Nuclear Receptor Nur77 Controls Cardiac Fibrosis through Distinct Actions on Fibroblasts and Cardiomyocytes

Fibrosis is a hallmark of adverse cardiac remodeling, which promotes heart failure, but it is also an essential repair mechanism to prevent cardiac rupture, signifying the importance of appropriate regulation of this process. In the remodeling heart, cardiac fibroblasts (CFs) differentiate into myofibroblasts (MyoFB), which are the key mediators of the fibrotic response. Additionally, cardiomyocytes are involved by providing pro-fibrotic cues. Nuclear receptor Nur77 is known to reduce cardiac hypertrophy and associated fibrosis; however, the exact function of Nur77 in the fibrotic response is yet unknown. Here, we show that Nur77-deficient mice exhibit severe myocardial wall thinning, rupture and reduced collagen fiber density after myocardial infarction and chronic isoproterenol (ISO) infusion. Upon Nur77 knockdown in cultured rat CFs, expression of MyoFB markers and extracellular matrix proteins is reduced after stimulation with ISO or transforming growth factor–β (TGF-β). Accordingly, Nur77-depleted CFs produce less collagen and exhibit diminished proliferation and wound closure capacity. Interestingly, Nur77 knockdown in neonatal rat cardiomyocytes results in increased paracrine induction of MyoFB differentiation, which was blocked by TGF-β receptor antagonism. Taken together, Nur77-mediated regulation involves CF-intrinsic promotion of CF-to-MyoFB transition and inhibition of cardiomyocyte-driven paracrine TGF-β-mediated MyoFB differentiation. As such, Nur77 provides distinct, cell-specific regulation of cardiac fibrosis.     

Combining Protein and Strain Engineering for the Production of Glyco-Engineered Horseradish Peroxidase C1A in Pichia pastoris

Horseradish peroxidase (HRP), conjugated to antibodies and lectins, is widely used in medical diagnostics. Since recombinant production of the enzyme is difficult, HRP isolated from plant is used for these applications. Production in the yeast Pichia pastoris (P. pastoris), the most promising recombinant production platform to date, causes hyperglycosylation of HRP, which in turn complicates conjugation to antibodies and lectins. In this study we combined protein and strain engineering to obtain an active and stable HRP variant with reduced surface glycosylation. We combined four mutations, each being beneficial for either catalytic activity or thermal stability, and expressed this enzyme variant as well as the unmutated wildtype enzyme in both a P. pastoris benchmark strain and a strain where the native α-1,6-mannosyltransferase (OCH1) was knocked out. Considering productivity in the bioreactor as well as enzyme activity and thermal stability, the mutated HRP variant produced in the P. pastoris benchmark strain turned out to be interesting for medical diagnostics. This variant shows considerable catalytic activity and thermal stability and is less glycosylated, which might allow more controlled and efficient conjugation to antibodies and lectins.     

Design and design methods for unified multiplier and inverter and its application for HECC

This paper describes two novel architectures for a unified multiplier and inverter (UMI) in GF(2^m): the UMI merges multiplier and inverter into one unified data-path. As such, the area of the data-path is reduced. We present two options for hyperelliptic curve cryptography (HECC) using UMIs: an FPGA-based high-performance implementation (Type-I) and an ASIC-based lightweight implementation (Type-II). The use of a UMI combined with affine coordinates brings a smaller data-path, smaller memory and faster scalar multiplication.Both implementations use curves defined by h(x)=x and f(x)=x⁵+f₃x³+x²+f₀. The high throughput version uses 2316 slices and 2016 bits of block RAM on a Xilinx Virtex-II FPGA, and finishes one scalar multiplication in . The lightweight version uses only 14.5 kGates, and one scalar multiplication takes 450 ms.     

High-performance Public-key Cryptoprocessor for Wireless Mobile Applications

We present a high-speed public-key cryptoprocessor that exploits three-level parallelism in Elliptic Curve Cryptography (ECC) over GF(2 ⁿ ). The proposed cryptoprocessor employs a Parallelized Modular Arithmetic Logic Unit (P-MALU) that exploits two types of different parallelism for accelerating modular operations. The sequence of scalar multiplications is also accelerated by exploiting Instruction-Level Parallelism (ILP) and processing multiple P-MALU instructions in parallel. The system is programmable and hence independent of the type of the elliptic curves and scalar multiplication algorithms. The synthesis results show that scalar multiplication of ECC over GF(2¹⁶³) on a generic curve can be computed in 20 and 16 μs respectively for the binary NAF (Non-Adjacent Form) and the Montgomery method. The performance can be accelerated furthermore on a Koblitz curve and reach scalar multiplication of 12 μs with the TNAF (τ-adic NAF) method. This fast performance allows us to perform over 80,000 scalar multiplications per second and to enhance security in wireless mobile applications.

Extending ECC-based RFID authentication protocols to privacy-preserving multi-party grouping proofs

Since the introduction of the concept of grouping proofs by Juels, which permit RFID tags to generate evidence that they have been scanned simultaneously, various new schemes have been proposed. Their common property is the use of symmetric-key primitives. However, it has been shown that such schemes often entail scalability, security and/or privacy problems. In this article, we extend the notion of public-key RFID authentication protocols and propose a privacy-preserving multi-party grouping-proof protocol which relies exclusively on the use of elliptic curve cryptography (ECC). It allows to generate a proof which is verifiable by a trusted verifier in an offline setting, even when readers or tags are potentially untrusted, and it is privacy-preserving in the setting of a narrow-strong attacker. We also demonstrate that our RFID grouping-proof protocol can easily be extended to use cases with more than two tags, without any additional cost for an RFID tag. To illustrate the implementation feasibility of our proposed solutions, we present a novel ECC hardware architecture designed for RFID.     

Comparison of non-parametric confidence intervals for the area under the ROC curve of a continuous-scale diagnostic test

The accuracy of a diagnostic test with continuous-scale results is of high importance in clinical medicine. It is often summarised by the area under the ROC curve (AUC). In this article, we discuss and compare nine non-parametric confidence intervals of the AUC for a continuous-scale diagnostic test. Simulation studies are conducted to evaluate the relative performance of the confidence intervals for the AUC in terms of coverage probability and average interval length. A real example is used to illustrate the application of the recommended methods.     

Mutual Information Analysis: a?Comprehensive Study

Mutual Information Analysis is a generic side-channel distinguisher that has been introduced at CHES 2008. It aims to allow successful attacks requiring minimum assumptions and knowledge of the target device by the adversary. In this paper, we compile recent contributions and applications of MIA in a comprehensive study. From a theoretical point of view, we carefully discuss its statistical properties and relationship with probability density estimation tools. From a practical point of view, we apply MIA in two of the most investigated contexts for side-channel attacks. Namely, we consider first-order attacks against an unprotected implementation of the DES in a full custom IC and second-order attacks against a masked implementation of the DES in an 8-bit microcontroller. These experiments allow to put forward the strengths and weaknesses of this new distinguisher and to compare it with standard power analysis attacks using the correlation coefficient.