Hyaluronan Synthase and Hyaluronidase Expression in Serous Ovarian Carcinoma is Related to Anatomic Site and Chemotherapy Exposure

The present study investigated the expression and clinical role of hyaluronan synthases (HAS1-3) and hyaluronidases (Hyal1-3) in serous ovarian carcinoma. HAS and HYAL mRNA expression was analyzed in 97 tumors (61 effusions, 27 primary carcinomas, 9 solid metastases) using PCR and further studied for association with clinicopathologic parameters, including survival. HAS1 mRNA was overexpressed in effusions compared to primary carcinomas and solid metastases (p < 0.001), and an alternatively spliced HAS1 was expressed only in effusions. HAS2 mRNA was overexpressed in solid metastases and primary carcinomas compared to effusions (p = 0.043), and HAS3 mRNA was overexpressed in primary carcinomas and effusions compared to solid metastases (p = 0.008). HYAL1 mRNA was absent in all specimens, whereas HYAL2 was expressed as two splice variants, of which HYAL2-var2 was overexpressed in solid metastases compared to effusions and primary carcinomas (p < 0.001). HYAL3 mRNA was expressed as wild-type and variant 1–3 form, the latter more highly in primary carcinomas and effusions compared to solid metastases (p = 0.006). HAS1 mRNA was overexpressed in pre- compared to post-chemotherapy effusions (p < 0.001), with opposite finding for HYAL2-var1 and HYAL3-WT (p = 0.016 and p = 0.024, respectively). Higher HYAL2-var1 and HAS1 splice variant mRNA expression in effusions was associated with longer (p = 0.033) and shorter (p = 0.047) overall survival, respectively. These data are the first to document a role for HAS and Hyal members in tumor progression in ovarian carcinoma, as evidenced by their differential expression as function of anatomic site and chemotherapy exposure, with a possible prognostic role for patients with malignant effusions.     

Role of the alpha-glucanase Agn2p in ascus-wall endolysis following sporulation in fission yeast

During sporulation in the ascomyceteous fungus Schizosaccharomyces pombe, diploid cells undergo differentiation into asci containing four haploid ascospores, which are highly resistant to environmental stresses. Although the morphogenetic processes involved in ascospore formation have been studied extensively, little is known about the molecular mechanism that ensures the release of mature ascospores from the ascus, allowing their dispersal into the environment. Recently, we identified Agn2p as the paralogue of the characterized endo-(1,3)-alpha-glucanase Agn1p, and observed that asci deleted for agn2 are defective in ascospore dispersal. Here, we focus on the cellular and biochemical functions of Agn2p. By placing agn2 under the control of an inducible promoter, we show that expression of agn2 is required for the efficient release of ascospores from their asci. Furthermore, we characterize the enzyme activity of purified recombinant Agn2p and show that Agn2p, like Agn1p, is an endo-(1,3)-alpha-glucanase that produces predominantly (1,3)-alpha-glucan pentasaccharides. Finally, we demonstrate that exogenous addition of purified Agn2p liberated the ascospores from asci deleted for agn2. We propose that Agn2p participates in the endolysis of the ascus wall by hydrolysing its (1,3)-alpha-glucan, thereby assisting in the release of ascospores.     

Calembour: an implicit method based on an enriched kinematical thin-plate model for sheet-metal forming simulation

In this paper, the main features of an implicit sheet-metal forming simulation code, named Calembour, are presented. Special emphasis is put on the way of expressing the contact conditions and of taking into account the geometrical non-linearity of which they comprise. An enriched kinematical thin-plate model, involving seven independent fields defined on the medium surface of the undeformed plate, is suggested. The constitutive laws used to model the material behavior and the friction phenomenon are given. A standard bilinear finite-element method is used to approximate the continuous total Lagrangian formulation of the global mechanical problem. Finally, some numerical results enlighting the effectiveness of the present approach are given.     

Microstructure and electrical conductivity of La0.9Sr0.1 Ga0.8Mg0.2O2.85-Ce0.8Gd0.2O1.9 composite electrolytes for SOFCs

(100-x) wt.% La_0.9Sr_0.1 Ga_0.8Mg_0.2O_2.85 - x wt.% Ce_0.8Gd_0.2O_1.9 (x = 0, 5, 10, 20) electrolytes were prepared by solid-state reaction. The composition, microstructure, and electrical conductivity of the samples were investigated. At 300 ~ 600°C, the pure La_0.9Sr_0.1 Ga_0.8Mg_0.2O_2.85 electrolyte has a higher conductivity compared to the composite electrolytes, but at 650 ~ 800°C the 95 wt.% La_0.9Sr_0.1 Ga_0.8Mg_0.2O_2.85 - 5 wt.% Ce_0.8Gd_0.2O_1.9 composite electrolyte presents the highest conductivity, reaching 0.035 S cm⁻¹ at 800°C. The cell performances based on La_0.9Sr_0.1 Ga_0.8Mg_0.2O_2.85-Ce_0.8Gd_0.2O_1.9 electrolytes were measured using Sr₂CoMoO₆-La_0.9Sr_0.1 Ga_0.8Mg_0.2O_2.85 as anode and Sr₂Co_0.9Mn_0.1NbO₆ -La_0.9Sr_0.1 Ga_0.8Mg_0.2O_2.85 as cathode, respectively. At 800°C, the measured open-circuit voltages are higher than 1.08 V, and the maximum power density and current density of the fuel cell prepared with 95 wt.% La_0.9Sr_0.1 Ga_0.8Mg_0.2O_2.85 - 5 wt.% Ce_0.8Gd_0.2O_1.9 electrolyte reach 192 mW cm⁻² and 720 mA cm⁻², respectively.     

The Role of Network Topology and the Spatial Distribution and Structure of Knowledge in Regional Innovation Policy: A Calibrated Agent-Based Model Study

Recently, new regional innovation policy paradigms emerged that transcend a long-lived dispute on whether either regional specialization, diversification, or rather related variety is most conducive to regional innovativeness. This includes ‘smart specialization’ in which regions are deliberately specialized and connected following technological relatedness, ‘gatekeepers’ in which there are pipelines between dense regional networks, and a ‘regional mix’ of knowledge that allows sustained ‘branching’. We develop and use an agent-based model to study the conjecture that, to stimulate (supra)regional innovativeness, social planners need to consider both, in conjunction, the mix of technological knowledge in regions and the (inter)regional innovation network topology. We use this agent-based model to evaluate the performance of and study the internal mechanisms of these new policy paradigms in a variety of scenarios. To increase the external validity of our findings, we calibrate the knowledge graph searched by the agents in our model to the OECD patent database. We confirm that access to related variety is important, yet that, on top of that, access to incidentally related knowledge is crucial to prevent high-level lock-in and ensure long term technological progress. Moreover, we find that networks with regional gatekeepers are particularly innovative, because these gatekeepers form ‘knowledge hubs’, create short paths to potential partners, and enlarge the total pool of knowledge. In case agents have few relationships, we find exceptionally high performance for the gatekeeper network in combination with regional diversification. The smart specialization network is a solid second option, although it lacks access to incidentally related knowledge and thus will ultimately fall behind whenever agents have relatively few relationships. The study elaborates on specific scenarios to reveal intricacies in the relationship between knowledge distribution, network topology, and the structure of interrelationships between knowledge fields.     

Dynamics of a six degrees-of-freedom parallel robot actuated by three two-wheel carts

This paper deals with a new, six degrees-of-freedom parallel manipulator comprising a platform, three links and three two-wheel carts supporting the links. The wheels are independently driven, allowing the manipulator a workspace which is limited only by the lengths of the links and the size of the plane on which the carts move. The direct and inverse dynamic problems of the manipulator are solved. It is shown that the Jacobian associated with the direct problem becomes identically singular when used to solve the inverse problem, and hence must be redefined; and that once redefined, it losses its standard structure and cannot be used to solve the direct problem. Three solution methods to the inverse problem are presented and are shown to lead to indistinguishable results.