AMiBA: Broadband Heterodyne CMB Interferometry

The Y. T. Lee Array for Microwave Background (AMiBA) has reported the first science results on the detection of galaxy clusters via the Sunyaev Zel'dovich effect. The science objectives required small reflectors in order to sample large scale structures (20') while interferometry provided modest resolutions (2'). With these constraints, we designed for the best sensitivity by utilizing the maximum possible continuum bandwidth matched to the atmospheric window at 86-102GHz, with dual polarizations. A novel wide-band analog correlator was designed that is easily expandable for more interferometer elements. MMIC technology was used throughout as much as possible in order to miniaturize the components and to enhance mass production. These designs will find application in other upcoming astronomy projects. AMiBA is now in operations since 2006, and we are in the process to expand the array from 7 to 13 elements.Comment: 10 pages, 6 figures, ApJ in press; a version with high resolution figures available at http://www.asiaa.sinica.edu.tw/~keiichi/upfiles/AMiBA7/mtc_highreso.pd

AMiBA: scaling relations between the integrated Compton-y and X-ray derived temperature, mass, and luminosity

We investigate the scaling relations between the X-ray and the thermal Sunyaev-Zel'dovich Effect (SZE) properties of clusters of galaxies, using data taken during 2007 by the Y.T. Lee Array for Microwave Background Anisotropy (AMiBA) at 94 GHz for the six clusters A1689, A1995, A2142, A2163, A2261, and A2390. The scaling relations relate the integrated Compton-y parameter Y_{2500} to the X-ray derived gas temperature T_{e}, total mass M_{2500}, and bolometric luminosity L_X within r_{2500}. Our results for the power-law index and normalization are both consistent with the self-similar model and other studies in the literature except for the Y_{2500}-L_X relation, for which a physical explanation is given though further investigation may be still needed. Our results not only provide confidence for the AMiBA project but also support our understanding of galaxy clusters.Comment: Accepted by ApJ; 8 pages, 3 figures, 5 table

HDAC8 Inhibition Specifically Targets Inv(16) Acute Myeloid Leukemic Stem Cells by Restoring p53 Acetylation

SummaryAcute myeloid leukemia (AML) is driven and sustained by leukemia stem cells (LSCs) with unlimited self-renewal capacity and resistance to chemotherapy. Mutation in the TP53 tumor suppressor is relatively rare in de novo AML; however, p53 can be regulated through post-translational mechanisms. Here, we show that p53 activity is inhibited in inv(16)+ AML LSCs via interactions with the CBFβ-SMMHC (CM) fusion protein and histone deacetylase 8 (HDAC8). HDAC8 aberrantly deacetylates p53 and promotes LSC transformation and maintenance. HDAC8 deficiency or inhibition using HDAC8-selective inhibitors (HDAC8i) effectively restores p53 acetylation and activity. Importantly, HDAC8 inhibition induces apoptosis in inv(16)+ AML CD34+ cells, while sparing the normal hematopoietic stem cells. Furthermore, in vivo HDAC8i administration profoundly diminishes AML propagation and abrogates leukemia-initiating capacity of both murine and patient-derived LSCs. This study elucidates an HDAC8-mediated p53-inactivating mechanism promoting LSC activity and highlights HDAC8 inhibition as a promising approach to selectively target inv(16)+ LSCs

AMiBA Wideband Analog Correlator

A wideband analog correlator has been constructed for the Yuan-Tseh Lee Array for Microwave Background Anisotropy. Lag correlators using analog multipliers provide large bandwidth and moderate frequency resolution. Broadband IF distribution, backend signal processing and control are described. Operating conditions for optimum sensitivity and linearity are discussed. From observations, a large effective bandwidth of around 10 GHz has been shown to provide sufficient sensitivity for detecting cosmic microwave background variations.Comment: 28 pages, 23 figures, ApJ in press

Cbl negatively regulates nlrp3 inflammasome activation through glut1-dependent glycolysis inhibition

Activation of the nod-like receptor 3 (NLRP3) inflammasomes is crucial for immune defense, but improper and excessive activation causes inflammatory diseases. We previously reported that Cbl plays a pivotal role in suppressing NLRP3 inflammasome activation by inhibiting Pyk2-mediated apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization. Here, we showed that Cbl dampened NLRP3 inflammasome activation by inhibiting glycolysis, as demonstrated with Cbl knockout cells and treatment with the Cbl inhibitor hydrocotarnine. We revealed that the inhibition of Cbl promoted caspase-1 cleavage and interleukin (IL)-1β secretion through a glycolysis-dependent mechanism. Inhibiting Cbl increased cellular glucose uptake, glycolytic capacity, and mitochondrial oxidative phosphorylation capacity. Upon NLRP3 inflammasome activation, inhibiting Cbl increased glycolysis-dependent activation of mitochondrial respiration and increased the production of reactive oxygen species, which contributes to NLRP3 inflammasome activation and IL-1β secretion. Mechanistically, inhibiting Cbl increased surface expression of glucose transporter 1 (GLUT1) protein through post-transcriptional regulation, which increased cellular glucose uptake and consequently raised glycolytic capacity, and in turn enhanced NLRP3 inflammasome activation. Together, our findings provide new insights into the role of Cbl in NLRP3 inflammasome regulation through GLUT1 downregulation. We also show that a novel Cbl inhibitor, hydrocortanine, increased NLRP3 inflammasome activity via its effect on glycolysis