Explore the vast range of titles available.

We demonstrate a wideband diplexed focal plane suitable for observing low-frequency foregrounds that are important for cosmic microwave background polarimetry. The antenna elements are composed of slotted bowtie antennas with 60% bandwidth that can be partitioned into two bands. Each pixel is composed of two interleaved 12 × 12 pairs of linearly polarized antenna elements forming a phased array, designed to synthesize a symmetric beam with no need for focusing optics. The signal from each antenna element is captured in-phase and uniformly weighted by a microstrip summing tree. The antenna signal is diplexed into two bands through the use of two complementary, six-pole Butterworth filters. This filter architecture ensures a contiguous impedance match at all frequencies, and thereby achieves minimal reflection loss between both bands. Subsequently, out-of-band rejection is increased with a bandpass filter and the signal is then deposited on a transition-edge sensor bolometer island. We demonstrate the performance of this focal plane with two distinct bands, 30 and 40 GHz, each with a bandwidth of ∼20 and 15 GHz, respectively. The unequal bandwidths between the two bands are caused by an unintentional shift in diplexer frequency from its design values. The end-to-end optical efficiency of these detectors is relatively modest, at 20%–30%, with an efficiency loss due to an unknown impedance mismatch in the summing tree. Far-field beam maps show good optical characteristics, with edge pixels having no more than ∼5% ellipticity and ∼10%–15% peak-to-peak differences for A–B polarization pairs.

In the post-pandemic age, technology has grown significantly to create an impact on the art world. Whether it is planning an immersive art experience, hosting exhibitions and selling art in decentralized spaces, art organizations such as museums and galleries have begun to incorporate the use of technology as part of their program as an additional strategy to increase audience engagement and traffic even when they are not physically present. This thesis compares a case study (Part 1) and a business plan (Part 2), with the purpose of investigating the actual performance of the technology in art. I will apply the case study of the collaboration between The Mill and Tate Britain to my business of creative marketing studio with a focus on marketing and design through cutting-edge technology.

Beer is one of the most popular beverages in the world and it has an irreplaceable place in culture. Although invented later than ale, lager beers dominate the current market. Many factors relating to the appearance (colour, clarity and foam stability) and sensory characters (favour, taste and aroma) of beer, and other psychological determinants affect consumers' perception of the product and defines its drinkability. This review takes a wholistic approach to scrutinise favour generation in the brewing process, focusing particularly on the contribution of the raw ingredients and the yeasts to the final favour profiles of lager beers. In addition, we examine current developments to improve lager beer favour profiles for the modern consumers.

In the past, microglia were broadly categorized into two “states”: “resting” and “activated”. In the healthy mature CNS, microglia have ramified morphologies with small soma and many thin processes, which were classified as in the “resting” state. However, any disturbance in the homeostasis of CNS, such as infection and injury, can trigger microglia to shorten processes and enlarge cell soma, resembling a more traditional macrophage-like “amoeboid” phenotype (Kettenmann et al., 2011). The phenotype shift is accompanied with changes in gene expression and functional behaviors, which were collectively summarized as “microglia activation” (Hanisch & Kettenmann, 2007; Kettenmann et al., 2011). Activated microglia can actively migrate to injury or infection sites following chemotactic gradients or increase local densities through proliferation (Hanisch & Kettenmann, 2007). Until recently, studies on microglia focused only on their roles as inflammatory cells in the contexts of CNS disturbances such as injuries and neurodegenerative diseases. However, recent studies showed that microglia are far more complex and the “resting” state microglia have been active in neuron network surveillance, protruding and retracting their processes constantly, contributing to neonatal synaptic pruning and adult synaptic plasticity (Harry, 2013; Schafer et al., 2012). In this thesis, we used multi-photon imaging along with other optical techniques to investigate microglia’s behaviors and functions in a variety of different scenarios.

We demonstrate a wide-band diplexed focal plane suitable for observing low-frequency foregrounds that are important for cosmic microwave background polarimetry. The antenna elements are composed of slotted bowtie antennas with 60% bandwidth that can be partitioned into two bands. Each pixel is composed of two interleaved 12\\(\\)12 pairs of linearly polarized antenna elements forming a phased array, designed to synthesize a symmetric beam with no need for focusing optics. The signal from each antenna element is captured in-phase and uniformly weighted by a microstrip summing tree. The antenna signal is diplexed into two bands through the use of two complementary, six-pole Butterworth filters. This filter architecture ensures a contiguous impedance match at all frequencies, and thereby achieves minimal reflection loss between both bands. Subsequently, out-of-band rejection is increased with a bandpass filter and the signal is then deposited on a transition-edge sensor bolometer island. We demonstrate the performance of this focal plane with two distinct bands, 30 and 40 GHz, each with a bandwidth of \\(\\)20 and 15 GHz, respectively. The unequal bandwidths between the two bands are caused by an unintentional shift in diplexer frequency from its design values. The end-to-end optical efficiency of these detectors are relatively modest, at 20-30%, with an efficiency loss due to an unknown impedance mismatch in the summing tree. Far-field beam maps show good optical characteristics with edge pixels having no more than \\(\\) 5% ellipticity and \\(\\)10-15% peak-to-peak differences for A-B polarization pairs.

TIFUUN (THz Integral Field Units with Universal Nanotechnology) is an ultra-wideband mm-submm wave imaging spectrometer that capitalizes on the highly scalable integrated superconducting spectrometer technology. TIFUUN has two slots for integral field units (IFUs), which can jointly be optimized as open-hardware for each astronomical observation in terms of spatial and spectral coverage. These IFUs can have observation frequencies in the range of 90--360 GHz, with spectral resolution up to \\(R F/ F 1,000\\), with up to \\(\\)18,000 kinetic inductance detectors (shared by the two IFUs with a flexible ratio). The ultra-wide 4:1 (2 octave) bandwidth optics fits in a remarkably compact volume, by means of thin silicon lenses and a high chief ray angle design. The first pair of IFUs are being developed for the SUBLIME (Study of the Universe By Line Intensity Mapping Experiments) experiment that aims to map CII emission at redshift \\(\\)6 to trace the cosmic large-scale structure and the buildup of galaxies during reionization, using TIFUUN on the ASTE 10-m telescope. The scalability, flexibility and compactness makes TIFUUN a highly compatible and portable system suited also for upcoming telescope facilities in the vicinity, such as FYST and AtLAST/LST.

The BICEP3 and BICEP Array polarimeters are small-aperture refracting telescopes located at the South Pole designed to measure primordial gravitational wave signatures in the Cosmic Microwave Background (CMB) polarization, predicted by inflation. Constraining the inflationary signal requires not only excellent sensitivity, but also careful control of instrumental systematics. Both instruments use antenna-coupled orthogonally polarized detector pairs, and the polarized sky signal is reconstructed by taking the difference in each detector pair. As a result, the differential response between detectors within a pair becomes an important systematic effect we must control. Additionally, mapping the intensity and polarization response in regions away from the main beam can inform how sidelobe levels affect CMB measurements. Extensive calibration measurements are taken in situ every austral summer for control of instrumental systematics and instrument characterisation. In this work, we detail the set of beam calibration measurements that we conduct on the BICEP receivers, from deep measurements of main beam response to polarized beam response and sidelobe mapping. We discuss the impact of these measurements for instrumental systematics studies and design choices for future CMB receivers.

In this paper, we address the problem of cost-sensitive hyperparameter optimization (HPO) built upon freeze-thaw Bayesian optimization (BO). Specifically, we assume a scenario where users want to early-stop the HPO process when the expected performance improvement is not satisfactory with respect to the additional computational cost. Motivated by this scenario, we introduce utility in the freeze-thaw framework, a function describing the trade-off between the cost and performance that can be estimated from the user's preference data. This utility function, combined with our novel acquisition function and stopping criterion, allows us to dynamically continue training the configuration that we expect to maximally improve the utility in the future, and also automatically stop the HPO process around the maximum utility. Further, we improve the sample efficiency of existing freeze-thaw methods with transfer learning to develop a specialized surrogate model for the cost-sensitive HPO problem. We validate our algorithm on established multi-fidelity HPO benchmarks and show that it outperforms all the previous freeze-thaw BO and transfer-BO baselines we consider, while achieving a significantly better trade-off between the cost and performance. Our code is publicly available at https://github.com/db-Lee/CFBO.

Neoantigens generated by somatic nonsynonymous mutations are key targets of tumor-specific T cells, but only a small number of mutations predicted to be immunogenic are presented by MHC molecules on cancer cells. Vaccination studies in mice and patients have shown that the majority of neoepitopes that elicit T cell responses fail to induce significant antitumor activity, for incompletely understood reasons. We report that radiotherapy upregulates the expression of genes containing immunogenic mutations in a poorly immunogenic mouse model of triple-negative breast cancer. Vaccination with neoepitopes encoded by these genes elicited CD8+ and CD4+ T cells that, whereas ineffective in preventing tumor growth, improved the therapeutic efficacy of radiotherapy. Mechanistically, neoantigen-specific CD8+ T cells preferentially killed irradiated tumor cells. Neoantigen-specific CD4+ T cells were required for the therapeutic efficacy of vaccination and acted by producing Th1 cytokines, killing irradiated tumor cells, and promoting epitope spread. Such a cytotoxic activity relied on the ability of radiation to upregulate class II MHC molecules as well as the death receptors FAS/CD95 and DR5 on the surface of tumor cells. These results provide proof-of-principle evidence that radiotherapy works in concert with neoantigen vaccination to improve tumor control.

An X-ray structure of human P2Y 12 receptor, a clinical drug target for platelet aggregation inhibitors, is presented in complex with an agonist, providing insight into the δ-group of class A G-protein-coupled receptors. Key platelet aggregation GPCR structures Two papers in this issue of Nature present the crystal structures of the human P2Y 12 receptor, first in complex with the antithrombotic drug AZD1283, and second, bound to a full agonist (a close analogue of endogenous agonist ADP) and to a partial agonist. P2Y receptors are a family of purinergic G-protein-coupled receptors (GPCRs) that are activated by extracellular nucleotides. The P2Y 12 receptor is found mainly on the surface of platelets, where it regulates platelet activation and thrombus formation, and it is the target of several important antithrombotic drugs. In overall structure, P2Y 12 receptor is found to be similar to other GPCRs, although both the shape and location of the ligand-binding pocket are unusual. Comparisons of the three newly determined structures reveal that agonist binding induces a large-scale rearrangement of the extracellular domains of the GPCR. The P2Y 12 receptor (P2Y 12 R), one of eight members of the P2YR family expressed in humans, is one of the most prominent clinical drug targets for inhibition of platelet aggregation. Although mutagenesis and modelling studies of the P2Y 12 R provided useful insights into ligand binding 1 , 2 , 3 , 4 , the agonist and antagonist recognition and function at the P2Y 12 R remain poorly understood at the molecular level. Here we report the structures of the human P2Y 12 R in complex with the full agonist 2-methylthio-adenosine-5′-diphosphate (2MeSADP, a close analogue of endogenous agonist ADP) at 2.5 Å resolution, and the corresponding ATP derivative 2-methylthio-adenosine-5′-triphosphate (2MeSATP) at 3.1 Å resolution. These structures, together with the structure of the P2Y 12 R with antagonist ethyl 6-(4-((benzylsulfonyl)carbamoyl)piperidin-1-yl)-5-cyano-2-methylnicotinate (AZD1283) 5 , reveal striking conformational changes between nucleotide and non-nucleotide ligand complexes in the extracellular regions. Further analysis of these changes provides insight into a distinct ligand binding landscape in the δ-group of class A G-protein-coupled receptors (GPCRs). Agonist and non-nucleotide antagonist adopt different orientations in the P2Y 12 R, with only partially overlapped binding pockets. The agonist-bound P2Y 12 R structure answers long-standing questions surrounding P2Y 12 R–agonist recognition, and reveals interactions with several residues that had not been reported to be involved in agonist binding. As a first example, to our knowledge, of a GPCR in which agonist access to the binding pocket requires large-scale rearrangements in the highly malleable extracellular region, the structural and docking studies will therefore provide invaluable insight into the pharmacology and mechanisms of action of agonists and different classes of antagonists for the P2Y 12 R and potentially for other closely related P2YRs.