Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma

Loss of function of the von Hippel-Lindau (VHL) tumor suppressor gene is a hallmark of clear cell renal cell carcinoma (ccRCC). The importance of heterogeneity in the loss of this tumor suppressor has been under reported. To study the impact of intratumoral VHL heterogeneity observed in human ccRCC, we engineered VHL gene deletion in four RCC models, including a new primary tumor cell line derived from an aggressive metastatic case. The VHL gene-deleted (VHL-KO) cells underwent epithelial-to-mesenchymal transition (EMT) and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing (VHL+) cells. Renal tumors with either VHL+ or VHL-KO cells alone exhibit minimal metastatic potential. Combined tumors displayed rampant lung metastases, highlighting a novel cooperative metastatic mechanism. The poorly proliferative VHL-KO cells stimulated the proliferation, EMT, and motility of neighboring VHL+ cells. Periostin (POSTN), a soluble protein overexpressed and secreted by VHL non-expressing (VHL-) cells, promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular escape. Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models. This work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor

Fuzzy modelling of acid mine drainage environments using geochemical, ecological and mineralogical indicators

Fuzzy logic was applied to model acid mine drainage (AMD) and to obtain a classification index of the environmental impact in a contaminated riverine system. The data set used to develop this fuzzy model (a fuzzy classifier) concerns an abandoned mine in Northern Portugal— Valdarcas mining site. Here, distinctive drainage environments (spatial patterns) can be observed based on the AMD formed in the sulphide-rich waste-dumps. Such environments were established, as the effluent flows through the mining area, using several kinds of indicators. These are physical–chemical, ecological and mineralogical parameters, being expressed in a quantitative or qualitative basis. The fuzzy classifier proposed in this paper is a min– max fuzzy inference system, representing the spatial behaviour of those indicators, using the AMD environments as patterns. As they represent different levels (classes) of contamination, the fuzzy classifier can be used as a tool, allowing a more reasonable approach, compared with classical models, to characterize the environmental impact caused by AMD. In a general way it can be applied to other sites where sulphide-rich waste-dumps are promoting the pollution of superficial water through the generation of AMD

Analiza porównawcza wytrzymałości na rozerwanie dzianin warstwowych

This study presents the mechanical properties of weft knitted sandwich fabrics (bursting strength) and the effect of the raw materials used. Two types of fabrics, with and without reinforcing yarns, were analyzed. To determine the influence of the raw material type, a combination of three structure variants were obtained by changing the position in the structure architecture of two types of raw material: Kevlar® and linen yarns. Each of these variants was studied at three levels of density, given by the position of the quality cam, in order to determine the influence of this parameter. Tests were organized in two stages: the first concerned the bursting behavior of single layer fabrics, and the second considered the study of more layers of sandwich fabrics with different orientation. Satisfactory results were obtained after this study regarding the possibility of replacing the high-performance yarns with natural ones.Praca przedstawia właściwości mechaniczne wątkowych dzianin warstwowych, w tym wpływ stosowanego surowca na wytrzymałość na zerwanie. Dla stwierdzenia wpływu stosowanego materiału wyprodukowano 3 warianty strukturalne zmieniając strukturę warstw wykonanych z Kevlaru i włókien lnianych. Każdy z wariantów był badany przy 3 rożnych wartościach gęstości poprzez zmianę pozycji krzywki w celu określenia wpływu na badane parametry. Testy przeprowadzono w dwóch stopniach. Pierwszy uwzględniał badanie wytrzymałości na zerwanie dzianin jednowarstwowych, drugi uwzględniał udział większej ilości warstw wielowarstwowej struktury dzianiny przy rożnej orientacji. Uzyskano zadowalające wyniki uwzględniające możliwość zastąpienia wysokowytrzymałych przędz poprzez przędze surowców naturalnych

On-chip stochastic communication

As CMOS technology scales down into the deep-submicron (DSM) domain, the Systems-On-Chip (SoCs) are becoming increasingly complex and the costs of design and verification are rap-idly increasing due to the inefficiency of traditional CAD tools. Relaxing the requirement of "100 % correctness " for devices and interconnects drastically reduces the costs of design but, at the same time, requires that SoCs be designed with some degree of system-level fault-tolerance. This thesis introduces a novel communication paradigm for SoCs, called stochastic communication. The newly proposed scheme not only separates communication from computation, but also pro-vides the required built-in fault-tolerance to DSM failures, is scalable and cheap to implement. For a generic network-on-chip (NoC) architecture, we show how a ubiquitous multimedia application (an MP3 encoder) can be implemented using stochastic communication in an efficient and robust manner. More precisely, by using this communication scheme, up to 70 % data upsets, 80 % packet losses because of buffer overflow, and severe levels of synchronization failures can be tolerated, while providing a much lower latency than a traditional, bus-based implementation. The present thesis also introduces a new concept, called on-chip diversity, which means mix-ing different architectures and/or technologies in a multiple voltage/frequency island setup in order to achieve the highest levels of performance, fault-tolerance, and the needed flexibility in SoC design. We outline how stochastic communication can enable the overall integration of such systems, and how it can become the base for several hybrid communication architec-tures. We believe that the ideas and the results presented here will open up a whole new area of research with deep implications for on-chip network design and the future generations of SoCs

A Comparative Study of Iron-Based Film Deposition from Iron Pentacarbonyl at 248 nm and 488 nm

Thin film deposition by laser irradiation of Fe(CO)5 at two radiation wavelengths (248 nm and 488 nm) was performed. A perpendicular geometry of irradiation was used. Maximum deposition rates of 14 Å/s at λ = 248 nm and 1.5 Å/s at λ = 488 nm were obtained, indicating a diffusion limited process. SEM analysis of film morphologies showed significant differencies in the nucleation and growth of films deposited at 248 nm and 488 nm. XPS surface analysis revealed a higher carbon content and carbidic phases in the surface of films deposited at 488 nm on SiO2 (quartz) substrates. Oxidized surface Fe phases were found in films, with increasing the exposure time to laser radiation. The film properties are discussed in connection with irradiation conditions and specific mechanisms involved