Rational Design, Synthesis and Biological Evaluation of Pyrimidine-4,6-diamine derivatives as Type-II inhibitors of FLT3 Selective Against c-KIT.

FMS-like Tyrosine Kinase 3 (FLT3) is a clinically validated target for acute myeloid leukemia (AML). Inhibitors targeting FLT3 have been evaluated in clinical studies and have exhibited potential to treat FLT3-driven AML. A frequent, clinical limitation is FLT3 selectivity, as concomitant inhibition of FLT3 and c-KIT is thought to cause dose-limiting myelosuppression. Through a rational design approach, novel FLT3 inhibitors were synthesized employing a pyridine/pyrimidine warhead. The most potent compound identified from the studies is compound 13a, which exhibited an IC50 value of 13.9 ± 6.5 nM against the FLT3 kinase with high selectivity over c-KIT. Mechanism of action studies suggested that 13a is a Type-II kinase inhibitor, which was also supported through computer aided drug discovery (CADD) efforts. Cell-based assays identified that 13a was potent on a variety of FLT3-driven cell lines with clinical relevance. We report herein the discovery and therapeutic evaluation of 4,6-diamino pyrimidine-based Type-II FLT3 inhibitors, which can serve as a FLT3-selective scaffold for further clinical development

AtKinesin-13A is located on Golgi-associated vesicle and involved in vesicle formation/budding in Arabidopsis root-cap peripheral cells

<p>Abstract</p> <p>Background</p> <p>AtKinesin-13A is an internal-motor kinesin from Arabidopsis (<it>Arabidopsis thaliana</it>). Previous immunofluorescent results showed that AtKinesin-13A localized to Golgi stacks in plant cells. However, its precise localization and biological function in Golgi apparatus is unclear.</p> <p>Results</p> <p>In this paper, immunofluorescent labeling and confocal microscopic observation revealed that AtKinesin-13A was co-localized with Golgi stacks in Arabidopsis root tip cells. Immuno-electron microscopic observations indicated that AtKinesin-13A is primarily localized on Golgi-associated vesicles in Arabidopsis root-cap cells. By T-DNA insertion, the inactivation of the <it>AtKinesin-13A </it>gene (NM-112536) resulted in a sharp decrease of size and number of Golgi vesicles in root-cap peripheral cells. At the same time, these cells were vacuolated in comparison to the corresponding cells of the wild type.</p> <p>Conclusion</p> <p>These results suggest that AtKinesin-13A decorates Golgi-associated vesicles and may be involved in regulating the formation of Golgi vesicles in the root-cap peripheral cells in Arabidopsis.</p

Topological Electropoles in 4+1 Dimensional EYMCS Theory

A class of explicit exact solutions of Einstein Yang Mills Chern Simons (EYMCS) theory corresponding to topological solitons carrying non-Abelian topological electric charge is obtained. This verifies a conjecture made in Ref.[1,2] regarding the stabilization of the corresponding charged configurations in the theory without gravity .Comment: 11 pages ,Plain TeX,IOPB/BBSR/94-11. Minor typos in eqns(4),(7), (13a),(13b),(21) correcte

Pion spectra in Ar+Sc interactions at SPS energies

This contribution discusses recent results from analysis of Ar+Sc interactions recorded with the NA61/SHINE detector at six beam momenta: 13A, 19A, 30A, 40A, 75A, 150A GeV/c at the CERN SPS. Rapidity and transverse mass spectra of pions obtained with the "h-" analysis method are presented and compared to results from p+p, Be+Be and Pb+Pb collisions.Comment: Presented at the Critical Point and Onset of Deconfinement 2016, Wroclaw, Poland, May 30th - June 4th, 201

JUPITER-II Program: ANL analysis of ZPPR-13A and ZPPR-13B

The ZPPR-13 experiments provide basic physics data for radial heterogeneous LMFBR cores of approximately 700MWe size. Assemblies ZPPR-13A, ZPPR-13B and ZPPR-13A comprised the JUPITER-II cooperative program between the U.S. Department of Energy (US DOE) and PNC of Japan. The measurements were made between August 1982 and April 1984. The core designs and the measurements were planned jointly by the two parties with substantial input from U.S. industrial interests to ensure coverage of the design requirements. This report describes in detail the results of the Argonne National Laboratory (ANL) analyses of phases 13A and 13B/1 and includes preliminary results for the later assemblies of phase 13B.

ENHANCING ACTIVITIES STUDENTS LEARNING COURSE USING STRUCTURE ALGEBRAIC MODEL TYPE COOPERATIVE LEARNING STAD IN MATH EDUCATION CLASS 2013A Prodi UMMY SOLOK

The purpose of this stady is to reveal the extent to which STAD type cooperative learning model can improve students' learning activities subject to the algebraic structure 13A Prodi MAT math education UMMY Solok. This research is a classroom action research conducted three cycles. Each cycle consists of four phases: planning, action, observation and reflection. Subjects were students of mathematics education Prodi MAT 13A UMMY Solok with the number of students 22 people. Data was collected through observation sheets lapangan.Teknik student activities and records data analysis used is descriptive analysis. The results showed that all student activity increased from the first cycle to the third cycle. So learning STAD Cooperative Learning Model can increase the activity of the subjects studied algebra structure 13A Prodi MAT math education UMMY Solok

Volume 92 Issue 13a

https://dc.swosu.edu/the_southwestern/1552/thumbnail.jp

SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF CERTAIN SCHIFF BASES OF OCTAHYDRO-1H-PYRROLO [3, 4-B] PYRIDINE DERIVATIVES

Objective: Synthesis, characterization and biological screening of some new 1,6-disubstituted Octahydro-1H-pyrrolo[3,4-b]pyridine Schiff base (13a-n) derivatives.Methods: The scaffold of Octahydro-1H-pyrrolo [3,4-b]pyridine Schiff bases was prepared, synthesised and screened for their biological activity.Results: The structure of newly synthesized compounds was characterized by spectral data and screened for their biological activity like antioxidant, antimicrobial, antifungal, and chelating efficacy activities against various bacteria and fungi strains. Screening revealed that several of these compounds (13a-n) showed potential biological activity.Conclusion: Investigation on newly synthesised 1,6-disubstituted Octahydro-1H-pyrrolo[3,4-b]pyridine Schiff base (13a-n) derivatives for their biological activity revealed that some of the compounds showed good antioxidant, chelating and antimicrobial properties. The fact that the newly synthesised Schiff bases in this study are chemically related to the current medication and suggests further work is clearly warranted and to be explored.Â

Multiplicity fluctuations in Ar+Sc collisions at the CERN SPS from NA61/SHINE

Multiplicity fluctuations were investigated in Ar+Sc collisions at 13A, 19A, 30A, 40A, 75A, 150A GeV/c using the NA61/SHINE detector at the SPS. Centrality selection is based on the nucleon-spectator energy in the forward hemisphere as measured by the Projectile spectator detector. Preliminary results on the scaled variance {\omega} and the strongly intensive measure {\Omega} were obtained for the multiplicity distribution of all, negatively and positively charged hadrons. Results are discussed and compared with p+p results and Pb+Pb data of NA49 and EPOS 1.99 simulations.Comment: Presented at the Critical Point and Onset of Deconfinement 2016, Wroclaw, Poland, May 30th - June 4th, 201

Seeded Bermudagrass Cultivar Evaluation

A year after seeding, the stand of ‘F.K.#1’ appeared better than stands of 10 of the other 13 seeded entries. By fall, 2014, stands of ‘KF-13A,’ ‘KF-13B,’ and ‘SWI-800’ along with ‘F.K.#1’ were better than stands of four of the other seeded entries. Late-summer production was higher for KF-13A and ‘Midland 99,’ the sprigged check, than for five of the other entries