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The type IIB matrix model, also known as the IKKT model, has been proposed as a promising candidate for a non-perturbative formulation of superstring theory. Based on this proposal, various attempts have been made to explain how our four-dimensional space-time can emerge dynamically from superstring theory. In this article, we review the progress in numerical studies on the type IIB matrix model. We particularly focus on the most recent results for the Euclidean and Lorentzian versions, which are obtained using the complex Langevin method to overcome the sign problem. We also review the earlier results obtained using conventional Monte Carlo methods and clarify the relationship among different calculations. [ABSTRACT FROM AUTHOR]

An editorial is presented on the theme of noncommutativity and its implications in physics, particularly in the context of noncommutative geometry and its applications in various fields such as the Standard Model, quantum gravity, and condensed matter physics. Topics discussed include the interdisciplinary nature of noncommutative geometry, its theoretical foundations, and practical applications in understanding fundamental aspects of the universe.

Stroke constitutes the second highest cause of morbidity and mortality worldwide while also impacting the world economy, triggering substantial financial burden in national health systems. High levels of blood glucose, homocysteine, and cholesterol are causative factors for atherothrombosis. These molecules induce erythrocyte dysfunction, which can culminate in atherosclerosis, thrombosis, thrombus stabilization, and post-stroke hypoxia. Glucose, toxic lipids, and homocysteine result in erythrocyte oxidative stress. This leads to phosphatidylserine exposure, promoting phagocytosis. Phagocytosis by endothelial cells, intraplaque macrophages, and vascular smooth muscle cells contribute to the expansion of the atherosclerotic plaque. In addition, oxidative stress-induced erythrocytes and endothelial cell arginase upregulation limit the pool for nitric oxide synthesis, leading to endothelial activation. Increased arginase activity may also lead to the formation of polyamines, which limit the deformability of red blood cells, hence facilitating erythrophagocytosis. Erythrocytes can also participate in the activation of platelets through the release of ADP and ATP and the activation of death receptors and pro-thrombin. Damaged erythrocytes can also associate with neutrophil extracellular traps and subsequently activate T lymphocytes. In addition, reduced levels of CD47 protein in the surface of red blood cells can also lead to erythrophagocytosis and a reduced association with fibrinogen. In the ischemic tissue, impaired erythrocyte 2,3 biphosphoglycerate, because of obesity or aging, can also favor hypoxic brain inflammation, while the release of damage molecules can lead to further erythrocyte dysfunction and death. [ABSTRACT FROM AUTHOR]

The IKKT matrix model is a promising candidate for a nonperturbative formulation of superstring theory. In this model, spacetime is conjectured to emerge dynamically from the microscopic matrix degrees of freedom in the large-N limit. Indeed in the Lorentzian version, Monte Carlo studies suggested the emergence of (3+1)-dimensional expanding spacetime. Here we study the Euclidean version instead, and investigate an alternative scenario for dynamical compactification of extra dimensions via the spontaneous symmetry breaking (SSB) of 10D rotational symmetry. We perform numerical simulations based on the complex Langevin method (CLM) in order to avoid a severe sign problem. Furthermore, in order to avoid the singular-drift problem in the CLM, we deform the model and determine the SSB pattern as we vary the deformation parameter. From these results, we conclude that the original model has an SO(3) symmetric vacuum, which is consistent with previous results obtained by the Gaussian expansion method (GEM). We also apply the GEM to the deformed matrix model and find consistency with the results obtained by the CLM. [ABSTRACT FROM AUTHOR]

In this work, the shape reconstruction problem of acoustically penetrable bodies from the far-field data corresponding to time-harmonic plane wave incidence is investigated within the framework of the factorization method. Although the latter technique has received considerable attention in inverse scattering problems dealing with impenetrable scatterers and it has not been elaborated for inverse transmission problems with the only exception being a work by the first two authors and co-workers. We aim to bridge this gap in the field of acoustic scattering; the paper on one hand focuses on establishing rigorously the necessary theoretical framework for the application of the factorization method to the inverse acoustic transmission problem. The main outcome of the investigation undertaken is the derivation of an explicit formula for the scatterer's characteristic function, which depends solely on the far-field data feeding the inverse scattering scheme. Extended numerical examples in three dimensions are also presented, where a variety of different surfaces are successfully reconstructed by the factorization method, thus, complementing the method's validation from the computational point of view. [ABSTRACT FROM AUTHOR]

A household-scalewastewater treatment systemwas operatedwith domestic sewage. The systemcould recover gardening/irrigation water from raw sewage or secondary effluent by low pressure ultrafiltration (UF). The UF membranes (surface area= 3.5 m2, pore size= 0.04 μm) were operated at constant transmembrane pressure (0.13 bar). The proposed technologywas examined for approximately 2 months without membrane cleaning. Membrane operation was performed periodically (one or two times per week), simulating water usage for gardening irrigation. During raw sewage filtration (chemical oxygen demand (COD) total= 242± 71 mg L-1, COD soluble= 105± 51 mg L-1, suspended solids= 188±58mg L-1), lowpermeate COD was achieved (52±25mg L-1), whereas nitrogen and phosphorus were recovered in the permeate. The water recovered during 1 h of operation displayed a gradual decrease from42 to 22 L m-2 h-1 during the 50-d time period. For the secondary effluent filtration, theUF module achieved consistently a recovery rate of 39.6±8.0 L m-2 h-1, with an average permeate COD of 37 mg L-1. In this case, the fouling layer (cake layer)was completely reversible after the relaxation period, rendering the process suitable for unattended household applications. [ABSTRACT FROM AUTHOR]

In this study we propose a threshold accepting based hyperheuristic for solving in a single run both the resource-constrained project scheduling problem or resource allocation, and the resource leveling problem. Having their roots in the field of artificial intelligence, hyperheuristics operate in the “low-level” heuristics domain rather than in the solutions domain. The hyperheuristic has been implemented within a commercial project management software package. Low-level heuristics operate on the solution domain defined by the priority values that the software uses for resource allocation. A case example from the literature and computational experiments on randomly generated projects demonstrate that the hyperheuristic achieves good performance in a timely manner, improving the results provided by the software. [ABSTRACT FROM AUTHOR]

The greedy randomized adaptive search procedure (GRASP) is a well-known computational procedure for handling combinatorial optimization problems. Hyperheuristics, or heuristics to choose heuristics, are higher-level algorithms that operate on low-level heuristics, which in turn work in the solution domain. In this paper, a GRASP-inspired hyperheuristic is proposed for solving the resource-constrained project scheduling problem (RCPSP), one of the most important challenges facing construction project schedulers. The hyperheuristic is the main component of a multilevel procedure that runs within a commercial project management software system. On the basis of simple moves such as 'swap' and 'replace,' the low-level heuristics operate on the priority values that the software uses for scheduling activities. The efficiency of this prioritization-based algorithm has been addressed through a series of computational experiments on randomly generated projects. Moreover, the proposed procedure shows the advantages of utilizing the hyperheuristic approach to deal with optimization problems in the construction field. [ABSTRACT FROM AUTHOR]

When decentralized strategies are considered for managing wastewater, natural systems for wastewater treatment (NSWT) (constructed wetlands) seem to be strongly preferred in comparison with the conventional activated sludge wastewater treatment systems. However, because of their high land requirements, land-use suitability analysis should be conducted to specify adequate areas for their accommodation. Multicriteria spatial decision support systems have emerged as the technology that takes into account both decision criteria and constraints in complex land-use planning problems. This study presents a multiattribute decision analysis approach called the spatial fuzzy Analytic Hierarchy Process (SFAHP) to support raster-based land-use suitability studies for the implementation of NSWT. The SFAHP enables decision makers to circumvent vagueness when they perform evaluations using linguistic variables. Its application in a region of Northeastern Greece using a two-level criteria hierarchical model demonstrates its potential use for suitability analyses. [ABSTRACT FROM AUTHOR]

Most multicriteria methods try to model human thinking and insert the results of this modelling into their procedures. Following this path, the proposed multicriteria approach first captures the imprecision and vagueness of data by using linguistic variables. At a second level, it utilises human processes of decision-making by creating decision rules and modelling them with functions used in fuzzy sets theory. This method also is compatible with the way fuzzy logic models and combines fuzzy propositions. The proposed method considers the ideal solution and the anti-ideal solution and assesses each alternative in terms of distance as well as similarity to the ideal solution and the anti-ideal solution. Distance and similarity measures for fuzzy numbers are used and their aggregation is guided by the decision rules in order to construct decision functions. Further, OWA operators with maximal entropy are used to aggregate across all criteria and determine the overall score of each alternative. It is shown that the proposed method presents flexibility in modelling the decision maker’s preferences and it is also appropriate and effective to handle multicriteria problems of considerable complexity. [Copyright &y& Elsevier]

• Monitoring by thermal properties the influence of crystallinity of thermoplastic laminates. • Evaluation on impact properties in thermoplastic composites. • Influence of crystallinity on fracture resistance of thermoplastic laminates. The crystallization behavior of thermoplastic matrix is considered as an important property which can highly affect for the mechanical and thermal properties of laminated composite structures. This manuscript aims to evaluate the influence of different degrees of crystallinity induced in polyphenylene sulfide (PPS) / carbon fiber laminates, processed by hot compression molding. In the present study, the morphology, thermal and mechanical properties (compression, interlaminar shear stress, impact and end notch flexure) of the processed laminates were evaluated. From the mechanical testing results obtained, an increase in the in plane compressive and interlaminar shear strengths respectively, as well as impact resistance is observed for composite coupons processed with lower cooling rates. Based on end-notch flexure (ENF) tests, the mode-II fracture toughness is also strongly dependent on the degree of crystallinity of the thermoplastic matrix, as lower cooling rates yield stronger interfacial bonds. In this way, the present study demonstrates that the mechanical properties of thermoplastic laminates can be optimized by taking into account the matrix cooling rate during processing cycle. [ABSTRACT FROM AUTHOR]

The article discusses the highlights of the 2nd School and Workshop on Quantum Gravity and Quantum Geometry held in Corfu, Greece on September 13 to 20, 2009. The event focused on the study of geometry of quantum spacetime. It tackled topics such as the kinematical properties of noncommutative spacetime structures relevant in gravity, loop quantum gravity and Fourier transforms on spaces of connections.

Hormones are secreted by the endocrine glands and reach their targets after circulating in the blood. Many studies have documented that erythrocytes can bind hormones, and possible interactions have been reported. Erythrocytes are responsive to signaling initiated after binding of epinephrine, norepinephrine, estrogen, progesterone, thyroid hormones, parathyroid hormone, and angiotensin. Signaling results in regulation of cellular metabolism and membrane fluidity. In addition, erythrocytes are circulating pools for dopamine, thyroid hormones, cortisol, and aldosterone. Erythrocyte function and structure are regulated by endocrine signals, while erythrocytes are important constituents for the transport of hormones in the body. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic liver resection offers a safe and feasible option primarily for the excision of hepatic neoplasms. Timely recovery of liver volume is a key factor for improving prognosis and post-operative mortality of patients undergone liver resection. The aim of the present study was to compare liver regeneration after laparoscopic over open partial hepatectomy.Methods: Wistar rats were subjected to laparoscopic 70% hepatectomy (group LAP-HEP), open 70% hepatectomy (group HEP), sham operation (group Sham) or no intervention (group Control). At various timepoints following operation (1 h-2 weeks), the liver was excised to assess relative liver weight, thiobarbituric acid reactive substances (TBARS) levels, mitotic activity, tissue expression of Nuclear Factor-κB (NFκB), Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) and the histopathologic profile.Results: No differences were seen in relative liver weight between hepatectomy groups. Mitotic index was increased in all operative study groups, being higher in group LAP-HEP than in group HEP. TBARS levels were higher in group LAP-HEP compared to group HEP. NFκB and VCAM-1 tissue expression scores were increased in all operative study groups with VCAM-1 being higher in group HEP, while ICAM-1 was overexpressed only in hepatectomy groups. Mild histopathologic lesions were noted in hepatectomy groups with the histopathologic score being higher in group HEP (24 h).Conclusions: Laparoscopic liver resection enhanced hepatocyte mitotic activity which was accompanied by mild oxidative stress and a less pronounced local inflammatory response and tissue injury to that of the open technique. [ABSTRACT FROM AUTHOR]

Despite efforts to unravel the pathogenetic mechanisms of non-alcoholic fatty liver disease (NAFLD), there is still a need for approved treatments and biomarkers. Interestingly, red blood cells present alterations in their characteristics during NAFLD. The phosphatidylcholine to phosphatidylethanolamine ratio, fatty acid profile, red blood cell count and red cell distribution width reflect molecular changes that are taking place in the liver. In addition, glycosylated hemoglobin, chemokine binding and release, and phosphatidylserine exposure actively participate in NAFLD pathogenesis. In this review, we describe the neglected red blood cell dysfunction in NAFLD, with the aim to unveil potent biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Stroke is a major cause of functional disability and is increasing in frequency. Therefore, stroke prognosis must be both accurate and timely. Among other biomarkers, heart rate variability (HRV) is investigated in terms of prognostic accuracy within stroke patients. The literature research of two databases (MEDLINE and Scopus) is performed to trace all relevant studies published within the last decade addressing the potential utility of HRV for stroke prognosis. Only the full-text articles published in English are included. In total, forty-five articles have been traced and are included in the present review. The prognostic value of biomarkers of autonomic dysfunction (AD) in terms of mortality, neurological deterioration, and functional outcome appears to be within the range of known clinical variables, highlighting their utility as prognostic tools. Moreover, they may provide additional information regarding poststroke infections, depression, and cardiac adverse events. AD biomarkers have demonstrated their utility not only in the setting of acute ischemic stroke but also in transient ischemic attack, intracerebral hemorrhage, and traumatic brain injury, thus representing a promising prognostic tool whose clinical application may greatly facilitate individualized stroke care. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is recognised as a pandemic in the developed world. However, the importance of prudent sun exposure tends to be overlooked, which is responsible for this pandemic. Methods: We investigated the vitamin D status in 326 adults, 165 females and 161 males: 99 Osteoporosis patients, 53 Type 1 Diabetes patients, 51 Type 2 Diabetes patients, and 123 Athletic Healthy individuals, from Northern Greece, through the measurement of total calcidiol in winter and summer by immunoenzymatic assay. Results: In the Whole Sample 23.31% had severe deficiency, 13.50% mild deficiency, 17.48% insufficiency, and 45.71% adequacy at the end of winter. Mean concentrations differed significantly (p <0.001) between males and females. The prevalence of deficiency in the young was significantly lower than in the middle-aged (p = 0.004) and in the elderly (p <0.001), while it was significantly lower (p = 0.014) in the middle-aged than in the elderly. The best vitamin D status was found in the Athletic Healthy individuals, followed by the Type 1 and Type 2 Diabetic patients, while Osteoporotic patients had the poorest status. The difference in mean concentrations between winter and summer was significant (p <0.001). Conclusions: Vitamin D status deteriorated with increasing age and it was better in males than in females. Our findings suggest that outdoor physical activity in a Mediterranean country can cover the vitamin D needs of the young and the middle-aged, but not of the elderly, without the need for dietary supplements. [ABSTRACT FROM AUTHOR]

The world has been facing a pandemic for the past 2 years. COVID-19 still leads to millions of deaths worldwide, while deteriorating the global economy. The need for therapeutic targets, thus, remains. Interestingly, red blood cells, apart from gas exchange, also serve as modulators of innate and adaptive immunity. This function is accommodated mainly by surface molecules (proteins, lipids, and carbohydrates) and increased antioxidant capacity. However, under the circumstances of a disease state, red blood cells can become proinflammatory cells. Recent evidence has shown that, in the context of COVID-19, erythrocytes present protein oxidation, decreased antioxidant capacity, increased glycolysis, altered membrane lipidome, increased binding of Cytosine-Guanine (CpG) DNA and complement proteins, and low CD47 levels. These changes lead to an erythrocyte-dependent inflammation, which possibly participates in the hyperinflammation status of COVID-19. The current knowledge for the dysfunction of red blood cells during COVID-19 implies that the BAND3 protein and toll-like receptor 9 are potential therapeutic targets for COVID-19. [ABSTRACT FROM AUTHOR]

The present study investigated the potential nephro‐ and pneumoprotective effect of silibinin (Si) after hepatic ischemia–reperfusion (I/R) injury, by measuring pro‐inflammatory factors. Sixty‐three rats were randomly assigned into three groups, as follows: (a) the sham group (n = 7 rats), subjected to opening and closing the abdomen; (b) the control group (n = 28 rats), subjected to 45‐min hepatic ischemia followed by reperfusion; and (c) the silibinin group (n = 28), subjected to 45‐min hepatic ischemia followed by intravenous administration of lyophilised SLB‐HP‐β‐CD before reperfusion. Control and silibinin groups were further subdivided into time‐point groups, according to the duration of reperfusion. TNF‐α, IL‐6 and MCP‐1 expressions were determined immunohistochemically and by qrT‐PCR at each time‐point. Kidney TNF‐α expression was significantly lower at 180 and 240 min, while lung TNF‐α expression was significantly lower at 240 min. Comparison between the control and Si group at the same time‐points showed very strong evidence of difference at 240 min, with the levels of IL‐6 shifting towards lower values in the Si group. Finally, we found a high MCP‐1 expression after 120 min. We conclude that hepatic I/R injury remotely increases pro‐inflammatory mediators in the kidney and lung, whereas silibinin shows a time‐dependent nephro‐ and pneumoprotective effect. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) constitutes a global pandemic. An intricate network among cytokines and lipids possesses a central role in NAFLD pathogenesis. Red blood cells comprise an important source of both cytokines and signaling lipids and have an important role in molecular crosstalk during immunometabolic deregulation. However, their role in NAFLD has not been thoroughly investigated. Methods: Conditioned media from erythrocytes derived from 10 NAFLD patients (4 men, 6 women, aged 57.875±15.16) and 10 healthy controls (4 men, 6 women, aged 39.3±15.55) was analyzed for the cytokines IFN-γ, TNF-α, CCL2, CCL5, IL-8, IL-1β, IL-12p40, IL-17, MIP-1ß, the signaling lipids sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA), and cholesterol. Their effect on the cytokine profile released by RAW 264.7 macrophages was also studied. Results: MCP1 levels were greater in conditioned growth medium from NAFLD patient erythrocytes than in that from healthy controls (37±40 vs 6.51±5.63 pg/ml). No statistically significant differences were found between patients and healthy controls with regard to S1P, LPA, cholesterol, or eight other cytokines. TNFa release by RAW 264.7 cells was greater after incubation with patient-derived erythrocyte-conditioned medium than in medium without RAW 264.7 cells from either healthy or NAFLD subjects. Conclusions: Erythrocytes may contribute to liver infiltration by monocytes, and macrophage activation, partially due to CCL2 release, in the context of NAFLD. [ABSTRACT FROM AUTHOR]

We investigated the potential beneficial effect of the antioxidant 2-mercaptoethane-sulfonate (mesna) against oxidative stress induced by pneumoperitoneum in splanchnic organs. Wistar rats were subjected to either (a) CO2 pneumoperitoneum (15 mmHg for 60 min) (group P), (b) pretreatment with mesna (400 mg/kg, p.o.) followed by pneumoperitoneum with a 180 min interval (group MP), (c) sham operation (group S), or (d) administration of mesna only (group M). Forty-five minutes after desufflation (groups P and MP), 60 + 45 min after the induction of anesthesia (group S), or 180 min after mesna administration (group M), tissue specimens were excised from liver, kidneys, jejunum and stomach. Tissue oxidative state was assessed on the basis of glutathione-to-glutathione disulfide ratio, malondialdehyde concentration , and superoxide dismutase activity. Pneumoperitoneum deteriorated all the oxidative stress markers in the organs studied. Mesna prevented the occurrence of oxidative stress following pneumoperitoneum in all the organs studied. In the absence of pneumoperitoneum, the administration of mesna caused mild enhancement of the oxidative state of liver, stomach, and kidneys compared to sham controls. Prophylaxis with mesna prevents oxidative stress induced by pneumoperitoneum in splanchnic organs. [ABSTRACT FROM AUTHOR]

Objectives We investigated the positive effect of silibinin after IV administration as silibininhydroxypropyl-ß-cyclodextrin lyophilized product, by measuring gene expression and liver tissue protein levels of tumor necrosis factor-a, interleukin-6, monocyte chemoattractant protein-1, matrix metalloproteinases matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases-2. Methods 63 Wistar rats of age 13.24±4.40 weeks underwent ischemia/reperfusion (I/R) injury of the liver. The animals were randomized into three groups: Sham (S; n = 7); Control (C; n-28); silibinin (Si; n-28). The C and Si groups underwent 45 min ischemia. Si received silibinin-hydroxypropyl-ß-cyclodextrin intravenously immediately before reperfusion at a dose of 5 mg/kg. Both groups were further divided into 4 subgroups, based on euthanasia time (i.e., 60, 120, 180 and 240 min). Key findings qRT-PCR results confirmed the statistically significant reduction of the expression of the pro-inflammatory factors at 240 min after I/R injury (tumor necrosis factor-a: P < 0.05; MCR1: P < 0.05) and matrix metalloproteinases (matrix metalloproteinases 2: P < 0.05; matrix metalloproteinases 3: P < 0.05) and the increase of tissue inhibitor of matrix metalloproteinases-2 in liver tissue in the Si group. Moreover, results of immunohistochemistry levels confirmed that at 240 min pro-inflammatory factors (tumor necrosis factor-a: P < 0.05; MCR1: P < 0.05) and matrix metalloproteinases (matrix metalloproteinases 2: P < 0.05; matrix metalloproteinases 3: P < 0.05) had a statistically significantly lower expression in the Si group while tissue inhibitor of matrix metalloproteinases-2 had a higher expression. Conclusions Silibinin may have a beneficial effect on the protection of the liver. [ABSTRACT FROM AUTHOR]

The Euro-Mediterranean Energy Partnership between the 15 EU member states and the 12 Mediterranean countries of North Africa and Eastern Mediterranean is functioning since 1995 with an action plan for the development of a Free Trade Area by the year 2010. The process is highly motivated by the mutual interests that both parties have. The Mediterranean countries see it as a vehicle to associate themselves with their partner in the north and secure technical assistance, while for the EU, the process is expected to create a favourable and stable climate for energy investments and to secure access to the energy sources available in the region. The policy instruments have been established and the basis of the dialogue has been agreed through the adoption of three energy policy objectives, namely security of supply, competitiveness of the energy industry and environmental protection. The paper aims to present in a coherent way the energy policy status of the Mediterranean countries involved in the Partnership and identify the challenges and the priorities to be addressed. Though a policy paper, the authors aim to cultivate the ground and provide a solid basis for future research derived from the need to develop guidelines for the achievement of the above objectives. [Copyright &y& Elsevier]

• Machine learning was used for LDL estimation from cholesterol, HDL and triglycerides. • Both shallow and deep machine learning was used. • Shallow methods perform in general as well as deep ones. • If the data to train the model is good, all algorithms will give good results. • Model interpretability and model drift should be considered. Accurate determination of low-density lipoprotein cholesterol (LDL) is important for coronary heart disease risk assessment and atherosclerosis. Apart from direct determination of LDL values, models (or equations) are used. A more recent approach is the use of machine learning (ML) algorithms. ML algorithms were used for LDL determination (regression) from cholesterol, HDL and triglycerides. The methods used were multivariate Linear Regression (LR), Support Vector Machines (SVM), Extreme Gradient Boosting (XGB) and Deep Neural Networks (DNN), in both larger and smaller data sets. Also, LDL values were classified according to both NCEP III and European Society of Cardiology guidelines. The performance of regression was assessed by the Standard Error of the Estimate. ML methods performed better than established equations (Friedewald and Martin). The performance all ML methods was comparable for large data sets and was affected by the divergence of the train and test data sets, as measured by the Jensen-Shannon divergence. Classification accuracy was not satisfactory for any model. Direct determination of LDL is the most preferred route. When not available, ML methods can be a good substitute. Not only deep neural networks but other, less computationally expensive methods can work as well as deep learning. [ABSTRACT FROM AUTHOR]

Background: Objectives: Hepatitis C virus requires and induces changes in liver lipidome for its life cycle. In addition, alterations in plasma and erythrocyte lipidome are observed during a range of chronic liver diseases. Methods: A total of six subjects (three males and three females) were included in our study. All subjects were HCV positive according to virus RNA detection. Erythrocyte ghosts were prepared from blood and collected upon diagnosis and also at the end of the treatment with Direct Antiviral Agents (DAA). Lipids were extracted from the erythrocyte ghosts, and cholesterol and phospholipids were analyzed by thin layer chromatography. A semi-quantitative estimation of cholesterol (CHOL), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylcholine (PC) and sphingomyelin (SM) was performed by densitometric analysis of the chromatographs. Results: After the antiviral treatment, PE percentage decreased, whereas the PC/PE and CHOL/PE ratio increased significantly. There were also other weaker differences for CHOL, PI, PS, PC and SM. Before DAA there was a very weak correlation between ALT and PC/PE ratio. In contrast, there was a steep negative correlation between these two parameters after DAA. Conclusions: Red blood cell lipid composition and especially the PC/PE ratio could be a candidate real time biological marker for inflammation resolution during hepatitis C treatment. [ABSTRACT FROM AUTHOR]

As of July 2017, the emissions type-approval of light-duty vehicles in Europe is based on the Worldwide Harmonized Light-duty vehicles Test Procedure (WLTP), introduced to replace the old and outdated New European Driving Cycle (NEDC) test procedure. Since some elements of the European Legislation are still based on the NEDC (2020 CO 2 emission targets, vehicle labelling, national vehicle taxation policies, etc.) in order to allow sufficient lead time to vehicle manufacturers and national authorities to adapt to the new procedure, a simulation-based approach was chosen to calculate CO 2 emissions and fuel consumption according to the NEDC regime in the period 2017–2020. To achieve this objective without significantly increasing the cost and duration of the certification procedure, existing regulation foresees that vehicles are tested over the WLTP for CO 2 emissions, the test results are used as input in a simulation model that then calculates the corresponding CO 2 according to the NEDC test protocol. A dedicated vehicle simulation model (CO 2 MPAS) was developed for the purpose and is currently used for the type-approval of new vehicles in Europe. The development specifications of CO 2 MPAS were challenging, as it had to be highly accurate, exhibit fast operation, and function with a limited number of input data. This paper presents the development principles and process followed, details of the physical models employed in CO 2 MPAS, and provides information regarding its accuracy, validity and in use operation. CO 2 MPAS achieves low errors in the prediction of the NEDC cycle that in the controlled sample used for its development are of the order of 1% with a standard deviation of 3%, while the respective in-use numbers are of the order of 1.5% and 5%. In parallel, random sampling and testing of a 10% of the type-approved vehicles also occurs in order to guarantee the quality of the CO 2 MPAS results and the validity of the process. It is concluded that CO 2 MPAS can be used to accurately estimate emissions of conventional vehicles within a ±4% accuracy range, even when limited input data are available. In addition, the in-use data analyzed suggest that the use of the tool enables the certification of about 2/3 of the new vehicle models without the need of additional experimental tests. This is an important achievement as it reduces the costs and time necessary to certify light-duty vehicle CO 2 emissions during the transitional period. Finally, it can be concluded that the use of CO 2 MPAS does not affect the declared CO 2 emissions of vehicles over NEDC conditions. [ABSTRACT FROM AUTHOR]

Background. Several investigators have suggested the possibility that the expression of both EGFR and HER2 could be utilized for molecularly targeted therapy in urinary bladder cancer. We tried to evaluate the expression of HER2 and EGFR and activation of the AKT/PTEN/mTOR pathway in urothelial carcinomas and if there is any association between them and cellular adhesion molecules (CAMs). Materials and Methods. Forty-one paraffin-embedded urothelial cancer tissue blocks were collected. Immunostains for HER2, EGFR, MIB1, phospho-AKT, PTEN, phospho-mTOR, e-cadherin, p-cadherin, and b-catenin were performed on tissue microarrays sections. The immunohistochemical results were correlated with clinicopathological parameters. Results. The overexpression of HER2 was found in 19.6% of the cases and it was associated with high grade tumors with a high mitotic index and phosphorylation of AKT and mTOR. Muscle-invasive tumors presented both cytoplasmic and nuclear losses of PTEN expression. There was no association between HER/AKT/mTOR pathway activation and CAM expression. Although cadherins were often coexpressed, only p-cadherin immunoreactivity was associated with tumor grade and high proliferative index. Conclusions. HER2 overexpression is found in a respective proportion of urothelial carcinomas. P-cadherin expression is associated with high grade UCs but it is not affected by HER2 overexpression or by activation of HER/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

The European Commission is preparing a new regulatory initiative for monitoring CO 2 emissions and fuel consumption of Heavy-Duty Vehicles in Europe. The new methodology is based on a combination of component testing and computer simulation of the vehicles' fuel consumption. A study was launched aiming to demonstrate that the approach is accurate and representative of the actual performance of vehicles. Experiments were conducted on two trucks, a 40 t Euro VI long haul truck and an 18 t Euro V rigid truck. Measurements were performed both on the chassis dyno and on the road. Simulation software was used for simulating the tests. Its ability to capture vehicle performance and fuel consumption was assessed against the measured data. Simulation results closely matched those of the dyno tests with the final simulated fuel consumption deviating by about ±2–4% compared to the measured value. Over the tests performed on the road, the final fuel consumption laid within a ±3.5% from the measurement. Given the variability of the actual measurement (σ ≥ 2%), it is concluded that a future official vehicle certification scheme can be based on this approach and achieve both high representativeness, compared to the vehicle's actual performance and high vehicle-to-vehicle, accuracy. [ABSTRACT FROM AUTHOR]

In order to elucidate some basic principles for protein–ligand interactions, a subset of 87 structures of human proteins with their ligands was obtained from the PDB databank. After a short molecular dynamics simulation (to ensure structure stability), a variety of interaction energies and structural parameters were extracted. Linear regression was performed to determine which of these parameters have a potentially significant contribution to the protein–ligand interaction. The parameters exhibiting relatively high correlation coefficients were selected. Important factors seem to be the number of ligand atoms, the ratio of N, O and S atoms to total ligand atoms, the hydrophobic/polar aminoacid ratio and the ratio of cavity size to the sum of ligand plus water atoms in the cavity. An important factor also seems to be the immobile water molecules in the cavity. Nine of these parameters were used as known inputs to train a neural network in the prediction of seven other. Eight structures were left out of the training to test the quality of the predictions. After optimization of the neural network, the predictions were fairly accurate given the relatively small number of structures, especially in the prediction of the number of nitrogen and sulfur atoms of the ligand. [ABSTRACT FROM AUTHOR]

Background and Aim: We investigated the role of the prophylactic administration of the antioxidant 2-mercaptoethane sulfonate (mesna) on the hepatocyte-regenerating capacity following partial hepatectomy (PH) with concurrent Pringle maneuver. Methods: Wistar rats were subjected to PH (70% hepatectomy), 30 min Pringle maneuver, PH plus Pringle with or without mesna pretreatment (400 mg/kg, per os, 3 h before Pringle), or sham operation. At 24 h, 48 h, 72 h, and 1 week after operation, relative liver weight, hepatocyte mitotic activity (mitotic index), the histopathological score and serum aspartate aminotransferase, and alanine aminotransferase concentrations were assessed. At 1 h after operation, oxidative stress markers (glutathione to glutathione disulfide ratio, malondialdehyde concentration, and superoxide dismutase activity) and nuclear factor-κB (NF-κB) activity were assessed. Results: Hepatectomy stimulated the regenerating process and induced mild oxidative stress and the activation of NF-κB in hepatocytes, while causing tissue injury in the remnant liver. When PH was performed under Pringle maneuver, hepatocyte mitotic activity was substantially suppressed, although Pringle alone initiated a delayed regenerating response. Furthermore, Pringle maneuver deteriorated oxidative stress markers, markedly increased NF-κB activity, and aggravated tissue injury, as compared to hepatectomy alone. Mesna pretreatment prevented the Pringle-induced antimitotic effect and the induction of oxidative stress, inhibited the activation of NF-κB, while attenuating liver injury after PH under Pringle. Conclusion: The excessive activation of NF-κB is related to the suppression of hepatocyte-regenerating activity following PH with concurrent liver ischemia. Mesna pretreatment protects the liver against the Pringle-induced antimitotic effect after PH via the prevention of oxidative stress and the inhibition of NF-κB activation. [ABSTRACT FROM AUTHOR]

Background and Aim: Mesna (2-mercaptoethane-sulfonate) has been shown to attenuate oxidative injury induced by ischemia reperfusion (I/R) in the kidneys, the liver, and the intestine; however, its mechanism of action has not been fully elucidated. We sought to determine a prophylactic admininstration schedule of mesna that would confer optimal antioxidant protection on the intestinal mucosa following I/R and to investigate whether mesna's action is mediated via inhibition of nuclear factor-κB (NF-κB) activity. Methods: Wistar rats were subjected to one of the following: (a) induction of 30 min ischemia followed by 60 min reperfusion (I30/R60) of the intestine, (b) pretreatment with intraperitoneal or oral mesna at various time- and dose- administration schedules plus I30/R60, (c) sham operation, (d) no operation (controls), or (e) oral mesna alone. At the end of the reperfusion period or at various time points after mesna alone administration, the oxidative state of the intestinal mucosa was assessed in terms of glutathione to glutathione disulfide ratio, malondialdehyde concentration, and superoxide dismutase activity. In addition, NF-κB activity in the intestinal mucosa was assessed immunohistochemically in the oral mesna plus I/R and in the oral mesna alone groups. Results: Sham operation caused mild stress, while I/R caused substantial oxidative stress in the intestinal mucosa. Mesna pretreatment had an antioxidant effect which varied from attenuation to prevention of oxidative stress. Over the two routes of administration, the oral proved to be more effective and had a time- and dose- dependent effect. The antioxidant action of mesna was not related to enhancement of the intestinal mucosa oxidative state. Furthermore, I/R induced NF-κB activation in the intestinal mucosa which was inhibited by mesna pretreatment. In the absence of oxidative damage, mesna led to downregulation of activated NF-κB. Conclusions: Prophylaxis with mesna prevents oxidative stress induced by I/R in the intestine via inhibition of NF-κB activation. [ABSTRACT FROM AUTHOR]