bluuebunny/crossref_metadata_2025 huggingface dataset:
An Approach to In Vitro Manufacturing of Hypertrophic Cartilage Matrix for Bone Repair
Authors: Quang Le Bach , Van Blitterswijk Clemens , De Boer Jan
Published: April 2017

Devitalized hypertrophic cartilage matrix (DCM) is an attractive concept for an off-the-shelf bone graft substitute. Upon implantation, DCM can trigger the natural endochondral ossification process, but only when the hypertrophic cartilage matrix has been reconstituted correctly. In vivo hypertrophic differentiation has been reported for multiple cell types but up-scaling and in vivo devitalization remain a big challenge. To this end, we developed a micro tissue-engineered cartilage (MiTEC) model using the chondrogenic cell line ATDC5. Micro-aggregates of ATDC5 cells (approximately 1000 cells per aggregate) were cultured on a 3% agarose mold consisting of 1585 microwells, each measuring 400 µm in diameter. Chondrogenic differentiation was strongly enhanced using media supplemented with combinations of growth factors e.g., insulin, transforming growth factor beta and dexamethasone. Next, mineralization was induced by supplying the culture medium with beta-glycerophosphate, and finally we boosted the secretion of proangiogenic growth factors using the hypoxia mimetic phenanthroline in the final stage of in vivo culture. Then, ATDC5 aggregates were devitalized by freeze/thawing or sodium dodecyl sulfate treatment before co-culturing with human mesenchymal stromal cells (hMSCs). We observed a strong effect on chondrogenic differentiation of hMSCs. Using this MiTEC model, we were able to not only upscale the production of cartilage to a clinically relevant amount but were also able to vary the cartilage matrix composition in different ways, making MiTEC an ideal model to develop DCM as a bone graft substitute.
Coconut (Cocos nucifera) Ethanolic Leaf Extract Reduces Amyloid-β (1-42) Aggregation and Paralysis Prevalence in Transgenic Caenorhabditis elegans Independently of Free Radical Scavenging and Acetylcholinesterase Inhibition
Authors: Manalo Rafael , Silvestre Maries , Barbosa Aza , Medina Paul
Published: April 2017

Virgin coconut oil (VCO) has been the subject of several studies which have aimed to alleviate Alzheimer’s disease (AD) pathology, focusing on in vitro antioxidant and acetylcholinesterase (AChE) inhibitory activities. Here, we studied an underutilized and lesser-valued part of the coconut tree, specifically the leaves, using in vitro and in vivo approaches. Coconut leaf extract (CLE) was screened for antioxidant and AChE inhibitory properties in vitro and therapeutic effects in two strains of transgenic Caenorhabditis elegans expressing amyloid-β1–42 (Aβ1-42) in muscle cells. CLE demonstrated free radical scavenging activity with an EC50 that is 79-fold less compared to ascorbic acid, and an AChE inhibitory activity that is 131-fold less compared to Rivastigmine. Surprisingly, in spite of its low antioxidant activity and AChE inhibition, CLE reduced Aβ deposits by 30.31% in CL2006 in a dose-independent manner, and reduced the percentage of paralyzed nematodes at the lowest concentration of CLE (159.38 μg/mL), compared to dH2O/vehicle (control). Phytochemical analysis detected glycosides, anthocyanins, and hydrolyzable tannins in CLE, some of which are known to be anti-amyloidogenic. Taken together, these findings suggest that CLE metabolites alternatively decrease AB1–42 aggregation and paralysis prevalence independently of free radical scavenging and AChE inhibition, and this warrants further investigation on the bioactive compounds of CLE.
A Mass Appraisal Model Based on Market Segment Parameters
Authors: Ciuna Marina , Milazzo Laura , Salvo Francesca
Published: April 2017

The proposed evaluation scheme is a uni-equation model to evaluate properties of Mass Appraisal (MA) in terms of widespread availability of sample data. It all allows the use of statistical models and in the opposite conditions of the absence of data of comparable properties, the functions of similar market areas are known as well as the ones near to those for which you want to estimate the function. Of course, the accuracy of the evaluation increases with the amount of available data, with other equal conditions and evaluations carried out without data (but in the presence of other market information). It requires extra-statistical appraisal procedures involving a complete knowledge of the real estate market. However, such knowledge is also required in the MA performed by quantitative models with regard to the data sampling and performance monitoring process. The model considers micro-level characteristics of the properties and macro-level parameters of the real estate market segments. The appraisal model defines the prediction function with both the statistical models and estimation procedures. For this purpose, the model considers four specific situations: the construction of a statistical model operating with a sufficiently large sample of market prices; the construction of a prediction function operating with a very few number of market prices samples; in this situation, the appraisal function of market value is defined by using a sample of market prices referred to comparable properties, and these are few for statistical use but perfectly suitable to the appraisal process; the construction of a prediction function operating with only one market price; the construction of a prediction function operating in the absence of real estate data but with similar functions of market areas with other estimated proprieties. The presented model provides a uniform method of estimating the market value of properties (and fees), through the modular functions. The model studied is able to operate also with reduced information, considering the practical circumstances, the boundary conditions, the application precautions and the significance of the results.
Cancer Chemotherapy Specific to Acidic Nests
Authors: Kobayashi Hiroshi
Published: April 2017

The realization of cancer therapeutics specific to cancer cells with less of an effect on normal tissues is our goal. Many trials have been carried out for this purpose, but this goal is still far from being realized. It was found more than 80 years ago that solid cancer nests are acidified, but in vitro studies under acidic conditions have not been extensively studied. Recently, in vitro experiments under acidic conditions were started and anti-cancer drugs specific to acidic areas have been identified. Many genes have been reported to be expressed at a high level under acidic conditions, and such genes may be potent targets for anti-cancer drugs specific to acidic nests. In this review article, recent in vitro, in vivo, and clinical achievements in anti-cancer drugs with marked efficacy under acidic conditions are summarized, and the clinical use of anti-cancer drugs specific to acidic nests is discussed.
Reliability of NAND Flash Memories: Planar Cells and Emerging Issues in 3D Devices
Authors: Spinelli Alessandro , Compagnoni Christian , Lacaita Andrea
Published: April 2017

We review the state-of-the-art in the understanding of planar NAND Flash memory reliability and discuss how the recent move to three-dimensional (3D) devices has affected this field. Particular emphasis is placed on mechanisms developing along the lifetime of the memory array, as opposed to time-zero or technological issues, and the viewpoint is focused on the understanding of the root causes. The impressive amount of published work demonstrates that Flash reliability is a complex yet well-understood field, where nonetheless tighter and tighter constraints are set by device scaling. Three-dimensional NAND have offset the traditional scaling scenario, leading to an improvement in performance and reliability while raising new issues to be dealt with, determined by the newer and more complex cell and array architectures as well as operation modes. A thorough understanding of the complex phenomena involved in the operation and reliability of NAND cells remains vital for the development of future technology nodes.
Nuclear Molecular Imaging Strategies in Immune Checkpoint Inhibitor Therapy
Authors: Guldbrandsen Kasper , Hendel Helle , Langer Seppo , Fischer Barbara
Published: April 2017

Immune checkpoint inhibitor therapy (ICT) is a new treatment strategy developed for the treatment of cancer. ICT inhibits pathways known to downregulate the innate immune response to cancer cells. These drugs have been shown to be effective in the treatment of a variety of cancers, including metastatic melanoma and lung cancer. Challenges in response evaluation of patients in ICT have risen as immune related side effects and immune cell infiltration may be confused with progressive disease. Furthermore, the timing of the evaluation scan may be challenged by relatively slow responses. To overcome this, new response criteria for evaluating these patients with morphologic imaging have been proposed. The aim of this paper is to review and discuss the current evidence for the use of molecular imaging, e.g., PET/CT (Positron Emission Tomography/Computer Tomography) with 18F-Fluorodeoxyglucoes (FDG) as an alternative imaging method for monitoring patients undergoing ICT. Following the currently available evidence, this review will primarily focus on patients with malignant melanoma.
Entropy in Natural Time and the Associated Complexity Measures
Authors: Sarlis Nicholas
Published: April 2017

Natural time is a new time domain introduced in 2001. The analysis of time series associated with a complex system in natural time may provide useful information and may reveal properties that are usually hidden when studying the system in conventional time. In this new time domain, an entropy has been defined, and complexity measures based on this entropy, as well as its value under time-reversal have been introduced and found applications in various complex systems. Here, we review these applications in the electric signals that precede rupture, e.g., earthquakes, in the analysis of electrocardiograms, as well as in global atmospheric phenomena, like the El Niño/La Niña Southern Oscillation.
Evaluating Heat Flux Profiles in Aluminum Reheating Furnace with Regenerative Burner
Authors: Zhang Hang , Deng Shengxiang
Published: April 2017

Properly understanding heat flux characteristics is a crucial prerequisite to efficiently applying a regenerative burner in an aluminum reheating furnace. A series of experiments was conducted in this study in order to establish a database of the best available burners according to furnace temperature, excess air ratio, and flame combustion mode as they affect heat flux characteristics at the burner plane (Z = 0 mm). A heat flux model was developed to estimate heat transfer in the furnace, and the heat flux proportions of the other two horizontal levels (Z = 400 mm and Z = 750 mm) were investigated. The contour profile of heat flux indicates that total heat flux (THF) and radiation heat flux (RHF) increases with furnace temperature increment (900–1100 °C). Low excess air ratio (1.2–1.3, at furnace temperature 1100 °C) not only reduced the heat flux gradient, but also contributed to enlarge high THF areas and the maximum RHF. The flameless combustion mode displayed larger average THF and RHF uniformity than that of conventional combustion mode. Therefore, the burning effect of operating condition 1 (gas velocity, 90 m/s; excess air ratio, 1.2; flameless combustion) is better than the other conditions. A change of furnace temperature and excess air ratio had mildly effect on convection coefficient, but combustion mode was in contrast. The estimated heat flux distribution from the measured heat flux at the whole burner plane was in agreement with the fitted line of the axis of burner B. Although the intercept of the simulated equation was slightly underestimated, the error can be eliminated by improving the experimental conditions. The results presented here similarly apply to all regenerative burners. A comparison of heat flux among the three horizontal levels indicated that the RHF proportion comprised about 80% of the THF at each level, and a slightly increase (21.1 kW/m2) of THF in the high level from the low levels.
Optimal Energy Scheduling and Transaction Mechanism for Multiple Microgrids
Authors: Kim Boram , Bae Sunghwan , Kim Hongseok
Published: April 2017

In this paper, we propose a framework for optimal energy scheduling combined with a transaction mechanism to enable multiple microgrids to exchange their energy surplus/deficit with others while the distributed networks of microgrids remain secure. Our framework is based on two layers: a distributed network layer and a market layer. In the distributed network layer, we first solve optimal power flow (OPF) using a predictor corrector proximal multiplier algorithm to optimally dispatch diesel generation considering renewable energy and power loss within a microgrid. Then, in the market layer, the agent of microgrid behaves either as a load agent or generator agent so that the auctioneer sets a reasonable transaction price for both agents by using the naive auction-inspired algorithm. Finally, energy surplus/deficit is traded among microgrids at a determined transaction price while the main grid balances the transaction. We implement the proposed mechanism in MATLAB (Matlab Release 15, The MathWorks Inc., Natick, MA, USA) using an optimization solver, CVX. In the case studies, we compare four scenarios depending on whether OPF and/or energy transaction is performed or not. Our results show that the joint consideration of OPF and energy transaction achieves as minimal a cost as the ideal case where all microgrids are combined into a single microgrid (or called grand-microgrid) and OPF is performed. We confirm that, even though microgrids are operated by private owners who are not collaborated, a transaction-based mechanism can mimic the optimal operation of a grand-microgrid in a scalable way.
Thermal-Flow Analysis of a Simple LTD (Low-Temperature-Differential) Heat Engine
Authors: Kim Yeongmin , Chun Wongee , Chen Kuan
Published: April 2017

A combined thermal and flow analysis was carried out to study the behavior and performance of a simple, commercial LTD (low-temperature-differential) heat engine. Laminar-flow solutions for annulus and channel flows were employed to estimate the viscous drags on the piston and the displacer, and the pressure difference across the displacer. Temperature correction factors were introduced in the thermal analysis to account for the departures from the ideal heat transfer processes. The flow analysis results indicate that the work required to overcome the viscous drags on engine moving parts is very small for engine speeds below 10 RPS (revolutions per second). The work required to move the displacer due to the pressure difference across the displacer is also one-to-two orders of magnitude smaller than the moving-boundary work of the piston for temperature differentials in the neighborhood of 20 °C and engine speeds below 10 RPS. A comparison with experimental data reveals large degradations from the ideal heat transfer processes inside the engine.
Research on the Common Rail Pressure Overshoot of Opposed-Piston Two-Stroke Diesel Engines
Authors: Lu Yi , Zhao Changlu , Zuo Zhe , Zhang Fujun , Zhang Shuanlu
Published: April 2017

The common rail pressure has a direct influence on the working stability of Opposed-Piston Two-Stroke (OP2S) diesel engines, especially on performance indexes such as power, economy and emissions. Meanwhile, the rail pressure overshoot phenomenon occurs frequently due to the operating characteristics of OP2S diesel engines, which could lead to serious consequences. In order to solve the rail pressure overshoot problem of OP2S diesel engines, a nonlinear concerted algorithm adding a speed state feedback was investigated. First, the nonlinear Linear Parameter Varying (LPV) model was utilized to describe the coupling relationship between the engine speed and the rail pressure. The Linear Quadratic Regulator (LQR) optimal control algorithm was applied to design the controller by the feedback of speed and rail pressure. Second, cooperating with the switching characteristics of injectors, the co-simulation of MATLAB/Simulink and GT-Power was utilized to verify the validity of the control algorithm and analyze workspaces for both normal and special sections. Finally, bench test results showed that the accuracy of the rail pressure control was in the range of ±1 MPa, in the condition of sudden 600 r/min speed increases. In addition, the fuel mass was reduced 76.3% compared with the maximum fuel supply quantity and the rail pressure fluctuation was less than 20 MPa. The algorithm could also be appropriate for other types of common rail system thanks to its universality.
Assessing OpenStreetMap Data Using Intrinsic Quality Indicators: An Extension to the QGIS Processing Toolbox
Authors: Sehra Sukhjit , Singh Jaiteg , Rai Hardeep
Published: April 2017

OpenStreetMap (OSM) is a recent emerging area in computational science. There are several unexplored issues in the quality assessment of OSM. Firstly, researchers are using various established assessment methods by comparing OSM with authoritative dataset. However, these methods are unsuitable to assess OSM data quality in the case of the non-availability of authoritative data. In such a scenario, the intrinsic quality indicators can be used to assess the quality. Secondly, a framework for data assessment specific to different geographic information system (GIS) domains is not available. In this light, the current study presents an extension of the Quantum GIS (QGIS) processing toolbox by using existing functionalities and writing new scripts to handle spatial data. This would enable researchers to assess the completeness of spatial data using intrinsic indicators. The study also proposed a heuristic approach to test the road navigability of OSM data. The developed models are applied on Punjab (India) OSM data. The results suggest that the OSM project in Punjab (India) is progressing at a slow peace, and contributors’ motivation is required to enhance the fitness of data. It is concluded that the scripts developed to provide an intuitive method to assess the OSM data based on quality indicators can be easily utilized for evaluating the fitness-of-use of the data of any region.
A Study of the Triggers of Conflict and Emotional Reactions
Authors: Caldara Michael , McBride Michael , McCarter Matthew , Sheremeta Roman
Published: April 2017

We study three triggers of conflict and explore their resultant emotional reactions in a laboratory experiment. Economists suggest that the primary trigger of conflict is monetary incentives. Social psychologists suggest that conflicts are often triggered by fear. Finally, evolutionary biologists suggest that a third trigger is uncertainty about an opponent’s desire to cause harm. Consistent with the predictions from economics, social psychology, and evolutionary biology, we find that conflict originates from all three triggers. The three triggers differently impact the frequency of conflict, but not the intensity. Also, we find that the frequency and intensity of conflict decrease positive emotions and increase negative emotions and that conflict impacts negative emotions more than positive emotions.
The Betic Ophiolites and the Mesozoic Evolution of the Western Tethys
Authors: Puga Encarnación , Díaz de Federico Antonio , Fanning Mark , Nieto José , Rodríguez Martínez-Conde José , Díaz Puga Miguel , Lozano José , Bianchini Gianluca , Natali Claudio , Beccaluva Luigi
Published: April 2017

The Betic Ophiolites consist of numerous tectonic slices, metric to kilometric in size, of eclogitized mafic and ultramafic rocks associated to oceanic metasediments, deriving from the Betic oceanic domain. The outcrop of these ophiolites is aligned along 250 km in the Mulhacén Complex of the Nevado-Filábride Domain, located at the center-eastern zone of the Betic Cordillera (SE Spain). According to petrological/geochemical inferences and SHRIMP (Sensitive High Resolution Ion Micro-Probe) dating of igneous zircons, the Betic oceanic lithosphere originated along an ultra-slow mid-ocean ridge, after rifting, thinning and breakup of the preexisting continental crust. The Betic oceanic sector, located at the westernmost end of the Tethys Ocean, developed from the Lower to Middle Jurassic (185–170 Ma), just at the beginning of the Pangaea break-up between the Iberia-European and the Africa-Adrian plates. Subsequently, the oceanic spreading migrated northeastward to form the Ligurian and Alpine Tethys oceans, from 165 to 140 Ma. Breakup and oceanization isolated continental remnants, known as the Mesomediterranean Terrane, which were deformed and affected by the Upper Cretaceous-Paleocene Eo-Alpine high-pressure metamorphic event, due to the intra-oceanic subduction of the Jurassic oceanic lithosphere and the related continental margins. This process was followed by the partial exhumation of the subducted oceanic rocks onto their continental margins, forming the Betic and Alpine Ophiolites. Subsequently, along the Upper Oligocene and Miocene, the deformed and metamorphosed Mesomediterranean Terrane was dismembered into different continental blocks collectively known as AlKaPeCa microplate (Alboran, Kabylian, Peloritan and Calabrian). In particular, the Alboran block was displaced toward the SW to occupy its current setting between the Iberian and African plates, due to the Neogene opening of the Algero-Provençal Basin. During this translation, the different domains of the Alboran microplate, forming the Internal Zones of the Betic and Rifean Cordilleras, collided with the External Zones representing the Iberian and African margins and, together with them, underwent the later alpine deformation and metamorphism, characterized by local differences of P-T (Pressure-Temperature) conditions. These Neogene metamorphic processes, known as Meso-Alpine and Neo-Alpine events, developed in the Nevado-Filábride Domain under Ab-Ep amphibolite and greenschists facies conditions, respectively, causing retrogradation and intensive deformation of the Eo-Alpine eclogites.
Association between Serum Selenium Concentrations and Levels of Proinflammatory and Profibrotic Cytokines—Interleukin-6 and Growth Differentiation Factor-15, in Patients with Alcoholic Liver Cirrhosis
Authors: Prystupa Andrzej , Kiciński Paweł , Luchowska-Kocot Dorota , Błażewicz Anna , Niedziałek Jarosław , Mizerski Grzegorz , Jojczuk Mariusz , Ochal Andrzej , Sak Jarosław , Załuska Wojciech
Published: April 2017

According to some authors, serum selenium levels are strongly associated with the severity of liver diseases, including liver cirrhosis. The aim of this study was to determine the relationship between the concentration of selenium and pro-inflammatory and profibrotic cytokines—interleukin-6 (IL-6) and growth differentiation factor 15 (GDF-15) in patients with alcoholic liver cirrhosis. The parameters studied were determined in the serum of 99 patients with alcoholic liver cirrhosis divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. In patients with liver cirrhosis, the serum selenium concentration was statistically lower, whereas serum IL-6 and GDF-15 concentrations were higher than those in the control group. Moreover, the concentration of selenium negatively correlated with the levels of GDF-15 and IL-6. The above results may indicate a role of selenium deficiency in the pathogenesis and progression of alcoholic liver disease.
Evaluation of the Effects of Airborne Particulate Matter on Bone Marrow-Mesenchymal Stem Cells (BM-MSCs): Cellular, Molecular and Systems Biological Approaches
Authors: Abu-Elmagd Muhammad , Alghamdi Mansour , Shamy Magdy , Khoder Mamdouh , Costa Max , Assidi Mourad , Kadam Roaa , Alsehli Haneen , Gari Mamdooh , Pushparaj Peter , Kalamegam Gauthaman , Al-Qahtani Mohammed
Published: April 2017

Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with a range of acute and chronic diseases in humans. However, the specific effects they exert on the stem cells remain unclear. Here, we report the effects of PM collected from the city of Jeddah on proliferation, cell death, related gene expression and systems of biological analysis in bone marrow mesenchymal stem cells (BM-MSCs), with the aim of understanding the underlying mechanisms. PM2.5 and PM10 were tested in vitro at various concentrations (15 to 300 µg/mL) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM2.5 increased proliferation of BM-MSCs, while higher concentrations served to decrease it. PM10 decreased BM-MSCs proliferation in a concentration-dependent manner. The X-ray fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses demonstrated that heavy metals were associated with signaling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential expression of the apoptosis genes (BCL2, BAX); inflammation associated genes (TNF-α and IL-6) and the cell cycle regulation gene (p53). We conclude that PM causes inflammation and cell death, and thereby predisposes to chronic debilitating diseases.
A Systematic Review: Costing and Financing of Water, Sanitation, and Hygiene (WASH) in Schools
Authors: McGinnis Shannon , McKeon Thomas , Desai Richa , Ejelonu Akudo , Laskowski Stanley , Murphy Heather
Published: April 2017

Despite the success of recent efforts to increase access to improved water, sanitation, and hygiene (WASH) globally, approximately one-third of schools around the world still lack adequate WASH services. A lack of WASH in schools can lead to the spread of preventable disease and increase school absences, especially among women. Inadequate financing and budgeting has been named as a key barrier for integrating successful and sustainable WASH programs into school settings. For this reason, the purpose of this review is to describe the current knowledge around the costs of WASH components as well as financing models that could be applied to WASH in schools. Results show a lack of information around WASH costing, particularly around software elements as well as a lack of data overall for WASH in school settings as compared to community WASH. This review also identifies several key considerations when designing WASH budgets or selecting financing mechanisms. Findings may be used to advise future WASH in school programs.
The Cost of Arbovirus Disease Prevention in Europe: Area-Wide Integrated Control of Tiger Mosquito, Aedes albopictus, in Emilia-Romagna, Northern Italy
Authors: Canali Massimo , Rivas-Morales Stefano , Beutels Philippe , Venturelli Claudio
Published: April 2017

Aedes albopictus (tiger mosquito) has become the most invasive mosquito species worldwide, in addition to being a well-known vector of diseases, with a proven capacity for the transmission of chikungunya and dengue viruses in Europe as well as the Zika virus in Africa and in laboratory settings. This research quantifies the cost that needs to be provided by public-health systems for area-wide prevention of arboviruses in Europe. This cost has been calculated by evaluating the expenditure of the plan for Aedes albopictus control set up in the Emilia-Romagna region (Northern Italy) after a chikungunya outbreak occurred in 2007. This plan involves more than 280 municipalities with a total of 4.2 million inhabitants. Public expenditure for plan implementation in 2008–2011 was examined through simple descriptive statistics. Annual expenditure was calculated to be approximately €1.3 per inhabitant, with a declining trend (from a total of €7.6 million to €5.3 million) and a significant variability at the municipality level. The preventative measures in the plan included antilarval treatments (about 75% of total expenditure), education for citizens and in schools, entomological surveillance, and emergency actions for suspected viremias. Ecological factors and the relevance of tourism showed a correlation with the territorial variability in expenditure. The median cost of one antilarval treatment in public areas was approximately €0.12 per inhabitant. Organizational aspects were also analyzed to identify possible improvements in resource use.
Prospective Analysis of the Influence of Sport and Educational Factors on the Prevalence and Initiation of Smoking in Older Adolescents from Croatia
Authors: Zenic Natasa , Ban Djivo , Jurisic Sanja , Cubela Mladen , Rodek Jelena , Ostojic Ljerka , Jelicic Mario , Bianco Antonino , Sekulic Damir
Published: April 2017

The prevalence of smoking among Croatian adolescents is alarmingly high, but no previous study has prospectively examined the sport- and academic-factors associated with smoking and smoking initiation. This study aimed to prospectively examine the associations between scholastic (educational) achievement and sport factors and smoking in 16- to 18-year-old adolescents. This two-year prospective cohort study included 644 adolescents who were 16 years of age at baseline (46% females). Baseline testing was implemented at the beginning of the 3rd year of high school (September 2014) when participants were 16 years old. Follow-up testing was completed at the end of the fourth year of high school, which occurred 20 months later. The evaluated predictor variables were educational-achievement- and sport-related-factors. The outcome variables were (i) smoking at baseline; (ii) smoking at follow-up; and (iii) smoking initiation over the course of the study. We assessed the associations between predictors and outcomes using logistic regression models adjusted for age, gender, socioeconomic status, and conflict with parents. The educational variables were consistently associated with smoking, with lower grade-point-average (Baseline: odd ratio (OR): 2.01, 95% confidence interval (CI): 1.61–2.55; Follow-up: 1.59, 1.31–1.94), more frequent absence from school (Baseline: OR: 1.40, 95% CI: 1.19–1.69; Follow-up: 1.30, 1.08–1.58), and lower behavioral grades (Baseline: OR: 1.80, 95% CI: 1.10–2.89; Follow-up: 1.57, 1.03–2.41) in children who smoke. Adolescents who reported quitting sports were at greater odds of being smokers (Baseline: 2.07, 1.31–3.32; Follow-up: 1.66, 1.09–2.56). Sport competitive achievement at baseline was protective against smoking initiation during following two-year period (0.45, 0.21–0.91). While the influence of the educational variables on smoking initiation has been found to be established earlier; sport achievement was identified as a significant protective factor against initiating smoking in older adolescents. Results should be used in development of an anti-smoking preventive campaign in older adolescents.
Environmental Tobacco Smoke Exposure and Smoke-Free Rules in Homes among Socially-Disadvantaged Populations in Poland
Authors: Milcarz Katarzyna , Bak-Romaniszyn Leokadia , Kaleta Dorota
Published: April 2017

This study aims to examine the prevalence of exposure to environmental tobacco smoke (ETS) in homes among socially-disadvantaged populations in Poland, along with the prevalence and correlates of voluntary implementation of smoke-free home rules. Data concerning 1617 respondents from a cross-sectional study completed in the Piotrkowski District were used, which was part of the “Reducing Social Inequalities in Health” program. Overall, 19.4% of the respondents declared exposure to ETS at home. In the non-smokers group, 15.5%, including 6.6% males and 18.3% females, were exposed to ETS in their place of residence (p < 0.0001). Complete smoke-free rules were adopted by 22.1% of the study participants. Two factors, smoker status and lack of ETS-associated health risk awareness, were found to be significantly associated with no adoption of total smoking bans at home. Socially-disadvantaged non-smokers, especially females from rural areas in Poland, still constitute a large population exposed to ETS in their homes—a challenge from the perspective of public health. Focused efforts are required to address social norms around exposing others to ETS.
Who Is Using Outdoor Fitness Equipment and How? The Case of Xihu Park
Authors: Chow Hsueh-wen , Mowen Andrew , Wu Guan-lin
Published: April 2017

Outdoor fitness equipment (OFE) placed in public parks has the potential to encourage physical activity. However, little is known about OFE users and use patterns. This study employed onsite and video observations of OFE usage to describe user characteristics and patterns in Xihu Park. Results indicate that OFE in this park attracted considerable use, particularly in the early morning and late afternoon. During these peak-hour observations, approximately 12 users per hour used the OFE, with the majority being females and seniors. The triple arm stretch and air walker were the most popular stations. However, most OFE users interacted with less than three of the available six OFE stations. Furthermore, users spent an average of less than nine minutes on all OFE stations combined. While OFE equipment was well-used in this urban park, it appears users did not interact with OFE at rates to produce a sufficient bout or level of physical activity during their park visit. Further investigations of OFE are encouraged to determine their health impact.
Future Prospects for the Development of Cost-Effective Adenovirus Vaccines
Authors: Fougeroux Cyrielle , Holst Peter
Published: April 2017

Vaccination is one of the most efficient tools for disease prevention, and a continuously growing field of research. However, despite progress, we still need more efficient and cost-effective vaccines that would improve access to those in need. In this review, we will describe the status of virus-vectored vaccine technology with a focus on adenoviral-based vaccines. Adenovirus (Ad) vaccines have proven to be efficient in military vaccinations against Ad4 and Ad7 and as highly efficient vectored vaccines against rabies. The question of how other adenovirus-based vaccines can become as efficient as the rabies vaccine is the underlying theme in this review. Here, we will first give an overview of the basic properties of vectored vaccines, followed by an introduction to the characteristics of adenoviral vectors and previously tested modifications of the vector backbone and expression cassettes, with a focus on how they can contribute to increased vaccine cost-effectiveness. Finally, we will highlight a few successful examples of research that have attempted to improve the use of adenoviral-based vaccines by improving the transgene immunogenicity.
The Peculiar Glycolytic Pathway in Hyperthermophylic Archaea: Understanding Its Whims by Experimentation In Silico
Authors: Zhang Yanfei , Kouril Theresa , Snoep Jacky , Siebers Bettina , Barberis Matteo , Westerhoff Hans
Published: April 2017

Mathematical models are key to systems biology where they typically describe the topology and dynamics of biological networks, listing biochemical entities and their relationships with one another. Some (hyper)thermophilic Archaea contain an enzyme, called non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN), which catalyzes the direct oxidation of glyceraldehyde-3-phosphate to 3-phosphoglycerate omitting adenosine 5′-triphosphate (ATP) formation by substrate-level-phosphorylation via phosphoglycerate kinase. In this study we formulate three hypotheses that could explain functionally why GAPN exists in these Archaea, and then construct and use mathematical models to test these three hypotheses. We used kinetic parameters of enzymes of Sulfolobus solfataricus (S. solfataricus) which is a thermo-acidophilic archaeon that grows optimally between 60 and 90 °C and between pH 2 and 4. For comparison, we used a model of Saccharomyces cerevisiae (S. cerevisiae), an organism that can live at moderate temperatures. We find that both the first hypothesis, i.e., that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plus phosphoglycerate kinase (PGK) route (the alternative to GAPN) is thermodynamically too much uphill and the third hypothesis, i.e., that GAPDH plus PGK are required to carry the flux in the gluconeogenic direction, are correct. The second hypothesis, i.e., that the GAPDH plus PGK route delivers less than the 1 ATP per pyruvate that is delivered by the GAPN route, is only correct when GAPDH reaction has a high rate and 1,3-bis-phosphoglycerate (BPG) spontaneously degrades to 3PG at a high rate.
Regulation of Ubiquitin Enzymes in the TGF-β Pathway
Authors: Iyengar Prasanna
Published: April 2017

The transforming growth factor-β (TGF-β) pathway has a tumor suppressor role in normal and premalignant cells but promotes oncogenesis in advanced cancer cells. Components of the pathway are tightly controlled by ubiquitin modifying enzymes and aberrations in these enzymes are frequently observed to dysregulate the pathway causing diseases such as bone disorders, cancer and metastasis. These enzymes and their counterparts are increasingly being tested as druggable targets, and thus a deeper understanding of the enzymes is required. This review summarizes the roles of specific ubiquitin modifying enzymes in the TGF-β pathway and how they are regulated.
EDIM-TKTL1/Apo10 Blood Test: An Innate Immune System Based Liquid Biopsy for the Early Detection, Characterization and Targeted Treatment of Cancer
Authors: Coy Johannes
Published: April 2017

Epitope detection in monocytes (EDIM) represents a liquid biopsy exploiting the innate immune system. Activated monocytes (macrophages) phagocytose unwanted cells/cell fragments from the whole body including solid tissues. As they return to the blood, macrophages can be used for a non-invasive detection of biomarkers, thereby providing high sensitivity and specificity, because the intracellular presence of biomarkers is due to an innate immune response. Flow cytometry analysis of blood enables the detection of macrophages and phagocytosed intracellular biomarkers. In order to establish a pan-cancer test, biomarkers for two fundamental biophysical mechanisms have been exploited. The DNaseX/Apo10 protein epitope is a characteristic of tumor cells with abnormal apoptosis and proliferation. Transketolase-like 1 (TKTL1) is a marker for an anaerobic glucose metabolism (Warburg effect), which is concomitant with invasive growth/metastasis and resistant to radical and apoptosis inducing therapies. The detection of Apo10 and TKTL1 in blood macrophages allowed a sensitive (95.8%) and specific (97.3%) detection of prostate, breast and oral squamous cell carcinomas. Since TKTL1 represents a drugable target, the EDIM based detection of TKTL1 enables a targeted cancer therapy using the vitamin derivatives oxythiamine or benfo-oxythiamine.
ρ0 Cells Feature De-Ubiquitination of SLC Transporters and Increased Levels and Fluxes of Amino Acids
Authors: Medina André , Banaszczak Marcin , Ni Yang , Aretz Ina , Meierhofer David
Published: April 2017

Solute carrier (SLC) transporters are a diverse group of membrane transporter proteins that regulate the cellular flux and distribution of endogenous and xenobiotic compounds. Post-translational modifications (PTMs), such as ubiquitination, have recently emerged as one of the major regulatory mechanisms in protein function and localization. Previously, we showed that SLC amino acid transporters were on average 6-fold de-ubiquitinated and increased amino acid levels were detected in ρ0 cells (lacking mitochondrial DNA, mtDNA) compared to parental cells. Here, we elucidated the altered functionality of SLC transporters and their dynamic ubiquitination status by measuring the uptake of several isotopically labeled amino acids in both human osteosarcoma 143B.TK- and ρ0 cells. Our pulse chase analysis indicated that de-ubiquitinated amino acid transporters in ρ0 cells were accompanied by an increased transport rate, which leads to higher levels of amino acids in the cell. Finding SLC transport enhancers is an aim of the pharmaceutical industry in order to compensate for loss of function mutations in these genes. Thus, the ubiquitination status of SLC transporters could be an indicator for their functionality, but evidence for a direct connection between de-ubiquitination and transporter activity has to be further elucidated.
Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats
Authors: Warzecha Zygmunt , Sendur Paweł , Ceranowicz Piotr , Cieszkowski Jakub , Dembiński Marcin , Sendur Ryszard , Bonior Joanna , Jaworek Jolanta , Ambroży Tadeusz , Olszanecki Rafał , Kuśnierz-Cabala Beata , Tomasz Kaczmarzyk , Tomaszewska Romana , Dembiński Artur
Published: April 2017

Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Results: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.
A Systems Biology Approach Using Transcriptomic Data Reveals Genes and Pathways in Porcine Skeletal Muscle Affected by Dietary Lysine
Authors: Wang Taiji , Feugang Jean , Crenshaw Mark , Regmi Naresh , Blanton John , Liao Shengfa
Published: April 2017

Nine crossbred finishing barrows (body weight 94.4 ± 6.7 kg) randomly assigned to three dietary treatments were used to investigate the effects of dietary lysine on muscle growth related metabolic and signaling pathways. Muscle samples were collected from the longissimus dorsi of individual pigs after feeding the lysine-deficient (4.30 g/kg), lysine-adequate (7.10 g/kg), or lysine-excess (9.80 g/kg) diet for five weeks, and the total RNA was extracted afterwards. Affymetrix Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211 genes. Statistical ANOVA analysis of the microarray data showed that 674 transcripts were differentially expressed (at p ≤ 0.05 level); 60 out of 131 transcripts (at p ≤ 0.01 level) were annotated in the NetAffx database. Ingenuity pathway analysis showed that dietary lysine deficiency may lead to: (1) increased muscle protein degradation via the ubiquitination pathway as indicated by the up-regulated DNAJA1, HSP90AB1 and UBE2B mRNA; (2) reduced muscle protein synthesis via the up-regulated RND3 and ZIC1 mRNA; (3) increased serine and glycine synthesis via the up-regulated PHGDH and PSPH mRNA; and (4) increased lipid accumulation via the up-regulated ME1, SCD, and CIDEC mRNA. Dietary lysine excess may lead to: (1) decreased muscle protein degradation via the down-regulated DNAJA1, HSP90AA1, HSPH1, and UBE2D3 mRNA; and (2) reduced lipid biosynthesis via the down-regulated CFD and ME1 mRNA. Collectively, dietary lysine may function as a signaling molecule to regulate protein turnover and lipid metabolism in the skeletal muscle of finishing pigs.
Circadian Rhythm Neuropeptides in Drosophila: Signals for Normal Circadian Function and Circadian Neurodegenerative Disease
Authors: He Qiankun , Wu Binbin , Price Jeffrey , Zhao Zhangwu
Published: April 2017

Circadian rhythm is a ubiquitous phenomenon in many organisms ranging from prokaryotes to eukaryotes. During more than four decades, the intrinsic and exogenous regulations of circadian rhythm have been studied. This review summarizes the core endogenous oscillation in Drosophila and then focuses on the neuropeptides, neurotransmitters and hormones that mediate its outputs and integration in Drosophila and the links between several of these (pigment dispersing factor (PDF) and insulin-like peptides) and neurodegenerative disease. These signaling molecules convey important network connectivity and signaling information for normal circadian function, but PDF and insulin-like peptides can also convey signals that lead to apoptosis, enhanced neurodegeneration and cognitive decline in flies carrying circadian mutations or in a senescent state.
A Framework for Systematic Refinement of Trustworthiness Requirements
Authors: Mohammadi Nazila , Heisel Maritta
Published: April 2017

The trustworthiness of systems that support complex collaborative business processes is an emergent property. In order to address users’ trust concerns, trustworthiness requirements of software systems must be elicited and satisfied. The aim of this paper is to address the gap that exists between end-users’ trust concerns and the lack of implementation of proper trustworthiness requirements. New technologies like cloud computing bring new capabilities for hosting and offering complex collaborative business operations. However, these advances might bring undesirable side effects, e.g., introducing new vulnerabilities and threats caused by collaboration and data exchange over the Internet. Hence, users become more concerned about trust. Trust is subjective; trustworthiness requirements for addressing trust concerns are difficult to elicit, especially if there are different parties involved in the business process. We propose a user-centered trustworthiness requirement analysis and modeling framework. We integrate the subjective trust concerns into goal models and embed them into business process models as objective trustworthiness requirements. Business process model and notation is extended to enable modeling trustworthiness requirements. This paper focuses on the challenges of elicitation, refinement and modeling trustworthiness requirements. An application example from the healthcare domain is used to demonstrate our approach.