Highly multiplexed and quantitative cell-surface protein profiling using genetically barcoded antibodies.

Human cells express thousands of different surface proteins that can be used for cell classification, or to distinguish healthy and disease conditions. A method capable of profiling a substantial fraction of the surface proteome simultaneously and inexpensively would enable more accurate and complete classification of cell states. We present a highly multiplexed and quantitative surface proteomic method using genetically barcoded antibodies called phage-antibody next-generation sequencing (PhaNGS). Using 144 preselected antibodies displayed on filamentous phage (Fab-phage) against 44 receptor targets, we assess changes in B cell surface proteins after the development of drug resistance in a patient with acute lymphoblastic leukemia (ALL) and in adaptation to oncogene expression in a Myc-inducible Burkitt lymphoma model. We further show PhaNGS can be applied at the single-cell level. Our results reveal that a common set of proteins including FLT3, NCR3LG1, and ROR1 dominate the response to similar oncogenic perturbations in B cells. Linking high-affinity, selective, genetically encoded binders to NGS enables direct and highly multiplexed protein detection, comparable to RNA-sequencing for mRNA. PhaNGS has the potential to profile a substantial fraction of the surface proteome simultaneously and inexpensively to enable more accurate and complete classification of cell states

Design and performance of the antenna coupled lumped-element kinetic inductance detector

Focal plane arrays consisting of low-noise, polarisation-sensitive detectors have made possible the pioneering advances in the study of the cosmic microwave background (CMB). To make further progress, the next generation of CMB experiments (e.g. CMB-S4) will require a substantial increase in the number of detectors compared to the current stage 3 instruments. Arrays of kinetic inductance detectors (KIDs) provide a possible path to realising such large format arrays owing to their intrinsic multiplexing advantage and relative cryogenic simplicity. In this proceedings, we report on the design of a novel variant of the traditional KID design; the antenna-coupled lumped-element KID. A polarisation sensitive twin-slot antenna placed behind an optimised hemispherical lens couples power onto a thin-film superconducting microstrip line. The power is then guided into the inductive section of an aluminium KID where it is absorbed and modifies both the resonant frequency and quality factor of the KID. We present the various aspects of the design and preliminary results from the first set of seven-element prototype arrays and compare to the expected modelled performance

The orexigenic hormone acyl-ghrelin increases adult hippocampal neurogenesis and enhances pattern separation.

An important link exists between intact metabolic processes and normal cognitive functioning; however, the underlying mechanisms remain unknown. There is accumulating evidence that the gut hormone ghrelin, an orexigenic peptide that is elevated during calorie restriction (CR) and known primarily for stimulating growth hormone release, has important extra-hypothalamic functions, such as enhancing synaptic plasticity and hippocampal neurogenesis. The present study was designed to evaluate the long-term effects of elevating acyl-ghrelin levels, albeit within the physiological range, on the number of new adult born neurons in the dentate gyrus (DG) and performance on the Spontaneous Location Recognition (SLR) task, previously shown to be DG-dependent and sensitive to manipulations of plasticity mechanisms and cell proliferation. The results revealed that peripheral treatment of rats with acyl-ghrelin enhanced both adult hippocampal neurogenesis and performance on SLR when measured 8-10 days after the end of acyl-ghrelin treatment. Our data show that systemic administration of physiological levels of acyl-ghrelin can produce long-lasting improvements in spatial memory that persist following the end of treatment. As ghrelin is potentially involved in regulating the relationship between metabolic and cognitive dysfunction in ageing and neurodegenerative disease, elucidating the underlying mechanisms holds promise for identifying novel therapeutic targets and modifiable lifestyle factors that may have beneficial effects on the brain.This work was supported by grants from the Medical Research Council (grant G0902250/94306), The Royal Society and the Biotechnology and Biological Sciences Research Council (grant BB/G019002/1).This is the final version. It was first published by Elsevier at http://www.sciencedirect.com/science/article/pii/S030645301400399

How can mastery learning promote inclusion in the science classroom?

Mastery learning is not a new concept, as it has been around for many years and will continue to feature in the educational scene as educators explore how it can be utilised to promote learning, despite the varying views regarding its impact on pupils’ learning and progress. The purpose of this article is to amplify the concept of mastery learning and its place in promoting inclusive learning among science pupils, and to highlight reasons why this pedagogy should be considered by science teachers

We need to talk about… differentiation

Differentiation has been one of the main teaching strategies used to support inclusion in the classroom when teaching a diverse class of pupils who vary in ability and needs. In England, the Teachers’ Standards 5 (DFE, 2021) is clear that teachers need to ‘know when and how to differentiate appropriately, using approaches which enable pupils to be taught effectively’ (p.11). This aim is challenging, as differentiation is a complex and a broad teaching approach that incorporates many practices to improve inclusion. It involves a multitude of professional decisions that the teacher must make during a lesson. This article will explore differentiation, the misconceptions associated with it, and classroom practices to support differentiation

Advanced X-Ray Timing Array Mission: Conceptual Spacecraft Design Study

The Advanced X-Ray Timing Array (AXTAR) is a mission concept for submillisecond timing of bright galactic x-ray sources. The two science instruments are the Large Area Timing Array (LATA) (a collimated instrument with 2-50-keV coverage and over 3 square meters of effective area) and a Sky Monitor (SM), which acts as a trigger for pointed observations of x-ray transients. The spacecraft conceptual design team developed two spacecraft concepts that will enable the AXTAR mission: A minimal configuration to be launched on a Taurus II and a larger configuration to be launched on a Falcon 9 or similar vehicle

Cryogenic Propellant Storage and Transfer Technology Demonstration: Prephase A Government Point-of-Departure Concept Study

The primary purpose of this study was to define a point-of-departure prephase A mission concept for the cryogenic propellant storage and transfer technology demonstration mission to be conducted by the NASA Office of the Chief Technologist (OCT). The mission concept includes identification of the cryogenic propellant management technologies to be demonstrated, definition of a representative mission timeline, and definition of a viable flight system design concept. The resulting mission concept will serve as a point of departure for evaluating alternative mission concepts and synthesizing the results of industry- defined mission concepts developed under the OCT contracted studie