Concepts in Oncolytic Adenovirus Therapy

Oncolytic adenovirus therapy is gaining importance as a novel treatment option for the management of various cancers. Different concepts of modification within the adenovirus vector have been identified that define the mode of action against and the interaction with the tumour. Adenoviral vectors allow for genetic manipulations that restrict tumour specificity and also the expression of specific transgenes in order to support the anti-tumour effect. Additionally, replication of the virus and reinfection of neighbouring tumour cells amplify the therapeutic effect. Another important aspect in oncolytic adenovirus therapy is the virus induced cell death which is a process that activates the immune system against the tumour. This review describes which elements in adenovirus vectors have been identified for modification not only to utilize oncolytic adenovirus vectors into conditionally replicating adenoviruses (CRAds) that allow replication specifically in tumour cells but also to confer specific characteristics to these viruses. These advances in development resulted in clinical trials that are summarized based on the conceptual design.     

Identification of Suitable Ligands for a Transition Metal‐Catalyzed Reaction: Screening of a Modular Ligand Library in the Enantioselective Hydroboration of Styrene

Based on a general modular synthetic scheme, a variety of chiral bidentate P/P‐, P/S‐, P/N‐, and P/Se‐ligands is accessible in an efficient divergent manner starting from phenol or naphthol derived backbone systems. A library of 20 selected ligands was tested in the Rh‐catalyzed asymmetric hydroboration of styrene to give 1‐phenylethanol in up to 91% ee after oxidative work‐up. It was demonstrated that small variations of the ligand structures lead to pronounced, unpredictable differences in the performance of the in situ generated rhodium complexes. The modular approach should be applicable for the identification and optimization of suitable ligands for other transition metal‐catalyzed transformations with comparably low effort.     

Optimizing Frequencies in a Transit Network: a Nonlinear Bi-level Programming Approach

We consider the problem of optimizing the frequencies of transit lines in an urban transportation network. The problem is formulated first as a nonlinear nonconvex mixed integer programming problem and then it is converted into a bi-level Min–Min nonconvex optimization problem. This problem is solved by a projected (sub)gradient algorithm, where a (sub)gradient is obtained at each iteration by solving the lower level problem. Computational results obtained with this algorithm are presented for the transit networks of the cities of Stockholm, Sweden, Winnipeg, Man., Canada and Portland, OR, U.S.A.     

Graphene Oxide Framework Structures and Coatings: Impact on Cell Adhesion and Pre-Vascularization Processes for Bone Grafts

Graphene oxide (GO) is a promising material for bone tissue engineering, but the validation of its molecular biological effects, especially in the context of clinically applied materials, is still limited. In this study, we compare the effects of graphene oxide framework structures (F-GO) and reduced graphene oxide-based framework structures (F-rGO) as scaffold material with a special focus on vascularization associated processes and mechanisms in the bone. Highly porous networks of zinc oxide tetrapods serving as sacrificial templates were used to create F-GO and F-rGO with porosities >99% consisting of hollow interconnected microtubes. Framework materials were seeded with human mesenchymal stem cells (MSC), and the cell response was evaluated by confocal laser scanning microscopy (CLSM), deoxyribonucleic acid (DNA) quantification, real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and alkaline phosphatase activity (ALP) to define their impact on cellular adhesion, osteogenic differentiation, and secretion of vascular growth factors. F-GO based scaffolds improved adhesion and growth of MSC as indicated by CLSM and DNA quantification. Further, F-GO showed a better vascular endothelial growth factor (VEGF) binding capacity and improved cell growth as well as the formation of microvascular capillary-like structures in co-cultures with outgrowth endothelial cells (OEC). These results clearly favored non-reduced graphene oxide in the form of F-GO for bone regeneration applications. To study GO in the context of a clinically used implant material, we coated a commercially available xenograft (Bio-Oss^® block) with GO and compared the growth of MSC in monoculture and in coculture with OEC to the native scaffold. We observed a significantly improved growth of MSC and formation of prevascular structures on coated Bio-Oss^®, again associated with a higher VEGF binding capacity. We conclude that graphene oxide coating of this clinically used, but highly debiologized bone graft improves MSC cell adhesion and vascularization.     

Are the Main Methionine Sources Equivalent? A Focus on DL-Methionine and DL-Methionine Hydroxy Analog Reveals Differences on Rainbow Trout Hepatic Cell Lines Functions

The replacement of fishmeal by plant proteins in aquafeeds imposes the use of synthetic methionine (MET) sources to balance the amino acid composition of alternative diets and so to meet the metabolic needs of fish of agronomic interest such as rainbow trout (RT-Oncorhynchus mykiss). Nonetheless, debates still exist to determine if one MET source is more efficiently used than another by fish. To address this question, the use of fish cell lines appeared a convenient strategy, since it allowed to perfectly control cell growing conditions notably by fully depleting MET from the media and studying which MET source is capable to restore cell growth/proliferation and metabolism when supplemented back. Thus, results of cell proliferation assays, Western blots, RT-qPCR and liquid chromatography analyses from two RT liver-derived cell lines revealed a better absorption and metabolization of DL-MET than DL-Methionine Hydroxy Analog (MHA) with the activation of the mechanistic Target Of Rapamycin (mTOR) pathway for DL-MET and the activation of integrated stress response (ISR) pathway for MHA. Altogether, the results clearly allow to conclude that both synthetic MET sources are not biologically equivalent, suggesting similar in vivo effects in RT liver and, therefore, questioning the MHA efficiencies in other RT tissues.     

Formalizing non-interference for a simple bytecode language in Coq

In this paper, we describe the application of the interactive theorem prover Coq to the security analysis of bytecode as used in Java. We provide a generic specification and proof of non-interference for bytecode languages using the Coq module system. We illustrate the use of this formalization by applying it to a small subset of Java bytecode. The emphasis of the paper is on modularity of a language formalization and its analysis in a machine proof. C. B. Jones     

Same- and cross-gender attitudes toward persons with physical disabilities.

Used the Disability Factor Scale-General (DFS-G) of J. Siller et al (1967) to measure 147 male and 139 female 11th-graders' attitudes toward persons with physical disabilities. A subgroup of Ss responded to a specially prepared version of the DFS-G that referred to males with disabilities, while a 2nd subgroup responded to a 2nd version of the questionnaire that referred to females with disabilities. A multivariate analysis of variance (MANOVA) was performed, with scores on the 6 attitude scales of the DFS-G as the dependent variables. The 2 independent variables were Ss' gender and the sex of the person with the disability. Attitudes toward females with disabilities were less positive than attitudes toward males with disabilities. These less positive attitudes were expressed more by boys than by girls. Findings support the theoretical assumption that being disabled and female represents a double minority status. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of the TrFE Content on the Crystallization and SSA Thermal Fractionation of P(VDF-co-TrFE) Copolymers

In this contribution, we study the effect of trifluoro ethylene (TrFE) comonomer content (samples with 80/20, 75/25, and 70/30 VDF/TrFE molar ratios were used) on the crystallization in P(VDF-co-TrFE) in comparison with a PVDF (Poly(vinylidene fluoride)) homopolymer. Employing Polarized Light Optical Microscopy (PLOM), the growth rates of spherulites or axialites were determined. Differential Scanning Calorimetry (DSC) was used to determine overall crystallization rates, self-nucleation, and Successive Self-nucleation and Annealing (SSA) thermal fractionation. The ferroelectric character of the samples was explored by polarization measurements. The results indicate that TrFE inclusion can limit the overall crystallization of the copolymer samples, especially for the ones with 20 and 25% TrFE. Self-nucleation measurements in PVDF indicate that the homopolymer can be self-nucleated, exhibiting the classic three Domains. However, the increased nucleation capacity in the copolymers provokes the absence of the self-nucleation Domain II. The PVDF displays a monomodal distribution of thermal fractions after SSA, but the P(VDF-co-TrFE) copolymers do not experience thermal fractionation, apparently due to TrFE incorporation in the PVDF crystals. Finally, the maximum and remnant polarization increases with increasing TrFE content up to a maximum of 25% TrFE content, after which it starts to decrease due to the lower dipole moment of the TrFE defect inclusion within the PVDF crystals.     

Zur aushubbedingten Reduktion des Drucksondierwiderstandes

About the excavation induced reduction of the cone penetration resistance. With a finite element model the penetration process in non cohesive soils is simulated. The influence of stress state and relative density on the cone penetration resistance is investigated. This enables an estimation of the reduction of the cone penetration resistance due to a change in the stress state, for example due to excavation.