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Frontiers | Murine Models of Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a phenotypically and genetically heterogeneous hematologic malignancy. Extensive sequencing efforts have mapped the genomic landscape of adult and pediatric AML revealing a number of biologically and prognostically relevant driver lesions. Beyond identifying recurrent genetic aberrations, it …
Small-molecule inhibition of MLL activity by disruption of its
An increase in MLL complex concentration resulted in proportional increase in IC 50 values for WDR5-0103 (83±10 and 280±12 μM at concentrations of 500 and 1000 nM of the core trimeric MLL complex respectively). These data are consistent with a mechanism of action in which WDR5-0103 antagonizes the interaction of WDR5 with MLL by …
Microscopy Instrumentation and Nanopositioning at NSLS …
Focusing to 30 nm for 19.5 keV has been demonstrated at APS beamlines with a WSi2/Si MLL having 728 layers made at the APS. These same techniques were used to achieve a partial linear zone plate structure having a 5-nm outer most zone width and consisting of 1588 total layers as discussed below.
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Full Multilayer Laue Lens for Focusing Hard X-rays
Using a partial MLL we were able to focus 19.5-keV hard x-rays to a line focus of 16 nm with an efficiency of 31%. A full MLL is a complete linear MLL structure. It can be fabricated by bonding two partial MLL wafers, or by growing the full structure using magnetron sputtering without bonding. A 40-{mu}m full MLL, with a total of 5166 layers of ...
Structure, function and inhibition of critical protein–protein
Mixed lineage leukemia 1 (MLL1, also known as MLL or KMT2A) is an important transcription factor and histone-H3 lysine-4 (H3K4) methyltransferase. It is a master regulator for transcription of important genes (e.g., Hox genes) for embryonic development and hematopoiesis. However, it is largely dispensable in matured cells. …
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Menin Inhibitor DS-1594b Drives Differentiation and Induces …
Inhibition of the MLL-Menin interaction with novel Menin inhibitors has shown efficacy in both AML subsets, in pre- clinical and clinical studies. ... Results: 7 days treatment with DS-1594b reduced viability in MLLr and NPM1mut cell lines at low nM concentrations but did not affect growth of negative control U937 and HL60 . DS-1594b …
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Optics fabrication and metrology for nanofocusing of hard x …
Multilayer Laue Lens with 5-nm outermost zone - A scanning electron micrograph of a cross section of a 5-nm MLL structure is shown in Fig.1, below. The bilayer structure was WSi{sub 2}/Si and a total of 1588 layers were sputter deposited at the APS. The micrograph was read to obtain the data plotted in Fig. 2.
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2D MEMS-based multilayer Laue lens nanofocusing optics …
Developed planar 2D MLL structure has demonstrated astigmatism free point focus of ∼14 nm by ∼13 nm in horizontal and vertical directions, respectively, at 13.6 keV photon energy. Approaching 10 nm resolution with integrated 2D MLL optic is a significant step forward in applications of multilayer Laue lenses for high-resolution hard x-ray ...
Diffraction properties of multilayer Laue lenses with an …
The MLL was grown with parallel layer interfaces, and was designed to have a large focal length of 9.6 mm. The mounted lens was 2.7 mm in width. We found and quantified kinks and bending of sections of the MLL. ... Focusing to 30 nm for 19.5 keV has been demonstrated at APS beamlines with a WSi2/Si MLL having 728 layers made at …
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Rare MLL-ELL fusion transcripts in childhood acute myeloid …
FISH analysis also demonstrated that MLL was split. RNA-sequencing showed that the translocation had generated an MLL-ELL chimera in which exon 9 of MLL (nt 4241 in sequence with accession number NM_005933.3) was fused to exon 6 of ELL (nt 817 in sequence with accession number NM_006532.3).
Advances of semiconductor mode-locked laser for optical …
The 20 GHz two-section passive mode-locking design was conducted by using a 2048 μm cavity length with a 287 μm SA section as shown in Figure 8B. Figure 8C shows the square-like optical spectrum with the largest 3 dB bandwidth of 6.1 nm (58 lines, 80 lines within 10 dB) under optimized mode locking state of the Si-based MLL.
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Deep UV to NIR frequency combs via cascaded harmonic generation …
Compact, turnkey frequency combs in the deep ultraviolet (UV) to near-infrared (NIR) wavelength region are important for applications ranging from ultralow power spectroscopy and quantum memory to light–atom interactions. Translation of an IR (1550 nm) comb from a compact mode-locked laser (MLL) to visible wavelength region, using cascading of …
Full Multilayer Laue Lens for focusing hard x-rays.
Using a partial MLL we were able to focus 19.5-keV hard x-rays to a line focus of 16 nm with an efficiency of 31%. A full MLL is a complete linear MLL structure. It can be fabricated by bonding two partial MLL wafers, or by growing the full structure using magnetron sputtering without bonding. A 40-{mu}m full MLL, with a total of 5166 layers of ...
THE PREMIER LACROSSE LEAGUE AND MAJOR LEAGUE LACROSSE …
LOS ANGELES (December 16, 2020) – The Premier Lacrosse League ("PLL") and Major League Lacrosse ("MLL") have merged with subsequent season operations and activities to formally exist under the Premier Lacrosse League. As part of the merger, the PLL will immediately expand to include the Boston Cannons as the PLL's eighth team, under the …
Multilayer Laue Lens: A Path Toward One Nanometer X-Ray Focusing
The multilayer Laue lens (MLL) is a novel diffractive optic for hard X-ray nanofocusing, which is fabricated by thin film deposition techniques and takes advantage of the dynamical diffraction effect to achieve a high numerical aperture and efficiency. It overcomes two difficulties encountered in diffractive optics fabrication for focusing hard X-rays: (1) small …
Menin Inhibitors: A New Hope in MLL-Rearranged …
VTP50469 rapidly suppressed the gene expression program in MLL-rearranged cell lines and showed activity at low nM concentrations in various cellular contexts. Interestingly, the kinetics underlying the suppression of gene expression were more rapid than that seen with some other epigenetic therapies such as DOT1L inhibitors.
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Menin–MLL1 Interaction Small Molecule Inhibitors: A …
The IC50 values of MI-538 in inhibiting the leukemia cell lines (MV-4-11) carrying MLL fusion reached 21 nM. Treatment with MI-538 led to a strong downregulated expression of MEIS1 and HOXA9 genes (Figure 2 F). Meanwhile, MI-538 significantly reduced MV-4-11 tumor volume in vivo and did not cause obvious toxic symptoms, which …
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MLL-Rearranged Leukemias—An Update on Science and …
After its translation, wild-type MLL1 is proteolytically cleaved by the enzyme taspase-1 (19, 20).The resulting 320-kDa N-terminal fragment (MLL-N) contains all domains except the transcriptional activation domain and the SET domain, both of which are retained by the 180-kDa C-terminal fragment (MLL-C).MLL-N and MLL-C normally associate with …
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