Showing papers by "University of Patras published in 2010"

Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting.

Abstract: The expression of proteoglycans (PGs), essential macromolecules of the tumor microenvironment, is markedly altered during malignant transformation and tumor progression. Synthesis of stromal PGs is affected by factors secreted by cancer cells and the unique tumor-modified extracellular matrix may either facilitate or counteract the growth of solid tumors. The emerging theme is that this dual activity has intrinsic tissue specificity. Matrix-accumulated PGs, such as versican, perlecan and small leucine-rich PGs, affect cancer cell signaling, growth and survival, cell adhesion, migration and angiogenesis. Furthermore, expression of cell-surface-associated PGs, such as syndecans and glypicans, is also modulated in both tumor and stromal cells. Cell-surface-associated PGs bind various factors that are involved in cell signaling, thereby affecting cell proliferation, adhesion and motility. An important mechanism of action is offered by a proteolytic processing of cell-surface PGs known as ectodomain shedding of syndecans; this facilitates cancer and endothelial cell motility, protects matrix proteases and provides a chemotactic gradient of mitogens. However, syndecans on stromal cells may be important for stromal cell/cancer cell interplay and may promote stromal cell proliferation, migration and angiogenesis. Finally, abnormal PG expression in cancer and stromal cells may serve as a biomarker for tumor progression and patient survival. Enhanced understanding of the regulation of PG metabolism and the involvement of PGs in cancer may offer a novel approach to cancer therapy by targeting the tumor microenvironment. In this minireview, the implication of PGs in cancer development and progression, as well as their pharmacological targeting in malignancy, are presented and discussed.

Ni/CeO2-ZrO2 catalysts for the dry reforming of methane

Abstract: Nickel catalysts supported on binary CeO 2 –ZrO 2 carriers (28–100% CeO 2 molar content) were prepared and evaluated regarding their catalytic performance for the CO 2 reforming of CH 4 (Dry Reforming of Methane, DRM). The textural and structural properties of catalysts and supports were studied in their calcined, reduced and used state by N 2 adsorption–desorption, XRD, UV–vis DRS, TPR, SEM–EDS and TPH. Zirconium improves the textural properties of the CeO 2 –ZrO 2 supports and the corresponding catalysts and enhances their textural stability under thermal reductive treatment. XRD analysis shows the formation of Ce x Zr 1− x O 2 solid solution for all Ce/(Ce + Zr) ratios. Considerable alterations in the electronic environment of the cations and increased lattice defects in the binary solid solutions were detected by UV–vis DR spectroscopy. A significant increase in the reducibility of both supports and catalysts is observed in the presence of Zr. Compared to the zirconia-free sample, the Ni/CeO 2 -ZrO 2 catalysts exhibited much higher activity for the title reaction, accredited to the increase of the surface concentration of the active sites. However, the amount of carbonaceous deposits is not straightforward related to the activity but depends on the Ce/Zr ratio. Among the zirconium containing catalysts, the zirconium-rich one exhibited the higher activity and the stronger resistance to the formation of carbonaceous deposits.

Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin

Abstract: Hereditary persistence of fetal hemoglobin (HPFH) is characterized by persistent high levels of fetal hemoglobin (HbF) in adults. Several contributory factors, both genetic and environmental, have been identified but others remain elusive. HPFH was found in 10 of 27 members from a Maltese family. We used a genome-wide SNP scan followed by linkage analysis to identify a candidate region on chromosome 19p13.12-13. Sequencing revealed a nonsense mutation in the KLF1 gene, p.K288X, which ablated the DNA-binding domain of this key erythroid transcriptional regulator. Only family members with HPFH were heterozygous carriers of this mutation. Expression profiling on primary erythroid progenitors showed that KLF1 target genes were downregulated in samples from individuals with HPFH. Functional assays suggested that, in addition to its established role in regulating adult globin expression, KLF1 is a key activator of the BCL11A gene, which encodes a suppressor of HbF expression. These observations provide a rationale for the effects of KLF1 haploinsufficiency on HbF levels.

Automotive assembly technologies review: challenges and outlook for a flexible and adaptive approach

Abstract: In this paper, emerging technologies in the automotive assembly are discussed, along with techniques used in the vehicle assembly plants. The discussion involves technologies directly dealing with assembly processes such as handling, joining, human resources etc. as well as with supporting systems, mainly the information technologies. An overview of the existing technologies is provided. The assembly systems are unable to cope with the requirements of mass customization and need to be enriched with new technologies for a higher flexibility potential. Concepts integrating various new technologies into supporting both automated and human based assembly operations are presented and discussed versus this identified inability for mass customization. Future assembly plants need to utilize flexibility systematically, both for the system design and its operation. For this purpose, a close loop approach is discussed.

Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study

Abstract: Objective. To assess the efficacy of rituximab (RTX) in SSc. Methods. Fourteen patients with SSc were evaluated. Eight patients were randomized to receive two cycles of RTX at baseline and 24 weeks [each cycle consisted of four weekly RTX infusions (375 mg/m2)] in addition to standard treatment, whereas six patients (control group) received standard treatment alone. Lung involvement was assessed by pulmonary function tests (PFTs) and chest high-resolution CT (HRCT). Skin involvement was assessed both clinically and histologically. Results. There was a significant increase of forced vital capacity (FVC) in the RTX group compared with baseline (mean ± s.d.: 68.13 ± 19.69 vs 75.63 ± 19.73, at baseline vs 1-year, respectively, P = 0.0018). The median percentage of improvement of FVC in the RTX group was 10.25%, whereas that of deterioration in the controls was 5.04% (P = 0.002). Similarly, diffusing capacity of carbon monoxide (DLCO) increased significantly in the RTX group compared with baseline (mean ± s.d.: 52.25 ± 20.71 vs 62 ± 23.21, at baseline vs 1-year respectively, P = 0.017). The median percentage of improvement of DLCO in the RTX group was 19.46%, whereas that of deterioration in the control group was 7.5% (P = 0.023). Skin thickening, assessed with the Modified Rodnan Skin Score (MRSS), improved significantly in the RTX group compared with the baseline score (mean ± s.d.: 13.5 ± 6.84 vs 8.37 ± 6.45 at baseline vs 1-year, respectively, P < 0.001). Conclusion. Our results indicate that RTX may improve lung function in patients with SSc. To confirm our encouraging results we propose that larger scale, multicentre studies with longer evaluation periods are needed.

Compression behavior of single-layer graphenes.

Abstract: Central to most applications involving monolayer graphenes is its mechanical response under various stress states. To date most of the work reported is of theoretical nature and refers to tension and compression loading of model graphenes. Most of the experimental work is indeed limited to the bending of single flakes in air and the stretching of flakes up to typically ∼1% using plastic substrates. Recently we have shown that by employing a cantilever beam we can subject single graphenes to various degrees of axial compression. Here we extend this work much further by measuring in detail both stress uptake and compression buckling strain in single flakes of different geometries. In all cases the mechanical response is monitored by simultaneous Raman measurements through the shift of either the G or 2D phonons of graphene. Despite the infinitely small thickness of the monolayers, the results show that graphenes embedded in plastic beams exhibit remarkable compression buckling strains. For large length (l)-...

Biaxial nematic phases

Abstract: An overview over the current state of research in the field of biaxial nematic liquid crystalline materials is given. After a short introduction, providing some general aspects and summarizing the classical approaches, the main part focuses on recent developments of new concepts for designing biaxial nematics. First, the major theoretical concepts are outlined, including the classification to different symmetries, the importance of cooperativity and cluster formation for the development of biaxial order and the conditions for the establishment of field induced and spontaneous biaxiality in nematic phases. These new concepts also require the re-evaluation of the tools used for the identification of phase biaxiality, which are discussed briefly. In the second part, recent progress in the design of potential biaxial nematic materials, especially focussing on bent-core molecules with nematic phases, is reported and, finally, comparisons with phase biaxiality as observed in smectic liquid crystals are made.

Biohydrogen Production from Biomass and Wastes via Dark Fermentation: A Review

Abstract: The present review article aims to summarize the microbiological and technological background of the dark fermentation processes for hydrogen generation, emphasising on the exploitation of biomass and wastes as potential feedstocks. The basic principles, the microbiology and the current technology of the processes are outlined. Subsequently, the use of different types of biomass and wastes that have so far been tested as feedstocks is analysed focusing on the advantages, possible limitations and future prospects of their exploitation. Moreover, different types of so far suggested pretreatment methods for better utilisation of the feedstocks are presented, pointing out the advantages and disadvantages of each method. Finally, methods for possible further utilisation of the generated by-products are laid out as well as the present status of the real scale applications.

Hydrogen Sulfide Is an Endogenous Inhibitor of Phosphodiesterase Activity

Abstract: Objective— Recent studies have demonstrated that hydrogen sulfide (H 2 S) is produced within the vessel wall from l-cysteine regulating several aspects of vascular homeostasis. H 2 S generated from cystathione γ-lyase (CSE) contributes to vascular tone; however, the molecular mechanisms underlying the vasorelaxing effects of H 2 S are still under investigation. Methods and Results— Using isolated aortic rings, we observed that addition of l-cysteine led to a concentration-dependent relaxation that was prevented by the CSE inhibitors dl-propargylglyicine (PAG) and β-cyano-l-alanine (BCA). Moreover, incubation with PAG or BCA resulted in a rightward shift in sodium nitroprusside-and isoproterenol-induced relaxation. Aortic tissues exposed to PAG or BCA contained lower levels of cGMP, exposure of cells to exogenous H 2 S or overexpression of CSE raised cGMP concentration. RNA silencing of CSE expression reduced intracellular cGMP levels confirming a positive role for endogenous H 2 S on cGMP accumulation. The ability of H 2 S to enhance cGMP levels was greatly reduced by the nonselective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Finally, addition of H 2 S to a cell-free system inhibited both cGMP and cAMP breakdown. Conclusion— These findings provide direct evidence that H 2 S acts as an endogenous inhibitor of phosphodiesterase activity and reinforce the notion that this gasotransmitter could be therapeutically exploited.

Evaluation of the volatility basis-set approach for the simulation of organic aerosol formation in the Mexico City metropolitan area

Abstract: . New primary and secondary organic aerosol modules have been added to PMCAMx, a three dimensional chemical transport model (CTM), for use with the SAPRC99 chemistry mechanism based on recent smog chamber studies. The new modelling framework is based on the volatility basis-set approach: both primary and secondary organic components are assumed to be semivolatile and photochemically reactive and are distributed in logarithmically spaced volatility bins. This new framework with the use of the new volatility basis parameters for low-NOx and high-NOx conditions tends to predict 4–6 times higher anthropogenic SOA concentrations than those predicted with the older generation of models. The resulting PMCAMx-2008 was applied in Mexico City Metropolitan Area (MCMA) for approximately a week during April 2003 during a period of very low regional biomass burning impact. The emission inventory, which uses as a starting point the MCMA 2004 official inventory, is modified and the primary organic aerosol (POA) emissions are distributed by volatility based on dilution experiments. The predicted organic aerosol (OA) concentrations peak in the center of Mexico City, reaching values above 40 μg m−3. The model predictions are compared with the results of the Positive Matrix Factorization (PMF) analysis of the Aerosol Mass Spectrometry (AMS) observations. The model reproduces both Hydrocarbon-like Organic Aerosol (HOA) and Oxygenated Organic Aerosol (OOA) concentrations and diurnal profiles. The small OA underprediction during the rush-hour periods and overprediction in the afternoon suggest potential improvements to the description of fresh primary organic emissions and the formation of the oxygenated organic aerosols, respectively, although they may also be due to errors in the simulation of dispersion and vertical mixing. However, the AMS OOA data are not specific enough to prove that the model reproduces the organic aerosol observations for the right reasons. Other combinations of contributions of primary and secondary organic aerosol production rates may lead to similar results. The model results strongly suggest that, during the simulated period, transport of OA from outside the city was a significant contributor to the observed OA levels. Future simulations should use a larger domain in order to test whether the regional OA can be predicted with current SOA parameterizations. Sensitivity tests indicate that the predicted OA concentration is especially sensitive to the volatility distribution of the emissions in the lower volatility bins.

Solar Light-Responsive Pt/CdS/TiO2 Photocatalysts for Hydrogen Production and Simultaneous Degradation of Inorganic or Organic Sacrificial Agents in Wastewater

Abstract: Photocatalytic degradation of waste material in aqueous solutions and simultaneous production of hydrogen was studied with the double purpose of environmental remediation and renewable energy production. Both powdered and immobilized Pt/CdS/TiO(2) photocatalysts were used to oxidize model inorganic (S(2-)/SO(3)(2-)) and organic (ethanol) sacrificial agents/pollutants in water. Powdered Pt/CdS/TiO(2) photocatalysts of variable CdS content (0-100%) were synthesized by precipitation of CdS nanoparticles on TiO(2) (Degussa P25) followed by deposition of Pt (0.5 wt %) and were characterized with BET, XRD, and DRS. Immobilized photocatalysts were deposited either on plain glass slides or on transparent conductive fluorine-doped SnO(2) electrodes. The results show that it is possible to produce hydrogen efficiently (20% quantum efficiency at 470 nm) by using simulated solar light and by photocatalytically consuming either inorganic or organic substances. CdS-rich photocatalysts are more efficient for the photodegradation of inorganics, while TiO(2)-rich materials are more effective for the photodegradation of organic substances.

Introduction to multivariate regression analysis.

Abstract: Statistics are used in medicine for data description and inference. Inferential statistics are used to answer questions about the data, to test hypotheses (formulating the alternative or null hypotheses), to generate a measure of effect, typically a ratio of rates or risks, to describe associations (correlations) or to model relationships (regression) within the data and, in many other functions. Usually point estimates are the measures of associations or of the magnitude of effects. Confounding, measurement errors, selection bias and random errors make unlikely the point estimates to equal the true ones. In the estimation process, the random error is not avoidable. One way to account for is to compute p-values for a range of possible parameter values (including the null). The range of values, for which the p-value exceeds a specified alpha level (typically 0.05) is called confidence interval. An interval estimation procedure will, in 95% of repetitions (identical studies in all respects except for random error), produce limits that contain the true parameters. It is argued that the question if the pair of limits produced from a study contains the true parameter could not be answered by the ordinary (frequentist) theory of confidence intervals1. Frequentist approaches derive estimates by using probabilities of data (either p-values or likelihoods) as measures of compatibility between data and hypotheses, or as measures of the relative support that data provide hypotheses. Another approach, the Bayesian, uses data to improve existing (prior) estimates in light of new data. Proper use of any approach requires careful interpretation of statistics1,2.

Responsive reversible hydrogels from associative “smart” macromolecules

Abstract: The present review highlights the recent developments on the reversible hydrogels which are formed through self-assembling and association mechanisms of well-defined macromolecular entities and which are able to respond to external stimuli like temperature, pH, light and chemical triggers. Thanks to the great progress on macromolecular engineering, especially the enormous development of the “living”/controlled polymerization methods, together with the ability to create artificial peptide-based macromolecules through the recombinant DNA methods, novel “smart” macromolecules capable to form responsive transient 3D networks have been designed and evaluated. Nowadays it has been made possible to create macromolecules with tunable macromolecular architectural characteristics, like chain length of low polydispersity, block topology, hydrophobic/hydrophillic balance and specific functionality, that self assemble in specific environments forming tailor made hydrogels with tunable gel properties, such as injectability and responsiveness (i.e. precise sol to gel transitions triggered by one or more stimuli) mesh size, mechanical strength and dynamics.

Routing and Spectrum Allocation in OFDM-Based Optical Networks with Elastic Bandwidth Allocation

Abstract: Orthogonal Frequency Division Multiplexing (OFDM) has been recently proposed as a modulation technique for optical networks, due to its good spectral efficiency and impairment tolerance. Optical OFDM is much more flexible compared to traditional WDM systems, enabling elastic bandwidth transmissions. We consider the planning problem of an OFDM-based optical network where we are given a traffic matrix that includes the requested transmission rates of the connections to be served. Connections are provisioned for their requested rate by elastically allocating spectrum using a variable number of OFDM subcarriers. We introduce the Routing and Spectrum Allocation (RSA) problem, as opposed to the typical Routing and Wavelength Assignment (RWA) problem of traditional WDM networks, and present various algorithms to solve the RSA. We start by presenting an optimal ILP RSA algorithm that minimizes the spectrum used to serve the traffic matrix, and also present a decomposition method that breaks RSA into two substituent subproblems, namely, (i) routing and (ii) spectrum allocation (R+SA) and solves them sequentially. We also propose a heuristic algorithm that serves connections one-by-one and use it to solve the planning problem by sequentially serving all traffic matrix connections. To feed the sequential algorithm, two ordering policies are proposed; a simulated annealing meta-heuristic is also used to obtain even better orderings. Our results indicate that the proposed sequential heuristic with appropriate ordering yields close to optimal solutions in low running times.

Lung dysfunction following cardiopulmonary bypass.

Abstract: Background: It is well known by now that during open heart surgery many detrimental factors are involved in lung injury. The influence mainly of cardiopulmonary bypass (CPB), anesthesia, hypothermia, operation itself, as well as medication and transfusion, can cause a diffuse injury in the lungs, which most often leads to a postoperative pulmonary edema and abnormal gas exchange. Methods: We performed an unrestricted search of Pubmed Medline and EMBASE from 1966 through 2008. Clinical, experimental, basic science, and review papers were included. Results: The hypothesis that a systemic inflammatory reaction takes place after the use of CPB, could explain most of these effects influences in the lung. On the other hand, the release of various pro-inflammatory cytokines like TNF-a, IL-1, IL-2, IL-6, IL-8, and endotoxin during CPB can lead to the entrapment of neutrophils in the pulmonary capillaries. Consequently, the following chain of reactions is likely to occur: an endothelial cell swelling, plasma and protein extravasation into the interstitial tissue, release of proteolytic enzymes, congestion of the alveoli with plasma, erythrocytes and inflammatory debris. Conclusion: In this review we highlight the possible pathophysiological mechanisms implicated in the observed postoperative lung dysfunction.(J Card Surg 2010;25:47-55)

Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis.

Abstract: Aim: Adipokines are protein products of adipose tissue with paracrine and endocrine actions, which have been implicated in the pathogenesis of cardiovascular disease. Locally produced adipokines, especially by periadventitial adipose tissue, may affect vascular physiology and pathology. We investigated the expression of adiponectin, visfatin, leptin and novel adipokines chemerin and vaspin in human periaortic and epicardial adipose tissue, as well as their correlation to aortic and coronary atherosclerosis.Methods: Standard immunohistochemical staining for the adipokines was performed on samples of human periaortic, pericoronary and apical epicardial adipose tissue. Atherosclerotic lesions of the adjacent vascular wall were assessed using the AHA classification.Results: Adipokines were expressed in periadventitial and apical epicardial adipose tissue and - except for adiponectin - in vascular smooth muscle cells and foam cells in atherosclerotic lesions. Aortic atherosclerosis was positively correlated with chemerin, vaspin, visfatin and leptin periaortic fat expression. Coronary atherosclerosis was positively correlated with chemerin and visfatin pericoronary fat expression. Adipose tissue adiponectin expression was negatively correlated to atherosclerosis in both locations. Expression of adipokines in apical epicardial fat was not associated with atherosclerosis.Conclusions: Our results show: a) a different expression pattern of adiponectin, visfatin, leptin, chemerin and vaspin in periaortic, pericoronary and apical epicardial adipose tissue, b) a correlation of these adipokines with either aortic or coronary atherosclerosis or both in a pattern characteristic for each adipokine and suggest that locally produced adipokines might differently affect the atherosclerotic process in different locations.

Evidence that Dkk‐1 is dysfunctional in ankylosing spondylitis

Abstract: Objective Dkk-1 is an inhibitory molecule that regulates the Wnt pathway, which controls osteoblastogenesis. This study was undertaken to explore the potential role of Dkk-1 in ankylosing spondylitis (AS), a prototypical bone-forming disease. Methods Serum Dkk-1 levels were measured in 45 patients with AS, 45 patients with rheumatoid arthritis (RA), 15 patients with psoriatic arthritis (PsA), and 50 healthy subjects by sandwich enzyme-linked immunosorbent assay (ELISA). A functional ELISA was used to assess the binding of Dkk-1 to its receptor (low-density lipoprotein receptor–related protein 6). Furthermore, we studied the effect of sera from patients with AS and healthy subjects on the activity of the Wnt pathway in the Jurkat T cell model, with and without a neutralizing anti–Dkk-1 monoclonal antibody, by Western immunoblotting. Results Serum Dkk-1 levels were significantly increased in patients with AS (mean ± SEM 2,730 ± 135.1 pg/ml) as compared with normal subjects (P = 0.040), patients with RA (P = 0.020), and patients with PsA (P = 0.049). Patients with AS receiving anti–tumor necrosis factor α (anti-TNFα) treatment had significantly higher serum Dkk-1 levels than patients with AS not receiving such treatment (P = 0.007). Patients with AS studied serially prior to and following anti-TNFα administration exhibited a significant increase in serum Dkk-1 levels (P = 0.020), in contrast to patients with RA, who exhibited a dramatic decrease (P < 0.001). Jurkat cells treated with serum from AS patients exhibited increased Wnt signaling compared with cells treated with control serum. In that system, Dkk-1 blockade significantly enhanced Wnt signaling in control serum–treated, but not AS serum–treated, Jurkat T cells. Conclusion Our findings indicate that in patients with AS, circulating bone formation–promoting factors functionally prevail. This can be at least partially attributed to decreased Dkk-1–mediated inhibition.

Nanoparticle-induced widening of the temperature range of liquid-crystalline blue phases

Abstract: Liquid-crystalline blue phases exhibit exceptional properties for applications in the display and sensor industry. However, in single component systems, they are stable only for very narrow temperature range between the isotropic and the chiral nematic phase, a feature that severely hinders their applicability. Systematic high-resolution calorimetric studies reveal that blue phase III is effectively stabilized in a wide temperature range by mixing surface-functionalized nanoparticles with chiral liquid crystals. This effect is present for two liquid crystals, yielding a robust method to stabilize blue phases, especially blue phase III. Theoretical arguments show that the aggregation of nanoparticles at disclination lines is responsible for the observed effects.

Yarrowia lipolytica: A model microorganism used for the production of tailor‐made lipids

Abstract: This paper presents a review of studies related with the production of specialty lipids by the yeast Yarrowia lipolytica during growth on various fatty agro-industrial residues utilized as substrates. In a first approach, the potential for growth on stearin (a low-cost industrial derivative of tallow composed of saturated free fatty acids) was assessed; significant biomass production was obtained, accompanied by notable intracellular accumulation of lipid which occurred as a primary anabolic activity regardless of the extracellular nitrogen availability in the medium. Y. lipolytica consumed its own storage lipids in the stationary growth phase. The secretion of extracellular lipase in non-negligible quantities was also observed in cultures performed on stearin. Although Y. lipolytica tended to increase the intracellular level of stearic acid, its reserve lipid could be used as a cocoa butter substitute, provided that an oleic acid donor, such as chemically hydrolyzed rapeseed oil, is used as co-substrate together with stearin. Accordingly, predetermined lipids with composition similarities to cocoa butter were synthesized using low-cost substrates. Other strategies related with the production of microbial cocoa butter substitutes are also presented and comprehensively discussed.

Fuzzy Cognitive Maps: Basic Theories and Their Application to Complex Systems

Abstract: The challenging problem of modeling and controlling complex systems is investigated using Fuzzy Cognitive Maps (FCMs). A mathematical description of FCM models is presented, new construction methods and an algorithm are developed and extensively examined. The issue of modeling the supervisor of large complex systems is addressed and is modeled using a FCM. A manufacturing example is used to prove the usefulness of the proposed method. The problem of Decision Making process in Decision Analysis is considered and analyzed using FCM models. A successful application of FCM theory in a health problem is provided.

An approach to operational aircraft maintenance planning

Abstract: This paper describes a short-term planning methodology of the line maintenance activities of an airline operator, at the airports, during turn-around time (TAT). The proposed methodology supports decision making for deferring maintenance actions that affect the dispatching of the aircrafts, aiming at high fleet operability and low maintenance cost. Based on health assessment and additional information regarding operational and economical constraints at the operator's fleet level, a multi-criteria mechanism evaluates a set of generated maintenance plan alternatives. An alternative is defined as the possible allocation of all deferred maintenance tasks to a set of suitable airport resources. The selected decision making criteria are cost, remaining useful life (RUL), operational risk and flight delay. A series of experiments is conducted in order to validate and test the approach.