Development of novel synthetic and systems biology tools for investigating and obviating the effect of atherogenic blood flow on vascular cells

The high mortality from cardiovascular diseases is caused by atherosclerosis. Atherosclerosis develops due to multiple factors, including biomechanical factors, such as shear stress generated by the flow of blood on the inner lining of blood vessels. In order to tackle this serious life-threatening condition, we aimed to develop synthetic and systems biology tools for studying the effect of atherogenic shear stress regimes on vascular cells. Our tools could potentially also lead to the identification of drug targets and of drug candidates against cardiovascular disease. The first tool that we developed is a network of genes consisting of a shear stress sensor module, a reporter module and a linker module which signals from the sensor to the reporter module. This circuit is capable of processing the shear stress or ligand activation signal into a fluorescent readout, allowing screening for drug candidate compounds that modify the activity of the shear stress sensor. Instead of the reporter module, the gene network could be coupled to therapeutic genes in order to express these genes under atherogenic shear stress conditions. Our second developed tool is a flow chamber which facilitates exposure of vascular cells to linearly increasing shear stress along the length of the channel floor for in vitro cellular biomechanical studies. This device outperforms currently available linear shear stress inducing devices in terms of the magnitude of shear stress range, linearity of shear stress along the channel length, and the large sampling area granted by the uniformity of shear stress across the channel width. The third tool that we developed is an electroporation and flow device capable of inserting genetic material into primary vascular cells in their adherent state, exposing these cells to fluid flow. This device allows investigations into cardiovascular mechanotransduction pathways under relevant physiological flow conditions.Open Acces

A készletgazdálkodás optimalizálási módszereinek gyakorlati alkalmazása

A készletgazdálkodás színvonala a forgóeszköz-gazdálkodáson belül kiemelt szerepű és folyamatosan napirenden lévÅ‘ a vállalatok életében, ami a készletgazdálkodás gazdasági hatásaival magyarázható. A kapcsolódó forrásmunkákban közölt eredmények, a fogalmak értelmezése, az összefüggések gyakorlati alkalmazásának feltételrendszere stb. több ellentmondást is takar, sok esetben hiányos vagy rosszul értelmezett. Jelen tanulmányban a készletgazdálkodással összefüggésben azon ismert módszerek és algoritmusok képezik a kutatás tárgyát, melyeknek elméleti megalapozottsága nem vitatható, de gyakorlati alkalmazásuk több problémát is felvet, melyek az egyes készletgazdálkodási modellek gyakorlati alkalmazásakor, az összefüggésekben szereplÅ‘ változók gazdasági tartalmának értelmezésekor és számszerűsítésekor jelentkeznek. A tanulmány keretében feltárjuk az összefüggésekben szereplÅ‘ változók számszerűsítésének fontosságát, értelmezzük gazdasági tartalmukat, meghatározzuk gyakorlati alkalmazásuk esetén jelentkezÅ‘ problémákat, és javaslatot teszünk a változók számszerűsítésének és gyakorlati alkalmazásuk algoritmusára. ------------------------------------------------ The standard of stock management is always an important issue for the life of any company, chiefly because of the economic effects of stock management. There are numerous controversies in the findings published in the relevant literature, in the interpretation of concepts and in the practical application of the relevant correlations. They are often incomplete or incorrectly interpreted. This paper looks at methods and algorithms relevant to stock management that are unquestionably well-founded theoretically but the practical application of which raises various problems. These problems arise in the course of the practical application of certain stock management models, with respect to the interpretation of the economic meaning and the quantification of variables included in the various functions. The paper explains the importance of quantifying these variables, provides an interpretation of such variables in economic terms, identifies the issues arising in the course of their application in practice, and proposes algorithms for the quantification and practical application of such variables.forgótÅ‘ke, optimális rendelési tételnagyság, készlettartási ráta, készlettartási modellek, working capital, economic order quantity, holding cost (%), stock management models, Farm Management, Financial Economics,

The Road to BOFUSS: The Basic OpenFlow User-space Software Switch

Software switches are pivotal in the Software-Defined Networking (SDN) paradigm, particularly in the early phases of development, deployment and testing. Currently, the most popular one is Open vSwitch (OVS), leveraged in many production-based environments. However, due to its kernel-based nature, OVS is typically complex to modify when additional features or adaptation is required. To this regard, a simpler user-space is key to perform these modifications. In this article, we present a rich overview of BOFUSS, the basic OpenFlow user-space software switch. BOFUSS has been widely used in the research community for diverse reasons, but it lacked a proper reference document. For this purpose, we describe the switch, its history, architecture, uses cases and evaluation, together with a survey of works that leverage this switch. The main goal is to provide a comprehensive overview of the switch and its characteristics. Although the original BOFUSS is not expected to surpass the high performance of OVS, it is a useful complementary artifact that provides some OpenFlow features missing in OVS and it can be easily modified for extended functionality. Moreover, enhancements provided by the BEBA project brought the performance from BOFUSS close to OVS. In any case, this paper sheds light to researchers looking for the trade-offs between performance and customization of BOFUSS.Comment: 24 pages, 7 figures; submitted to Telecommunications Systems journa

The use of neutron analysis techniques for detecting the concentration and distribution of chloride ions in archaeological iron

Chloride (Cl) ions diffuse into iron objects during burial and drive corrosion after excavation. Located under corrosion layers, Cl is inaccessible to many analytical techniques. Neutron analysis offers non-destructive avenues for determining Cl content and distribution in objects. A pilot study used prompt gamma activation analysis (PGAA) and prompt gamma activation imaging (PGAI) to analyse the bulk concentration and longitudinal distribution of Cl in archaeological iron objects. This correlated with the object corrosion rate measured by oxygen consumption, and compared well with Cl measurement using a specific ion meter. High-Cl areas were linked with visible damage to the corrosion layers and attack of the iron core. Neutron techniques have significant advantages in the analysis of archaeological metals,including penetration depth and low detection limits

The role of patina on archaeological copper alloy coins in the outbreak and progression of bronze disease

Archaeological copper alloy objects form unique corrosion structures according to their manufacture and burial environment. Categorisation has identified protective Type I structures and chloride-containing Type II structures which may lead to bronze disease. Using visual examination to determine which of these exist on objects dictates conservation decisions; unfortunately, there is limited evidence linking surface features directly to corrosion risk. In this study, the chloride content of 39 archaeological copper alloy coins was determined non-destructively using prompt gamma-ray activation analysis. Their surfaces were examined through Raman spectroscopy, reflective transformation imaging and visually using descriptors reflecting Type I, Type II and ‘bronze disease’ surfaces. When subjected to high relative humidity, none of the coins exhibited bronze disease despite containing chlorides and showing characteristics of Type II structures. The results highlight the difficulty of determining risk and taking informed decisions for the management of archaeological copper alloy objects

Sensitivity of spring phenology simulations to the selection of model structure and driving meteorological data

Accurate estimation of the timing of intensive spring leaf growth initiation at mid and high latitudes is crucial for improving the predictive capacity of biogeochemical and Earth system models. In this study, we focus on the modeling of climatological onset of spring leaf growth in Central Europe and use three spring phenology models driven by three meteorological datasets. The MODIS-adjusted NDVI3g dataset was used as a reference for the period between 1982 and 2010, enabling us to study the long-term mean leaf onset timing and its interannual variability (IAV). The performance of all phenology model–meteorology database combinations was evaluated with one another, and against the reference dataset. We found that none of the constructed model–database combinations could reproduce the observed start of season (SOS) climatology within the study region. The models typically overestimated IAV of the leaf onset, where spatial median SOS dates were best simulated by the models based on heat accumulation. When aggregated for the whole study area, the complex, bioclimatic index-based model driven by the CarpatClim database could capture the observed overall SOS trend. Our results indicate that the simulated timing of leaf onset primarily depends on the choice of model structure, with a secondary contribution from the choice of the driving meteorological dataset

Systems and synthetic biology of the vessel wall.

Atherosclerosis is intimately coupled to blood flow by the presence of predilection sites. The coupling is through mechanotransduction of endothelial cells and approximately 2000 gene are associated with this process. This paper describes a new platform to study and identify new signalling pathways in endothelial cells covering an atherosclerotic plaque. The identified networks are synthesized in primary cells to study their reaction to flow. This synthetic approach might lead to new insights and drug targets