Dynamic Defaultable Term Structure Modelling beyond the Intensity Paradigm

The two main approaches in credit risk are the structural approach pioneered in Merton (1974) and the reduced-form framework proposed in Jarrow & Turnbull (1995) and in Artzner & Delbaen (1995). The goal of this article is to provide a unified view on both approaches. This is achieved by studying reduced-form approaches under weak assumptions. In particular we do not assume the global existence of a default intensity and allow default at fixed or predictable times with positive probability, such as coupon payment dates. In this generalized framework we study dynamic term structures prone to default risk following the forward-rate approach proposed in Heath-Jarrow-Morton (1992). It turns out, that previously considered models lead to arbitrage possibilities when default may happen at a predictable time with positive probability. A suitable generalization of the forward-rate approach contains an additional stochastic integral with atoms at predictable times and necessary and sufficient conditions for a suitable no-arbitrage condition (NAFL) are given. In the view of efficient implementations we develop a new class of affine models which do not satisfy the standard assumption of stochastic continuity. The chosen approach is intimately related to the theory of enlargement of filtrations, to which we provide a small example by means of filtering theory where the Azema supermartingale contains upward and downward jumps, both at predictable and totally inaccessible stopping times

Preclinical trial to examine the efficacy and safety of the treatment with the autologous chondrocyte transplantation ovine test sample co.don chondrosphere® (ACT3D-S)

Purpose of this study was to show the efficacy and safety of the investigational product co.don chondrosphere® (ACT3D-S). ACT3D-S is a product for autologous chondrocyte transplantation that we used in an animal model, the merino land sheep. We compared the treatment of ACT3D-S (Group A: Investigational product) with an untreated control (Group B: Control Intervention) in a bilateral model, what means that by randomization one hind limb was chosen to be treated with ACT3D-S while the remaining hind limb was left without treatment

Structural and signaling proteins in the Z-disk and their role in cardiomyopathies

The sarcomere is the smallest functional unit of muscle contraction. It is delineated by a protein-rich structure known as the Z-disk, alternating with M-bands. The Z-disk anchors the actin-rich thin filaments and plays a crucial role in maintaining the mechanical stability of the cardiac muscle. A multitude of proteins interact with each other at the Z-disk and they regulate the mechanical properties of the thin filaments. Over the past 2 decades, the role of the Z-disk in cardiac muscle contraction has been assessed widely, however, the impact of genetic variants in Z-disk proteins has still not been fully elucidated. This review discusses the various Z-disk proteins (alpha-actinin, filamin C, titin, muscle LIM protein, telethonin, myopalladin, nebulette, and nexilin) and Z-disk-associated proteins (desmin, and obscurin) and their role in cardiac structural stability and intracellular signaling. This review further explores how genetic variants of Z-disk proteins are linked to inherited cardiac conditions termed cardiomyopathies

When signalling goes wrong:pathogenic variants in structural and signalling proteins causing cardiomyopathies

Cardiomyopathies are a diverse group of cardiac disorders with distinct phenotypes, depending on the proteins and pathways affected. A substantial proportion of cardiomyopathies are inherited and those will be the focus of this review article. With the wide application of high-throughput sequencing in the practice of clinical genetics, the roles of novel genes in cardiomyopathies are recognised. Here, we focus on a subgroup of cardiomyopathy genes [TTN, FHL1, CSRP3, FLNC and PLN, coding for Titin, Four and a Half LIM domain 1, Muscle LIM Protein, Filamin C and Phospholamban, respectively], which, despite their diverse biological functions, all have important signalling functions in the heart, suggesting that disturbances in signalling networks can contribute to cardiomyopathies

The Utilisation of Hydrogels for iPSC-Cardiomyocyte Research

Cardiac fibroblasts’ (FBs) and cardiomyocytes’ (CMs) behaviour and morphology are influenced by their environment such as remodelling of the myocardium, thus highlighting the importance of biomaterial substrates in cell culture. Biomaterials have emerged as important tools for the development of physiological models, due to the range of adaptable properties of these materials, such as degradability and biocompatibility. Biomaterial hydrogels can act as alternative substrates for cellular studies, which have been particularly key to the progression of the cardiovascular field. This review will focus on the role of hydrogels in cardiac research, specifically the use of natural and synthetic biomaterials such as hyaluronic acid, polydimethylsiloxane and polyethylene glycol for culturing induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). The ability to fine-tune mechanical properties such as stiffness and the versatility of biomaterials is assessed, alongside applications of hydrogels with iPSC-CMs. Natural hydrogels often display higher biocompatibility with iPSC-CMs but often degrade quicker, whereas synthetic hydrogels can be modified to facilitate cell attachment and decrease degradation rates. iPSC-CM structure and electrophysiology can be assessed on natural and synthetic hydrogels, often resolving issues such as immaturity of iPSC-CMs. Biomaterial hydrogels can thus provide a more physiological model of the cardiac extracellular matrix compared to traditional 2D models, with the cardiac field expansively utilising hydrogels to recapitulate disease conditions such as stiffness, encourage alignment of iPSC-CMs and facilitate further model development such as engineered heart tissues (EHTs)

Combining metabolic phenotype determination with metabolomics and transcriptional analyses to reveal pathways regulated by hydroxycarboxylic acid receptor 2

Background The adaptation of cellular metabolism is considered a hallmark of cancer. Oncogenic signaling pathways support tumorigenesis and cancer progression through the induction of certain metabolic phenotypes associated with altered regulation of key metabolic enzymes. Hydroxycarboxylic acid receptor 2 (HCA(2)) is a G protein-coupled receptor previously shown to act as a tumor suppressor. Here, we aimed to unveil the connection between cellular metabolism and HCA(2) in BT-474 cells. Moreover, we intend to clarify how well this metabolic phenotype is reflected in transcriptional changes and metabolite levels as determined by global metabolomics analyses. Methods We performed both, siRNA mediated knockdown of HCA(2) and stimulation with the HCA(2)-specific agonist monomethyl fumarate. Seahorse technology was used to determine the role of HCA(2) in BT-474 breast cancer cell metabolism and its potential to induce a switch in the metabolic phenotype in the presence of different energy substrates. Changes in the mRNA expression of metabolic enzymes were detected with real-time quantitative PCR (RT-qPCR). Untargeted liquid chromatography-mass spectrometry (LC-MS) metabolic profiling was used to determine changes in metabolite levels. Results Knockdown or stimulation of HCA(2) induced changes in the metabolic phenotype of BT474 cells dependent on the availability of energy substrates. The presence of HCA(2) was associated with increased glycolytic flux with no fatty acids available. This was reflected in the increased mRNA expression of the glycolytic enzymes PFKFB4 and PKM2, which are known to promote the Warburg effect and have been described as prognostic markers in different types of cancer. With exogenous palmitate present, HCA(2) caused elevated fatty acid oxidation and likely lipolysis. The increase in lipolysis was also detectable at the transcriptional level of ATGL and the metabolite levels of palmitic and stearic acid. Conclusions We combined metabolic phenotype determination with metabolomics and transcriptional analyses and identified HCA(2) as a regulator of glycolytic flux and fatty acid metabolism in BT-474 breast cancer cells. Thus, HCA(2), for which agonists are already widely used to treat diseases such as psoriasis or hyperlipidemia, may prove useful as a target in combination cancer therapy

Automatic Underwater Image Enhancement using Improved Dark Channel Prior

Images taken under water are often of a monochromatic appearance, due to the physical interaction (absorption and reflection) between particles and light sources. Enhanced images with improved saturation, for which the monochromatic character has been corrected, are more suitable for generating 3D models and for identifying structures and materials by human experts. In this paper, we present an automatic method to identify the mean water color from a set of images. This mean color represents an average gray and is used to describe a new axis in CIELab color space. An extended color variance and a histogram equalization are simultaneously applied to the image. The main advantage of this method is the fully automatic enhancement process. An UUV (Unmanned Underwater Vehicle) can operate without providing a color reference scheme. The presented method was implemented in the software JEnhancer, which is freely available. JEnhancer was successfully tested in several documentation campaigns, and was integrated into the videogrammetric software pipeline Archaeo3D to produce 3D models from videos