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

Localisation of buried ferromagnetic objects based on minimum-norm-estimations: a simulation study

Purpose – The purpose of this paper is to examine the localisation of ferromagnetic objects buried in the underground. More specifically, it deals with the reconstruction of the XY-positions, the depths (Z-positions), the number, and the extension of the objects based on geomagnetic measurements. This paper introduces a minimum-norm reconstruction approach and evaluates its performance in a simulation study. Design/methodology/approach – Aminimum-L2-norm estimation based on the truncated singular value decomposition method with lead field weighting is proposed in order to localise geomagnetic sources. The sensor setup and positions are taken from real measurements. The source space is formed by an automatically generated grid. At each grid point, a magneto-static dipole is assumed. Findings – Sources with different depths and XY-positions could be successfully reconstructed. The proposed approach is not overly sensitive to errors/noise in measurement values and sensor positions. Originality/value – The approach described in this paper can be used for applications like geoprospection, archaeology, mine clearing, and the clean-up of former waste deposits

Инженерно-геологические условия и проект изысканий под строительство 10-ти этажного здания в микрорайоне Восточный (г. Томск)

Данная работа представляет собой проект изысканий на участке строительства жилого 10-ти этажного здания в микрорайоне Восточный города Томска. Цель дипломного проекта – дать характеристику инженерно-геологических условий площадки строительства жилого 10-ти этажного здания в микрорайоне Восточный города Томска и составить проект изысканий под данное здание.This work is a refined project on the site of construction of a residential 10-storey building in the Vostochny micro-district of the city of Tomsk. The purpose of the diploma project is to give a description of the engineering and geological conditions of the construction site for a 10-storey building in the residential area of the Eastern city of Tomsk and to design a refined project for the annotation of the building

Donnan effect on chloride ion distribution as a determinant of body fluid composition that allows action potentials to spread via fast sodium channels

Proteins in any solution with a pH value that differs from their isoelectric point exert both an electric Donnan effect (DE) and colloid osmotic pressure. While the former alters the distribution of ions, the latter forces water diffusion. In cells with highly Cl--permeable membranes, the resting potential is more dependent on the cytoplasmic pH value, which alters the Donnan effect of cell proteins, than on the current action of Na/K pumps. Any weak (positive or negative) electric disturbances of their resting potential are quickly corrected by chloride shifts

Membranbioreaktoren zur industriellen Abwasserreinigung

Membrane bioreactor (MBR) technology for treatment of organically contaminated wastewater is one of the notable developments in recent years. MBR technology is based on the ongoing development of biological water treatment with suspended biomass, where membranes are used to separate the biologically treated water from the biomass. Major benefits of MBR compared to existing technologies are the improved effluent quality and lower footprint. Both characteristics are of special interest in industrial applications, because in addition to environmental issues, the possibility exists for the direct/ indirect reuse of the treated water within the industrial process. However, applicability of MBRs relies on their technical feasibility and cost-effectiveness. Both criteria are primarily dependent on the filtration performance of the membrane unit, which determines membrane surface area required and operating costs, as well as on the cleaning efficiency or the treated effluent quality. In the municipal sector, there is substantial experience with MBR filtration and cleaning performance, due to the number of operating installations and similarity of the wastewater to be treated. In general, municipal MBR performance varies little between applications. In contrast, significant variations exist between industrial wastewater sectors, due to the highly application-dependent characteristics of industrial wastewaters. To date, most of the plants reflect specific applications and there is little detailed or transferable knowledge available to account for these differences in performance. In addition, much of the existing knowledge remains primarily with the technology providers and operators of MBR systems. In order to develop a basis for the optimal introduction of MBR technology within the industrial sector, a more accurate and comprehensive investigation of the differences in performance is required. Consequently, the primary goals of this work were to identify the key factors of MBR performance, to develop suitable methods for the characterization, quantification and – where feasible – prediction of MBR performance. Based on the gathered knowledge, advanced approaches for the improvement of MBR performance have been developed. Investigations of MBR performance were carried out by treating different water sources in MBR systems. Wastewaters were derived from the chemical, pharmaceutical, textile and paper industry as well as heavily loaded process wastewaters from solids disposal and biotreatment and sludge handling. The wastewaters used represent a wide range with respect to the types and concentrations of contaminants to be eliminated and their biodegradability. Consequently, a wide variety of filtration and cleaning performance was achieved during MBR treatment. For some of the treated wastewaters, a lack of performance indicated that MBR technology was not technically or economically viable. The biodegradability of soluble or low molecular weight organic compounds is a key factor in achieving the desired cleaning performance. A detailed assessment can be undertaken in analytical laboratory testing. In comparison, the molecular weight cut off of the applied micro- or ultrafiltration membranes is of minor importance. Desired filtration performance and especially variances from municipal applications are primarily determined by the fouling factors "colloidal fouling" and "scaling". Suitable methods have been developed to evaluate or forecast the fouling and scaling potential of mixed liquors and raw wastewaters. Further investigations indicated a high potential for optimizing performance. As an alternative to advanced treatment downstream the MBR, improvements in cleaning performance can be achieved by simultaneous addition of powdered activated carbon. Improvements of filtration performance through reduction of fouling and scaling potential were also successfully tested by upstream or simultaneous removal of related compounds. All approaches for optimization were critically evaluated to identify if and under which conditions a sustainable and economical increase in performance could be achieved. It is anticipated that the knowledge gathered in this work will help to solve operational problems of existing MBRs, improve MBR cost-effectiveness and further expand the applicability of MBRs to previously problematic industrial wastewater applications