Feeling Exhausted? Tuning Irf4 Energizes Dysfunctional T Cells.

The regulatory mechanisms governing T cell exhaustion remain incompletely understood. Man et al. (2017) and Wu et al. (2017) report that the T cell receptor responsive transcription factor Irf4 promotes T cell exhaustion in chronic viral infection but dampens exhaustion in response to tissue allografts

Suppression of Tcf1 by Inflammatory Cytokines Facilitates Effector CD8 T Cell Differentiation.

The formation of central CD8 T cell memory in response to infection depends on the transcription factor Tcf1 (Tcf7). Tcf1 is expressed at high levels in naive CD8 T cells but downregulated in most CD8 T cells during effector differentiation. The relevance of Tcf1 downregulation for effector differentiation and the signals controlling Tcf1 expression have not been elucidated. Here, we show that systemic inflammatory signals downregulated Tcf1 in CD8 T cells during dendritic cell vaccination and bacterial infections. The suppressive effect was mediated by the inflammatory cytokine interleukin 12 (IL-12), which acted via STAT4 in CD8 T cells. IL-12-induced Tcf1 downregulation required cell cycling, occurred at the transcriptional level, and was prevented in part by inhibiting DNA methyltransferases. Absence of Tcf1 during T cell priming circumvented the need of systemic inflammation for effector differentiation. We conclude that silencing of Tcf1 by systemic inflammation facilitates effector CD8 T cell differentiation

Characterization of deep level traps responsible for isolation of proton implanted GaAs

Deep level transient spectroscopy was employed to determine the electrical properties of defects induced in metalorganic chemical-vapor deposition grown n-type and p-type GaAs during proton bombardment. Thermal stability of these defects was investigated and correlation with defects responsible for isolation of GaAs by ion bombardment was discussed. The annealing temperature region (220–250 °C) is similar to proton isolated GaAs below the threshold dose for complete isolation. At least four of the five traps observed in n-type GaAs are not simple interstitial-vacancy pairs. For p-type GaAs we have observed an unknown level with apparent energy of ~0.64 eV

Federated Representation Learning for Automatic Speech Recognition

Federated Learning (FL) is a privacy-preserving paradigm, allowing edge devices to learn collaboratively without sharing data. Edge devices like Alexa and Siri are prospective sources of unlabeled audio data that can be tapped to learn robust audio representations. In this work, we bring Self-supervised Learning (SSL) and FL together to learn representations for Automatic Speech Recognition respecting data privacy constraints. We use the speaker and chapter information in the unlabeled speech dataset, Libri-Light, to simulate non-IID speaker-siloed data distributions and pre-train an LSTM encoder with the Contrastive Predictive Coding framework with FedSGD. We show that the pre-trained ASR encoder in FL performs as well as a centrally pre-trained model and produces an improvement of 12-15% (WER) compared to no pre-training. We further adapt the federated pre-trained models to a new language, French, and show a 20% (WER) improvement over no pre-training.Comment: Accepted at ISCA SPSC Symposium 3rd Symposium on Security and Privacy in Speech Communication, 202

Differences in the transduction of canonical wnt signals demarcate effector and memory CD8 T cells with distinct recall proliferation capacity.

Protection against reinfection is mediated by Ag-specific memory CD8 T cells, which display stem cell-like function. Because canonical Wnt (Wingless/Int1) signals critically regulate renewal versus differentiation of adult stem cells, we evaluated Wnt signal transduction in CD8 T cells during an immune response to acute infection with lymphocytic choriomeningitis virus. Whereas naive CD8 T cells efficiently transduced Wnt signals, at the peak of the primary response to infection only a fraction of effector T cells retained signal transduction and the majority displayed strongly reduced Wnt activity. Reduced Wnt signaling was in part due to the downregulation of Tcf-1, one of the nuclear effectors of the pathway, and coincided with progress toward terminal differentiation. However, the correlation between low and high Wnt levels with short-lived and memory precursor effector cells, respectively, was incomplete. Adoptive transfer studies showed that low and high Wnt signaling did not influence cell survival but that Wnt high effectors yielded memory cells with enhanced proliferative potential and stronger protective capacity. Likewise, following adoptive transfer and rechallenge, memory cells with high Wnt levels displayed increased recall expansion, compared with memory cells with low Wnt signaling, which were preferentially effector-like memory cells, including tissue-resident memory cells. Thus, canonical Wnt signaling identifies CD8 T cells with enhanced proliferative potential in part independent of commonly used cell surface markers to discriminate effector and memory T cell subpopulations. Interventions that maintain Wnt signaling may thus improve the formation of functional CD8 T cell memory during vaccination

Liquid crystal based nonlinear fishnet metamaterials

We study experimentally the nonlinear properties of fishnet metamaterials infiltrated with nematic liquid crystals and find that moderate laser powers result in significant changes of the optical transmission of the composite structures. We also show that the nonlinear response of our structure can be further tuned with a bias electric field, enabling the realization of electrically tunable nonlinear metamaterials.We acknowledge the support by the Australian Research Council, the Australian National Computational Infrastructure, and the ACT Node of Australian National Fabrication Facility

Tilted response of fishnet metamaterials at near-infrared optical wavelengths

We study experimentally the transmission properties of Au-TiO2 -Au fishnet metamaterials in the near-infrared spectral range and analyze the change in the transmission resonances at varying angles of incidence and different input polarizations. The results show that the main transmission peak through the fishnet is due to the excitation of hole modes. This high-transmission region is significantly influenced by surface plasmon coupling when the incident electric field has a component normal to the metal plates, while little change with respect to tilt is observed when the electric field is parallel to the two metal films of the fishnet

Dual-channel spontaneous emission of quantum dots in magnetic metamaterials

Metamaterials, artificial electromagnetic media realized by subwavelength nano-structuring, have become a paradigm for engineering electromagnetic space, allowing for independent control of both electric and magnetic responses of the material. Whereas mo

T Cell Factor 1-Expressing Memory-like CD8(+) T Cells Sustain the Immune Response to Chronic Viral Infections.

Chronic infections promote the terminal differentiation (or "exhaustion") of T cells and are thought to preclude the formation of memory T cells. In contrast, we discovered a small subpopulation of virus-specific CD8(+) T cells that sustained the T cell response during chronic infections. These cells were defined by, and depended on, the expression of the transcription factor Tcf1. Transcriptome analysis revealed that this population shared key characteristics of central memory cells but lacked an effector signature. Unlike conventional memory cells, Tcf1-expressing T cells displayed hallmarks of an "exhausted" phenotype, including the expression of inhibitory receptors such as PD-1 and Lag-3. This population was crucial for the T cell expansion that occurred in response to inhibitory receptor blockade during chronic infection. These findings identify a memory-like T cell population that sustains T cell responses and is a prime target for therapeutic interventions to improve the immune response in chronic infections

Characterizing temporary hydrological regimes at a European scale

Monthly duration curves have been constructed from climate data across Europe to help address the relative frequency of ecologically critical low flow stages in temporary rivers, when flow persists only in disconnected pools in the river bed. The hydrological model is 5 based on a partitioning of precipitation to estimate water available for evapotranspiration and plant growth and for residual runoff. The duration curve for monthly flows has then been analysed to give an estimate of bankfull flow based on recurrence interval. The corresponding frequency for pools is then based on the ratio of bank full discharge to pool flow, arguing from observed ratios of cross-sectional areas at flood 10 and low flows to estimate pool flow as 0.1% of bankfull flow, and so estimate the frequency of the pool conditions that constrain survival of river-dwelling arthropods and fish. The methodology has been applied across Europe at 15 km resolution, and can equally be applied under future climatic scenarios