Alpha and lambda interferon together mediate suppression of CD4 T cells induced by respiratory syncytial virus

The mechanism by which respiratory syncytial virus (RSV) suppresses T-cell proliferation to itself and other antigens is poorly understood. We used monocyte-derived dendritic cells (MDDC) and CD4 T cells and measured [(3)H]thymidine incorporation to determine the factors responsible for RSV-induced T-cell suppression. These two cell types were sufficient for RSV-induced suppression of T-cell proliferation in response to cytomegalovirus or Staphylococcus enterotoxin B. Suppressive activity was transferable with supernatants from RSV-infected MDDC and was not due to transfer of live virus or RSV F (fusion) protein. Supernatants from RSV-infected MDDC, but not MDDC exposed to UV-killed RSV or mock conditions, contained alpha interferon (IFN-alpha; median, 43 pg/ml) and IFN-lambda (approximately 1 to 20 ng/ml). Neutralization of IFN-alpha with monoclonal antibody (MAb) against one of its receptor chains, IFNAR2, or of IFN-lambda with MAb against either of its receptor chains, IFN-lambdaR1 (interleukin 28R [IL-28R]) or IL-10R2, had a modest effect. In contrast, blocking the two receptors together markedly reduced or completely blocked the RSV-induced suppression of CD4 T-cell proliferation. Defining the mechanism of RSV-induced suppression may guide vaccine design and provide insight into previously uncharacterized human T-cell responses and activities of interferons

Error-Tolerant Algebraic Side-Channel Attacks Using BEE

Algebraic side-channel attacks are a type of side-channel analysis which can recover the secret information with a small number of samples (e.g., power traces). However, this type of side-channel analysis is sensitive to measurement errors which may make the attacks fail. In this paper, we propose a new method of algebraic side-channel attacks which considers noisy leakages as integers restricted to intervls and finds out the secret information with a constraint programming solver named BEE. To demonstrate the efficiency of this new method in algebraic side-channel attacks, we analyze some popular implementations of block ciphers---PRESENT, AES, and SIMON under the Hamming weight or Hamming distance leakage model. For AES, our method requires the least leakages compared with existing works under the same error model. For both PRESENT and SIMON, we provide the first analytical results of them under algebraic side-channel attacks in the presence of errors. To further demonstrate the wide applicability of this new method, we also extend it to cold boot attacks. In the cold boot attacks against AES, our method increases the success rate by over $25\%$ than previous works

Making Masking Security Proofs Concrete - Or How to Evaluate the Security of any Leaking Device

We investigate the relationships between theoretical studies of leaking cryptographic devices and concrete security evaluations with standard side-channel attacks. Our contributions are in four parts. First, we connect the formal analysis of the masking countermeasure proposed by Duc et al. (Eurocrypt 2014) with the Eurocrypt 2009 evaluation framework for side-channel key recovery attacks. In particular, we re-state their main proof for the masking countermeasure based on a mutual information metric, which is frequently used in concrete physical security evaluations. Second, we discuss the tightness of the Eurocrypt 2014 bounds based on experimental case studies. This allows us to conjecture a simplified link between the mutual information metric and the success rate of a side-channel adversary, ignoring technical parameters and proof artifacts. Third, we introduce heuristic (yet well-motivated) tools for the evaluation of the masking countermeasure when its independent leakage assumption is not perfectly fulfilled, as it is frequently encountered in practice. Thanks to these tools, we argue that masking with non-independent leakages may provide improved security levels in certain scenarios. Eventually, we consider the tradeoff between measurement complexity and key enumeration in divide-and-conquer side-channel attacks, and show that it can be predicted based on the mutual information metric, by solving a non-linear integer programming problem for which efficient solutions exist. The combination of these observations enables significant reductions of the evaluation costs for certification bodies

The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

Reduced Lung Function in a Chronic Asthma Model Is Associated with Prolonged Inflammation, but Independent of Peribronchial Fibrosis

In asthma, mechanisms contributing to chronicity remain to be determined. Recent models of sensitisation with prolonged airway allergen challenges reproduce typical features of chronic asthma. However, the interplay between inflammation, structural changes and lung function is poorly understood. This study was performed to delineate functional, structural and immunological airway changes after cessation of long term challenges to elucidate factors contributing to the development of prolonged lung function changes.Mice sensitised systemically were consecutively challenged intranasally with ovalbumin for two or eight weeks. After the end of challenges, lung function, airway inflammation, features of airway remodelling, local T-cell cytokines and systemic ovalbumin-specific antibodies were monitored. Long term challenges resulted in airway hyperresponsiveness lasting 2 weeks and reduced baseline lung function for 6 weeks after their cessation. In contrast, these changes resolved within one week after short term challenges. Prolonged transforming growth factor beta (TGF-beta)1 production and marked peribronchial fibrosis were only induced by long term challenges. Importantly, fibrosis became apparent only after the onset of lung function changes and outlasted them. Further, long term challenges led to prolonged and intense airway inflammation with marked lymphocytosis, but moderate eosinophilia, sustained IL-5 production and ovalbumin-specific IgG2a antibodies, the latter suggesting a Th1 component to the immune response. In contrast, following short term challenges airway inflammation was dominated by eosinophils and associated with a strong, but transient IL-13 response.Prolonged lung function changes after long term allergen challenges seem to develop and resolve independently of the persistent peribronchial fibrosis. They are more closely associated with intense airway inflammation, marked lymphocytosis, prolonged IL-5 and TGF-beta1 production in the airways and a Th1 immune response

Very High Order Masking: Efficient Implementation and Security Evaluation

In this paper, we study the performances and security of recent masking algorithms specialized to parallel implementations in a 32-bit embedded software platform, for the standard AES Rijndael and the bitslice cipher Fantomas. By exploiting the excellent features of these algorithms for bitslice implementations, we first extend the recent speed records of Goudarzi and Rivain (presented at Eurocrypt 2017) and report realistic timings for masked implementations with 32 shares. We then observe that the security level provided by such implementations is uneasy to quantify with current evaluation tools. We therefore propose a new ``multi-model evaluation methodology which takes advantage of different (more or less abstract) security models introduced in the literature. This methodology allows us to both bound the security level of our implementations in a principled manner and to assess the risks of overstated security based on well understood parameters. Concretely, it leads us to conclude that these implementations withstand worst-case adversaries with >2^64 measurements under falsifiable assumptions

Single-Trace Side-Channel Attacks on Masked Lattice-Based Encryption

Although lattice-based cryptography has proven to be a particularly efficient approach to post-quantum cryptography, its security against side-channel attacks is still a very open topic. There already exist some first works that use masking to achieve DPA security. However, for public-key primitives SPA attacks that use just a single trace are also highly relevant. For lattice-based cryptography this implementation-security aspect is still unexplored. In this work, we present the first single-trace attack on lattice-based encryption. As only a single side-channel observation is needed for full key recovery, it can also be used to attack masked implementations. We use leakage coming from the Number Theoretic Transform, which is at the heart of almost all efficient lattice-based implementations. This means that our attack can be adapted to a large range of other lattice-based constructions and their respective implementations. Our attack consists of 3 main steps. First, we perform a template matching on all modular operations in the decryption process. Second, we efficiently combine all this side-channel information using belief propagation. And third, we perform a lattice-decoding to recover the private key. We show that the attack allows full key recovery not only in a generic noisy Hamming-weight setting, but also based on real traces measured on an ARM Cortex-M4F microcontroller

Pentraxin 3 (PTX3) Expression in Allergic Asthmatic Airways: Role in Airway Smooth Muscle Migration and Chemokine Production

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor with non-redundant functions in inflammation and innate immunity. PTX3 is produced by immune and structural cells. However, very little is known about the expression of PTX3 and its role in allergic asthma.We sought to determine the PTX3 expression in asthmatic airways and its function in human airway smooth muscle cells (HASMC). In vivo PTX3 expression in bronchial biopsies of mild, moderate and severe asthmatics was analyzed by immunohistochemistry. PTX3 mRNA and protein were measured by real-time RT-PCR and ELISA, respectively. Proliferation and migration were examined using (3)H-thymidine incorporation, cell count and Boyden chamber assays.PTX3 immunoreactivity was increased in bronchial tissues of allergic asthmatics compared to healthy controls, and mainly localized in the smooth muscle bundle. PTX3 protein was expressed constitutively by HASMC and was significantly up-regulated by TNF, and IL-1β but not by Th2 (IL-4, IL-9, IL-13), Th1 (IFN-γ), or Th-17 (IL-17) cytokines. In vitro, HASMC released significantly higher levels of PTX3 at the baseline and upon TNF stimulation compared to airway epithelial cells (EC). Moreover, PTX3 induced CCL11/eotaxin-1 release whilst inhibited the fibroblast growth factor-2 (FGF-2)-driven HASMC chemotactic activity.Our data provide the first evidence that PTX3 expression is increased in asthmatic airways. HASMC can both produce and respond to PTX3. PTX3 is a potent inhibitor of HASMC migration induced by FGF-2 and can upregulate CCL11/eotaxin-1 release. These results raise the possibility that PTX3 may play a dual role in allergic asthma

Cohesin-dependent globules and heterochromatin shape 3D genome architecture in S. pombe

Eukaryotic genomes are folded into three-dimensional structures, such as self-associating topological domains, the borders of which are enriched in cohesin and CCCTC-binding factor (CTCF) required for long-range interactions1-7. How local chromatin interactions govern higher-order folding of chromatin fibers and the function of cohesin in this process remain poorly understood. Here we perform genome-wide chromatin conformation capture (Hi-C) analysis8 to explore the high-resolution organization of the Schizosaccharomyces pombe genome, which despite its small size exhibits fundamental features found in other eukaryotes9. Our analyses of wild type and mutant strains reveal key elements of chromosome architecture and genome organization. On chromosome arms, small regions of chromatin locally interact to form “globules”. This feature requires a function of cohesin distinct from its role in sister chromatid cohesion. Cohesin is enriched at globule boundaries and its loss causes disruption of local globule structures and global chromosome territories. By contrast, heterochromatin, which loads cohesin at specific sites including pericentromeric and subtelomeric domains9-11, is dispensable for globule formation but nevertheless affects genome organization. We show that heterochromatin mediates chromatin fiber compaction at centromeres and promotes prominent interarm interactions within centromere-proximal regions, providing structural constraints crucial for proper genome organization. Loss of heterochromatin relaxes constraints on chromosomes, causing an increase in intra- and inter-chromosomal interactions. Together, our analyses uncover fundamental genome folding principles that drive higher-order chromosome organization crucial for coordinating nuclear functions