The Variational Homoencoder: Learning to learn high capacity generative models from few examples

Hierarchical Bayesian methods can unify many related tasks (e.g. k-shot classification, conditional and unconditional generation) as inference within a single generative model. However, when this generative model is expressed as a powerful neural network such as a PixelCNN, we show that existing learning techniques typically fail to effectively use latent variables. To address this, we develop a modification of the Variational Autoencoder in which encoded observations are decoded to new elements from the same class. This technique, which we call a Variational Homoencoder (VHE), produces a hierarchical latent variable model which better utilises latent variables. We use the VHE framework to learn a hierarchical PixelCNN on the Omniglot dataset, which outperforms all existing models on test set likelihood and achieves strong performance on one-shot generation and classification tasks. We additionally validate the VHE on natural images from the YouTube Faces database. Finally, we develop extensions of the model that apply to richer dataset structures such as factorial and hierarchical categories.Comment: UAI 2018 oral presentatio

μ-1,6-Dioxo-1,6-diphenylhexane-3,4-diolato-bis[(2,2′-bipyridine)chloridocopper(II)] dihydrate a; b; a

The reaction of CuCl2 with 1,6-diphenyl-1,3,5,6-hexanetetrone and 2,2′-bipyridine (bipy) in ethanol gave crystals of the corresponding bimetallic complex, [Cu2(C18H12O4)Cl2(C10H8N2)2]·2H2O. The molecule is centrosymmetric with each CuII ion coordinated to two oxygen atoms from the tetronediate, two nitrogen atoms from a bipy ligand and one coordinated chloride ion. A water molecule of crystallization forms hydrogen bonds to the chloride ions, linking the molecules into a chain parallel to the bc-face diagonal. © 2023 The Author(s)

Light infrastructures and intimate publics in the vertical city

This paper explores how the uneven distribution of light and darkness in the vertical city conditions residents’ capacities to form meaningful attachments to the places in which they dwell. Drawing on ethnographic material collected on a recent high-rise development in London, the paper explores how residents illuminate their homes in improvisatory engagement with the basic infrastructures that support their domestic lives and with the wider urban context. Four biographic vignettes reveal how people alter, adapt to or overturn the inadequacies of domestic infrastructures to carve out intimate spaces of inhabitation. The paper advances the idea of “light infrastructure” as a conceptual proposition for attending to the affective, esthetic and performative compositions of infrastructures in the night, and as an analytical proposition for developing a more hopeful and inclusive outlook on the ways people come to dwell, inhabit and feel at home in the vertical city at night

A multinational case series describing successful treatment of persistent SARS-CoV-2 infection caused by Omicron sublineages with prolonged courses of nirmatrelvir/ritonavir.

The optimum treatment for persistent infection with SARS-CoV-2 is not known. Our case series, across 5 hospitals in 3 countries, describes 11 cases where persistent SARS-CoV-2 infection was successfully treated with prolonged courses (median 10 days, range 10-18) of nirmatrelvir/ritonavir (Paxlovid). Most cases (9/11) had haematological malignancy and ten (10/11) had received CD20 depleting therapy. The median duration of infection was 103 days (IQR 85-138). The majority (10/11) were hospitalised, and seven (7/11) had severe/critical disease. All survived and 9/11 demonstrated viral clearance, almost half (4/9) of whom received nirmatrelvir/ritonavir as monotherapy. This case series suggests prolonged nirmatrelvir/ritonavir has a role in treating persistent infection

Assessment, teacher education and the emergence of professional expertise

This paper describes a new assessment tool that situates school literacy as a specific cultural, social and emotional practice. It reports evidence of the extent to which this tool seems to have helped student teachers to broker and balance different kinds of data and knowledge flows. The study shows that the tool was helpful in encouraging student teachers to deepen their understanding of individual domains and orchestrate across domain knowledge to account for why some children experience difficulty in learning to read. However, it also indicates that engagement in impactful, dynamic teaching situations helped the assessment tool to generate situated, meaningful knowledge and pedagogical understanding. This suggests that initial teacher education might need to re-think the range of student teachers’ practical experiences. The study suggests benefits in considering assessment tools and data that attend explicitly to the evidence of the wider learning context

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies