Computing a Minimum-Cost kk-hop Steiner Tree in Tree-Like Metrics

We consider the problem of computing a Steiner tree of minimum cost under a $k$-hop constraint which requires the depth of the tree to be at most $k$. Our main result is an exact algorithm for metrics induced by graphs of bounded treewidth that runs in time $n^{O(k)}$. For the special case of a path, we give a simple algorithm that solves the problem in polynomial time, even if $k$ is part of the input. The main result can be used to obtain, in quasi-polynomial time, a near-optimal solution that violates the $k$-hop constraint by at most one hop for more general metrics induced by graphs of bounded highway dimension

Mechanical modeling of the maturation process for tissue-engineered implants: application to biohybrid heart valves

The development of tissue-engineered cardiovascular implants can improve the lives of large segments of our society who suffer from cardiovascular diseases. Regenerative tissues are fabricated using a process called tissue maturation. Furthermore, it is highly challenging to produce cardiovascular regenerative implants with sufficient mechanical strength to withstand the loading conditions within the human body. Therefore, biohybrid implants for which the regenerative tissue is reinforced by standard reinforcement material (e.g. textile or 3d printed scaffold) can be an interesting solution. In silico models can significantly contribute to characterizing, designing, and optimizing biohybrid implants. The first step towards this goal is to develop a computational model for the maturation process of tissue-engineered implants. This paper focuses on the mechanical modeling of textile-reinforced tissue-engineered cardiovascular implants. First, we propose an energy-based approach to compute the collagen evolution during the maturation process. Then, we apply the concept of structural tensors to model the anisotropic behavior of the extracellular matrix and the textile scaffold. Next, the newly developed material model is embedded into a special solid-shell finite element formulation with reduced integration. Finally, we use our framework to compute two structural problems: a pressurized shell construct and a tubular-shaped heart valve. The results show the ability of the model to predict collagen growth in response to the boundary conditions applied during the maturation process. Consequently, we can predict the implant's mechanical response, such as the deformation and stresses of the implant.Comment: Preprint submitted to Elsevie

Towards Massively Parallel Computations in Algebraic Geometry

Introducing parallelism and exploring its use is still a fundamental challenge for the computer algebra community. In high-performance numerical simulation, on the other hand, transparent environments for distributed computing which follow the principle of separating coordination and computation have been a success story for many years. In this paper, we explore the potential of using this principle in the context of computer algebra. More precisely, we combine two well-established systems: The mathematics we are interested in is implemented in the computer algebra system Singular, whose focus is on polynomial computations, while the coordination is left to the workflow management system GPI-Space, which relies on Petri nets as its mathematical modeling language and has been successfully used for coordinating the parallel execution (autoparallelization) of academic codes as well as for commercial software in application areas such as seismic data processing. The result of our efforts is a major step towards a framework for massively parallel computations in the application areas of Singular, specifically in commutative algebra and algebraic geometry. As a first test case for this framework, we have modeled and implemented a hybrid smoothness test for algebraic varieties which combines ideas from Hironaka’s celebrated desingularization proof with the classical Jacobian criterion. Applying our implementation to two examples originating from current research in algebraic geometry, one of which cannot be handled by other means, we illustrate the behavior of the smoothness test within our framework and investigate how the computations scale up to 256 cores

A functional yeast survival screen of tumor-derived cDNA libraries designed to identify anti-apoptotic mammalian oncogenes

Yeast cells can be killed upon expression of pro-apoptotic mammalian proteins. We have established a functional yeast survival screen that was used to isolate novel human anti-apoptotic genes overexpressed in treatment-resistant tumors. The screening of three different cDNA libraries prepared from metastatic melanoma, glioblastomas and leukemic blasts allowed for the identification of many yeast cell death-repressing cDNAs, including 28% of genes that are already known to inhibit apoptosis, 35% of genes upregulated in at least one tumor entity and 16% of genes described as both anti-apoptotic in function and upregulated in tumors. These results confirm the great potential of this screening tool to identify novel anti-apoptotic and tumor-relevant molecules. Three of the isolated candidate genes were further analyzed regarding their anti-apoptotic function in cell culture and their potential as a therapeutic target for molecular therapy. PAICS, an enzyme required for de novo purine biosynthesis, the long non-coding RNA MALAT1 and the MAST2 kinase are overexpressed in certain tumor entities and capable of suppressing apoptosis in human cells. Using a subcutaneous xenograft mouse model, we also demonstrated that glioblastoma tumor growth requires MAST2 expression. An additional advantage of the yeast survival screen is its universal applicability. By using various inducible pro-apoptotic killer proteins and screening the appropriate cDNA library prepared from normal or pathologic tissue of interest, the survival screen can be used to identify apoptosis inhibitors in many different systems

Elevated circulating Hsp70 levels are correlative for malignancies in different mammalian species

Circulating Hsp70 levels were determined in feline and porcine cohorts using two different ELISA systems. These comparative animal models of larger organisms often reflect diseases, and especially malignant tumors, better than conventional rodent models. It is therefore essential to investigate the biology and utility of tumor biomarkers in animals such as cats and pigs. In this study, levels of free Hsp70 in the blood of cats with spontaneously occurring tumors were detected using a commercial Hsp70 ELISA (R&D Systems). Sub-analysis of different tumor groups revealed that animals with tumors of epithelial origin presented with significantly elevated circulating Hsp70 concentrations. In addition to free Hsp70 levels measured with the R&D Systems Hsp70 ELISA, levels of exosomal Hsp70 were determined using the compHsp70 ELISA in pigs. Both ELISA systems detected significantly elevated Hsp70 levels (R&D Systems: median 24.9 ng/mL; compHsp70: median 44.2 ng/mL) in the blood of a cohort of APC$^{1311/+}$ pigs diagnosed with high-grade adenoma polyps, and the R&D Systems Hsp70 ELISA detected also elevated Hsp70 levels in animals with low-grade polyps. In contrast, in flTP53$^{R167H}$ pigs, suffering from malignant osteosarcoma, the compHsp70 ELISA (median 674.32 ng/mL), but not the R&D Systems Hsp70 ELISA (median 4.78 ng/mL), determined significantly elevated Hsp70 concentrations, indicating that in tumor-bearing animals, the dominant form of Hsp70 is of exosomal origin. Our data suggest that both ELISA systems are suitable for detecting free circulating Hsp70 levels in pigs with high-grade adenoma, but only the compHsp70 ELISA can measure elevated, tumor-derived exosomal Hsp70 levels in tumor-bearing animals

Renal sympathetic denervation restores aortic distensibility in patients with resistant hypertension: data from a multi-center trial

Renal sympathetic denervation (RDN) is under investigation as a treatment option in patients with resistant hypertension (RH). Determinants of arterial compliance may, however, help to predict the BP response to therapy. Aortic distensibility (AD) is a well-established parameter of aortic stiffness and can reliably be obtained by CMR. This analysis sought to investigate the effects of RDN on AD and to assess the predictive value of pre-treatment AD for BP changes. We analyzed data of 65 patients with RH included in a multicenter trial. RDN was performed in all participants. A standardized CMR protocol was utilized at baseline and at 6-month follow-up. AD was determined as the change in cross-sectional aortic area per unit change in BP. Office BP decreased significantly from 173/92 ± 24/16 mmHg at baseline to 151/85 ± 24/17 mmHg (p < 0.001) 6 months after RDN. Maximum aortic areas increased from 604.7 ± 157.7 to 621.1 ± 157.3 mm2 (p = 0.011). AD improved significantly by 33% from 1.52 ± 0.82 to 2.02 ± 0.93 × 10-3 mmHg-1 (p < 0.001). Increase of AD at follow-up was significantly more pronounced in younger patients (p = 0.005) and responders to RDN (p = 0.002). Patients with high-baseline AD were significantly younger (61.4 ± 10.1 vs. 67.1 ± 8.4 years, p = 0.022). However, there was no significant correlation of baseline AD to response to RDN. AD is improved after RDN across all age groups. Importantly, these improvements appear to be unrelated to observed BP changes, suggesting that RDN may have direct effects on the central vasculature

Predictors of functional improvement in the short term after MitraClip implantation in patients with secondary mitral regurgitation

Background and objectives MitraClip implantation is an established therapy for secondary mitral regurgitation (MR) in high-risk patients and has shown to improve several important outcome parameters such as functional capacity. Patient selection is both challenging and crucial for achieving therapeutic success. This study investigated baseline predictors of functional improvement as it was quantified by the six-minute walk distance (6MWD) after transcatheter mitral valve repair. Methods and results We retrospectively analyzed 79 patients with secondary MR treated with MitraClip implantation at an academic tertiary care center. Before and four weeks after the procedure, all patients underwent comprehensive clinical assessment, six-minute walk tests and echocardiography. 6MWD significantly improved after MitraClip therapy (295 m vs. 265 m, p < 0.001). A linear regression model including seven clinical baseline variables significantly predicted the change in 6MWD (p = 0.002, R-2 = 0.387). Female gender, diabetes mellitus and arterial hypertension were found to be significant negative predictors of 6MWD improvement. At baseline, female patients had significant higher left ventricular ejection fraction (49% vs. 42%, p = 0.019) and lower 6MWD (240 m vs. 288 m, p = 0.034) than male patients. Conclusion MitraClip implantation in secondary MR significantly improves functional capacity in high risk patients even in the short term of four weeks after the procedure. Female gender, diabetes mellitus and arterial hypertension are baseline predictors of a less favourable functional outcome. While further validation in a larger cohort is recommended, these parameters may improve patient selection for MitraClip therapy