An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.

Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function of polycomb repressive complex 2 (PRC2) that mediates coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP), promoting evasion of T cell-mediated immunity. MHC-I APP gene promoters in MHC-I low cancers harbor bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine-induced upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological MHC-I silencing highlights a conserved mechanism by which cancers arising from these primitive tissues exploit PRC2 activity to enable immune evasion.Cancer Research UK Clinician Scientist Fellowship C53779/A20097 (M.L.B), Leukaemia Foundation Australia Senior Fellowship and Howard Hughes Medical Institute International Research Scholarship 55008729 (M.A.D), Peter and Julie Alston Centenary fellowship (K.D.S.), Wellcome Trust Principal Research Fellowship 101835/Z/13/Z (P.J.L), Peter MacCallum Postgraduate Scholarship (C.E.S), NHMRC Postgraduate Scholarship (K.L.C.), Maddie Riewoldt's Vision 064728 (Y-C.C), Victorian Cancer Agency (E.Y.N.L), CSL Centenary fellowship (S-J.D), National Breast Cancer Foundation Fellowship ECF-17-005 (P.A.B.), Addenbrooke’s Charitable Trust and NIHR Cambridge BRC (M.L.B., P.J.L), NHMRC grant 1085015, 1106444 (M.A.D) and 1128984 (M.A.D, S-J.D)

Globular cluster systems in nearby dwarf galaxies - II. Nuclear star clusters and their relation to massive Galactic globular clusters

(Abridged) Using luminosities and structural parameters of globular clusters (GCs) in the nuclear regions (nGCs) of low-mass dwarf galaxies from HST/ACS imaging we derive the present-day escape velocities (v_esc) of stellar ejecta to reach the cluster tidal radius and compare them with those of Galactic GCs with extended (hot) horizontal branches (EHBs-GCs). For EHB-GCs, we find a correlation between the present-day v_esc and their metallicity as well as (V-I)_0 colour. The similar v_esc, (V-I)_0 distribution of nGCs and EHB-GCs implies that nGCs could also have complex stellar populations. The v_esc-[Fe/H] relation could reflect the known relation of increasing stellar wind velocity with metallicity, which in turn could explain why more metal-poor clusters typically show more peculiarities in their stellar population than more metal-rich clusters of the same mass do. Thus the cluster v_esc can be used as parameter to describe the degree of self-enrichment. The nGCs populate the same Mv vs. rh region as EHB-GCs, although they do not reach the sizes of the largest EHB-GCs like wCen and NGC 2419. We argue that during accretion the rh of an nGC could increase due to significant mass loss in the cluster vicinity and the resulting drop in the external potential in the core once the dwarf galaxy dissolves. Our results support the scenario in which Galactic EHB-GCs have originated in the centres of pre-Galactic building blocks or dwarf galaxies that were later accreted by the Milky Way.Comment: MNRAS accepted, 12 pages, 6 figures, 4 Tables (3 & 4 available by request

Meditation and the EEG

Previous research on meditation and the EEG is described, and findings relating to EEG patterns during meditation are discussed. Comparisons of meditation with other altered states are reviewed and it is concluded that, on the basis of existing EEG evidence, there is some reason for differentiating between meditation and drowsing. Research on alpha-blocking and habituation of the blocking response during meditation is reviewed, and the effects of meditation on EEG patterns outside of meditation are described. In conclusion, the need for more precisely formulated research is pointed out

Simulation Toolkit for Scientific Discovery

<h2>Additions</h2> <ul> <li>initial support for DSL 2.0.<ul> <li>Graphs consisting of workflow and component templates</li> <li>Templates have a signature consisting of a name, an optional description, and an optional array of parameters. Parameters may come with default values</li> </ul> </li> </ul> <h2>Changes</h2> <ul> <li>update to pydantic v2.x</li> </ul>If you use this software, please cite it using the metadata from this file

Trends in Low Power Handset Software Defined Radio

Abstract. This paper presents an overview of trends in low power handset SDR implementations. With the market for SDR-enabled handsets expected to grow to 200M units by 2014, the barriers to efficient handset implementations – both hardware and software – have been removed based on new and innovative architectures. We describe advances in DSP architectures and compilers that are enabling SDR handset implementations and present some results for a specific SDR design

A static lowpower, high-performance 32-bit carry skip adder

In this paper, we present a full-static carry-skip adder designed to achieve low power dissipation and high-performance operation. To reduce the adder’s delay and power consumption, the adder is divided into variable-sized blocks that balance the inputs to the carry chain. The optimum block sizes for minimizing the critical path delay with complementary carry generation are achieved. Within blocks, highly optimized carry look-ahead logic, which computes block generate and block propagate signals, is used to further decrease delay. The adder architecture decreases power consumption by reducing the number of logic levels, glitches, and transistors. To achieve balanced delay, input bits are grouped unevenly in the carry chain. This grouping reduces active power by minimizing extraneous glitches and transitions. The adder has been implemented in 130nm CMOS technology. At 1.2V and 25C, typical performance is 1.086GHz and power dissipation normalized to 600MHz operation is 0.786mW. 1