Raman light scattering study and microstructural analysis of epitaxial films of the electron-doped superconductor La_{2-x}Ce_{x}CuO_{4}

We present a detailed temperature-dependent Raman light scattering study of optical phonons in molecular-beam-epitaxy-grown films of the electron-doped superconductor La_{2-x}Ce_{x}CuO_{4} close to optimal doping (x ~ 0.08, T_c = 29 K and x ~ 0.1, T_c = 27 K). The main focus of this work is a detailed characterization and microstructural analysis of the films. Based on micro-Raman spectroscopy in combination with x-ray diffraction, energy-dispersive x-ray analysis, and scanning electron microscopy, some of the observed phonon modes can be attributed to micron-sized inclusions of Cu_{2}O. In the slightly underdoped film (x ~ 0.08), both the Cu_{2}O modes and others that can be assigned to the La_{2-x}Ce_{x}CuO_{4} matrix show pronounced softening and narrowing upon cooling below T ~ T_c. Based on control measurements on commercial Cu_{2}O powders and on a comparison to prior Raman scattering studies of other high-temperature superconductors, we speculate that proximity effects at La_{2-x}Ce_{x}CuO_{4}/Cu_{2}O interfaces may be responsible for these anomalies. Experiments on the slightly overdoped La_{2-x}Ce_{x}CuO_{4} film (x ~ 0.1) did not reveal comparable phonon anomalies.Comment: 7 pages, 8 figure

Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing

Perineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment

Lightweight Authenticated Encryption Mode Suitable for Threshold Implementation

This paper proposes tweakable block cipher (TBC) based modes $\mathsf{PFB\_Plus}$ and $\mathsf{PFB}\omega$ that are efficient in threshold implementations (TI). Let $t$ be an algebraic degree of a target function, e.g.~$t=1$ (resp.~$t>1$) for linear (resp.~non-linear) function. The $d$-th order TI encodes the internal state into $d t + 1$ shares. Hence, the area size increases proportionally to the number of shares. This implies that TBC based modes can be smaller than block cipher (BC) based modes in TI because TBC requires $s$-bit block to ensure $s$-bit security, e.g. \textsf{PFB} and \textsf{Romulus}, while BC requires $2s$-bit block. However, even with those TBC based modes, the minimum we can reach is 3 shares of $s$-bit state with $t=2$ and the first-order TI ($d=1$). Our first design $\mathsf{PFB\_Plus}$ aims to break the barrier of the $3s$-bit state in TI. The block size of an underlying TBC is $s/2$ bits and the output of TBC is linearly expanded to $s$ bits. This expanded state requires only 2 shares in the first-order TI, which makes the total state size $2.5s$ bits. We also provide rigorous security proof of $\mathsf{PFB\_Plus}$. Our second design $\mathsf{PFB}\omega$ further increases a parameter $\omega$: a ratio of the security level $s$ to the block size of an underlying TBC. We prove security of $\mathsf{PFB}\omega$ for any $\omega$ under some assumptions for an underlying TBC and for parameters used to update a state. Next, we show a concrete instantiation of $\mathsf{PFB\_Plus}$ for 128-bit security. It requires a TBC with 64-bit block, 128-bit key and 128-bit tweak, while no existing TBC can support it. We design a new TBC by extending \textsf{SKINNY} and provide basic security evaluation. Finally, we give hardware benchmarks of $\mathsf{PFB\_Plus}$ in the first-order TI to show that TI of $\mathsf{PFB\_Plus}$ is smaller than that of \textsf{PFB} by more than one thousand gates and is the smallest within the schemes having 128-bit security

Liposome-Coupled Antigens Are Internalized by Antigen-Presenting Cells via Pinocytosis and Cross-Presented to CD8+ T Cells

We have previously demonstrated that antigens chemically coupled to the surface of liposomes consisting of unsaturated fatty acids were cross-presented by antigen-presenting cells (APCs) to CD8+ T cells, and that this process resulted in the induction of antigen-specific cytotoxic T lymphocytes. In the present study, the mechanism by which the liposome-coupled antigens were cross-presented to CD8+ T cells by APCs was investigated. Confocal laser scanning microscopic analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-based liposomes received processing at both MHC class I and class II compartments, while most of the antigens coupled to the surface of saturated-fatty-acid-based liposomes received processing at the class II compartment. In addition, flow cytometric analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-liposomes were taken up by APCs even in a 4°C environment; this was not true of saturated-fatty-acid-liposomes. When two kinds of inhibitors, dimethylamiloride (DMA) and cytochalasin B, which inhibit pinocytosis and phagocytosis by APCs, respectively, were added to the culture of APCs prior to the antigen pulse, DMA but not cytochalasin B significantly reduced uptake of liposome-coupled antigens. Further analysis of intracellular trafficking of liposomal antigens using confocal laser scanning microscopy revealed that a portion of liposome-coupled antigens taken up by APCs were delivered to the lysosome compartment. In agreement with the reduction of antigen uptake by APCs, antigen presentation by APCs was significantly inhibited by DMA, and resulted in the reduction of IFN-γ production by antigen-specific CD8+ T cells. These results suggest that antigens coupled to the surface of liposomes consisting of unsaturated fatty acids might be pinocytosed by APCs, loaded onto the class I MHC processing pathway, and presented to CD8+ T cells. Thus, these liposome-coupled antigens are expected to be applicable for the development of vaccines that induce cellular immunity

Antigen-expressing immunostimulatory liposomes as a genetically programmable synthetic vaccine

Liposomes are versatile (sub)micron-sized membrane vesicles that can be used for a variety of applications, including drug delivery and in vivo imaging but they also represent excellent models for artificial membranes or cells. Several studies have demonstrated that in vitro transcription and translation can take place inside liposomes to obtain compartmentalized production of functional proteins within the liposomes (Kita et al. in Chembiochem 9(15):2403–2410, 2008; Moritani et al.in FEBS J, 2010; Kuruma et al. in Methods Mol Biol 607:161–171, 2010; Murtas et al. in Biochem Biophys Res Commun 363(1):12–17, 2007; Sunami et al. in Anal Biochem 357(1):128–136, 2006; Ishikawa et al. in FEBS Lett 576(3):387–390, 2004; Oberholzer et al. in Biochem Biophys Res Commun 261(2):238–241, 1999). Such a minimal artificial cell-based model is ideal for synthetic biology based applications. In this study, we propose the use of liposomes as artificial microbes for vaccination. These artificial microbes can be genetically programmed to produce specific antigens at will. To show proof-of-concept for this artificial cell-based platform, a bacterial in vitro transcription and translation system together with a gene construct encoding the model antigen β-galactosidase were entrapped inside multilamellar liposomes. Vaccination studies in mice showed that such antigen-expressing immunostimulatory liposomes (AnExILs) elicited higher specific humoral immune responses against the produced antigen (β-galactosidase) than control vaccines (i.e. AnExILs without genetic input, liposomal β-galactosidase or pDNA encoding β-galactosidase). In conclusion, AnExILs present a new platform for DNA-based vaccines which combines antigen production, adjuvanticity and delivery in one system and which offer several advantages over existing vaccine formulations

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

The Ligand-Binding Domain of Siglec-G Is Crucial for Its Selective Inhibitory Function on B1 Cells

Siglec-G is an inhibitory receptor on B1 cells. Siglec-G-deficient mice show a large B1 cell expansion, owing to higher BCR-induced Ca2+ signaling and enhanced cellular survival. It was unknown why Siglec-G shows a B1 cell-restricted inhibitory function. With a new mAb we could show a comparable Siglec-G expression on B1 cells and conventional B2 cells. However, Siglec-G has a different ligand sialic acid-binding pattern on peritoneal B1 cells than on splenic B cells, and its sialic acid ligands are expressed differentially on these two B cell populations, suggesting that cis-ligand binding plays a crucial role on B1 cells. This observation was further studied by generation of Siglec-G knockin mice with a mutated ligand-binding domain. These mice show increased B1 cell numbers, increased B1 cell Ca2+ signaling, better B1 cell survival, and changes in the B1 cell Ig repertoire. These phenotypes are very similar to Siglec-G-deficient mice. The mutation of the ligand-binding domain of Siglec-G strongly reduces the Siglec-G-IgM association on the B cell surface. Thus, Siglec-G sialic acid-dependent binding to the BCR is crucial for the B1 cell-restricted inhibitory function of Siglec-G and is regulated in an opposite way to that of the related protein CD22 (Siglec-2) on B cells