Energy Metabolites as Biomarkers in Ischemic and Dilated Cardiomyopathy

With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 × 10⁻⁶). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets.     

The BG distributed simulation algorithm

We present a shared memory algorithm that allows a set of f+1 processes to wait-free “simulate” a larger system of n processes, that may also exhibit up to f stopping failures. Applying this simulation algorithm to the k-set-agreement problem enables conversion of an arbitrary k-fault-tolerant{\it n}-process solution for the k-set-agreement problem into a wait-free k+1-process solution for the same problem. Since the k+1-processk-set-agreement problem has been shown to have no wait-free solution [5,18,26], this transformation implies that there is no k-fault-tolerant solution to the n-process k-set-agreement problem, for any n. More generally, the algorithm satisfies the requirements of a fault-tolerant distributed simulation.\/ The distributed simulation implements a notion of fault-tolerant reducibility\/ between decision problems. This paper defines these notions and gives examples of their application to fundamental distributed computing problems. The algorithm is presented and verified in terms of I/O automata. The presentation has a great deal of interesting modularity, expressed by I/O automaton composition and both forward and backward simulation relations. Composition is used to include a safe agreement\/ module as a subroutine. Forward and backward simulation relations are used to view the algorithm as implementing a multi-try snapshot\/ strategy. The main algorithm works in snapshot shared memory systems; a simple modification of the algorithm that works in read/write shared memory systems is also presented. Received: February 2001 / Accepted: February 2001     

Reading speech and hearing print: Constraining models of visual word recognition by exploring connections with speech perception.

Current models of reading and speech perception differ widely in their assumptions regarding the interaction of orthographic and phonological information during language perception. The present experiments examined this interaction through a 2-alternative, forced-choice paradigm, and explored the nature of the connections between graphemic and phonemic processing subsystems. Exps 1 and 2 demonstrated a facilitation-dominant influence (i.e., benefits exceed costs) of graphemic contexts on phoneme discrimination, which is interpreted as a sensitivity effect. Exps 3 and 4 demonstrated a symmetrical influence (i.e., benefits equal costs) of phonemic contexts on grapheme discrimination, which can be interpreted as either a bias effect, or an equally facilitative/inhibitory sensitivity effect. General implications for the functional architecture of language processing models are discussed, as well as specific implications for models of visual word recognition and speech perception. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A new one-phase material model for the numerical prediction of critical material flow conditions in thixoforging processes

Thixoforging allows one-step forming processes of near-net shape components having excellent mechanical properties. However, the high sensitivity of thixoforging regarding process conditions requires precise modelling and determination of process related parameters. At the same time, simple numerical design proves challenging because of the inaccuracy of existing one-phase material models regarding the shear thinning flow behaviour of semi solid metals. Consequently, this paper deals with the development of a new one-phase material model providing a more precise simulation of materials’ shear rate dependency. By using this model, simulations could be performed, which allowed the prediction of solidification and flow-related component defects.     

Layilin, a novel talin-binding transmembrane protein homologous with C-type lectins, is localized in membrane ruffles

Changes in cell morphology and motility are mediated by the actin cytoskeleton. Recent advances in our understanding of the regulators of microfilament structure and dynamics have shed light on how these changes are controlled, and efforts continue to define all the structural and signaling components involved in these processes. The actin cytoskeleton-associated protein talin binds to integrins, vinculin, and actin. We report a new binding partner for talin that we have named layilin, which contains homology with C-type lectins, is present in numerous cell lines and tissue extracts, and is expressed on the cell surface. Layilin colocalizes with talin in membrane ruffles, and is recruited to membrane ruffles in cells induced to migrate in in vitro wounding experiments and in peripheral ruffles in spreading cells. A ten-amino acid motif in the layilin cytoplasmic domain is sufficient for talin binding. We have identified a short region within talin's amino-terminal 435 amino acids capable of binding to layilin in vitro. This region overlaps a binding site for focal adhesion kinase.     

Responses of the amphipod crustaceanGammarus palustris to waterborne secretions of conspecifics and congenerics

A choice-test apparatus designed to mimic field conditions was employed to test for the presence of waterborne attractants in the amphipod crustaceanGammarus palustris. It was found that both males and females were attracted to secretions from all conspecifics, but not to the secretions of a sympatric congener. When given the choice of secretions from different types of conspecifics, males behaved differently than females. Males were attracted more often to receptive females' and females were attracted more often to males' secretions. In the field, then, it is likely that all conspecifics travel toward each other, then sort themselves into competent heterosexual couples. The results suggest that this apparatus can be employed in future studies to determine the chemical nature of these pheromones.     

Constraint-based and SAT-based diagnosis of automotive configuration problems

We compare the concepts and computation of optimized diagnoses in the context of Boolean constraint based knowledge systems of automotive configuration, namely the preferred minimal diagnosis and the minimum weighted diagnosis. In order to restore the consistency of an over-constrained system w.r.t. a strict total order of the user requirements, the preferred minimal diagnosis tries to keep the most preferred user requirements and can be computed, for example, by the FASTDIAG algorithm. In contrast, partial weighted MinUNSAT solvers aim to find a set of unsatisfied clauses with the minimum sum of weights, such that the diagnosis is of minimum weight. It turns out that both concepts have similarities, i.e., both deliver an optimal minimal correction subset. We show use cases from automotive configuration where optimized diagnoses are desired. We point out theoretical commonalities and prove the reducibility of both concepts to each other, i.e., both problems are FP^NP-complete, which was an open question. In addition to exact algorithms we present greedy algorithms. We evaluate the performance of exact and greedy algorithms on problem instances based on real automotive configuration data from three different German car manufacturers, and we compare the time and quality tradeoff.     

Degradation behavior of novel Fe/ß-TCP composites produced by powder injection molding for cortical bone replacement

When it comes to bone replacement in load-bearing areas, there are currently no adequate biodegradable implants available. Several non-degradable metallic materials fulfill the requirements of biocompatibility and mechanical strength. However, besides magnesium, only iron is a degradable metallic material. The aim of this long-term degradation study was to investigate the effects of iron beta-tricalcium phosphate interpenetrating phase composite on degradation rate and strength in comparison to pure iron. Cylindrical samples with 0–50 vol% beta-tricalcium phosphate (ß-TCP) were prepared by powder injection molding. In addition to dense samples, porous iron samples with a porosity of 60.3 % were produced with polyoxymethylene as a placeholder. Dense and porous samples were immersed in 0.9 % sodium chloride solution (NaCl) or in phosphate buffered saline solution (PBS) for 56 days. Following immersion, the degradation rate, compressive yield strength, and ion release were determined. A maximum degradation rate of 196 µm/year was observed after 56 days for iron with 40 vol% ß-TCP. This was found to be 28 % higher than for pure iron. After immersion, the compressive yield strength of pure iron decreased by 44 % (NaCl) and 48 % (PBS). In comparison, iron with 40 % ß-TCP samples lost <1 % (NaCl) and 9 % (PBS) of strength following immersion. It was demonstrated that the solubility of calcium phosphate enhanced the corrosion processes and led to an increase in degradation, thus showing that the addition of ß-TCP to pure iron can be a promising route for a novel degradable bone substitute material, particularly for load-bearing areas due to the increased strength.     

The influence of the compatibilizer on the morphology and thermal properties of polypropylene‐layered double hydroxide composites

Polypropylene (PP)/layered double hydroxide (LDH) composites were prepared via melt‐compounding using both a carbonate‐LDH and an organo‐LDH (dodecyl benzene sulfonate DBS‐LDH) in different concentrations. Transmission electron microscopy and X‐ray diffraction analysis were used to investigate the morphology. The results showed that only by using DBS‐LDH the intercalation of polymer chains and a partial delamination were obtained. However, the introduction of maleic anhydride‐grafted polypropylene (PP‐g‐MAH), as coupling agent, favored the aggregation of the particles generating localized domains of aggregates. The thermo‐gravimetric analysis showed that PP/DBS‐LDH composites have a higher thermal stability than the pure matrix. Differential scanning calorimetry evidenced that both LDH and DBS‐LDH particles acted as nucleating agents increasing the crystallization temperature, even if, in the case of LDH the effect was observed only with the addition of the compatibilizer. The results collected by dynamic mechanical thermal analysis, beyond showing a significant increase of the matrix stiffness by incorporation of DBS‐LDH, evidenced an increase of the PP glass transition temperature (T_g) indicating a restriction of PP chain segment mobility due to the strong polymer‐particle interactions. POLYM. COMPOS., 2010. © 2009 Society of Plastics Engineers