji Sukoco. "PENGEMBANGAN MODEL PEMBELAJARAN BERBASIS PERMAINAN TRADISIONAL UNTUK MENINGKATKAN KEMAMPUAN MOTORIK KASAR ANAK TUNAGRAHITA RINGAN." Jurnal Keolahragaan 2, no. 2 (September 1, 2014): 119–29. http://dx.doi.org/10.21831/jk.v2i2.2608.

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Penelitian ini bertujuan untuk menghasilkan model pembelajaran berbasis permainan tradisional untuk meningkatkan kemampuan motorik kasar anak tunagrahita ringan yang layak digunakan. Penelitian pengembangan ini dilakukan dengan langkah-langkah sebagai berikut: (1) pengumpulan informasi, (2) analisis hasil informasi, (3) mengembangkan produk awal, (4) validasi ahli dan revisi, (5) uji coba skala kecil, (6) revisi, (7) uji coba skala besar, (8) revisi akhir, (9) pembuatan produk final, dan (10) diseminasi dan implementasi produk final. Uji coba skala kecil dilakukan terhadap 6 siswa tunagrahita ringan SLB Tunas Kasih 2 Turi. Uji coba skala besar dilakukan terhadap 12 siswa tuna-grahita ringan SLB ABCD Tunas Kasih Donoharjo. Teknik analisis data yang digunakan yaitu deskriptif kuantitatif dan deskriptif kualitatif. Penelitian ini menghasilkan model pembelajaran, yaitu: (1) balap sarung, (2) lempar karet, (3) dorong ban, (4) engkling, (5) pukul balon, (6) layang-layang, (7) lompat tali, dan (8) pesawat terbang. Dari hasil analisis data penilaian para ahli materi dan guru SLB, ditarik kesimpulan bahwa pengembangan model pembelajaran ini sangat baik dan efektif. Kata kunci: pengembangan, permainan tradisional, pembelajaran motorik kasar, anak tunagrahita ringan.
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4

Zawisza, Eugeniusz, Marcin Bigos, and Andrzej Gruchot. "Stabilizacja mieszanin popiołowo-żużlowych spoiwami hydraulicznymi do celów budownictwa drogowego." Przegląd Naukowy Inżynieria i Kształtowanie Środowiska 27, no. 2 (July 22, 2018): 123–31. http://dx.doi.org/10.22630/pniks.2018.27.2.12.

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The paper presents results of investigation on stabilization of the ash–slag mixture from the landfill of “Kraków” CHP Plant using: cement, lime, Terramix F22.5 and Solitex. The research included determining basic geotechnical characteristics as well as the compressive strength without and with addition of 3, 6 and 8% of a binder after 7 and 28 days of curing samples and after 28-day cycles of freezing and thawing. The results of the conducted tests and analyses were referenced to the relevant standards and the usability of the stabilized ash–slag mixture for road engineering purposes was assessed.
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5

Tiu, Ramon V., Jennifer J. Powers, Abdo Haddad, Ying Jiang, and Jaroslaw P. Maciejewski. "Differential Expression of SLAM Family Receptor Markers in Normal Human Hematopoietic Stem Cells and Their Malignant Counterpart in MDS and AML." Blood 108, no. 11 (November 16, 2006): 1897. http://dx.doi.org/10.1182/blood.v108.11.1897.1897.

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Abstract Members of the signaling lymphocytic activation molecule (SLAM) family, including CD150, CD48 and CD244, were shown to precisely distinguish more committed lineage restricted progenitor cells from pluripotent and multipotent murine hematopoietic stem cells (HSC; Kiel et al; 2005 Cell). Similar SLAM profiles may also be present on HSC subsets in humans. We hypothesized that these SLAM markers may be indicators not only of stem cell potential in normal hematopoiesis but also distinguish a subset of the most immature malignant precursors of leukemia. In agreement with the concept of a “cancer stem cell,” the presence of leukemic stem cell population may be an indicator of important clinical and biological properties. We first tested the distribution of CD150, CD48 and CD244 antigens on human CD34+ cells derived from 7 control individuals using 4-color flow cytometry. CD34+ cells were measured in the blast gate based on side scatter and CD45 expression. Within CD34+ blasts, expression of CD48, CD150, and CD244 was detected on 16.71%±9.69, 6.53%±2.93, and 26.92%±6.95 of cells respectively. Subsequently, we investigated SLAM expression in 9 immature leukemic cell lines, including KG-1, K562, U937, HEL, HL60, MKN-95, NB-4, Kasumi and UT7, and found increased expression of SLAM markers in KG-1 (CD48+, CD150+, CD244+) and Kasumi (CD48−, CD150−, CD244+). Consequently, none of the leukemic cells showed pluripotent/multipotent SLAM profiles. We then compared the SLAM marker expression on blasts from patients with AML and MDS with that of CD34+ cells from normal controls. We studied a total of 28 patients: 11 MDS (2 low grade, 5 advanced MDS, 3 MDS/MPD overlap) and 10 AML (FAB: 3 M1, 2 M2, 1 M3, 2 M4/M4E0 and 2 M6). In our cohort, 8/10 AML patients expressed one of the three SLAM markers; 6/10 were CD150−CD48−CD244+ (63.57%±6.96) and 2/10 were CD150+CD48−CD244−(46%±10.96) suggestive of the presence of either pluripotent or multipotent leukemic stem cell phenotype. In the MDS cohort, 8/11 patients expressed one of three SLAM markers, 7/11 were CD150−CD48−CD244+ (41.21% ± 8.9) and 1/11 were CD150+CD48−CD244− (1.26%±0.59) again consistent with a profile derived from either pluripotent or multipotent stem cells. None of the MDS and AML patients had either co-expression of CD244 and CD48 or increased expression of CD48 alone. Two of the M1 type AML patients with CD150−CD48−CD244+ phenotype received prior chemotherapy and achieved complete remission on bone marrow biopsy and flow cytometry using traditional blast markers. In some, we conclude that the SLAM receptor markers may be associated with certain types of leukemic blasts and may be useful in the identification of leukemic stem cell population in both MDS and AML.
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6

Nayel, Muataz, Ammar Khazaal, and Waleed Alabdraba. "Properties of Green Concrete Mixes Containing Metakaolin, Micro Silica, Steel Slag, and Recycled Mosaic Tiles." Tikrit Journal of Engineering Sciences 27, no. 3 (July 8, 2020): 45–60. http://dx.doi.org/10.25130/tjes.27.3.06.

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Recently, the constructions industry begins to make concrete more sustainable, side by side, with making its high performance. This paper aims to investigate the effect of (Metakaolin and Micro Silica) when they replace cement by (8, 12 and 16) % and (6, 9 and 12) % respectively, recycled steel slag when replaces fine aggregate by (10, 20 and 30) %, and recycled mosaic tiles when replaces coarse aggregate by (33.33, 66.67 and 100) % each one another on the slump, density, absorption and compressive strength of concrete. The experimental results showed that the maximum reduction ratio of cement reach (17%) (8% of metakaolin and 9% Micro Silica) while the optimum percentage of mosaic tiles and steel slag is (100%) and (20%) respectively. The optimum percentages obtained are combining to produce three basic green mixes: 1) 17% (8% of Metakaolin and 9% of Micro Silica) only, (2) A mix containing 17% of (Metakaolin and of Micro Silica) plus 100% of recycled mosaic, (3) 17% of (Metakaolin and Micro Silica), 100% of recycled mosaic and 20% of slag. Compressive strength at (7, 28, and 60) days, modulus of rupture at (28) days, absorption, fresh and hardened density are investigated. The best improvement in compressive strength compared with reference concrete was recorded (20.06, 10.855 and 9.983) % at (7, 28 and 60) days respectively for the mix containing (17% of cementitious materials plus 100% of recycled mosaic) while the ultimate flexure strength (24) % appeared in green mix containing (17% of cementitious materials, 100% of recycled mosaic and 20% of slag). Generally, an inverse relationship between density and absorption in all trail mixes which are conducted
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7

Louk, Michael Johanes H., and Pamuji Sukoco. "Pengembangan media audio visual dalam pembelajaran keterampilan motorik kasar pada anak tunagrahita ringan." Jurnal Keolahragaan 4, no. 1 (April 28, 2016): 24. http://dx.doi.org/10.21831/jk.v4i1.8132.

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Penelitian ini bertujuan untuk menghasilkan media audio visual dalam pembelajaran keterampilan motorik kasar pada anak tunagrahita ringan yang layak digunakan. Penelitian pengembangan ini dilakukan dengan langkah-langkah sebagai berikut: ((1) pengumpulan informasi, (2) analisis hasil informasi, (3) mengembangkan produk awal, (4) validasi ahli dan revisi, (5) uji coba skala kecil, (6) revisi, (7) uji coba skala besar, (8) revisi akhir, (9) pembuatan produk final, dan (10) diseminasi dan implementasi produk final. Uji coba kelompok kecil dilakukan terhadap enam peserta didik anak tunagrahita ringan di SLB Tunas Kasih 2 Turi. Uji coba kelompok besar dilakukan terhadap sepuluh peserta didik anak tunagrahita ringan di SLB Negeri I Bantul. Instrumen pengumpulan data yang digunakan yaitu: (1) angket para pakar, dan (2) lembar kuesioner praktisi. Teknik analisis data yang digunakan yaitu analisis deskriptif kuantitatif dan deskriptif kualitatif. Penelitian ini menghasilkan media untuk pembelajaran keterampilan motorik kasar pada anak tunagrahita ringan yaitu media pembelajaran keterampilan motorik kasar dengan (1) melompati bentuk, (2) bola panas bola dingin, (3) bola guling kain, (4) bola ringan, (5) menginjak ekor harimau, (6) bola kangguru, dan (7) senam gerak dan lagu.Kata kunci: pengembangan, media audio visual keterampilan motorik kasar, anak tunagrahita ringan kelas bawah Developing audio visual media to impart the learning of basic physical motor skill for mentally defectiveAbstractThis research aims to produce an audio visual media for teaching basic physical motor skill to mentally defective which is appropriate. This developmental research was done following developmental research steps as follows: (1) collecting information, (2) analysing information, (3) developing initial product, (4) experts validation and revision, (5) preliminary field testing, (6) revision, (7) main field testing, (8) final revision, (9) making the final product, and (10) dissemination and implementation the final product. The small group field testing was conducted to six mentally defective children in SLB Tunas Kasih 2 Turi. The bigger group field testing was conducted to 10 mentally defective children in SLB Negeri I Bantul. The data were analyzed using the quantitative descriptive analysis and qualitative descriptive analysis. The teaching media on physical motor skill consists of seven teaching media on physical motor skill by: (1) Leapfrogging objects, (2) Using hot ball and cold ball, (3) Using fabric bolster ball, (4) Using lightweight ball, (5) Stomping a tiger’s tail, (6) Using kangaroo’s ball, (7) Calisthenics and song.Keywords: developing audio video media impart learning physical motor skill mentally defective underaged children
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8

Nasution, Gita Tiara Dewi, Siti Aminah Sobana, and Leonardo Lubis. "Karakteristik anak epilepsi di Sekolah Luar Biasa Negeri (SLBN) Cileunyi Bandung tahun 2018." Bali Anatomy Journal 3, no. 1 (June 1, 2020): 1–10. http://dx.doi.org/10.36675/baj.v3i1.36.

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Background: Research regarding characteristics of epileptic children in special needs school in Indonesia had never been conducted. Aim: This research aims to provide education to the parents about the characteristics and to provide new reference for further researches. Methods: This descriptive cross-sectional research was conducted in September – November 2018 using a questionnaire inquiring about demographic, socio-economic condition, clinical picture, prenatal, perinatal and postnatal factors. The subjects of this research are class C students in public special needs school Cileunyi Bandung. Sample size was calculated using a categorical descriptive formula and was determined to be 13 subjects. Result and Conclusion: The most prevalent characteristics are male (8), age ≥16 year old (5), elementary school (7), tonic-clonic seizure type (7), present history of repeated seizure (11), one type of seizure (6), onset of seizure in newborn age (7), duration of seizure <15 minutes (9), term delivery (9), birth weight ≥ 2500 grams (9), spontaneous vaginal delivery (10), and present history of febrile seizure (7). Latar Belakang: Penelitian mengenai karakteristik anak dengan epilepsi di Sekolah Luar Biasa (SLB) di Indonesia belum pernah dilakukan. Tujuan: Penelitian ini bertujuan memberikan wawasan kepada orang tua mengenai karakteristik anak dengan epilepsi di SLB serta dapat menjadi referensi data untuk perkembangan ilmu pengetahuan dan penelitian selanjutnya. Metode: Penelitian ini merupakan studi deskriptif dengan desain potong lintang yang dilakukan pada bulan September - November 2018 menggunakan kuesioner yang berisi pertanyaan mengenai karakteristik demografis, sosial ekonomi, gambaran klinis, faktor prenatal, perinatal, dan postnatal. Subjek penelitian adalah siswa/siswi kelas C SLB Negeri Cileunyi Bandung. Penentuan jumlah sampel minimum menggunakan formula deskriptif kategorik dan didapatkan 13 subjek penelitian. Hasil dan Simpulan: Karakteristik yang paling banyak ditemukan adalah jenis kelamin laki-laki (8), usia ≥ 16 tahun (5), tingkat pendidikan Sekolah Dasar (7), jenis kejang tonik-klonik umum (7), terdapat riwayat kejang berulang (11), satu tipe kejang (6), onset kejang terjadi pada usia bayi (7), durasi kejang < 15 menit (9), usia persalinan cukup bulan ((9), berat badan lahir ≥ 2500 gram (9), persalinan secara spontan melalui vagina (10), dan memiliki riwayat kejang demam (7).
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9

Duan, Jing, Yuanlong Li, Lei Zhang, and Fan Wang. "Impacts of the Indian Ocean Dipole on Sea Level and Gyre Circulation of the Western Tropical Pacific Ocean." Journal of Climate 33, no. 10 (May 15, 2020): 4207–28. http://dx.doi.org/10.1175/jcli-d-19-0782.1.

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AbstractInterannual variabilities of sea level and upper-ocean gyre circulation of the western tropical Pacific Ocean (WTPO) have been predominantly attributed to El Niño–Southern Oscillation (ENSO). The results of the present study put forward important modulation effects by the Indian Ocean dipole (IOD) mode. The observed sea level in the WTPO shows significant instantaneous and lagged correlations (around −0.60 and 0.40, respectively) with the IOD mode index (DMI). A composite of 14 “independent” IOD events for 1958–2017 shows negative sea level anomalies (SLAs) of 4–7 cm in the WTPO during positive IOD events and positive SLAs of 6–8 cm in the following year that are opposite in sign to the El Niño effect. The IOD impacts are reproduced by large-ensemble simulations of a climate model that generate respectively 430 and 519 positive and negative independent IOD events. A positive IOD induces westerly winds over the western and central tropical Pacific and causes negative SLAs through Ekman upwelling, and it facilitates the establishment of a La Niña condition in the following year that involves enhanced Pacific trade winds and causes positive SLAs in the WTPO. Ocean model experiments confirm that the IOD affects the WTPO sea level mainly through modulating the tropical Pacific winds. Variability of the Indonesian Throughflow (ITF) induced by IOD winds has a relatively weak effect on the WTPO. The IOD’s impacts on the major upper-ocean currents are also considerable, causing anomalies of 1–4 Sv (1 Sv ≡ 106 m3 s−1) in the South Equatorial Current (SEC) and North Equatorial Countercurrent (NECC) volume transports.
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10

Cotilla Rodríguez, M. O. "The Santiago de Cuba earthquake of 11 June 1766: Some new insights." Geofísica Internacional 42, no. 4 (October 1, 2003): 589–602. http://dx.doi.org/10.22201/igeof.00167169p.2003.42.4.313.

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La información del terremoto reportado en Santiago de Cuba el día 11 de junio de 1766 ha sido re-evaluada en detalle. Para ello se han empleado datos del Archivo de Indias, Sevilla, y de otras fuentes bibliográficas. Este terremoto fue perceptible en un área muy extensa que incluyó a La Habana y a Jamaica. Fue posible cartografiar la distribución de los daños producidos en las diferentes poblaciones. El número total de fallecidos se situó entre 34 y 40 personas y en 700 los heridos. No se produjo tsunami. La localización aproximada del epicentro es 19.9°N, -76.1°W, dentro de la zona de fallas de Bartlett - Caimán. La profundidad focal se fijó a 25 km, mientras que la intensidad sísmica estimada fue IX (MSK) y la magnitud (Ms) alcanzó el valor de 6.8. Entre los años 1578 y 1842 en este sector marino se reportaron otros terremotos fuertes: cuatro de I=8 (MSK) y seis de I=7 (MSK). 170 �eep> �6 agua. Anomalous (high) b-values in the lower part of the slab were located at depths of 50-90 km and 50-160 km beneath Guatemala-El Salvador and Nicaragua, respectively. Anomalies observed at the upper part of the slab may be related to dehydration and successive increase in pore pressure in the down-going lithosphere, which may generate volcanism above the anomalies in the upper part of the slab. Anomalies on the lower surface of the Wadati-Benioff zone are likely to be associated with high thermal gradients between the slab and mantle. te �Nrop> �6 itosfera. Las anomalías en la parte inferior de la zona de Wadati-Benioff podrían estar asociadas con el alto gradiente térmico entre la litosfera y el manto.
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11

Jordan, Bruce W., and Yevgeny Zaytman. "On the bounded generation of arithmetic SL2." Proceedings of the National Academy of Sciences 116, no. 38 (September 4, 2019): 18880–82. http://dx.doi.org/10.1073/pnas.1907728116.

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Let K be a number field and S be a finite set of primes of K containing the archimedean valuations. Let 𝒪 be the ring of S-integers in K. Morgan, Rapinchuck, and Sury [A. V. Morgan et al., Algebra Number Theory 12, 1949–1974 (2018)] have proved that if the group of units 𝒪× is infinite, then every matrix in SL2(𝒪) is a product of at most 9 elementary matrices. We prove that under the additional hypothesis that K has at least 1 real embedding or S contains a finite place we can get a product of at most 8 elementary matrices. If we assume a suitable generalized Riemann hypothesis, then every matrix in SL2(𝒪) is the product of at most 5 elementary matrices if K has at least 1 real embedding, the product of at most 6 elementary matrices if S contains a finite place, and the product of at most 7 elementary matrices in general.
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12

Widianingsih, Onyas, and Zuraidah Zuraidah. "PROTOTIPE MODIFIKASI ERGOCYCLE DENGAN MEMANFAATKAN SEPEDA BEKAS SEBAGAI SOLUSI PEMENUHAN KEBUTUHAN AKTIVITAS AEROBIC TUNANETRA." Journal Physical Education, Health and Recreation 2, no. 2 (April 8, 2018): 124. http://dx.doi.org/10.24114/pjkr.v2i2.9556.

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Penelitian ini bertujuan untuk memenuhi kebutuhan aktivitas aerobik tunanetra melalui pengembangan alat bagi siswa SLB- A kelas V, VI, VII dan VIII Karya Murni Medan Johor. Penelitian ini menghasilkan produk pengembangan berupa prototipe modifikasi ergocycle dengan memanfaatkan sepeda bekas disesuaikan dengan kaidah yang sesungguhnya menurut para ahli, karakterstik kebutuhan tunanetra, ketersediaan sarana serta dana oleh pihak yayasan Sekolah Luar Biasa (SLB – A) Karya Murni Medan Johor juga ditinjau dari cukupnya ketersedian bahan baku pembuatan alat. Metode penelitian ini adalah penelitian dan pengembangan dengan tahapan penelitian sebagai berikut: (1) potensi dan masalah, (2) pengumpulan data, (3) desain produk, (4) validitas desain, (5) revisi desain, (6) uji coba skala kecil, (7) revisi produk, (8) uji coba skala besar, (9) revisi (penyempurnaan), (10) hasil akhir prototipe modifikasi ergocycle dengan memanfaatkan sepeda bekas sebagai solusi pemenuhan kebutuhan aktivitas aerobik tunanetra. Hasil penelitian dan pembahasan mengenai kepuasan konsumen yang tertuang dalam empat aspek yaitu; 1) keamanan, 2) kenyamanan, 3) estetika dan, 4) tampilan. Keempat aspek tersebut telah disesuaikan dengan karakteristik tunanetra sebagai konsumen pengguna alat, dan merupakan hasil dari diskusi pada ahli penjas adaptif dan ahli otomotif. Setelah dilakukan uji coba produk, maka diperoleh tingkat kepuasan sebesar 55,92% dari hasil uji coba skala kecil, dan diperoleh tingkat kepuasan sebesar 92,5% dari hasil uji coba skala besar. Disimpulkan bahwa pengembangan prototipe modifikasi ergocycle dengan memanfaatkan sepeda bekas ini mengalami peningkatan yang signifikan dan dapat digunakan untuk memenuhi kebutuhan aktivitas aerobik siswa SLB - A Karya Murni Medan Johor.
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Wen, Sicheng, Jill Kreiling, Mark S. Dooner, Elaine Papa, Mandy Pereira, Michael Del Tatto, Yan Cheng, Peter J. Quesenberry, and Laura R. Goldberg. "Age-Associated Changes in Bone Marrow-Derived Extracellular Vesicles May Alter Their Effects on Murine Hematopoietic Stem Cell Function." Blood 136, Supplement 1 (November 5, 2020): 37. http://dx.doi.org/10.1182/blood-2020-142444.

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Extracellular vesicles (EVs) are critical mediators of intercellular communication within the bone marrow niche and have been implicated in numerous features of aging. However, their role in natural hematopoietic stem cell (HSC) aging has not been fully elucidated. The goal of this work was to test the hypothesis that EVs from whole bone marrow (BM-EVs) can modulate the HSC aging phenotype in vivo. With respect to HSC aging, our prior work showed that, in contrast to the well-known reduced functional capacity and prominent myeloid skewing displayed by old immunophenotypically-defined HSCs, old unseparated whole bone marrow (WBM) (24-26-mo-old) had a 4-fold increase in functional HSCs compared to young (6-8-wk-old) WBM in limit dilution competitive bone marrow transplantation, and showed minimal to no myeloid skewing. In order to test the ability of BM-EVs derived from this total WBM population to alter HSC aging phenotype, we first isolated EVs from WBM flushed from old (24-26-month old) and young (6-8-week old) C57/BL6 (CD45.2) mice by differential centrifugation (2000 × g for 30 min, supernatant centrifuged 100,000 × g for 1 hour, BM-EV pellet collected). Utilizing nanoparticle tracking analysis, we found no difference in mean particle size between old and young BM-EVs, but there was an approximately 2-fold increase in the number of EVs from old WBM compared to young WBM. To test the ability of these BM-EVs to alter HSC function in vivo, we injected old CD45.2 mice with 2 x 109 young BM-EVs and young CD45.2 mice with 2 x 109 old BM-EVs mice via tail vein, daily x 3 days. Control mice were injected with age-matched BM-EVs or vehicle alone. At one-month post injection, we isolated total WBM and Lineage negative/c-Kit+/Sca-1+/CD150+ cells (LSK-SLAM) from the EV-exposed or vehicle control mice. We injected either 3 x 105 WBM cells or 400 LSK-SLAM mixed with 3 x 105 healthy WBM competitor cells from young B6.SJL (CD45.1) mice into lethally irradiated young CD45.1 hosts and measured peripheral blood chimerism and lineage contribution by flow cytometry up to 6 months post-transplant. For the young marrow, exposure to old BM-EVs had no appreciable effects on engraftment capacity or lineage distribution. However, old WBM exposed to young BM-EVs exhibited a significant decrease in engraftment (15% ± 5%) when compared to old WBM exposed to age-matched old BM-EVs (61% ± 14%) or vehicle control (47% ± 7%) (% average donor chimerism ± SEM, n=4-5 mice/group, p&lt;0.04). Similarly, there was a trend toward decreased engraftment capacity by old LSK-SLAM after young BM-EV exposure (7% ± 4%) and increased engraftment capacity by the old LSK-SLAM after old BM-EV exposure (27% ± 10%) compared to vehicle control (15% ± 2%) (% average donor chimerism ± SEM, n=4-5 mice/group, p=not significant (ns)). These results are consistent with our prior data discussed above in which old un-separated WBM, the source of the old BM-EVs, had increased engraftment capacity compared to young WBM. Interestingly, there was also a trend toward reversal of classic myeloid skewing when old LSK-SLAM were exposed to young BM-EVs (36% ± 11%) compared to vehicle control (64% ± 3%) (average myeloid % of donor-derived peripheral blood ± SEM, n=4-5mice/group, p=ns). In addition, consistent with the known increase in LSK-SLAM with age, our preliminary data showed that old mice exposed to young BM-EVs had an approximately 7-fold decrease in the number of LSK-SLAM in marrow, indicating that BM-EVs within the young bone marrow microenvironment may modulate HSC population size. Finally, microRNA (miR) expression profiling (NanoString Technologies) indicated that a number of miRs known to be involved in hematopoiesis, proliferation, self-renewal, differentiation, senescence and inflammation were differentially represented in old and young BM-EVs, with miR-29a, miR-24, and miR-21 significantly increased and miR-105 significantly decreased in old BM-EVs compared to young BM-EVs. Together, these data indicate that young BM-EVs, via transfer of differentially age-related cargo, may alter engraftment capacity, modify the lineage commitment and may regulate LSK-SLAM population size during natural aging. Future studies more clearly delineating age-associated BM-EV effects on HSCs and defining the molecular mechanisms underlying these effects could yield key insights into the natural aging of HSCs and facilitate restoration of healthy hematopoiesis in the elderly. Disclosures No relevant conflicts of interest to declare.
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Chen, Yu. "Homomorphisms of two-dimensional linear groups over Laurent polynomial rings and Gaussian domains." Mathematical Proceedings of the Cambridge Philosophical Society 109, no. 2 (March 1991): 287–97. http://dx.doi.org/10.1017/s0305004100069759.

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Let GL2(R) be the general linear group of 2 × 2 invertible matrices in M2(R) over a commutative ring R with 1 and SL2(R) be the special linear group consisting of 2 × 2 matrices over R with determinant 1. In this paper we determine the homomorphisms from GL2 and SL2, as well as their projective groups, over Laurent polynomial rings to those groups over Gaussian domains, i.e. unique factorization domains (cf. Theorems 1, 2, 3 below). We also consider more generally the homomorphisms of non-projective groups over commutative rings containing a field which are generated by their units (cf. Theorems 4 and 5). So far the homomorphisms of two-dimensional linear groups over commutative rings have only been studied in some specific cases. Landin and Reiner[7] obtained the automorphisms of GL2(R), where R is a Euclidean domain generated by its units. When R is a type of generalized Euclidean domain with a degree function and with units of R and 0 forming a field, Cohn[3] described the automorphisms of GL2(R). Later, Cohn[4] applied his methods to the case of certain rings of quadratic integers. Dull[6] has considered the automorphisms of GL2(R) and SL2(R), along with their projective groups, provided that R is a GE-ring and 2 is a unit in R. McDonald [9] examined the automorphisms of GL2(R) when R has a large unit group. The most recent work of which we are aware is that of Li and Ren[8] where the automorphisms of E2(R) and GE2(R) were determined for any commutative ring R in which 2, 3 and 5 are units.
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Sithole, N. T., F. Okonta, and F. Ntuli. "Mechanical Properties and Structure of Fly Ash Modified Basic Oxygen Furnace Slag Based Geopolymer Masonry Blocks." Journal of Solid Waste Technology and Management 46, no. 3 (August 1, 2020): 372–83. http://dx.doi.org/10.5276/jswtm/2020.372.

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The objective of this research was to investigate the effect of Fly ash as a source of Si and Na on the mechanical performance of the Basic Oxygen Furnace Slag based (BOFS) geopolymer. BOFS has the lowest SiO2, Al2 O3, Na2 O content compared to other aluminosilicate sources (fly ash, metakaolin, granulated blast furnace slag and mine tailings); which have been used to effectively in geopolymer synthesis. SiO2 and Al2 O3, contents of BOFS are respectively 5-7 times and 6-8 times lower than those of fly ash, metakaolin and granulated furnace slag (GBFS). This study evaluated the potential use of fly ash as a source of Si and Al to improve the mechanical performance of a BOFS based geopolymer. The influence of varying amount of Coal Fly Ash (FA) (10–50%) on UCS was studied. The effects of several factors on the UCS of BOFS geopolymer were also investigated. The test variables were molarities of sodium hydroxide (NaOH) (5 M, 10 M and 15 M); the solid to liquid ratio (20 %, 25 % and 30 %); and the curing temperature (20°C, 40°C, 80°C and 100°C). It was established that most favorable conditions for the geopolymer synthesis were FA was 10% of the mixture, 5M NaOH and 80°C curing temperature. Attempts has been made to relate the microstructure of BOFS/FA based composite with properties of geopolymer. Aggregation was identified as the main particulate process as established by the evolution of the particle size distribution (PSD) and its derived moments during the geopolymerisation process. The morphology of the particles appeared flaky and fluffy. The developed composite met the minimum requirement of ASTM C34-13 for a structural clay load bearing non exposed masonry and load bearing exposed side construction masonry.
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Laukaitis, Antanas, and Vytautas Lasauskas. "AKYTOJO BETONO GARSO ABSORBCIJOS TYRIMAI/POROUS CONCRETE SOUND ABSORPTION INVESTIGATION." JOURNAL OF CIVIL ENGINEERING AND MANAGEMENT 2, no. 8 (December 31, 1996): 67–72. http://dx.doi.org/10.3846/13921525.1996.10590174.

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Low-density porous concrete can be used as a sound absorbing material. This paper generalizes porous concrete sound absorption investigations. Porous concrete relative wave resistance modulus is longer than air wave resistance W=1 and that is why this material can be ascribed to materials with a high resistance to air flows, i.e. materials with a satisfactory sound absorption. Various thickness porous concrete sample sound absorption coefficients can be calculated according to equations (1), (2), (3), when wave parameter values are determinated (Table 1). Normal sound absorption coefficient measurement results (Fig. 1) show that for 35 mm and thicker samples the coefficient does not vary. It means that the samples apparent resistance (impleance) coincides with the materials wave resistance. The sound absorption coefficient increases (Fig. 2) with a decrease in porous concrete density. The asymmetric average dependency is expressed by a rectilinear curve (Fig. 3). The sound absorption coefficient depends not only on porous concrete density, but also on its nature (Fig. 4). The different sound absorption coefficient values for uniform density porous concrete can be explained by the various structure of porous concrete products, i.e. a change in pore dimensions, their amount and distribution (Fig. 5, Table 2). The production of acoustical slabs has shown that 280350 kg/m3 density porous concrete products are not sufficiently strong. It was therefore decided to increase their density to 460 kg/m3, with the purpose of increasing the sound absorption coefficient by using various special form resonators (cavity-type accelerators). The influence of the cuts on sound absorption is given in Fig. 6 (cut step is 22 mm). Measurements in a reverberation chamber have shown that the sound absorption coefficient value in porous concrete slabs with deeper or complex cuts increases, but it is harder to produce slabs with complex form cuts. It is easier to make a simple form resonator. Reverberated sound absorption for regular form resonators is given in Fig. 7. Porous concrete slab surface acoustical resistance decreases due to cuts and that is why there is an increase in sound absorption coefficients (Fig. 7, 2 and 3 curves).Porous concrete slabs with resonator cuts on both sides can be used in spacious constructions, for noise absorption in industrial premises. In this case, the construction sound absorption coefficient depends on the lay-out of these slabs. Three types of special lay-outs were investigated (Fig. 8, Table 3). Most of the investigated constructions have revertible sound absorption coefficients higher than 1. This is explained by sound diffraction phenomena on the slab edges. The most effective of all the investigated constructions are those where porous concrete slabs with two-sided perforations are hung jointly (Fig. 8, curves 6 and 10). They are effective in the entire distance between the slabs. The reverberation absorption coefficient decreases for all types of constructions (Fig. 8, curves 1 and 2, 5 and 6, 7–10). The special construction sound absorption coefficient can be changed by selecting porous concrete slab lay-out.
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Shirakawa, Tsuyoshi, Ken Kato, Naoki Takahashi, Hirokazu Shoji, Tetsuji Terazawa, Yoshitaka Honma, Satoru Iwasa, et al. "A retrospective comparison study of docetaxel and paclitaxel for patients with advanced or recurrent esophageal cancer who previously received fluoropyrimidine and platinum-based chemotherapy." Journal of Clinical Oncology 31, no. 4_suppl (February 1, 2013): 112. http://dx.doi.org/10.1200/jco.2013.31.4_suppl.112.

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112 Background: Fluoropyrimidine plus platinum (FP)-based chemotherapy has been widely used as a first-line regimen for advanced or recurrent esophageal cancer (EC). Although the taxanes have shown efficacy in esophageal cancer after FP-based chemotherapy, there is no standard regimen for second-line chemotherapy (SLC). We conducted a retrospective study to investigate the clinical features of taxane therapy in SLC of EC. Methods: The selection criteria were pathologically proven EC; advanced or recurrent disease that had previously been treated with FP at our hospital; performance status 0-2; and adequate organ functions. The FP regimens used included 5-FU or S-1 and cisplatin or nedaplatin. Docetaxel (DTX) was administerd at 70mg/m2 triweekly for 6 weeks with 1 week’s rest. Paclitaxel (PTX) was administered at 100mg/m2 weekly with the same schedule. Overall survival of PTX was compared to DTX with baseline prognostic factors adjusted, using Cox proportional hazard model. Results: The analysis covered 110 patients over the period from August 2006 to June 2012. The median age was 64 years (range 39-83); 97 males and 13 females; 108 squamous cell carcinomas and 2 adenocarcinomas; 34 advanced and 76 recurrent; cStage I/II/III/IV at diagnosis 8/21/49/32; PS 0/1/2 score 20/81/9; DTX treatment 82 patients and PTX treatment 28. Progression-free survival and overall survival were 2.3 & 6.1 months with PTX and 2.8 and 6.9 months with DTX (no significant difference). The response rates were PTX/DTX/Total 11.1%/3.7%/5.5%. Hazard ratio of overall survival between DTX and PTX was 1.054 with adjusted by PS, sex and number of metastasis. The rate of grade 3-4 neutropenia was higher with DTX (28%) than with PTX (7%). Grade 3 febrile neutropenia was seen in 3.7% of DTX-treated patients but in no PTX patients. Grade 2 or more fatigue was seen in 16% of DTX patients and 10% of PTX ones, and grade 2 or more neuropathy was seen in 1.2% of DTX patients and 32% of PTX ones. Conclusions: PTX and DTX were both effective in SLC of EC, but the toxicity profiles of the two regimens differed. In terms of febrile neutropenia or fatigue, PTX seems more appropriate for SLC of EC.
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Rutigliano, Grazia, Sergio Merlino, Amedeo Minichino, Rashmi Patel, Cathy Davies, Dominic Oliver, Andrea De Micheli, Philip McGuire, and Paolo Fusar-Poli. "Long term outcomes of acute and transient psychotic disorders: The missed opportunity of preventive interventions." European Psychiatry 52 (August 2018): 126–33. http://dx.doi.org/10.1016/j.eurpsy.2018.05.004.

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AbstractBackground:Acute and transient psychotic disorders (ATPD) are characterized by an acute onset and a remitting course, and overlap with subgroups of the clinical high-risk state for psychosis. The long-term course and outcomes of ATPD are not completely clear.Methods:Electronic health record-based retrospective cohort study, including all patients who received a first index diagnosis of ATPD (F23, ICD-10) within the South London and Maudsley (SLaM) National Health Service Trust, between 1 st April 2006 and 15th June 2017. The primary outcome was risk of developing persistent psychotic disorders, defined as the development of any ICD-10 diagnoses of non-organic psychotic disorders. Cumulative risk of psychosis onset was estimated through Kaplan-Meier failure functions (non-competing risks) and Greenwood confidence intervals.Results:A total of 3074 patients receiving a first index diagnosis of ATPD (F23, ICD-10) within SLaM were included. The mean follow-up was 1495 days. After 8-year, 1883 cases (61.26%) retained the index diagnosis of ATPD; the remaining developed psychosis. The cumulative incidence (Kaplan-Meier failure function) of risk of developing any ICD-10 non-organic psychotic disorder was 16.10% at 1-year (95%CI 14.83–17.47%), 28.41% at 2-year (95%CI 26.80–30.09%), 33.96% at 3-year (95% CI 32.25–35.75%), 36.85% at 4-year (95%CI 35.07–38.69%), 40.99% at 5-year (95% CI 39.12–42.92%), 42.58% at 6-year (95%CI 40.67–44.55%), 44.65% at 7-year (95% CI 42.66–46.69%), and 46.25% at 8-year (95% CI 44.17–48.37%). The cumulative risk of schizophrenia-spectrum disorder at 8-year was 36.14% (95% CI 34.09–38.27%).Conclusions:Individuals with ATPD have a very high risk of developing persistent psychotic disorders and may benefit from early detection and preventive treatments to improve their outcomes.
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Nuntadusit, Chayut, Prapas Muangjunburee, Nattaphum Suwanmala, and Makatar Wae-Hayee. "Study of Heat Transfer Characteristics and Kerf Quality of Flame Jet Cutting." Advanced Materials Research 931-932 (May 2014): 392–96. http://dx.doi.org/10.4028/www.scientific.net/amr.931-932.392.

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The aim of this research is to study heat transfer rate of impinging flame jet and cutting quality of steel plate using flame jet. The cutting torch was used for heating on the impingement surface, and it was used for cutting the steel plate samples. LPG at constant flow rate of 0.14 kg/s was mixed with pure oxygen at varied flow rate corresponding to equivalence ratio, =0.78, 0.93 and 1.16. The nozzle-to-plate distance was examined at h=3, 4, 5, 6, 7 and 8 mm. Heat transfer rate on the impingement surface was measured using water cooled heat flux sensor. In order to investigate cutting quality, steel plate with 6 mm in thickness was cut by this flame jet with cutting speed at 260 mm/min. The surface roughness, slag quantity and kerf characteristics were considered for cutting quality. The results show that the flame jet for condition of =0.78 at h=4 mm gives the highest heat transfer rate. The flame jet for condition of =0.93 at h=6 mm is optimal for using cutting steel plate in this study.
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20

Friday, Colleen, and John Derek Scasta. "Checklist of vascular plants for Wind River Indian Reservation (USA) high-elevation basins: ecological drivers of community assemblages." Plant Ecology and Evolution 153, no. 2 (July 8, 2020): 292–311. http://dx.doi.org/10.5091/plecevo.2020.1682.

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Background and aims – Native American reservations in the United States provide biodiversity critical for conservation and ecosystem functions. Unfortunately, botanical inventories are less common for reservations than other land jurisdictions. Such ecological importance and needs are apparent for the Wind River Indian Reservation (WRIR), the 7th largest reservation in the US (>890,000 ha) that is shared by the Eastern Shoshone and Northern Arapaho.Material and methods – A botanical study for two WRIR high-elevation basins (Saint Lawrence Basin (SLB) and Paradise Basin (PB)) to (1) reconcile a 1960 plant list, and (2) quantify plant communities ecologically was conducted. In 2017, 106 monitoring sites were established to quantify species presence. Across basins, 231 total vascular plant taxa (221 to species and 10 to genus) were identified, or > 3× more plant species than noted in the 1960 list. In SLB, 222 plant taxa (213 to species and 9 to genus) were identified and in PB 98 plant taxa (90 to species and 8 to genus) were identified. In 2018, sites were re-sampled to quantify species abundance, soil pH, organic matter, soil nutrients, CEC, salts, and texture. Key results – Slope and elevation explained species distributions in the topography ordination and soil organic matter, pH, texture, P, and K explained species distributions in the soil ordination. Eleven exotic species, and one rare endemic species were documented with implications for empowering tribal management. Using a classification approach followed by an indicator species analysis and fidelity (Phi) assessment, we identified 14 unique plant communities and related these to 6 alliances and 7 associations across 6 macrogroups from the US National Vegetation Classification database. These indicator species of communities included sedges (Carex aquatilus), grasses (Pseudoroegneria spicata, Elymus elymoides, Achnatherum lettermanii, Elymus trachycaulus subsp. trachycaulus, Poa glauca subsp. rupicola), forbs (Polygonum bistortoides, Balsamorhiza incana, Castilleja flava), shrubs (Artemisia tridentata, Betula glandulosa, Dasiphora fruticosa subsp. floribunda) and trees (Pinus contorta).Conclusion – The plant taxa, plant communities, and ecological drivers documented in this study will enhance tribal and federal monitoring of these high-elevation WRIR basins.
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21

Acar, Hilal, Mustafa Caglar, and Ayse Y. Altinok. "Experimental validatıon of peripheral dose distribution of electron beams for eclipse electron Monte Carlo algorithm." Journal of Radiotherapy in Practice 17, no. 3 (July 23, 2018): 279–88. http://dx.doi.org/10.1017/s1460396917000784.

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AbstractAimThe accuracy of two calculation algorithms of the Varian Eclipse treatment planning system (TPS), the electron Monte Carlo algorithm (eMC) and general Gaussian pencil beam algorithm (GGPB) for calculating peripheral dose distribution of electron beams was investigated.MethodsPeripheral dose measurements were carried out for 6, 9, 12, 15, 18 and 22 MeV electron beams using parallel plate ionisation chamber and EBT3 film in the slab phantom. Measurements were performed for 6×6, 10×10 and 25×25 cm2 cone sizes at dmax of each energy up to 20 cm beyond the field edges. The measured and TPS calculated data were compared.ResultsThe TPS underestimated the out-of-field doses. The difference between measured and calculated doses increase with the cone size. For ionisation chamber measurement, the largest deviation between calculated and measured doses is <4·29% using the eMC, but can increase up to 8·72% of the distribution using GGPB. For film measurement, the minimum gamma analysis passing rates between measured and calculated dose distributions for all field sizes and energies used in this study were 91·2 and 74·7% for eMC and GGPB, respectively.FindingsThe use of GGPB for planning large field treatments with 6 MeV could lead to inaccuracies of clinical significance.
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Nishio, S., N. Katsumata, K. Matsumoto, H. Tanabe, Y. Kato, K. Yonemori, T. Kouno, C. Shimizu, M. Ando, and Y. Fujiwara. "Analysis of third-line and fourth-line chemotherapy for recurrent ovarian cancer treated with first-line platinum/taxane regimens." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 15045. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.15045.

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15045 Background: Limited information is available regarding to the usefulness of third-line chemotherapy (TLC) and forth-line chemotherapy (FLC) for recurrent ovarian cancer treated with first-line platinum/taxane (PT) regimens. Methods: We retrospectively reviewed the medical records of patients (pts) with ovarian cancer treated with PT regimens at the National Cancer Center Hospital from 1998 to 2004. The aim of this study is to investigate the important clinical factor such as response rate (RR), time to treatment progression (TTP), overall survival (OS) and predictor of response to TLC and FLC. Kaplan-Meier method was used for estimating TTP and OS. Wilcoxon test was performed for survival times and p-values < 0.05 were considered to be statistically significant. Results: There were 183 pts received first-line PT regimens in study period, 77 of 183 pts received second-line chemotherapy (SLC), 61 of 77 progressed after SLC and 55 of 61 pts received TLC. The RR to TLC was 34.5%. The median TTP was 5 months (mo) (range; 1–19 mo) and the median OS was 12 mo (range; 2–38 mo). The TLC regimen was consisted of P and/or T regimens of 36 pts and the other regimens of 19 pts. The RR according to the duration of response of previous chemotherapy (DRPC) (< 6 mo and ≥ 6 mo) were 31.4% and 37.3%, respectively. The median OS of DRPC (< 6 mo and ≥ 6 mo) were 8 mo (range; 2–33 mo) and 12 mo (range; 2–38 mo), respectively (p = 0.002). After TLC 47 pts progressed and 29 pts received FLC. The RR to FLC was 27.5%. The median TTP was 3 mo (range; 0–11 mo). The median OS of 18 pts who didn’t receive FLC and 29 pts received FLC were 2 mo (range; 2–16 mo) and 7 mo (range; 2–25 mo), respectively (p = 0.01). The RR according to DRPC (< 4 mo and ≥ 4mo) were 22.2% and 30%, respectively. The median OS of DRPC (< 4 mo and ≥ 4 mo) were 3 mo (range; 2–23 mo) and 6 mo (range; 2–25 mo), respectively (p = 0.4). Conclusions: The DRPC is considered to be predictor of response to TLC but not to FLC. Giving TLC and FLC if the pts have tolerable may improve OS, however this analysis is prone to several well-established potential biases and limitations. Further prospective study is warranted. [Table: see text]
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Siidra, O. I., N. V. Chukanov, I. V. Pekov, S. V. Krivovichev, A. Magganas, A. Katerinopoulos, and P. Voudouris. "Pb2(AsO2OH)Cl2, a new phase from the Lavrion ancient slags, Greece: occurrence and characterization." Mineralogical Magazine 76, no. 3 (June 2012): 597–602. http://dx.doi.org/10.1180/minmag.2012.076.3.10.

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AbstractTransparent prismatic crystals of Pb2(AsO2OH)Cl2 were collected in black metallurgical slag on the coast in the Punta Zeza area, 3 km south of the town of Lavrion, Greece. Analyses by energy-dispersive X-ray spectrometry (EDS) provided the following chemical composition: PbO 73.04, As2O3 15.97, Cl 11.42, O=Cl –2.58, total 97.85 wt.%. The empirical formula calculated on the basis of As = 1 is HxPb2.03(AsO3)1.00Cl1.995 (x = 0.96). The infrared spectrum of Pb2(AsO2OH)Cl2 has characteristic AsO33– bands at 707 and 594 cm–1, O–H stretching vibrations at 3310 and 2900 cm–1 and a band at 1107 cm–1 which is assigned to As–O–H bending vibrations. The structure, which is monoclinic P21/m, a = 6.4235(8), b = 5.5399(7), c = 9.321(1) Å, β = 90.767(2)°, V = 331.67(7) Å3, R1 = 0.035, is identical to that of synthetic Pb2(AsO2OH)Cl2 and contains two symmetrically unique Pb sites and one As site. The crystal structure is based on [Pb2AsO2OH]2+ double chains interconnected via weak Pb–Cl bonds to produce a three-dimensional framework which is closely related to that of Pb oxysalt minerals containing [O2Pb3]2+ chains of oxocentred [OPb4]6+ tetrahedra including mendipite, damaraite, rickturnerite and plumboselite.
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Çavuşoğlu, Enver, and Metin Petek. "Effects of different floor materials on the welfare and behaviour of slow- and fast-growing broilers." Archives Animal Breeding 62, no. 1 (June 14, 2019): 335–44. http://dx.doi.org/10.5194/aab-62-335-2019.

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Abstract. Litter quality and fast growth rate are the two main issues in broiler welfare. This study aimed to evaluate the effects of genotype and floor material on broiler welfare and behaviour. In the study, slow-growing (Hubbard JA57) and fast-growing (Ross 308) broilers on a slatted floor and deep litter were used; there were four main groups (2 genotype × 2 housing) and each treatment group consisted of 5 replicates. Each replicate group consisted of 10 male chicks, and 200 birds were used in total. The experiment lasted for 8 weeks. The welfare parameters were recorded in weeks 6, 7, and 8, whereas behaviour data were collected in week 8 only. Results showed that welfare parameters of broiler chickens were affected by genotype and floor type. Slow-growing broilers had better welfare parameters than fast-growing broilers. The slatted floor had a positive effect on main welfare parameters of the birds. Slower-growing broilers had a longer distance in the avoidance distance test. Tonic immobility reaction was longer in slow-growing broilers compared to fast-growing broiler. On the other hand, floor type did not affect behaviour parameters. As a conclusion, slow-growing broilers had better welfare parameters than fast-growing broilers and slat flooring could be beneficial to improve broiler welfare, but further behavioural investigations are needed such as dust bathing and walking behaviour.
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Brecht, M. O., L. E. Datnoff, T. A. Kucharek, and R. T. Nagata. "Influence of Silicon and Chlorothalonil on the Suppression of Gray Leaf Spot and Increase Plant Growth in St. Augustinegrass." Plant Disease 88, no. 4 (April 2004): 338–44. http://dx.doi.org/10.1094/pdis.2004.88.4.338.

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Silicon, applied as calcium silicate slag (20% Si), was evaluated for its potential to suppress gray leaf spot (Magnaporthe grisea) and increase plant growth in newly planted St. Augustinegrass in the summers of 2000 and 2001. Calcium silicate was applied (1,000 kg Si/ha) to three sites that contained Si-deficient Histosols prior to sprigging St. Augustinegrass, cv. Floratam, in southern Florida. This treatment was compared with foliar sprays of chlorothalonil, calcium silicate plus chlorothalonil, and an untreated control. Immediately after planting, applications of chlorothalonil (720 g/liter) were made every 10 days for a total of seven sprays at a rate of 7.6 kg a.i./ha with a commercial sprayer. Based on area under the disease progress curve (AUDPC) values for the treatments calcium silicate alone, chlorothalonil, and calcium silicate plus chlorothalonil, gray leaf spot was reduced by 7, 65, and 68% at site one, 28, 34, and 59% at site two, and 41, 55, and 68% at site three, respectively when compared with the untreated control. The application of calcium silicate alone significantly reduced the final AUDPC of gray leaf spot when compared with the control at site two only. However, when disease severities were analyzed by week, the calcium silicate treatment significantly reduced the percentage of disease at weeks 2, 6, and 8 at site one and weeks 3 to 8 at site three when compared with the control. The final percent bare ground coverage for St. Augustinegrass was increased significantly using calcium silicate by 17 and 34% over the control at sites one and two, respectively (P ≤ 0.05). Silicon was the only element to significantly increase in the leaf tissue for treatments amended with calcium silicate. Levels of Si in leaves for treatments amended with calcium silicate were from 1.2 to 1.3%, while those not receiving calcium silicate had only 0.6 to 0.7%. Amendments with calcium silicate slag for St. Augustinegrass sod production on Si-deficient soils may be an option to reduce gray leaf spot development in newly sprigged fields and promote earlier ground coverage of grass when the environment is favorable for disease.
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Perland, Emelie, Sonchita Bagchi, Axel Klaesson, and Robert Fredriksson. "Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression." Open Biology 7, no. 9 (September 2017): 170142. http://dx.doi.org/10.1098/rsob.170142.

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Solute carriers (SLCs) are vital as they are responsible for a major part of the molecular transport over lipid bilayers. At present, there are 430 identified SLCs, of which 28 are called atypical SLCs of major facilitator superfamily (MFS) type. These are MFSD1, 2A, 2B, 3, 4A, 4B, 5, 6, 6 L, 7, 8, 9, 10, 11, 12, 13A, 14A and 14B; SV2A, SV2B and SV2C; SVOP and SVOPL; SPNS1, SPNS2 and SPNS3; and UNC93A and UNC93B1. We studied their fundamental properties, and we also included CLN3, an atypical SLC not yet belonging to any protein family (Pfam) clan, because its involvement in the same neuronal degenerative disorders as MFSD8. With phylogenetic analyses and bioinformatic sequence comparisons, the proteins were divided into 15 families, denoted atypical MFS transporter families (AMTF1-15). Hidden Markov models were used to identify orthologues from human to Drosophila melanogaster and Caenorhabditis elegans . Topology predictions revealed 12 transmembrane segments (for all except CLN3), corresponding to the common MFS structure. With single-cell RNA sequencing and in situ proximity ligation assay on brain cells, co-expressions of several atypical SLCs were identified. Finally, the transcription levels of all genes were analysed in the hypothalamic N25/2 cell line after complete amino acid starvation, showing altered expression levels for several atypical SLCs.
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Zaman, Ashfaq, Muhammad Basim Kakakhel, and Amjad Hussain. "A comparison of Monte Carlo, anisotropic analytical algorithm (AAA) and Acuros XB algorithms in assessing dosimetric perturbations during enhanced dynamic wedged radiotherapy deliveries in heterogeneous media." Journal of Radiotherapy in Practice 18, no. 1 (August 6, 2018): 75–81. http://dx.doi.org/10.1017/s1460396918000262.

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AbstractBackgroundA comparison of anisotropic analytical algorithm (AAA) and Acuros XB (AXB) dose calculation algorithms with Electron Gamma Shower (EGSnrc) Monte Carlo (MC) for modelling lung and bone heterogeneities encountered during enhanced dynamic wedged (EDWs) radiotherapy dose deliveries was carried out.Materials and methodsIn three heterogenous slab phantoms: water–bone, lung–bone and bone–lung, wedged percentage depth doses with EGSnrc, AAA and AXB algorithms for 6 MV photons for various field sizes (5×5, 10×10 and 20×20 cm2) and EDW angles (15°, 30°, 45° and 60°) have been scored.ResultsFor all the scenarios, AAA and AXB results were within ±1% of the MC in the pre-inhomogeneity region. For water–bone AAA and AXB deviated by 6 and 1%, respectively. For lung–bone an underestimation in lung (AAA: 5%, AXB: 2%) and overestimation in bone was observed (AAA: 13%, AXB: 4%). For bone–lung phantom overestimation in bone (AAA: 7%, AXB: 1%), a lung underdosage (AAA: 8%, AXB: 5%) was found. Post bone up to 12% difference in the AAA and MC results was observed as opposed to 6% in case of AXB.ConclusionThis study demonstrated the limitation of the AAA (in certain scenarios) and accuracy of AXB for dose estimation inside and around lung and bone inhomogeneities. The dose perturbation effects were found to be slightly dependent on the field size with no obvious EDW dependence.
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28

James, Jijo, Ebenezer Paul Billy Graham David, Mahalakshmi Nagarathinam, Mohan Kumar Thaniyarasu, and Jayapal Madhu. "Pozzolanic benefit of fly ash and steel slag blends in the development of uniaxial compressive strength of lime stabilized soil." Revista Facultad de Ingeniería 28, no. 49 (August 7, 2018): 7–21. http://dx.doi.org/10.19053/01211129.v28.n49.2018.8544.

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This investigation involved the examination of pozzolanic benefits that resulted from the amendment of lime stabilization of a soil by using a combination of two industrial wastes viz. Fly ash (FA) and Steel Slag (SS). Two lime contents (6% and 8%), which represented the control specimens, were selected for stabilizing the soil, one above the Initial Consumption of Lime (ICL) and the other above the Optimum Lime Content (OLC), respectively. The lime to total solid waste ratio was maintained as 1:1, and the FA/SS ratio varied within the total solid waste content adopted for amending lime stabilization. The unconfined compressive strength (UCS) of the stabilized samples were determined by casting UCS specimens of 38 x 76 mm and cured for 2 hours, 7, 14 and 28 days. After curing, the specimens were strained until failure, to study the pozzolanic benefits of adding FA-SS. The results revealed that the addition of FA and SS improved the pozzolanic strength, ranging from 3.5% to 15%. The optimal dosage of FA and SS also varied with the lime content adopted. For the 6% lime content, a FA/SS ratio of 1:1 was found to be optimal, whereas for the 8% lime content, a FA/SS ratio of 3:1 was found to develop the maximum strength. The amendment of lime stabilization with FA/SS clearly brought about the difference in lime stabilization stages, unseen when only lime was adopted as stabilizer.
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29

Chakrabarti, Srijib, and Jayantha Kodikara. "Direct tensile failure of cementitiously stabilized crushed rock materials." Canadian Geotechnical Journal 44, no. 2 (February 1, 2007): 231–40. http://dx.doi.org/10.1139/t06-102.

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Tensile behaviour plays a very significant role in the performance of cement-stabilized pavements under traffic, as well as under environmental loading. This paper reports the results of direct tensile strength tests undertaken using new equipment. The tests were performed on specimens of crushed basaltic rock stabilized with three binders, namely, general purpose Portland (GP) cement, general blended (GB) cement, and alkali activated slag (AAS), with application rates of 2%, 3%, and 4% by dry weight. Some tests were conducted by adding 6% and 15% highly plastic clay to crushed basaltic rock. The tests showed that while the tensile strength increased with curing time, the failure tensile strain decreased. The ratio of unconfined compressive strength to tensile strength decreased with curing time, but it stabilized within the range 8–12 after about 7 days of curing. For AAS and GB cement, the failure tensile strain decreased with curing time, stabilizing at about 50 microstrains after 7 days of curing, whereas for GP cement, the failure tensile strain did not change significantly during curing, displaying a value around 40 microstrains. The test results also indicated that the presence of reactive fine-grained soil may have had a significant adverse effect on the potential for cracking in the stabilized pavement materials.Key words: pavement materials, cement stabilization, tensile strength, cracking potential.
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30

Kudzys, Algirdas. "VERIFICATION ANALYSIS OF CAST-IN-SITU REINFORCED CONCRETE STRUCTURES OF FRAMED MULTISTORY BUILDINGS/DAUGIAAUKŠČIŲ PASTATŲ MONOLITINIŲ RĖMINIŲ GELŽBETONINIŲ KONSTRUKCIJŲ TIKRINAMASIS SKAIČIAVIMAS." JOURNAL OF CIVIL ENGINEERING AND MANAGEMENT 5, no. 3 (June 30, 1999): 193–99. http://dx.doi.org/10.3846/13921525.1999.10531461.

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The reliability of reinforced concrete structures of multistory residential and office buildings subjected to gravity and reiterated lateral loading is under consideration. Slab-wall and beam-column structures and their joints of reinforced concrete buildings should be designed to resist normal and shear action effects resulting from gravity forces caused by permanent and useful live loads and lateral forces caused by reiterated short duration episodic wind gusts or seismic actions (Fig 1). A random loading and overloading of relatively rigid joints by reiterated and variable in time transient lateral forces are very dangerous in reliability sense. Therefore, the strength analysis of flexural members of redundant systems must be formulated and solved in the probabilistic approach methods. Nonlinear behaviour of members are caused by material and geometrical non-linearity and depends on the inelastic hysteretic response of the slabs and beams in bending and shear. The equilibrium equation of the non-linear hysteretic system is presented in formula (2) where M is the mass matrix; C is the damping matrix; K is the stiffness matrix; L is the load vector; Ü, U, U are the model accelerations, velocities and displacements vectors. The action effect of horizontal or vertical members can be evaluated by the formulae (3,4,5), where α j is the transposed row of the influence matrix α. The probability distribution of member's strength and gravity forces is close to the normal one [4, 5, 6]. The probability distribution of annual extreme values of wind gusts obey Gumbel or Fisher-Tipet distribution laws [7, 8]. Therefore, for structural safety analysis of flat floor slabs, frame beams, and joint cores of their connections to walls and columns can be adjusted by the method of limit transient action effect based on the compound Poisson-Gumbel distribution law. The long duration safety factor for flexural members can be evaluated by formulae (26), (28) and (37). Here “r” is the number of reiteration episodic lateral loads. The method of limit transient action effect as simplified and rather accurate probabilistic approach to the verification analysis and structural quality estimation of reinforced concrete slab-wall and beam-column structural members and their joints permit to enlarge the successive progressive versions of Eurocode 1.
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Giwa, L., A. Siddiqui, and G. Packer. "Motec Wrist Arthroplasty: 4 Years of Promising Results." Journal of Hand Surgery (Asian-Pacific Volume) 23, no. 03 (September 2018): 364–68. http://dx.doi.org/10.1142/s2424835518500388.

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Background: The Motec cementless modular metal-on-metal ball-and-socket wrist arthroplasty is an implant with promising intermediate results. An alternative to primary wrist fusion, total wrist arthroplasty is an option for active patients, who wish to retain their wrist function. It is indicated in cases of degenerative osteoarthritis, post-traumatic arthritis and rheumatoid (inflammatory) arthritis. Methods: A prospective review of patient demographics, pre and post-operative Disabilities of the Arm Shoulder and Hand (DASH), MAYO scores, range of movements and grip strengths. All complications in follow up were recorded across the 4 year period. Results: 25 implants on 23 patients over 5.5 years, mean age 61; 8 females and 15 male. 10 patients with SLAC, 3 SNAC, 5 inflammatory and 7 patients with generalized osteoarthritis. The patients showed significant improvements of MAYO and DASH scores post-operatively, as well as the flexion/extension arc and grip strengths. There was just one case of implant loosening- the radial screw after a wound infection, which was revised with a longer screw. Two implants were converted to Motec fusion due to pain. One implant was dislocated and relocated. The remaining patients have had good wrist function. Only 6 patients were unable to return to work. Conclusions: Similar to published studies, this series shows the Motec implant to be a good motion preserving alternative to total wrist fusion.
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Ceretta, Carlos Alberto, Aurélio Pavinato, Paulo Sérgio Pavinato, Isabel Cristina Lopes Moreira, Eduardo Girotto, and Éder Efraim Trentin. "Micronutrientes na soja: produtividade e análise econômica." Ciência Rural 35, no. 3 (June 2005): 576–81. http://dx.doi.org/10.1590/s0103-84782005000300013.

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A disponibilidade de produtos comerciais contendo micronutrientes tem aumentado nos últimos anos, embora existam resultados experimentais mostrando grande variabilidade, o que torna este tema contraditório. A diminuição do custo relativo no uso de micronutrientes e a expectativa de ganhos em escala, nos últimos anos, tem motivado produtores a utilizar micronutrientes como cobalto, boro e molibdênio, pela sua influência na fixação simbiótica de nitrogênio na soja. O objetivo do trabalho foi de determinar a viabilidade técnica e econômica da aplicação de alguns micronutrientes, com destaque para Mo e Co, na produtividade de grãos da soja. O experimento foi conduzido nos anos agrícolas 2001/02 e 2002/03, na Fazenda Paineira, da SLC Agrícola Ltda, em Coronel Bicaco, RS, em Latossolo Vermelho Distroférrico típico há oito anos sob plantio direto. O delineamento experimental foi de blocos ao acaso com três repetições, com parcelas de 10 x 50 m. A implantação da soja foi em 18/11 de 2001 e em 24/11 de 2002, com população de 225 e 190 mil plantas ha-1, para os dois anos agrícolas, respectivamente. O espaçamento entre linhas foi de 0,40 m e a cultivar foi a RS-10 para os dois anos. Os tratamentos em 2001/02 foram: (1) CoMo; (2)CoMo+Mo; (3) CoMo +Mo+Mo; (4) CoMo+Mo+P30; (5) CoMo +B; (6) B; (7) Mo; (8) Mo+Mo; e (9) Testemunha. Em 2003/04, os tratamentos foram: (1) CoMo+2x Mo; (2)CoMo+2x Mo+B; (3) CoMo+2x Mo+Phitosol PK; (4) CoMo+2x Fortifol CaB; (5) CoMo+2x Mo + LBE-PT1; (6) CoMo+2x Mo+P30; (7) CoMo+2x Mo+Stimulate; e (8) Testemunha. O uso de micronutrientes, especialmente Mo e Co, mostrou-se contraditório na avaliação da produtividade física de grãos através de comparação de médias. Entretanto, na maioria dos casos, o retorno econômico da aplicação dos micronutrientes foi positivo, mas evidenciou sua dependência de altas produtividades e preços favoráveis no momento da comercialização.
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Emmanuel, Gbadamosi Alaba. "Effect of Watering Regimes and Water Quantity on the Early Seedling Growth of Picralimanitida (Stapf)." Sustainable Agriculture Research 3, no. 2 (February 24, 2014): 35. http://dx.doi.org/10.5539/sar.v3n2p35.

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A study was conducted on the effect of watering regimes and water quantity on seedlings growth of <em style="mso-bidi-font-style: normal;">P. nitida</em>. Seedlings were raised from seeds, transplanted in polythene bags and subjected to watering at full capacity daily, once in 3 days, 5 days; 20 ml daily, 3 days, 5 days; 15 ml daily, 3 days, 5 days; 10 ml daily, 3 days, 5 days; and flooding. The growth traits assessed were plant height, collar diameter, number of leaves; shoot, root and leaf dry weights as well as leaf area. The effect of watering regime and water quantity were significant (P ? 0.05) on quantitative morphological parameters of seedlings. Total dry weight and root dry weight were lower in both water-stressed and waterlogging than well-watered conditions, but the lowest values were obtained under flooding. However, specific leaf area (SLA) and leaf area ratio (LAR) were higher in water-stressed conditions than well-watered conditions. Relative growth rate of seedlings is related more to the net assimilation rate values than LAR and SLA. Also, root/shoot ratio was highest under daily full capacity watering. 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34

Rocha, Mateus do Carmo, Thais Binow Dias, Junimara Sarmento Chaves, Alisson Rangel Albuquerque, and Milena Pupo Raimam. "Preliminary analysis of steelworks residues and their application in a sandy soil." Research, Society and Development 10, no. 5 (May 3, 2021): e17910514520. http://dx.doi.org/10.33448/rsd-v10i5.14520.

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The steel residues application (SR) in sandy soils, under a proper handling management, can result in a benefits range, among which, the soil acidity correction. This study investigated the gralunometric composition of three slags and one exhaustion powder from a steel mill, in the municipality of Marabá-PA, in addition to the ability of soil pH correction. To identify the granulometric fractions were used number 8, 10, 16 and 18 mesh sieves. The pH correction experiment were made in factorial scheme, evaluated 3 doses of each RS (1.5 t ha-1, 2.0 t ha-1 and 2.5 t ha-1) in vases with Neosol, for 60 days. Residues from the steel refining (EAFS, LDS and EAFD) showed a particle size predominantly under 1.00 mm, and promoted pH values above to 7.0. The blast furnace slag obtained domain of particle sizes > 2.00 mm, with 77% of the material retained in the sieves, and their soil disposition promoted similar results to dolomitic limestone, used traditionally to pH correction in acid soils, representing an alternative in soil preparation. Others residues also showed the soil pH correction capacity, although the used dosages proved to be above the ideal, with values above 7 and alkalinity tendency. The necessity of an investigation of EAFS, LDS and EAFD residues dosage are essential to pH soil correction, in order to condition the soil to pH ranges considered ideals (6-6.5).
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Carretta, Yves, Romain Boman, Nicolas Legrand, Maxime Laugier, and J. P. Ponthot. "Numerical Simulations of Asperity Crushing Using Boundary Conditions Encountered in Cold-Rolling." Key Engineering Materials 554-557 (June 2013): 850–57. http://dx.doi.org/10.4028/www.scientific.net/kem.554-557.850.

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The general framework of this paper is in the field of numerical simulation of asperity crushing. Different material forming processes, such as strip-rolling and deep drawing, imply mixed lubrication. In this lubrication regime, two types of contact are present at the same time: a direct contact between the two solids at the asperity level and also valleys filled with pressurized oil. Theses contact conditions have a large influence on friction and wear taking place during the upsetting process. As this mixed type of contact is not yet fully understood from the physics point of view, numerical models are essential to achieve a better understanding. For example, semi-analytical asperity crushing models have been developed by Wilson&Sheu [1] and Sutcliffe [2] to take into account the influence of bulk plastic deformations on asperity crushing. The finite element method has also been used to model asperity crushing. Ike&Makinouchi [3] studied the behavior of 2D triangular-shaped asperities under different boundary conditions. Krozekwa et al. [4] modeled 3D triangular asperities behavior, for various bulk strain directions. More recently, Lu et al. [5] compared experimental results of pyramid-shaped asperity and ridge-shaped asperity crushing with finite element simulation results. As in the three former references mentioned above, it has been decided, to study the interaction between a rigid plane and a simplified geometry asperity without lubricant. In this article, numerical asperity crushing results obtained with Metafor[6], a home made large strains software, will be presented. Those results will illustrate the influence of boundary conditions, contact pressure, large bulk strain and geometry of asperities on the evolution of the contact area. As the asperity crushing behaviour is known to be very sensitive to the boundary conditions, in this article, we will also present results using boundary conditions from a cold rolling model named MetaLub. MetaLub [7-8] is a software developed at the University of Liege in partnership with ArcelorMittal R&D center. It iteratively solves the equations resulting from the discretisation using the slab method of the strip coupled to a mixed lubrication model at the interface. This lubrication model takes into account the evolution of the oil film thickness as well as the asperity crushing along the roll bite. We will compare the evolution of the relative contact area obtained with MetaLub to the results obtained with finite elements simulations using the same boundary conditions. [1] Wilson, W.R.D and Sheu, S. Real area of contact and boundary friction in metal forming. Int. J. Mech. Sci. 1988, 30(7), 475-489. [2] Sutcliffe, M.P.F Surface asperity deformation in metal forming processes. Int. J. Mech. Sci., 1988, 30(11), 847-868. [3] Ike, H. and Makinouchi, A. Effect of lateral tension and compression on plane strain flattening processes of surface asperities lying over a plastically deformable bulk. Wear, 1990, 140, 17-38. [4] Korzekwa, D.A., Dawson, P.R. and Wilson W.R.D., Surface asperity deformation during sheet forming. Int. J. Mech. Sci., 1992, 34(7), 521-539. [5] Lu, C., Wei, D., Jiang, Z., and Tieu, K., Experimental and theoretical investigation of the asperity flattening process under large bulk strain, Proc. Inst. Mech. Eng. J. 222 (2008), 271–278. [6] LTAS-MN2L. ULg. http://metafor.ltas.ulg.ac.be/. [7] Stéphany, A., Contribution à l’étude numérique de la lubrification en régime mixte en laminage à froid. PhD dissertation (in French), Université de Liège (2008) [8] Carretta, Y., Stephany, A., Legrand, N., Laugier, M., and Ponthot, J.-P., MetaLub – A slab method software for the numerical simulation of mixed lubrication regime. Application to cold rolling. In Proceedings of the 4th International Conference on Tribology In Manufacturing Processes (ICTMP), 2010,799-808.
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36

Yazici, Ozan, Gokhan Ucar, Vamvakopoulou Vasileia, Serdar Nazim Turhal, Birol Yildiz, Michalis Karamouzis, Sinan Yavuz, et al. "Current Status of mCRC in East Europe and Middle East." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 853. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.853.

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853 Background: Results obtained in trials may not necessarily translate into prolonged survival of metastatic colorectal cancer (mCRC) patients (pts) in real life.This multinational registry study aimed to evaluate the real life data effecting survival of pts with mCRC. Methods: Multinational, retrospective registry study.Those mCRC pts with at least 3 year follow up data OR died before 3 year time period:diagnosis in between 2005 – 2012. Results: Totally 208 (57%) male,156 female (43%) mCRC pts were included.Median age was 62 years (min:23 max:85).Primary locations; right (n = 71, 19.5%), transvers (n = 13, 3.6%), left colon (n = 276,75%). Sites of metastasis: liver 69.7%, lung:27.4%, local relapse %12.6, peritoneum 12%, distant lymph node 10%, CNS: 1.6%. Metastasectomy (mtc) was done in 38.5%, mtc regions: liver (22.3%), lung (4.7%), other (%11.5 ). K-N RAS and BRAF wild pts were 37.4%, 16.5% and 14.3%. Aflibercept was available for %57 of pts. MSI rate was 1.6%. Most common first line chemotherapy (FLC); Oxaliplatin (O) based combination (C) 29.9%, irinotecan (İ) C with bevacizumab (bev) 16.5%, O with bev. 16.5%. Responses to FLC; CR: 8%, PR: 30.5% stable: 28.3%, progres: 24.7%. Median OS of FLC; combination with bev: 35 months (m) (95%CI, 29.1 – 40.8), anti-EGFR:38 m (95%CI, 30.1–45.8 ),only chemotherapy: 32 m (95%CI 26.3 - 37.6), p > 0.05. Second mtc was done 10.2%.Second LC was given to %66.7 of pts. İ combination with bev (24.5%) was most common SLC. Responses to SLC; CR:4.9%, PR: 15.1% , stable:13.2% progres:29.1%. Total %31.3 and 22% of pts had third and fourth LC, most common one was single agent 5-FU. Median PFS1: 10 m (95%CI 8.3 – 11.6 ), PFS2: 7 m (95%CI 6.2 –7.7 ), PFS3: 6 m (95% CI 4.6 – 7.3 ). Median OS of all pts were 35 m (95%CI 30.7 – 39.2 ). In pts with metastasectomy compared with others median OS was; 43 m (95%CI 34.4 – 51.5) vs 29 m (95% CI 25.8 vs 32.1), respectively , p: < 0.001. Median OS in right, transvers and left colon was; 25 m (95%CI, 16.6 – 33.3), 33 m (95%CI, 8.7 – 52.7), 37 m (95%CI 32.4 – 41.5), (p = 0.25). In K-N Ras wild group median PFS; anti-EGFR:13 m (95 % CI, 9.3 - 16.6) bev:13 m (95 %CI, 4.4 - 21.5), chemo:9 m (95 % CI, 6.3 - 11.6), (p: 0.3). Conclusions: The current study demonstrated median OS and prognosis of left-transvers-right colon was consistent with the phase trials.
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37

Blayney, Douglas W., Lan Huang, and Ramon Mohanlal. "A Randomized Phase 3 Clinical Trial of the Combination of Plinabulin (plin) + Pegfilgrastim (peg) Versus (vs) Peg Alone for Tac (docetaxel, doxorubicin, cyclophosphamide) Induced Neutropenia (cin)." Blood 134, Supplement_1 (November 13, 2019): 3590. http://dx.doi.org/10.1182/blood-2019-127310.

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Trial in Progress: Granulocyte colony stimulating factors (G-CSFs) (including Peg) reduce, but do not completely ameliorate CIN. Plinabulin is a novel, small molecule, single-dose-per cycle therapy, with equal activity against docetaxel CIN vs. Peg, but with several advantages: Plin has 1. Less bone pain, 2. Anticancer effects, and 3. Dosing 30 min after chemotherapy (chemo). The CIN nadir with Plin occurs in week 2 and with Peg in week 1 of the chemo cycle. All these features suggest a mechanism of action (MoA) with Plin that is different from Peg (Blayney, ASCO 2018; IASLC 2018). Neutrophil demargination with Plin and a reduced neutrophil transit time consistent with IL-6 signaling, and reversal of a LSK block in bone marrow, suggest protective rather than a stimulatory MoA for Plin in CIN (Blayney, SLB 2018; Ghosh, AACR 2018, Suwa, Am J Physiol 2000). Due to their differences in MoA, there is a strong rationale to combine Plin and Peg, as this offers the potential of better protection against CIN in both week 1 and 2 in the chemo cycle. In the Phase II portion of study BPI2358-106 (Study 106., NCT03294577), we evaluated the effects of the Plin combined with Peg on CIN and Bone Pain. Study 106 treated breast cancer (BC) patients with TAC with 6 mg Peg alone (Peg6), or Peg6+Plin. Plin dose was 20 mg/m2. Grade (Gr) 3 and 4 neutropenia frequency, duration of Gr 3 and 4 neutropenia (DSMN), and neutrophil nadir was based on absolute neutrophil counts, obtained on days 0, 1, 3, 6, 7, 8, 9, 10, 11, 12, 13, 15. Bone pain was assessed by a validated questionnaire on days 1, 2, 3, 4, 6, 7, 8, 9, and expressed as % of patients reporting bone pain. Phase II Results. The confirmatory phase 3 portion of study 106 will test addition of Plin to Peg6, which may offer superior protection against TAC CIN vs Peg alone without bone pain. The Plin/Peg combination is a novel CIN approach with the potential to optimize chemotherapy, by minimizing chemotherapy dose modifications due to CIN or bone pain.*p&lt;0.05; **p&lt;0.001; ***P&lt;0.01 Peg+Plin vs Peg 6mg Table Disclosures Blayney: BeyondSpring Pharmaceuticals: Research Funding. Huang:BeyondSpring Pharmaceuticals: Employment. Mohanlal:BeyondSpring Pharmaceuticals: Employment.
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38

Kernder, A., J. G. Richter, R. Fischer-Betz, B. Winkler-Rohlfing, R. Brinks, M. Schneider, and G. Chehab. "Quality of care predicts outcome in systemic lupus erythematosus: a cross-sectional analysis of a German long-term study (LuLa cohort)." Lupus 29, no. 2 (January 28, 2020): 136–43. http://dx.doi.org/10.1177/0961203319896626.

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Objective Our aim was to study the quality of medical care in patients with systemic lupus erythematosus (SLE) to understand gaps and to analyze the association with outcome of the disease. Methods Information on demographics and medical care was assessed by self-reported questionnaires among SLE patients (LuLa cohort, 2011, n = 580). In total, 21 aspects of medical care were analyzed. Univariate analysis selected 10 predictor variables for further analysis: (1) urine examination and (2) blood test in the previous year, (3) taking antimalarials, (4) taking vitamin D and calcium if the dosage of prednisolone was greater than 7.5 mg/day, counseling regarding (5) lipid metabolism, (6) vaccination, and (7) blood pressure, and treatment of the comorbidities (8) hypertension, (9) osteoporosis and (10) lipid metabolism disorder. The association of these 10 items with the outcome of the disease, assessed in 2015, was analyzed by linear regression analysis, adjusted for age, disease duration and sex. Results On average six of the 10 items were met (±1.7). Receiving more clinical care in 2013 was predictive for low disease activity (SLAQ, p = 0.024, β = –0.104, corr. R2 = 0.048), low progress in disease-related damage (Delta Brief Index of Lupus Questionnaire, p = 0.048, β = –0.132, corr. R2 = 0.036) and high health-related quality of life (SF-12 physical, p = 0.035, β = 0.100, corr. R2 = 0.091) in 2015. Conclusion Our study illustrates a link between the quality of care and the SLE outcome parameters disease activity, disease-related damage and quality of life. Consistent considerations of these care parameters, which are recommended in several management guidelines, could therefore be a good approach to improve the outcome of patients with SLE.
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39

Dahal, Sunita, and Rajan Suwal. "Seismic Behavior Analysis of Composite Buildings with Respect to RCC Buildings." Journal of the Institute of Engineering 15, no. 1 (January 31, 2019): 54–61. http://dx.doi.org/10.3126/jie.v15i1.27705.

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Steel concrete composite construction has gained wide acceptance worldwide as an alternative to pure steel and pure concrete construction. The use of steel in construction industry is very low in Nepal compared to many developing countries. There is a great potential for increasing the volume of steel in construction, especially in the current development needs. Not using steel as an alternative construction material and not using it where it is economical is a heavy loss for the country. Use of composite material is of particular interest, due to its significant potential in improving the overall performance through rather modest changes in manufacturing and constructional technologies. Steel concrete composite construction means the concrete slab is connected to the composite beam with the help of shear connectors so that they act as a single unit. In the present work, steel concrete composite (both full and half composite) with RCC options are considered for comparative study of seismic behavior of 10 multistoried commercial buildings (4-storied, 5-storied, 6-storied, 7-storied, 8-storied, 9-storied, 10-storied, 12-storied, 16-storied and 20-storied which is situated in earthquake zone V and for earthquake loading, the provisions of IS:1893 (Part1)-2002 is considered. For modeling of composite and RCC structures, SAP2000 software is used. Steel-concrete composite construction system is an efficient, economical and innovative method for seismic resistance of multi storied buildings. Equivalent static method of seismic analysis is used in the analysis of models. Comparison of parameters like time period, axial force, shear force, bending moment, deflection, storey drifts, base shear, storey stiffness is done for full composite (beam-column both composite), half composite (column composite) and RCC structures. The results are compared and found that composite structure is better in several aspects.
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Mohammadi, Ayub, Sadra Karimzadeh, Khalil Valizadeh Kamran, and Masashi Matsuoka. "Extraction of Land Information, Future Landscape Changes and Seismic Hazard Assessment: A Case Study of Tabriz, Iran." Sensors 20, no. 24 (December 8, 2020): 7010. http://dx.doi.org/10.3390/s20247010.

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Exact land cover inventory data should be extracted for future landscape prediction and seismic hazard assessment. This paper presents a comprehensive study towards the sustainable development of Tabriz City (NW Iran) including land cover change detection, future potential landscape, seismic hazard assessment and municipal performance evaluation. Landsat data using maximum likelihood (ML) and Markov chain algorithms were used to evaluate changes in land cover in the study area. The urbanization pattern taking place in the city was also studied via synthetic aperture radar (SAR) data of Sentinel-1 ground range detected (GRD) and single look complex (SLC). The age of buildings was extracted by using built-up areas of all classified maps. The logistic regression (LR) model was used for creating a seismic hazard assessment map. From the results, it can be concluded that the land cover (especially built-up areas) has seen considerable changes from 1989 to 2020. The overall accuracy (OA) values of the produced maps for the years 1989, 2005, 2011 and 2020 are 96%, 96%, 93% and 94%, respectively. The future potential landscape of the city showed that the land cover prediction by using the Markov chain model provided a promising finding. Four images of 1989, 2005, 2011 and 2020, were employed for built-up areas’ land information trends, from which it was indicated that most of the built-up areas had been constructed before 2011. The seismic hazard assessment map indicated that municipal zones of 1 and 9 were the least susceptible areas to an earthquake; conversely, municipal zones of 4, 6, 7 and 8 were located in the most susceptible regions to an earthquake in the future. More findings showed that municipal zones 1 and 4 demonstrated the best and worst performance among all zones, respectively.
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Blayney, Douglas W., Stephan Ogenstad, Yuankai Shi, Qingyuan Zhang, Jifeng Feng, Tao Sun, Lihua Du, Lan Huang, and Ramon Mohanlal. "Comparison of pegfilgrastim (Peg), plinabulin (Plin), and the combination for chemotherapy (Chemo) induced neutropenia (CIN) prevention: Rationale for the combination." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e12030-e12030. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e12030.

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e12030 Background: Peg is used for prevention of CIN. Plin, a novel non-GSF small molecule with anti-cancer activity has equal efficacy against CIN as Peg; Plin does not cause bone pain and mitigates thrombocytopenia and the immune suppressive hematologic profile (Blayney ASCO, ESMO, SITC 2018). Plin has a mechanism of action (MoA) consistent with IL-6 -dependent granulocyte progenitor cell expansion, increased neutrophil demargination and transit from the bone marrow (Suwa, Am J Physiol 2000; Blayney SLB/IEIIS 2018). In single agent (SA) Peg and Plin phase (Ph) 2 data, CIN with Peg occurs in the 1st week (~day (D) 7) post Chemo, and with Plin in the 2nd week (~ D15) post Chemo, presumably due to different MoAs (NCT03102606, NCT03294577). We evaluated whether combining these two agents/MoAs would protect against CIN throughout the entire Chemo cycle (C). Methods: Early stage Breast Cancer Ph 2 patients received high febrile neutropenia (FN) risk TAC (docetaxel, doxorubicin, cyclophosphamide) and either SA standard dose Peg 6 mg (Peg; n=22) or SA Plin (20 mg/m2; n= 15), or Peg 6mg combined with Plin 20 mg/m2 (Peg/Plin; n=16). Peg was given ~24 hrs after TAC, and Plin ~30 min after TAC. Blood draws for ANC were taken daily from predose to Day (D)15, and validated bone pain assessments were done from predose D1 to D8 in C1. Results: On D7 (week 1) of C1, Plin but not Peg maintained mean ANC within normal; P<0.0001 for Plin vs Peg mean ANC. On D15 (week 2 of C1) Peg, but not Plin maintained ANC within normal; P<0.0001 for Peg vs Plin mean ANC. Plin added to Peg maintained mean and median ANC within normal throughout C1. (ANC normal range is 1.5 - 8 x10E9/L.) Frequency of Grade (Gr) 4 and 3/4 CIN was ~35 % lower (P<0.05 for Gr3/4) and median ANC nadir was 2 times higher (1.00 vs 0.46) in Peg/Plin vs Peg in C1. FN occurred in 1 pt each with Peg and Peg/Plin. Incidence of bone pain was 95% vs 6% with Peg vs Peg/Plin (P<0.0001). Conclusions: Adding Plin to standard dose Peg offers superior CIN protection throughout the entire high FN risk Chemo cycle, while almost eradicating bone pain vs Peg alone. Clinical trial information: NCT03294577 .[Table: see text]
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42

Yengkhom, Indibor singh. "Ir-192 pellet source HDR brachytherapy using wax surface mould applicators in head and neck cancer: A single institute experience." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e17029-e17029. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e17029.

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e17029 Background: Surface mould brachytherapy is suitable for radiation treatment of superficial lesions in head and cancer and it is the choice of radiotherapy technique. Various isotopes viz, Radium, Cs-137, Ir-192 wire, co-60, Sr-90 has been used. Earlier customized acrylic mould with hollow needle or catheters were used. With the advent of Ir-192 HDR pellet source we used tissue equivalent thermo malleable wax surface moulds. Single plane was used but in lips, pinna and ala of nose double planar sandwich technique was used with good dosimitry and cosmetic effect. BED is calculated by using LQ model. Methods: A retrospective analysis of 20 cases superficial H & N epithelial cancers treated with surface mould Brachytherapy using wax mould during 2008 to 2010 at RIMS is retrieved from the archive. HDR Ir-192 pellet source surface mould was used by positioning the flexible catheters in proper positions without distortion of geometry. The mould is made with wax plates by warming upto 70 degree Celsius in thermal water bath. The thickness of the slab is 1 cm and catheters embedded on surface and kept 1 to 1.5 cm gap and parallel to each other which can be bent or curved according to the surface contour. The fixation is reinforced with transpore /cellotapes. The dose delivered varies 500cgy 6 to 8 doses or daily 300 cgy for 5 to 7 fractions with BED calculated for LDR 2500cgy to 3000 cgy. Results: 20 cases were analysed: 8 Basal cell ca on face. SCC inner canthus 2, lips 2, pinna 1, ala nasi 2, alveolus 1, 1 hard palate, and 4 cheeks. One lip and one cheek has undergone resection with margin not free. All had disease less than 4 cm size and infiltration less than .5 cm. and clinically Node negative. At median follow up of 30 months 18 had no evidence of disease with good cosmesis and one patient with Ca. hard palate had local failure and one upper eyelid has recurrence after 9 months. Conclusions: The study though small in number indicates practicability and satisfactory results of using locally available tissue equivalent wax surface mould application therapy of HDR pellet source for very superficial T1 N0 lesions as primary mode or adjuvant radiotherapy in head and neck areas.
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Lewis, Tim S., Devra Olson, Kristine Gordon, Sharsti Sandall, Marsha Quick, Margo Finn, Lori Westendorf, et al. "SGN-CD48A: a Novel Humanized Anti-CD48 Antibody-Drug Conjugate for the Treatment of Multiple Myeloma." Blood 128, no. 22 (December 2, 2016): 4470. http://dx.doi.org/10.1182/blood.v128.22.4470.4470.

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Abstract Multiple myeloma (MM) is an incurable hematologic malignancy of transformed plasma cells. New targeted biological therapeutics are needed to increase the stringency and durability of remissions. In this study we describe SGN-CD48A, a potent CD48-targeting antibody-drug conjugate (ADC) utilizing a novel glucuronide-monomethylauristatin E (MMAE) linker, under development for the treatment of MM. CD48, or SLAMF2 (Signaling Lymphocyte Activation Molecule family member 2), is a GPI-anchored membrane protein in the SLAM family of immunoreceptors. CD48 is expressed on B and T lymphocytes, natural killer (NK) cells, and other immune cell types where it functions to modulate immune cell activation, proliferation, and differentiation. CD48 is also a tumor antigen broadly expressed in MM. We observed CD48 expression on the surface of malignant plasma cells in 90% (90/100) of human multiple myeloma patient samples examined by flow cytometry. Monoclonal antibodies (mAbs) specific for human CD48 were evaluated and a lead antibody was selected based on binding characteristics and cytotoxic activity against myeloma cells as an auristatin ADC. SGN-CD48A is a humanized anti-CD48 mAb to which eight molecules of MMAE, a potent microtubule disrupting cytotoxic drug, have been conjugated via a β-glucuronidase-cleavable linker. This novel glucuronide-MMAE drug-linker incorporates a PEG side chain and self-stabilizing maleimide to achieve homogenous drug-to-antibody ratio (DAR) 8 conjugates with decreased plasma clearance and increased preclinical antitumor activity. Following binding of CD48 at the myeloma cell surface, SGN-CD48A internalizes and traffics to lysosomal vesicles. Intracellular MMAE drug released from SGN-CD48A in myeloma cells induced cell cycle arrest at G2/M phase, phospho-histone H3 (Ser-10) phosphorylation, and caspase 3/7 dependent apoptotic cell death. SGN-CD48A demonstrated potent cytotoxic activity (EC50 values 1.0 - 11 ng/mL) against a panel of human MM cell lines, with CD48 expression levels of 135,000 - 480,000 receptors per cell. In contrast, SGN-CD48A had negligible cytotoxic activity against normal resting human B, NK, and T lymphocytes. We evaluated the in vivo antitumor activity of SGN-CD48A in disseminated MM cell line mouse xenograft models. In the NCI-H929 and EJM xenograft models, a single intraperitoneal dose of 0.3 mg/kg SGN-CD48A produced durable complete remissions in 8/8 and 6/8 mice, respectively. Similarly, in the U-266 xenograft model, a single dose of 1.0 mg/kg SGN-CD48A produced durable complete remissions in 7/8 mice. Neither unconjugated mAb nor a non-binding control MMAE ADC were active in these MM xenograft models, demonstrating that targeted delivery of MMAE drug through CD48 binding is required for activity. In summary, CD48 is a highly expressed new multiple myeloma target and the novel glucuronide-MMAE ADC SGN-CD48A shows potent antitumor activity against cell line models of MM. Disclosures Lewis: Seattle Genetics, Inc.: Employment, Equity Ownership. Olson:Seattle Genetics, Inc.: Employment, Equity Ownership. Gordon:Seattle Genetics, Inc.: Employment, Equity Ownership. Sandall:Seattle Genetics, Inc.: Employment, Equity Ownership. Quick:Seattle Genetics, Inc.: Employment, Equity Ownership. Finn:Seattle Genetics, Inc.: Employment, Equity Ownership. Westendorf:Seattle Genetics, Inc.: Employment, Equity Ownership. Linares:Seattle Genetics, Inc.: Employment, Equity Ownership. Leiske:Seattle Genetics, Inc.: Employment, Equity Ownership. Nesterova:Seattle Genetics, Inc.: Employment, Equity Ownership. Law:Seattle Genetics, Inc.: Employment, Equity Ownership.
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44

Thomas, Sheeba K., Jatin J. Shah, Armando Morin, Ashley N. Morphey, Hans C. Lee, Elisabet E. Manasanch, Krina K. Patel, et al. "Update of a Phase II Study of Lenalidomide-Elotuzumab As Maintenance Therapy Post-Autologous Stem Cell Transplant (AuSCT) in Patients (Pts) with Multiple Myeloma (MM)." Blood 136, Supplement 1 (November 5, 2020): 46–47. http://dx.doi.org/10.1182/blood-2020-139934.

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Background: Lenalidomide (LEN) monotherapy has been effective in extending progression free survival (PFS) after AuSCT in pts with MM. Elotuzumab (ELO), a humanized IgG1 immunostimulatory monoclonal antibody against signaling lymphocytic activation molecule F7 (SLAM F7), is FDA approved in combination with LEN and dexamethasone (DEX) for treatment of MM pts who have received 1-3 prior therapies. We report updated results of this phase 2 trial evaluating the efficacy and safety of adding ELO to LEN as maintenance therapy post- AuSCT. Patients and Methods: Between 4/15/2015-1/27/2016, 27 evaluable pts were treated on 28 day cycles with ELO, 10 mg/kg iv weekly for cycles 1-2, q2weeks for cycles 3-6, then 20 mg/kg once monthly for cycles 7+. Pts enrolled after 1/28/2016 (n=73 pts) have received ELO, 10 mg/kg IV weekly for cycles 1-2, and 20 mg/kg on day 1 from cycle 3 until disease progression (PD). LEN has been dosed at 10 mg/day for cycles 1-3, with a dose increase to 15 mg/day at physician discretion starting with cycle 4, in the absence of non-hematologic toxicity &gt; grade 1 and significant cytopenias (ANC &lt; 1000/mL, platelet count &lt; 100,000/ml). For the 1st 8 weeks, pts &lt;75 yrs receive 28 mg of DEX 3-24 hours pre-infusion, while pts ≥75yrs receive 8 mg; pts receive 4-10 mg iv DEX pre-infusion for all cycles. Zoster and thromboembolic prophylaxis is prescribed, commensurate with standard recommendations. The study's primary endpoint is PFS, defined as time from AuSCT to PD or death (whichever occurs first), or censored at date of last contact. Secondary objectives are best response, OS, incidence of second primary malignancies (SPMs) and adverse event (AE) profile. Total enrollment of 100 evaluable pts was completed on 6/5/2019. Patients are followed until death, withdrawal of consent or removal from study. Eligible pts received ≤2 lines of induction therapy, and were 60-210 days post-AuSCT. Results: Pts (n=100) have been treated for a median of 27.5 cycles (4-67). At study entry, 37 (37%) had complete response (CR), 40 (40%) very good partial response (VGPR), 22 (22%) partial response (PR) and 1 (1%) minor response (MR). Best response achieved to date on study is CR in 61 pts (61%), VGPR in 29 pts (29%) and PR in 10 pts (10%). Median time for conversion to CR on study is 1 month. Of pts in CR and tested for minimal residual disease (MRD) to date, 42/48 are negative (flow cytometry on ≥ 2 x106 cells). Eleven of 42 have converted from VGPR to MRD negative CR while on study. With a median follow up of 41 months, 90% of pts (n=90) remain alive. Eighteen pts have had PD; of these, 10 had high-risk cytogenetics. Three died of PD while receiving salvage therapy, 1 of pneumonia, 4 of second malignancies and 1 of unknown cause at another facility. One additional pt died on study in VGPR, after developing acute cerebral encephalopathy with refractory status epilepticus of unclear etiology. Estimated 4 year PFS is 75%. High-risk cytogenetics (n =31) adversely affected PFS (p=0.01); 14/31 pts remain on study. Of 23 pts transitioned to another therapy, median 2nd PFS has not been reached. Grade 3-4 Hematologic AEs (no. of pts/102 pts) were: neutropenia 32% (33), febrile neutropenia 15% (15), thrombocytopenia 7% (7), and anemia 10% (10). Grade 3-4 non-Hematologic AEs (no. of pts): hypophosphatemia 29% (30), respiratory infections 21% (21), diarrhea 15% (15), fatigue 12% (12), peripheral neuropathy 8% (8), other infections 7% (7), myalgias 5% (5), dyspnea 5% (5). SPMs include cutaneous basal and squamous cell carcinomas (8), AML (1), B-cell ALL (1), t-MDS (4), osteosarcoma (1), intra-epidermal adenocarcinoma of the neck (1), mucinous appendiceal neoplasm (1), mucinous epidermoid carcinoma of parotid (1), prostate cancer (1). Renal cell carcinoma was diagnosed in 1 pt, 15 months after removal from study for PD. Conclusions: Lenalidomide-elotuzumab is a well-tolerated maintenance therapy on which 38% of pts have had improvement in quality of response while on therapy, including 27% who converted to CR. SPM rates seem consistent with those observed in CALGB 100104 and IFM 2005-02 trials of lenalidomide alone. Longer follow up is required to determine how median PFS and OS will compare with those from lenalidomide monotherapy trials, and how SPM rates will continue to evolve. Table 1 Disclosures Thomas: X4 Pharma: Research Funding; Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Xencor: Research Funding; Pharmacyclics: Other: Advisory Boards; Genentech: Research Funding. Shah:Karyopharm: Current Employment, Current equity holder in publicly-traded company. Lee:Regeneron: Research Funding; Daiichi Sankyo: Research Funding; Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech: Consultancy. Manasanch:JW Pharma: Research Funding; Merck: Research Funding; Quest Diagnostics: Research Funding; Takeda: Honoraria; BMS: Honoraria; Glaxo Smith Kline: Honoraria; Adaptive Biotechnologies: Honoraria; Novartis: Research Funding; Sanofi: Honoraria, Research Funding. Patel:Oncopeptides: Consultancy; Takeda: Consultancy, Research Funding; Cellectis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Nektar: Consultancy, Research Funding; Precision Biosciences: Research Funding; Poseida: Research Funding. Kaufman:Bristol Myers Squibb: Research Funding; Karyopharm: Honoraria; Janssen: Research Funding. Iyer:Trillium: Research Funding; Daiichi Sankyo: Consultancy; Legend Biotech: Consultancy; Merck: Research Funding; Rhizen: Research Funding; Seattle Genetics, Inc.: Research Funding; Target Oncology: Honoraria; Afffimed: Research Funding; CRISPR: Research Funding; Spectrum: Research Funding; Curio Biosciences: Honoraria. Qazilbash:Angiocrine: Research Funding; Bioclinica: Consultancy; Janssen: Research Funding; Bioline: Research Funding; Amgen: Research Funding. Bashir:Amgen: Other: Advisory Board; Purdue: Other: Advisory Board; Takeda: Other: Advisory Board, Research Funding; Acrotech: Research Funding; StemLine: Research Funding; Celgene: Research Funding; KITE: Other: Advisory Board. Orlowski:Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; STATinMED Research: Consultancy. OffLabel Disclosure: Elotuzumab (ELO), a humanized IgG1 immunostimulatory monoclonal antibody against SLAM F7. It is FDA approved in combination with Lenalidomide and dexamethasone (DEX) for treatment of MM pts who have received 1-3 prior therapies. This is a phase 2 trial evaluating the efficacy and safety of adding ELO to LEN as maintenance therapy post-autologous stem cell transplant.
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Sumner, D. R., S. C. Phatak, and D. E. Carling. "First Report of Rhizoctonia solani AG-2-4 on Carrot in Georgia." Plant Disease 87, no. 10 (October 2003): 1264. http://dx.doi.org/10.1094/pdis.2003.87.10.1264c.

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Anastomosis group-2-4 (AG-2-4) of Rhizoctonia solani Kühn was formally described in 2002 (1), but it was first collected in 1983 in Georgia from corn (Zea mays L.) exhibiting symptoms of crown and brace root rot. Although occasionally present on diseased corn roots, the role that isolates of AG-2-4 play in crown and brace root rot of corn is not specifically known (2). More recently, as part of a broad multi-year (1996 to 2000) survey of root diseases in field grown carrot (Daucus carota L.), isolates of R. solani AG-2-4 were recovered from diseased carrot plants in various stages of growth from fields of sandy loam soil at many locations in southern Georgia, including commercial fields in Coffee and Tift counties. During the 1996 to 2000 growing seasons, 123 isolates of Rhizoctonia sp. (including multinucleate and binucleate types) were collected from lesions on developing and mature carrot roots. Of these, 34% were AG-2-4, 10% were AG-2-2IV, 6% were AG-4, and 32% were binucleate Rhizoctonia sp. The remaining 18% were lost prior to AG typing. An additional 40 isolates were collected from carrot seedlings or soil and of these, 55% were AG-4, 18% were AG-2-2IV but none were AG-2-4. Virulence on carrot seedlings by two isolates of AG-2-4 (777R1P5-SL2 and 758C) was compared with virulence of isolates of AG-4, AG-2-2IV, AG-2-1, and binucleate Rhizoctonia sp. Carrot seeds soaked for 5 min in 0.5% NaOCl were planted in petri dishes containing moist autoclaved sandy loam soil. Each dish was inoculated in the center with a 10-mm-diameter disk cut from a 9-day-old potato dextrose agar (PDA) culture of the appropriate isolate. Petri dishes were placed in a 26°C incubator for 9 days, and then the seedlings were rated for disease. Virulence on mature carrot root tissue was also assessed on the same set of isolates. Cross sections of carrot roots (5 to 10 mm thick) were surface disinfested in 0.5% NaClO for 5 min. Three cross sections were placed on moist filter paper in sterile petri dishes and each was inoculated with a 5-mm-diameter disk of inoculum cut from 8- to 10-day-old cultures growing on PDA. All treatments were rated for damage following incubation on a lab bench at 21 to 24°C for 7 days. Isolate 777R1P5-SL2 caused moderate damage to seedlings but minimal rotting of mature carrot root tissue. Isolate 758C did no damage to either seedlings or root tissue. The AG-4 and AG-2-2IV isolates killed all seedlings and caused extensive rot on mature root tissue. The AG-2-1 isolate caused moderate damage to seedlings and mature root tissue, whereas isolates of binucleate Rhizoctonia sp. damaged neither seedling nor mature root tissue. These data suggest that some isolates of R. solani AG-2-4 may be capable of causing minor damage to carrot seedlings in the field in Georgia, but isolates of R. solani AG-4 and AG-2-2IV pose greater threat to seedlings and mature roots of carrot. Published data shows that isolates of AG-2-4 can kill seedlings of lettuce, cauliflower, and broccoli in the laboratory (1). R. solani AG-2-4 also may be capable of killing these crops in the field, all of which are grown commercially in Georgia. To our knowledge, this is the first report of R. solani AG-2-4 on carrot in Georgia. References: (1) D. E. Carling et al. Phytopathology 92:43, 2002. (2) D. R. Sumner and D. K. Bell. Phytopathology 72:86.
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Stocker, Nicolas, Agathe Farge, Laure Ricard, Vincent Jachiet, Clemence Mediavilla, Eolia Brissot, Giorgia Battipaglia, et al. "A Delayed Innate T Cell Reconstitution Is Associated with Epstein-Barr Virus Reactivation after Haploidentical Hematopoietic Stem Cell Transplantation Using Anti-Thymoglobulin and High-Dose Post-Transplant Cyclophosphamide." Blood 132, Supplement 1 (November 29, 2018): 3398. http://dx.doi.org/10.1182/blood-2018-99-111449.

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Abstract Background: Allogeneic hematopoietic stem cell transplantation (allo-HCT) using a haploidentical donor (haplo-HCT) using post-transplant high-dose cyclophosphamide (PTCy) is increasingly used for patients lacking a matched related or unrelated donor. We recently noticed a relatively high incidence of infectious complications, especially Epstein-Barr virus (EBV) reactivation after haplo-HCT. However, the mechanisms underlying the increased incidence of this complication in the haplo-HCT setting are unknown. We hypothesized that the use of PTCy may be associated with a deficit in innate-like effector T cells essential for preventing EBV reactivation.This study aimed to analyze immune reconstitution following haplo-HCT using peripheral blood stem cells (PBSC) grafts and to evaluate the correlations with EBV reactivation and outcomes. Patients and Methods: One hundred and twenty-three consecutive patients who underwent allo-HCT for hematological malignancies between 2013 and 2016 were included in this single-center retrospective study. All patients received G-CSF mobilized PBSC grafts and ATG 2.5-5 mg/Kg total dose. All patients received a combination of cyclosporine A and mycophenolate mofetil for GvHD prophylaxis, except for patients with a matched related donor (MRD) who received cyclosporine A alone and patients with an haploidentical donor who received PTCy (50mg/kg/d at d3+/-d5). α/β T cells (CD3+, CD4+ and CD8+), γ/δ T cells (pan γ/δ and Vδ2+), mucosal-associated T cells wich express a highly restricted TCR comprising a semi-variant Vα7.2-Jα33 (MAIT), invariant NK T cells, NK cells, B cells, Tregs, monocytes subsets and dendritic cells (myeloid DC, plasmacytoid DC and Slan-DC) were analyzed by multi-color flow cytometry at months (M) 1, 3, 6 and 12 following allo-HCT. Clinical data [acute GvHD (aGvHD), relapse incidence, chronic GvHD (cGvHD), viral reactivations, bacterial and fungal infections, non-relapse mortality (NRM), progression-free survival (PFS), refined GvHD-free and progression-free survival (GPFS), overall survival (OS)] were assessed together with sequential quantitative evaluation of immune subsets. Results: Median age was 55 (range, 17-70) years, with 32 male patients (26%) receiving a graft from a female donor. Diagnoses were myeloid malignancies (66%) or lymphoid malignancies (34%). Thirty-three patients (27%) received a graft from a MRD, 65 from an unrelated donor (MUD, 53%), and 25 from a haplo-identical donor (20%). Thirty patients (24%) with refractory disease received a sequential conditioning regimen while the remaining (n=93, 76%) received a RIC/RTC regimen based on fludarabine, busulfan +/- thiotepa. At d180, the cumulative incidences (CIs) of grade II-IV and grade III-IV aGvHD were 34% and 5%, respectively. The 2 years CIs of cGvHD, extensive cGvHD and relapse were 23%, 8% and 17%, respectively. At 2 years, NRM was 7%, PFS was 77%, GPFS was 66% and OS was 83%. The rate of EBV reactivation was significantly increased in haplo-HCT recipients as compared to fully-matched donor recipients (respectively, 68% versus 26%, P< .001). At one month after allo-HCT, the median counts of all immune cells subsets (except monocytes) was significantly lower in haplo-HCT recipients as compared to MRD or MUD recipients. At 3 months, α/β T cells, iNK T cells, NK cells, B cells, Tregs and Slan-DC reached similar median counts in haplo-HCT recipients as compared to MRD or MUD recipients. In contrast, Vδ2+ T cells and MAIT cells median counts remained significantly lower at 3, 6 and 12 months in haplo-HCT recipients compared to MRD or MUD recipients (at M1, M3, M6, M12, the median Vδ2+ T cells counts were 0.05/µL, 0.24/µL, 1.38/µL and 2.97/µL, and MAIT cells were 0.07/µL, 0.70/µL, 1.00/µL and 1.21/µL, respectively). Lower Vδ2+ T-cells and MAIT cells counts at one month was associated with a significantly increased CI of EBV reactivation (respectively, P=.04 and P<.0001) in landmark study. Conclusion: Immunological reconstitution of innate T cells is significantly delayed after haplo-HCT and low-dose ATG and PTCy. This prolonged deficiency is associated with an increased risk of EBV reactivation. Development of new strategies for innate-T cells expansion are necessary after haplo-HCT. Disclosures Mohty: MaaT Pharma: Consultancy, Honoraria.
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47

Thomas, Sheeba K., Jatin J. Shah, Ashley N. Morphey, Hans C. Lee, Elisabet E. Manasanch, Krina K. Patel, Carla P. Miller, et al. "Updated Results of a Phase II Study of Lenalidomide-Elotuzumab As Maintenance Therapy Post-Autologous Stem Cell Transplant (AuSCT) in Patients (Pts) with Multiple Myeloma (MM)." Blood 132, Supplement 1 (November 29, 2018): 1982. http://dx.doi.org/10.1182/blood-2018-99-116464.

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Abstract Background: Lenalidomide (LEN) monotherapy has been effective in extending progression free survival (PFS) after myeloablative AuSCT in pts with MM. Elotuzumab (ELO), a humanized IgG1 immunostimulatory monoclonal antibody against signaling lymphocytic activation molecule F7 (SLAM F7), is FDA approved in combination with LEN and dexamethasone (DEX) for treatment of MM pts who have received 1-3 prior therapies. The objective of this phase 2 trial is to evaluate the efficacy and safety of adding ELO to LEN as maintenance therapy post-myeloablative AuSCT. We report updated results of the primary (PFS) and secondary (overall survival [OS] and toxicity) endpoints. Patients and Methods: Between 4/15/2015-1/27/2016, 27 evaluable pts were treated on 28 day cycles with ELO, 10 mg/kg iv weekly for cycles 1-2, q2weeks for cycles 3-6, then 20 mg/kg once monthly for cycles 7+. Pts enrolled after 1/28/2016 (n=57 pts) have received ELO, 10 mg/kg IV weekly for cycles 1-2, and 20 mg/kg on day 1 from cycle 3 until disease progression (PD). LEN has been dosed at 10 mg/day for cycles 1-3, with a dose increase to 15 mg/day at physician discretion starting with cycle 4, in the absence of non-hematologic toxicity > grade 1 and significant cytopenias (ANC < 1000/mL, platelet count < 100,000/ml). For the 1st 8 weeks, pts <75 yrs receive 28 mg of DEX 3-24 hours pre-infusion, while pts ≥75yrs receive 8 mg; pts receive 4-10 mg iv DEX immediately pre-infusion for all cycles. Pts also receive zoster and thromboembolic prophylaxis commensurate with standard recommendations. The study's primary endpoint is PFS, defined as time from AuSCT to PD or death (whichever occurs first), or time of last contact. Secondary objectives are best response, OS, incidence of second primary malignancies (SPMs) and adverse event (AE) profile. Total enrollment of 100 pts is planned. Patients are followed until death, withdrawal of consent or removal from study. Eligible pts received ≤2 lines of induction therapy, and are 60-210 days post-AuSCT. Results: Pts (n=84) have been treated for a median of 16 cycles (2-43). At study entry, 27 (32%) had complete response (CR), 36 (43%) had very good partial remission (VGPR), 20 (24%) had partial remission (PR) and 1 (2%) had minor remission (MR). Best response achieved to date on study is CR in 44 pts (52%), VGPR in 31 pts (37%) and PR in 9 pts (11%). For those who have converted to CR on study, median time to CR was 2 months. Of 22 pts in CR who have been tested for minimal residual disease (MRD) to date, 20 are negative by flow cytometry (minimum of 2 million cells evaluated). Three of 20 have converted from VGPR to MRD negativity while on study. With a median follow up of 23 months, 96% of pts (n=81) remain alive. Ten pts have had PD; of these, 6 had high risk cytogenetics. Two died of PD while receiving salvage therapy. One additional pt died on study in VGPR, after developing acute cerebral encephalopathy with refractory status epilepticus of unclear etiology. Four pts withdrew for personal reasons, 4 were removed at physician discretion (prolonged cytopenias [1], drug rash [1], worsening memory impairment [1], therapy related myelodysplastic syndrome (t-MDS) [1]), and 2 lost insurance coverage. Estimated 3 year PFS is 81%. High risk cytogenetics adversely affected PFS (p=0.02). Grade 3-4 Hematologic AEs (no. of pts) were: neutropenia 32% (27), febrile neutropenia 15% (13), thrombocytopenia 8% (7), and anemia 7% (6). Grade 3-4 non-Hematologic AEs (no. of pts): respiratory infections 17% (15), diarrhea 14% (12), fatigue 13% (11), other infections 8% (7), peripheral neuropathy 7% (6), myalgias 6% (5), nausea/vomiting 4% (3), dizziness 2% (2), memory impairment 2% (2), maculopapular rash 2% (2), edema 1% (1). SPMs include intra-epidermal adenocarcinoma of the neck (1), mucinous appendiceal neoplasm (1), t-MDS (1), prostate cancer (1), and melanoma (1). Renal cell carcinoma was diagnosed in 1 pt, 15 months after removal from study for PD. Conclusions: Lenalidomide-elotuzumab is a well-tolerated maintenance therapy during which 33% of 84 pts had improvement in quality of response while on therapy, including 20% who converted to CR. The number of pts experiencing improvement may be underestimated due to ELO interference with paraprotein measurement on electrophoretic studies. Additional follow up is required to determine if the improved quality of responses translate into improvements in PFS and OS. Available data supports conduct of a Phase 3 trial. Disclosures Thomas: Array Pharma: Research Funding; Amgen Inc: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Celgene: Research Funding. Shah:Karyopharm Therapeutics: Employment. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Patel:Abbvie: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Poseida Therapeutics, Inc.: Research Funding.
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48

El-Agmy, Reda M., and Najm M. Al-Hosiny. "Thermal analysis and CW laser operation at 1.998 µm in end pumped Tm:YAP lasers." Photonics Letters of Poland 11, no. 4 (December 31, 2019): 103. http://dx.doi.org/10.4302/plp.v11i4.938.

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We report on thermal analysis and a continuous wave (CW) laser operation at (1.998µm) of end pumped Tm: YAP cylindrical laser rod. The Tm: YAP laser rod is pumped at a wavelength of 1.064 µm emitting from Nd: YAG laser source. A 3W incident pump power is used to generate a maximum laser output of 700 mW, representing 18% slope efficiency. The power of thermally induced lens in Tm:YAP laser rod is numerically analyzed and validated experimentally. The focal lengths of the thermally induced lens are directly measured using Shack-Hartmann wavefront sensor. We have detected blue up-conversion fluorescence emission before laser operation at 1.998 µm. The obtained experimental results were in good agreement with the numerical calculations. Full Text: PDF ReferencesI. F. Elder, J. Payne, "Diode-pumped, room-temperature Tm:YAP laser", Applied Optics 36 (33), 8606 (1997) CrossRef Y. Li, B. Yao, Y. Wang, Y. Ju, G. Zhao, Y. Zong, J. Xu, "High efficient diode-pumped Tm:YAP laser at room temperature", Chinese Opt. Lett. 5 (5), 286 (2007). DirectLink H. Ni, S. C. Rand, "Avalanche upconversion in Tm:YALO3", Opt. Lett. 16 (8), 1424 (1991). CrossRef Z. G. Wang, C. W. Song, Y. F. Li, Y. L. Ju, Y. Z. Wang, "CW and pulsed operation of a diode-end-pumped Tm:GdVO4 laser at room temperature", Laser Phys. Lett. 6 (2), 105 (2009). CrossRef Baoquan Yao, Yi Tian, Wei Wang, Gang Li, Yuezhu Wang, "Analysis and compensation of thermal lens effects in Tm:YAP lasers", Chinese Opt. Lett. 8 (10), 996 (2010). CrossRef F. Cornacchia, D. Parisi, C. Bernardini, M. Toncelli, "Efficient, diode-pumped Tm3+:BaY2F8 vibronic laser", Opt. Expr. 12 (9), 1982 (2004). CrossRef Xiaojin Cheng, Mi Fan, Jiandong Cao, Jianhua Shang, "Research on the thermal effect and laser resonator of diode-pumped thin-slab Tm:YAP lasers", Optik 176, 32 (2019). CrossRef W. Koechner, Solid-state Laser Engineering, Springer, (2013). DirectLink https://www.crytur.cz DirectLink http://www.laserlabcomponents.com/ DirectLink R. M. El-Agmy, N.AlHosiny, "2.31 [micro sign]m laser under up-conversion pumping at 1.064 [micro sign]m in Tm3+:ZBLAN fibre lasers", Elect. Lett. 46 (13), 936 (2010). CrossRef R. M. El-Agmy, N. M. Al-Hosiny, "870 mW blue laser emission at 480 nm in a large core thulium doped ZBLAN fiber laser", Laser Phys. 20 (4), 838 (2010). CrossRef R. M. El-Agmy, N. M. Al-Hosiny, "Power scaling of end-pumped Nd:YLF lasers, modeling and experiments", Optik 140, 584 (2017). CrossRef R. M. El-Agmy, N. Al-Hosiny, "Thermal analysis and experimental study of end-pumped Nd: YLF laser at 1053 nm", Photonic sensors 7 (4), 329 (2017). CrossRef S. C. Tidwell, J. F. Seamans, M. S. Bowers, A. K. Cousins, "Scaling CW diode-end-pumped Nd:YAG lasers to high average powers", IEEE J. Quantum Electron. 28, 997 (1992). CrossRef P. J. Hardman, W. A. Clarkson, G. J. Friel, M. Pollnau, D. C. Hanna, "Energy-transfer upconversion and thermal lensing in high-power end-pumped Nd:YLF laser crystals", IEEE Journal of Quantum Electronics 35, 647 (1999). CrossRef
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49

Shota, Hoshika, Hiroyuki Sugaya, Norimasa Takahashi, Keisuke Matsuki, Morihito Tokai, Takeshi Morioka, Yusuke Ueda, Hiroshige Hamada, and Yasutaka Takeuchi. "Arthroscopic Soft Tissue Stabilization for Traumatic Anterior Shoulder Instability in Elite Collision Athletes: Is it Sufficient?" Orthopaedic Journal of Sports Medicine 7, no. 7_suppl5 (July 2019): 2325967119S0027. http://dx.doi.org/10.1177/2325967119s00270.

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Objectives: Surgical options for shoulder instability in collision athletes remain controversial. Although arthroscopic soft tissue stabilization is widely accepted treatment for shoulder instability, many surgeons prefer coracoid transfer for collision athletes with or without glenoid defect due to potential high recurrence rate after arthroscopic soft tissue Bankart repair (ABR). In the meantime, Hill-Sacks remplissage (HSR) has been gaining popularity as an effective arthroscopic augmentation procedure. Since 2002, we performed rotator interval closure (RIC) as an augmentation in addition to ABR or arthroscopic bony Bankart repair (ABBR) for collision athletes and obtained satisfactory outcome. However, teen players demonstrated higher recurrence rate compared to twenties and thirties. Therefore, from 2012, we performed HSR as an additional augmentation for teen players besides ABR/ABBR and RIC. The purpose of this study was to assess the outcomes after arthroscopic stabilization in collision athletes who underwent shoulder stabilization under our treatment strategy. Methods: Between 2012 through 2015, 95 consecutive collision athletes underwent shoulder stabilization. Among those, only 2 patients (2%) underwent arthroscopic bony procedure for poor capsular integrity. Among the remaining 93 patients who underwent soft tissue stabilization, 65 were available for minimum 2 year follow-up (70%). Therefore, subjects consisted of 65 players including 54 rugby and 11 American football players (Table 1). There were 13 national top league, 24 collegeate, 21 junior or senior high school, and 7 recreational players. The mean age at surgery was 20 years (range, 16-36). The mean follow-up was 37 months (range, 24-64). We retrospectively reviewed intraoperative findings and surgical procedures using patient records including surgical reports and videos. We also investigated the mean time for sports return, functional outcome and recurrence rate. Pre- and postoperative Rowe scores were compared using paired t test. Results: Preoperative 3DCT of the glenoid demonstrated bony Bankart (fragment type) in 43 players (66%), attritional type in 16 (25%), and normal glenoid in 6 (9%). Mean glenoid bone loss was 15% (range, 0-25) and all of the glenoid with more than 10% bone loss retained bony fragment (Table 2). All 65 players demonstrated Bankart lesion and 15 had concomitant SLAP lesion (23%) which required repair. In addition, 5 players demonstrated capsule tear (8%), which were also repaired. Twenty four players (36%) underwent ABR or ABBR with RIC and forty one players (64%) underwent ABR or ABBR combined with HSR (Table 1).The mean time for sports return was 7 months (range, 4-13) after surgery. The mean Rowe score significantly improved after surgery from 65 (range, 55-75) to 92 (range, 65-100) (P < .001). Recurrence appeared in 2 cases (3%), both of which were junior or senior high school players who underwent ABR with HSR. Conclusion: Soft tissue stabilization combined with selective augmentation procedures for shoulder instability in collision athletes demonstrated satisfactory outcomes with low recurrence rate. Since the incidence of having bony Bankart lesion in collision athletes was very high, arthroscopic bony Bankart repair worked in many patients even with significant glenoid bone loss. Further, HSR seemed to be effective additional augmentation especially in young collision athletes. [Table: see text][Table: see text]
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50

Friedman, Alan D., Hong Guo, Ou Ma, Leonard I. Zon, Ilya Shestopalov, Dan S. Kaufman, and Patrick I. Ferrell. "The RUNX1-Regulated Cebpa +37 Kb Enhancer Directs Human CD4 Transgene Expression To Long-Term Hematopoietic Stem Cells and Preferentially To Myeloid Compared With Lymphoid Or Erythroid Progenitors." Blood 122, no. 21 (November 15, 2013): 2442. http://dx.doi.org/10.1182/blood.v122.21.2442.2442.

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Abstract We found that adult mice lacking RUNX1 have increased monopoiesis relative to granulopoiesis correlated with reduce Cebpa RNA expression in myeloid progenitors and that RUNX1 binds and activates Cebpa reporters via two sites in the Cebpa promoter and four conserved sites in a 450 bp +37 kb enhancer (Guo et al, Blood, 2012). This enhancer interacts with p300 and contains the H3K4me1 enhancer mark in myeloid cells. Previously reported ChIP-Seq data had demonstrated interaction of RUNX1 with the +37 kb enhancer, along with GATA2, SCL, Gfi-1b, MEIS1, Fli-1, ERG, PU.1, Lyl1, and LMO2. We have now generated transgenic C57BL/6 mice in which the Cebpa +37 kb enhancer positioned upstream of its 845 bp promoter (-720 to +125) directs expression of cytoplasmically truncated human CD4 (hCD4). Two founders with germ line transmission have been identified – both have detectable hCD4 RNA in marrow, at approximately 10-fold increased levels in one line compared to the other, with hCD4 expression detectable by FACS only in the higher expressing line. Analysis of 4-7 mice reveals that hCD4 expression is detected only in a small subset of mature hematopoietic cells, present in 6% of Mac-1+Gr-1+ neutrophils, 31% of Mac-1+Gr-1- monocytes, 4% of CD3+ T cells, 3% of CD19+ or 7% of B220+ B-cells, and 5% of Ter119+ erythroid cells. 6.5+/-1.9% of total marrow mononuclear cells and 13+/-4% of Lin- marrow cells express hCD4. At the progenitor level, hCD4 was evident in 56+/-7% of CMP, 70+/-5% of GMP, 36+/-9% of CLP, and only 1.5+/-1.0% of MEP. There was>100-fold enrichment of myeloid CFU but a 2-fold decrease in B-lymphoid colonies comparing hCD4+ versus hCD4- fractions of total marrow. Staining LSK cells for CD34 and FcγR demonstrated that 91+/-10% of multi-potent progenitors (MPP), 61+/-8% of ST-HSC, and 17+/-8% of LT-HSC express hCD4. Similarly, staining for the SLAM markers demonstrated that 19+/-9% of LSK-CD48-CD150+ LT-HSC express hCD4. Mean fluorescence index of hCD4 staining was about 2-fold higher in LSK, MPP, ST-HSC, CMP, and GMP compared with CLP and LT-HSC and about 3-fold higher than mature blood myeloid cells. 2E6 hCD4+ or hCD4- CD45.2 marrow cells were transplanted into lethally irradiated CD45.1 syngeneic recipients. 5/5 mice receiving hCD4- cells died at 2 weeks, reflecting lack of even progenitor engraftment, whereas 5/5 mice receiving hCD4+ cells were alive at 20 weeks, reflecting expression of the transgene in functional LT-HSC, with secondary transplanted mice viable at 4 week to date. The marrow cells of surviving mice were almost exclusively CD45.2, with hCD4+ expression in Lin- or Lin-c-kit+ marrow cells similar to that of donor mice. Although our second founder does not allow hCD4 detection by FACS, analysis of hCD4 RNA in marrow stem and progenitor subsets for this line is in progress, as is competitive transplantation of hCD4- versus hCD4+ marrow cells from the higher-expressing line. Murine E13.5 fetal liver hematopoietic stem and progenitor cells express hCD4 in a pattern similar to adult marrow. In zebrafish, the murine Cebpa +37 kb enhancer directs ZsGreen expression specifically to the caudal hematopoietic territory (CHT), analogous to the murine fetal liver, at 72 hour post-fertilization. Murine Cebpa +37 kb enhancer:ZsGreen transgene expression, lacking the Cebpa promoter, overlaps in the CHT with that of murine Runx1 +23 kb enhancer:mCherry in compound transgenic fish. The Cebpa and Runx1 enhancers direct similar tdTomato expression from a Sleeping Beauty vector in the K562 cell line, and these vectors are being compared for expression in hESC derived hematopoietic cells. In summary, the Cebpa gene contains an enhancer active in both LT-HSC and myeloid progenitors. Further characterization of its regulation may provide insights into the development of these hematopoietic stem and progenitor subsets and into how Cebpa expression is impaired in myelodysplastic syndromes or in acute myeloid leukemia. In addition, the Cebpa enhancer may prove useful in efforts to optimize LT-HSC formation from hESC. Disclosures: Zon: FATE Therapeutics, Inc: Consultancy, Equity Ownership, Founder Other, Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties; Stemgent, Inc: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Stocks, Stocks Other; Scholar Rock: Consultancy, Equity Ownership, Founder, Founder Other, Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties.
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