Heralded phase-contrast imaging using an orbital angular momentum phase-filter

We utilise the position and orbital angular momentum (OAM) correlations between the signal and idler photons generated in the down-conversion process to obtain ghost images of a phase object. By using an OAM phase filter, which is non-local with respect to the object, the images exhibit isotropic edge-enhancement. This imaging technique is the first demonstration of a full-field, phase-contrast imaging system with non-local edge enhancement, and enables imaging of phase objects using significantly fewer photons than standard phase-contrast imaging techniques

Restoration of lysosomal acidification rescues autophagy and metabolic dysfunction in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. High levels of free fatty acids in the liver impair hepatic lysosomal acidification and reduce autophagic flux. We investigate whether restoration of lysosomal function in NAFLD recovers autophagic flux, mitochondrial function, and insulin sensitivity. Here, we report the synthesis of novel biodegradable acid-activated acidifying nanoparticles (acNPs) as a lysosome targeting treatment to restore lysosomal acidity and autophagy. The acNPs, composed of fluorinated polyesters, remain inactive at plasma pH, and only become activated in lysosomes after endocytosis. Specifically, they degrade at pH of ~6 characteristic of dysfunctional lysosomes, to further acidify and enhance the function of lysosomes. In established in vivo high fat diet mouse models of NAFLD, re-acidification of lysosomes via acNP treatment restores autophagy and mitochondria function to lean, healthy levels. This restoration, concurrent with reversal of fasting hyperglycemia and hepatic steatosis, indicates the potential use of acNPs as a first-in-kind therapeutic for NAFLD.J.L.Z. and A.M. were supported by a BU Nano Cross-disciplinary fellowship from the BU Nano center at Boston University. J.L.Z. was supported by a Presidential Postdoctoral Fellowship from Nanyang Technological University, Grant/Award Number: 021229-00001. C.H.L. was supported by Dean’s Postdoctoral Fellowship, Nanyang Technological University, Lee Kong Chian School of Medicine, Grant/Award Number: 021207-00001. E.A. was supported by Azrieli Fellowship (The Azrieli Foundation). This work was also supported in part by funding from the National Institutes of Health (R01AA026914, OSS ML; R21AG063373, MWG OSS; and R21AG06045, OSS

Ameliorated ConA-Induced Hepatitis in the Absence of PKC-theta

Severe liver injury that occurs when immune cells mistakenly attack an individual's own liver cells leads to autoimmune hepatitis. In mice, acute hepatitis can be induced by concanavalin A (ConA) treatment, which causes rapid activation of CD1d-positive natural killer (NK) T cells. These activated NKT cells produce large amounts of cytokines, which induce strong inflammation that damages liver tissues. Here we show that PKC-θ−/− mice were resistant to ConA-induced hepatitis due to essential function of PKC-θ in NKT cell development and activation. A dosage of ConA (25 mg/kg) that was lethal to wild-type (WT) mice failed to induce death resulting from liver injury in PKC-θ−/− mice. Correspondingly, ConA-induced production of cytokines such as IFNγ, IL-6, and TNFα, which mediate the inflammation responsible for liver injury, were significantly lower in PKC-θ−/− mice. Peripheral NKT cells had developmental defects at early stages in the thymus in PKC-θ−/− mice, and as a result their frequency and number were greatly reduced. Furthermore, PKC-θ−/− bone marrow adoptively transferred to WT mice displayed similar defects in NKT cell development, suggesting an intrinsic requirement for PKC-θ in NKT cell development. In addition, upon stimulation with NKT cell-specific lipid ligand, peripheral PKC-θ−/− NKT cells produced lower levels of inflammatory cytokines than that of WT NKT cells, suggesting that activation of NKT cells also requires PKC-θ. Our results suggest PKC-θ is an essential molecule required for activation of NKT cell to induce hepatitis, and thus, is a potential drug target for prevention of autoimmune hepatitis

Critical Role of TCF-1 in Repression of the IL-17 Gene

Overwhelming activation of IL-17, a gene involved in inflammation, leads to exaggerated Th17 responses associated with numerous autoimmune conditions, such as experimental autoimmune encephalomyelitis (EAE). Here we show that TCF-1 is a critical factor to repress IL-17 gene locus by chromatin modifications during T cell development. Deletion of TCF-1 resulted in increased IL-17 gene expression both in thymus and peripheral T cells, which led to enhanced Th17 differentiation. As a result, TCF-1-/- mice were susceptible to Th17-dependent EAE induction. Rag1-/- mice reconstituted with TCF-1-/- T cells were also susceptible to EAE, indicating TCF-1 is intrinsically required to repress IL-17. However, expression of wild-type TCF-1 or dominant negative TCF-1 did not interfere with Th17 differentiation in mature T cells. Furthermore, expression of TCF-1 in TCF-1-/- T cells could not restore Th17 differentiation to wild-type levels, indicating that TCF-1 cannot affect IL-17 production at the mature T cell stage. This is also supported by the normal up-regulation or activation in mature TCF-1-/- T cells of factors known to regulate Th17 differentiation, including RORγt and Stat3. We observed hyperacetylation together with trimethylation of Lys-4 at the IL-17 locus in TCF-1-/- thymocytes, two epigenetic modifications indicating an open active state of the gene. Such epigenetic modifications were preserved even when TCF-1-/- T cells migrated out of thymus. Therefore, TCF-1 mediates an active process to repress IL-17 gene expression via epigenetic modifications during T cell development. This TCF-1-mediated repression of IL-17 is critical for peripheral T cells to generate balanced immune responses

When in Doubt, Throw It Out! The Complicated Decision to Consume (or Waste) Food by Date Labels

Consumers find food date labels confusing. Industry groups and policy makers intend to resolve the confusion by creating a single label for safety and another for quality. In a survey of consumers concerning anticipated consumption given various date labels, we find differential responses across products, leading us to conclude that new labels may not necessarily reduce waste

Low-latency speaker spotting with online diarization and detection

International audienceThis paper introduces a new task termed low-latency speaker spotting (LLSS). Related to security and intelligence applications, the task involves the detection, as soon as possible, of known speakers within multi-speaker audio streams. The paper describes differences to the established fields of speaker diarization and automatic speaker verification and proposes a new protocol and metrics to support exploration of LLSS. These can be used together with an existing, publicly available database to assess the performance of LLSS solutions also proposed in the paper. They combine online diarization and speaker detection systems. Diarization systems include a naive, over-segmentation approach and fully-fledged online diarization using segmental i-vectors. Speaker detection is performed using Gaussian mixture models, i-vectors or neural speaker embeddings. Metrics reflect different approaches to characterise latency in addition to detection performance. The relative performance of each solution is dependent on latency. When higher latency is admissible, i-vector solutions perform well; embeddings excel when latency must be kept to a minimum. With a need to improve the reliability of online diarization and detection, the proposed LLSS framework provides a vehicle to fuel future research in both areas. In this respect, we embrace a reproducible research policy; results can be readily reproduced using publicly available resources and open source codes