Restricted overlapping balancing domain decomposition methods and restricted coarse problems for the Helmholtz problem

Overlapping balancing domain decomposition methods and their combination with restricted additive Schwarz methods are proposed for the Helmholtz equation. These new methods also extend previous work on non-overlapping balancing domain decomposition methods toward simplifying their coarse problems and local solvers. They also extend restricted Schwarz methods, originally designed to overlapping domain decomposition and Dirichlet local solvers, to the case of non-overlapping domain decomposition and/or Neumann and Sommerfeld local solvers. Finally, we introduce coarse spaces based on partitions of unity and planes waves, and show how oblique projection coarse problems can be designed from restricted additive Schwarz methods. Numerical tests are presented.     

Large deviation theorems for empirical types of Markov chainsconstrained to thin sets

An irreducible Markov chain with stationary transition probabilities on a finite directed graph is considered. The probability of large deviations of the random variable denoting the empirical type of the first n transitions is investigated     

Train Tracks and Confluent Drawings

Confluent graphs capture the connection properties of train tracks, offering a very natural generalization of planar graphs, and—as the example of railroad maps shows—are an important tool in graph visualization. In this paper we continue the study of confluent graphs, introducing strongly confluent graphs and tree-confluent graphs. We show that strongly confluent graphs can be recognized in NP (the complexity of recognizing confluent graphs remains open). We also give a natural elimination ordering characterization of tree-confluent graphs, and we show that this class coincides with the (6,2)-chordal bipartite graphs. Finally, we define outerconfluent graphs and identify the bipartite permutation graphs as a natural subclass.     

Correlates of osteopenia in patients with cystic fibrosis

The responses to heat shock in Tritrichomonas mobilensis, a squirrel monkey parasite and Tritrichomonas augusta, an amphibian trichomonad, were evaluated by means of metabolic labeling with [35S]methionine. Electrophoretically separated trichomonad proteins synthesized at different temperatures were visualized by autoradiography and the label incorporation quantitated by a trichloroacetic acid precipitation procedure. A considerable difference in thermotolerance between the two species was found as the protein synthesis reached a maximum at 41 C in T. mobilensis and 37 C in T. augusta. The latter tolerated temperature increases 13 C above normal cultivation temperatures as compared to only 4 C thermotolerance range above normal in T. mobilensis. Major heat shock proteins (Hsps) were expressed in both T. mobilensis (with apparent Mr 94, 72, and 58 kDa) and T. augusta (Mr 94, 70, and 56 kDa) as revealed by autoradiography. Western blot analysis with polyclonal antibody against DnaK of Escherichia coli showed the presence of antigenic Hsp70 homologs in both trichomonads. Similarly, a polyclonal antibody against Hsp60 with broad interspecies cross-reactivity detected Hsp60 homologs in both T. mobilensis and T. augusta. The anti-DnaK antibody cross-reacted with a T. mobilensis protein localized in Golgi apparatus as demonstrated by immunoelectron microscopy. Immunocytochemistry on trichomonad frozen sections revealed the presence of the Hsp60 homolog in light-microscopic granules corresponding to hydrogenosomes.     

Method for determining musculotendon parameters in subject-specific musculoskeletal models of children developed from MRI data

Accurate knowledge of muscle-tendon parameters in biomechanical models is critical for accurate simulation and analyses of human movement. An excellent example of this is the creation of subject-specific models from magnetic resonance imaging (MRI). When Hill-type muscle models are used to calculate muscle forces, the determination of muscle attachment points, optimal fiber length, tendon slack length and maximum isometric force all have a significant influence on the joint moment-angle behavior of the model. In the present study a method was developed for customizing the values of muscle-tendon parameters in a generic model to create subject-specific biomechanical models from MRI. The method was applied by generating musculoskeletal models for the biomechanical simulation platform OpenSim, but the workflow is equally well applicable to other simulation platforms. New computational algorithms are described for identifying joint centers and for reconstructing the centroids of the muscle bellies from MRI. A?process is also described for the extraction of the muscle paths and for identifying the positions of ??via-points?? used to model muscles wrapping over bones. Finally, a new algorithm is described for adjusting the values of optimal fiber length, tendon slack length and maximum isometric force based on a comparison of the model results with experiment. We tested our computational algorithms by developing subject-specific biomechanical models of five typically developed children (age 9.5±1.7?years) from MRI. The joint moment-angle relationships calculated for the subject-specific models were similar to those determined for corresponding scaled generic models. The results indicate that the proposed methodology is suitable for developing subject-specific models of healthy children. Future studies should investigate how abnormalities of the musculoskeletal system, such as tibial torsion and muscle spasticity, can be integrated into the modeling process.     

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.     

Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) still remains a difficult to cure malignancy. In recent years, the focus has shifted to lipid metabolism for the treatment of HCC. Very little is known about hepatitis B virus (HBV) and C virus (HCV)-related hepatic lipid disturbances in non-malignant and cancer tissues. The present study showed that triacylglycerol and cholesterol concentrations were similar in tumor adjacent HBV and HCV liver, and were not induced in the HCC tissues. Higher levels of free cholesterol, polyunsaturated phospholipids and diacylglycerol species were noted in non-tumorous HBV compared to HCV liver. Moreover, polyunsaturated phospholipids and diacylglycerols, and ceramides declined in tumors of HBV infected patients. All of these lipids remained unchanged in HCV-related HCC. In HCV tumors, polyunsaturated phosphatidylinositol levels were even induced. There were no associations of these lipid classes in non-tumor tissues with hepatic inflammation and fibrosis scores. Moreover, these lipids did not correlate with tumor grade or T-stage in HCC tissues. Lipid reprogramming of the three analysed HBV/HCV related tumors mostly resembled HBV-HCC. Indeed, lipid composition of non-tumorous HCV tissue, HCV tumors, HBV tumors and HBV/HCV tumors was highly similar. The tumor suppressor protein p53 regulates lipid metabolism. The p53 and p53S392 protein levels were induced in the tumors of HBV, HCV and double infected patients, and this was significant in HBV infection. Negative correlation of tumor p53 protein with free cholesterol indicates a role of p53 in cholesterol metabolism. In summary, the current study suggests that therapeutic strategies to target lipid metabolism in chronic viral hepatitis and associated cancers have to consider disease etiology.     

Engineering of Janus-Like Dendrimers with Peptides Derived from Glycoproteins of Herpes Simplex Virus Type 1: Toward a Versatile and Novel Antiviral Platform

Novel antiviral nanotherapeutics, which may inactivate the virus and block it from entering host cells, represent an important challenge to face viral global health emergencies around the world. Using a combination of bioorthogonal copper-catalyzed 1,3-dipolar alkyne/azide cycloaddition (CuAAC) and photoinitiated thiol–ene coupling, monofunctional and bifunctional peptidodendrimer conjugates were obtained. The conjugates are biocompatible and demonstrate no toxicity to cells at biologically relevant concentrations. Furthermore, the orthogonal addition of multiple copies of two different antiviral peptides on the surface of a single dendrimer allowed the resulting bioconjugates to inhibit Herpes simplex virus type 1 at both the early and the late stages of the infection process. The presented work builds on further improving this attractive design to obtain a new class of therapeutics.