Exercise is an effective therapy against the metabolic syndrome. However, the molecular pathways underlying the advantageous effects of exercise are elusive. Glucagon receptor signaling is essential for exercise benefits, and recent evidence indicates that a downstream effector of glucagon, fibroblast growth factor 21 (FGF21), is implicated in this response. Therefore, we tested the hypothesis that FGF21 action is necessary in mediating metabolic effects of exercise. We utilized acute exhaustive treadmill exercise in Wistar rats to identify a putative, concomitant increase in plasma glucagon and FGF21 with the increase in glucose and lactate following exercise. To test the necessity of FGF21 action in the exercise response, we exposed FGF21 congenitally deficient mice (Fgf21(-/-)) and their wild-type (Wt) littermates to chronic high-fat (HF) feeding and inoperable (sedentary) or operable (exercise) voluntary running wheels. Physiological tests were performed to assess the role of FGF21 in the beneficial effect of exercise on glucose metabolism. Wt and Fgf21(-/-) littermates exhibited similar running behavior, and exercise was effective in suppressing weight and fat mass gain and dyslipidemia independently of genotype. However, exercise failed to positively affect hepatic triglyceride content and glucose tolerance in HF diet-fed Fgf21(-/-) mice. Furthermore, Fgf21(-/-) mice exhibited an impaired adaptation to exercise training, including reduced AMP-activated protein kinase activity in skeletal muscle. This study demonstrates that FGF21 action is necessary to achieve the full metabolic benefits of exercise during chronic HF feeding.


The paper is focused on the new method which could be used for
the reconstruction of forest development. We used the model
town Novaky with its surroundings (southern part of the
Prievidzska Basin in Slovakia). This method is called
cultural-landscape layers (CLL) and it is an alternative way of
evaluating the forest transformations in the landscape.
Historical development of the forest on the CLL profiles of our
case study in Slovakia was elaborated according to the
large-scale maps from years 1782/84, 1845, 1882, 1900, 1938,
1956 and 1994 transformed into a uniform scale (1: 25 000).
Using cultural-landscape modelling, the development of forest
on the choric model of local country within specific time
horizons from the Young and Late Bronze Age (ca 1,200 – 800 BC)
until 2025/30 were conducted. Method of cultural-landscape
profiles has the potential to become one of the alternative
ways for studying the development of forest and its
anthropogenic exploitation with emphasis representation of
horizontal and vertical dependencies and relationships between
natural components of the landscape.


Cubital tunnel syndrome is the second-most-common compressive neuropathy. With the increasing prevalence of entrapment neuropathies, the presentation of ulnar nerve compression with a painful upper extremity appears to be more common. Although our knowledge and understanding of this disease are increasing, the principles of management remain constant. We are obliged to reach a timely and appropriate diagnosis to minimize the extent of neurologic injury and institute an appropriate treatment regimen to preserve and restore normal neural function. Although there are many ways to reach these goals, the avoidance of complications is paramount to achieve a reliable and pain-free outcome. Preventing injury to the medial antebrachial cutaneous nerve, complete release of all sites of compression, and avoidance of creating new compressive sites are the keys to this end.


Student participation in work-integrated learning (WIL) is commonly held to enhance graduate employability and employment outcomes. Nevertheless, there exists significant research that questions the nature of this relationship. For many reasons, universities are unlikely to reduce their efforts and interest in WIL for students. However, for both quality assurance and quality improvement processes, it is important for institutions to evaluate the contribution of WIL to graduate employability and employment. Based on a critical review of the research literature, the rationale for an institutional proposal for the evaluation of the contribution of WIL to graduate employability and employment is developed and presented. The research literature suggests that the relationship between WIL and graduate outcomes is likely to be complex and context dependent. A methodology that others can adopt, adapt, or use as a stimulus for thinking, in their own unique institutional context is offered here.


The aim of this study was to determine the effect of ethanolic extract of propolis (EEP) and an herbal mixture (Rumex crispus, Potentilla anserina, and Polygonum aviculare) on diarrhea course, hematological and biochemical parameters, and acid-base balance of rabbits. Twenty-four meat rabbits (Hyplus) were divided into four groups of eight animals. The rabbits were randomly divided into the following groups: HR - healthy rabbits, DR - rabbits with diarrhea symptoms, H - treated with 10% herbal extract, and EEP - treated with 10% ethanolic extract of propolis at 4 mL/L. The extracts were supplemented for 10 days into the drinking water. Hematological and biochemical blood parameters were examined, as well as the parameters of acid-base balance and antioxidant status. All the rabbits were subjected to clinical examination and their stool samples were tested for the presence of enteropathogenic E. Coli. The used amounts of herbal mixture or ethanolic extract of propolis added to drinking water for rabbits with chronic diarrhea caused a decrease in the duration of diarrhea, concurrently improving feed intake and final body weight. Both the ethanolic extract of propolis and the herbal extract resulted in normalization of the acid-base balance and hematological parameters. The ethanolic extract of propolis has also shown explicit hepatoprotective effects.


One of the most important techniques of information hiding is a steganography. Steganography is the art of hiding information within other information or carriers (i.e. text, image, video or audio) in such a way that it is hard or even impossible to tell that it is there. In This paper, a new text steganography method is proposed. The main goal of this method is to use text file as a carrier for the secret message data in such a manner that the resultant text file attracts no attention and hold the same meaning of the original file.


A high-quality sized FeFe(CN)6 was synthesized as a cathode material for a non-aqueous potassium-ion battery. The electrode delivered a reversible capacity of 124 mA h g−1 at the current rate of 0.5C and still retained a reversible capacity of 93 mA h g−1 after 500 cycles at 5C with a columbic efficiency of 100%. Structural evolution and redox couples of low and high spin FeIII/FeII were investigated by ex situ X-ray diffraction, Mossbauer spectroscopy, and X-ray photoelectric spectroscopy. The negligible volume change during the electrochemical process should be responsible for the excellent cyclic stability.


This paper investigates the deployment of stacks of three legged single degree of freedom parallel deployable mechanisms. All the revolute joints in the stacks are replaced with single axis exural hinges. This minimizes the number of components and eliminates friction and backlash in the joints. Constant stiffness springs are used to model the compliant hinges. The novelty of this work is that it brings out a methodology for determining the stiffness of the exures in each stack such that as they deploy, the individual stacks latch and rigidise progressively from the basal end which is crucial for structural stability of the deploying system. This paper also discusses the deployment controlled by a tether (string) attached at the center of the topmost stack to regulate its motion.


Hip fractures in cats occupy a significant share in traumatology and bone diverse area . Comparative advantages and disadvantages are described using cerclage fracture remedy to the method of fixation with plate and screws. The results presented are obtained from the method on four cases of fracture fixation with plate and remedied by screws, 11 cases of pelvic fracture fixation remedied by cerclage and 2 cases of bilateral fracture of the iliac blade which have been corrected compared to the two methods . The study shows that the method is more laborious but cerclage better protect musculature area and gives a very good resistance .


This paper focuses on the integration of CSR in the SMEs' strategies and points out socially responsible practices of Lebanese SMEs looking for a three-dimensional equilibrium, economic, social and environmental, in their activities. To do this, a quantitative method has been established based on data collected from a survey sent to Lebanese SMEs. The sample of Lebanese SMEs shows the existence of certain socially responsible practices and also focuses on the SMEs' challenges to engage in CSR. It has also underlined the importance of standards and the role of networks in promoting CSR in Lebanese SMEs. Finally, this article will identify the conditions to promote learning about CSR and the commitment of Lebanese SMEs in CSR.


Introduction Anaemia and undernutrition, is a common problem in children below 5 years of age and women in reproductive age group. Poor nutritional status predisposes the individual to several diseases, which further deteriorates their nutritional status leading to a vicious cycle. Nutritional Intervention Programmes focuses on women in reproductive age group, pre-school children and adolescent girls. There are no active measures taken to improve the nutritional status of boys. Methodology The study was conducted in seventh standards students of a public school in Mumbai. A written consent of the school authorities and parents was taken prior to undertaking the study. Haemoglobin and Body Mass Index was assessed along with nutrition education emphasising on the importance of iron rich food and balanced diet using interactive teaching methodology. Results Haemoglobin and Body Mass Index was assessed in 116 and 114 students respectively. Mean age of of the students was 12.97 years. Only 9.5% of the students had normal haemoglobin; 7% boys and 11.9% girls. Undernutrition was found in 62.3% of the students; 64.9% boys and 59.6% girls. The observed difference between boys and girls was found to be statistical significant. Conclusion The higher percentage of boys with anaemia and under nutrition is a cause of concern. Weekly iron folic acid supplementation for the girls by the government seems to have contributed to a slightly lower prevalence of anaemia in girls as compared to boys. It is time that adolescent boys are also included in the nutritional intervention programmes.


Background: Minimally invasive parathyroidectomy is the treatment of choice for single-gland primary hyperparathyroidism. However, the exact location of the abnormal gland has to be established. Sestamibi scintigraphy, computed tomography and ultrasound (US) are commonly used modalities. We describe our experience in a non-academic center with surgeon-performed US (S-US) of the neck as preoperative localization study in patients with primary hyperparathyroidism (PHPT). Methods: Patients with a biochemically proven diagnosis of PHPT and preoperative S-US were included. Data were recorded prospectively. Perioperative gland location was compared to the preoperative S-US to determine sensitivity, specificity and accuracy rates. Results: Two of the 50 patients who underwent S-US were not subjected to surgery. In 85% of the patients analyzed by S-US, the appropriate abnormal gland(s) were identified. In 11%, no gland was identified, but abnormal glands were found during surgery. Sensitivity of S-US in our hospital is 85%, with a positive predictive value of 97%. Conclusions: We achieved a satisfactory sensitivity rate. S-US provides anatomic information to the surgeon which enables a more detailed operation planning, and it is a valuable diagnostic modality for patients with PHPT in our opinion. We hope that our data encourage other centers to implement this technique as well.


Novel mesoporous B–N–O–H nanofoam was prepared using CuB23 and ammonium chloride precursors under O2 in ionic liquids via a solution plasma technique. It had a large specific surface area of 1023 m2 g−1, and exhibited high electrical conductivity of 20.8 S m−1 and good specific capacity of 184 F g−1 in 600 mg L−1 methylene blue aqueous solution at a current density of 0.2 mA cm−2. Furthermore, the nanofoam exhibited a high adsorption capacity for cationic dyes, especially methylene blue, with well-controlled recycling behavior. Meanwhile, the methylene blue/acid orange 7 mixture could be easily separated for reuse by the strong electrostatic interaction. The good separation of methylene blue/Rhodamine B was attributed to the stronger coordination between methylene blue and the B–N–O–H nanofoams in comparison with that of Rhodamine B, and the advantage of the smaller methylene blue in competitive adsorption at higher flow rates. These results indicate that the present B–N–O–H nanofoam may have promising applications in the field of water purification, including enrichment or even total separation of dyes during wastewater treatment for reuse.


In this paper, a low-power pulse-triggered flip-flop (FF) designed and a simple two-transistor AND gate is designed to reduce the circuit complexity. Second, a conditional pulse-enhancement technique is devised to speed up the discharge along the critical path only when needed. As a result, transistor sizes in delay inverter and pulse-generation circuit can be reduced for power saving. Various post layout simulation results based on UMC CMOS 50-nm technology reveal that the proposed design features the best power-delay-product performance in several FF designs under comparison. Its maximum power saving against rival designs is up to 18.2% and the average leakage power consumption is also reduced by a factor of 1.52.


Background: Chronic periodontitis (CP) is greatly prevalent condition of inflammatory behavior. Salivary biomarker total antioxidants capacity (T-AOC) status, may be related to both periodontal condition and oral hygiene. Aims of the study: To assess the level of salivary T-AOC of patients with chronic periodontitis in comparison to healthy control and to correlate between the level of this marker with the clinical periodontal parameters (plaque index (PLI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL)). Materials and Methods: Ninety subjects of males and females with an age ranged between (35-55) years were participated in this study. Participants were divided into two groups: the first group was CP group that consisted of fiftyfive subjects and the second group consisted of thirty-five subjects as control group with healthy periodontium and both groups systemically healthy. The whole unstimulated salivary samples were collected, and then periodontal evaluation that including the assessment of clinical periodontal parameter (PLI, GI, BOP, PPD, and CAL) were done for all participants. Enzyme-linked immune– sorbent assay (ELISA) used to determine the level of T-AOC in saliva. Results: The two studied groups showed a highly significant difference regarding the salivary level of T-AOC, and it revealed that the mean value of salivary level of T-AOC was statistically lower in CP group than the control group. Regarding Pearson Correlation Coefficient, this study revealed that there is strong negative correlations between clinical periodontal parameters (GI, BOP, PPD, and CAL) with salivary level of T-AOC. Conclusion: Salivary T-AOC could be used as a reliable marker of chronic periodontitis activity.


This study reports on the kind of school leadership style that best suits for promoting teachers' job satisfaction in primary schools in Tanzania. The study employed cross sectional research design with samples of 200 teachers from 20 selected primary schools in Songea and Morogoro districts. Interviews, documentary analysis and questionnaires were used to collect data. The data were analyzed both qualitatively and quantitatively using tables, frequencies and percentages. It was found that the democratic leadership style was the most dominant in best performing primary schools. It is therefore suggested that there is much to be learnt with democratic leadership style as a copying strategy in least performing primary schools. Moreover, level of teachers' job satisfaction was reportedly high in best performing schools compared to least performing schools. The findings commended that democratic leadership style is the one which promotes high teachers' job satisfaction among teachers in primary schools.

 Keywords: Leadership, leadership styles, primary schools, teachers and job satisfaction.


Abstract. According to current experimental evidence, coral reefs could disappear within the century if CO2 emissions remain unabated. However, recent discoveries of diverse and high cover reefs that already thrive under extreme conditions seem to contradict these projections. Volcanic CO2 vents, semi-enclosed lagoons and mangrove estuaries are unique study sites where one or more ecologically relevant parameters for life in the oceans are close or even worse than currently projected for the year 2100. These natural analogues of future conditions hold new hope for the future of coral reefs and provide unique natural laboratories to explore how reef species could keep pace with climate change. To achieve this, it is essential to characterize their environment as a whole, and accurately consider all possible environmental factors that may differ from what is expected in the future and that may possibly alter the ecosystem response. In this study, we focus on the semi-enclosed lagoon of Bouraké (New Caledonia, SW Pacific Ocean) where a healthy reef ecosystem thrives in warm, acidified and deoxygenated water. We used a multi-scale approach to characterize the main physical-chemical parameters and mapped the benthic community composition (i.e., corals, sponges, and macroalgae). The data revealed that most physical and chemical parameters are regulated by the tide, strongly fluctuate 3 to 4 times a day, and are entirely predictable. The seawater pH and dissolved oxygen decrease during falling tide and reach extreme low values at low tide (7.2 pHT and 1.9 mg O2 L−1 at Bouraké, vs 7.9 pHT and 5.5 mg O2 L−1 at reference reefs). Dissolved oxygen, temperature, and pH fluctuates according to the tide of up to 4.91 mg O2 L−1, 6.50 °C, and 0.69 pHT units on a single day. Furthermore, the concentration of most of the chemical parameters was one- to 5-times higher at the Bouraké lagoon, particularly for organic and inorganic carbon and nitrogen, but also for some nutrients, notably silicates. Surprisingly, despite extreme environmental conditions and altered seawater chemical composition, our results reveal a diverse and high cover community of macroalgae, sponges and corals accounting for 28, 11 and 66 species, respectively. Both environmental variability and nutrient imbalance might contribute to their survival under such extreme environmental conditions. We describe the natural dynamics of the Bouraké ecosystem and its relevance as a natural laboratory to investigate the benthic organism's adaptive responses to multiple stressors like future climate change conditions.


This article explores the role of paddy field farmers' local knowledge in the context of adaptation to a post-disaster setting. The Tohoku earthquake and tsunami of 2011 heavily damaged the northeast coastal region and swept away virtually all human spaces, including agricultural fields. Many small-scale farmers abandoned cultivation, and the government instead facilitated large-scale farmers. Those who restarted rice production expanded the cultivated land. I examine this socio-cultural context focusing on the dynamism and complexities of the farmers' local knowledge. The most important aspect in this knowledge can be seen as time manipulation contributing to labor efficiency. Local knowledge has three dimensions: maturation process, environment, and biological response. While the first two of these are oriented to tradition and the collective, the last is rather individualistic and is innovative in nature. Embracing these three types of knowledge in communities has supported agricultural adaptation in the post-disaster context.


Mesange is a medium-size quarterly macro-econometric model of the French economy (about 500 equations, three sectors). The model describes short-term Keynesian dynamics and its long-term equilibrium is driven by supply-side determinants. Its reestimation on data from the national accounts base 2000 with fixed-base volumes is presented in a recent working paper (Klein and Simon, 2010). This first version of the model has been optimized for simulation use. Other applications of the Mesange model (short-term forecasting, analyses of the past) required its adaptation to the published data from the quarterly accounts with chained-linked volumes, as well as the integration of the recent crisis episode. A second version of the Mesange model has, therefore, been developed for this purpose. This version is presented in this working paper. First, the problems raised for macroeconomic modelling by national accounts with chained-linked volumes are explained and the solutions chosen to adapt the model to these new conventions are discussed. The applications of the version of the model with chained-linked volumes are, then, explained and illustrated with examples. Last, the main reestimated equations are detailed. The differences with respect to the version of the model with fixed-base volumes are commented. They stem from estimations based on non-identical data, but also from the different uses made of the two versions of Mesange and the resulting various needs and constraints that have conditioned the methodological choices that have been made. As for the version of the model with chained-linked volumes, priority has been given to the quality of the adjustment to the data rather than to the underlying theoretical framework. Nonetheless, the philosophy and general structure of the two versions of the model remain very much alike.


Mosquitoes represent the major vectors involved in the spread of deadly diseases like Malaria, Lymphatic filariasis,Chikungunyaand arboviruses like dengue virus and Zika virus. These diseases have emerged with the rise of urbanization and the use of chemical insecticides around the world. The insecticides such as DDT (Dichlorodiphenyltrichloroethane), organophosphates, carbamates, and organochlorineshave caused resistance in mosquitoes against typical chemical control methodsthrough excessive use over the years. Different biological control methods aresustainable, eco-friendly and target major diseases spreading mosquito's species. This review outlines major biological control methods being used ortested in different parts of the world. Some of these are the use of plant extract, Wolbachiaspp, larvivorous fishes, insecticidal bacterial spp, predator mosquitoes and predator copepods.Limitations associated with each method are also discussed.All these methods will givea better understanding of developing an integrated approach for effective mosquitoes control that will reduce dependency on insecticide based approaches.


It is not easy to solve the troubles around the openings at the detail design stage, because there are a lot of concerning locations. There are not also clear design rules of classification societies. For more detailed strength analysis around holes on the longitudinal girder or transverse web below deck plate, it is also very difficult to decide the boundary condition (B.C) at both ends. Grillage analysis, which considers B.C and more detailed member arrangement, is used in simple analysis. Furthermore, refined mesh method, which use a part of member in the strength analysis, is used to decide S.I.Fs around holes. Component loads are applied to a refined mesh model separately and S.I.Fs according to component loading are calculated. S/F and B/M are decided from the grillage analysis and S.I.F for a given hole location is deduced from database and the results of grillage analysis.


Between 1960 and 1965 Leith Stevens taught
"Film Scoring," a two-unit course at the University of California at Los Angeles Extension School, advertised as "the first offering of a professional level course in this area." The impetus for the course was Stevens' increasing dissatisfaction with contemporary composers and arrangers, a sentiment that can be traced in many of Stevens' writings and pronouncements over the years.

The course was open to "the professional musician
and the interested auditor" but in practice was limited
to graduate students and practicing composers. There were fifteen two-hour lectures and on his syllabus Stevens stipulated that "except in the case of observers, it is assumed the members of this class will have a well-rounded knowledge of the materials used in composition and orchestration." As part of the requirements for the course, students were required to view films and television programs with dialogue and sound effects, but without music. They were then asked to determine where music should be used in the film, time the selected sections, write the music and orchestrate it. They were also invited to visit film studios in Hollywood.

The text provides Stevens' view of the principles of film scoring and his compositional process. In presenting the material I chose not to follow the chronological order in Stevens' course syllabus. From the recorded lectures it is evident Stevens did not strictly adhere to the syllabus and often jumped around from subject to subject, expounding on completely different topics within the same lecture. The material is presented instead in thematic progression, first providing Stevens' philosophical views on film scoring before moving on to his consideration of the score as a whole, then to specific practical techniques such as timing and synchronization, before finishing with a discussion of various practical challenges that film and television composers faced in the mid-1960s.


This study reviews 209 original articles published in the journal Arquivos Brasileiros de Nutricao (1944/1968), a periodical edited by Josue de Castro, physician, specialist in nutrition, and founder-director of the Institute of Nutrition at the University of Brazil (now the Federal University of Rio de Janeiro). Our methodology was based on quantitative and qualitative analyses, aimed at summarizing both the topic itself and the authors' backgrounds. Results showed that 134 of the articles (64%) adopted a biological perspective to nutrition, mostly focusing on laboratory research concerning the chemical composition and nutritional value of Brazilian foodstuffs. On the other hand, 75 articles (36%) took a social perspective, testifying to the first efforts by Brazilian nutritional experts to create and improve specific methodological tools for investigating our population's nutritional conditions, thereby helping to consolidate the field of nutrition in the country.


Morphology of the neuroendocrine stomach tumours, including carcinoid tumours (CT) and so-called carcinoids of complex structure is studied (189 tumours of patients operated in the Institute), 164 tumours are studied using routine histological methods including Grimelius methods. Immunophenotyping with the use of antibodies to VIII type keratin, carcinoembryonic antigen, meconial intestinal antigen B1MA, Factor VIII, IV-type collagen and laminin were performed in 25 cases. Neuroendocrine carcinomas represented a group of 86 tumours (45.5%), 28 (14.4%) of them were carcinoid tumours and 58 (30.7%)--complex carcinoids. Among CT, moderately differentiated tumours predominated (18), 4 tumours were poorly differentiated and there was a combination of structures in 6 tumours. The conclusion is made that neuroendocrine stomach carcinomas are epithelial tumours with a complex functional differentiation manifesting in different types of secretion: neuroendocrine and non-endocrine characteristic of stomach epithelium.


High aerodynamic efficiency is a key design driver for airborne wind energy systems as it strongly affects the achievable energy output. Conventional fixed-wing systems generally use aerofoils with a high thickness-to-chord ratio to achieve high efficiency and wing loading. The box wing concept suits thinner aerofoils as the load distribution can be changed with a lower wing span and structural reinforcements between the upper and lower wings. This paper presents an open-source toolchain for reliable aerodynamic simulations of parameterized box wing configurations, automating the design, meshing, and simulation setup processes. The aerodynamic tools include the steady 3D panel method solver APAME and the CFD-solver OpenFOAM, which use a steady Reynolds-Averaged Navier–Stokes approach with k-ω SST turbulence model. The finite-volume mesh for the CFD-solver is generated automatically with Pointwise using eight physical design parameters, five aerofoil profiles and mesh refinement specifications. The panel method provided accurate and fast results in the linear lift region. For higher angles of attack, CFD simulations with high- to medium-quality meshes were required to obtain good agreement with measured lift and drag coefficients. The CFD simulations showed that the upper wing stall lagged behind the lower wing, increasing the stall angle of attack compared to conventional fixed-wing kites. In addition, the wing tip boundary layer separation was delayed compared to the wing root for the straight rectangular box wing. Choosing the design point and operational envelope wisely can enhance the aerodynamic performance of airborne wind energy kites, which are generally operated at a large angle of attack to maximise the wing loading and tether force, and through that, the power output of the system.


Sex refers to any biological process selected for genetic exchange but the reason for why sex is so common in Eukaryotes continues to resist understanding. Bacteria appear to adapt and proliferate despite the fact that they lack genes for sex. To understand why sex has evolved, we must answer two crucial questions: i) what are the key differences between eukaryotes and bacteria and ii) why do some eukaryotes use asexual reproduction. Recently, new ideas about the evolution of sex are being proposed which point out that sex and recombination could be the result of very primitive interactions.


The Wetland in India support subsistence and livelihood to thousands of people through fishing, collecting edible plants, agriculture, irrigation, water transport and commercial fisheries, besides rich biodiversity. In the present study, 20 water samples were collected from 20 sampling stations during Monsoon (June to Aug-2009) and post-monsoon (Sept. to Nov.-2009) season. The relevant parameters such as Temp., pH, TSS, TDS, DO, free CO2, alkalinity, hardness, chloride, sulphate, phosphate and heavy metals (Mn, Co, Zn, Fe, Cu, Ni, Cr, Cd) were analyzed for water samples by various standard methods.


Issues concerning the advanced numerical analysis of concrete building structures in sophisticated computing systems currently require the involvement of nonlinear mechanics tools. The efforts to design safer, more durable and mainly more economically efficient concrete structures are supported via the use of advanced nonlinear concrete material models and the geometrically nonlinear approach. The application of nonlinear mechanics tools undoubtedly presents another step towards the approximation of the real behaviour of concrete building structures within the framework of computer numerical simulations. However, the success rate of this application depends on having a perfect understanding of the behaviour of the concrete material models used and having a perfect understanding of the used material model parameters meaning. The effective application of nonlinear concrete material models within computer simulations often becomes very problematic because these material models very often contain parameters (material constants) whose values are difficult to obtain. However, getting of the correct values of material parameters is very important to ensure proper function of a concrete material model used. Today, one possibility, which permits successful solution of the mentioned problem, is the use of optimization algorithms for the purpose of the optimization-based inverse material parameter identification. Parameter identification goes hand in hand with experimental investigation while it trying to find parameter values of the used material model so that the resulting data obtained from the computer simulation will best approximate the experimental data. This paper is focused on the optimization-based inverse identification of the parameters of a concrete cap material model which is known under the name the Continuous Surface Cap Model. Within this paper, material parameters of the model are identified on the basis of interaction between nonlinear computer simulations, gradient based and nature inspired optimization algorithms and experimental data, the latter of which take the form of a load-extension curve obtained from the evaluation of uniaxial tensile test results. The aim of this research was to obtain material model parameters corresponding to the quasi-static tensile loading which may be further used for the research involving dynamic and high-speed tensile loading. Based on the obtained results it can be concluded that the set goal has been reached.


Conserving hay at moisture concentrations 200 g kg 1 is known to cause spontaneous heating and negative effects on forage nutritive value. While these relationships have been evaluated extensively for alfalfa (Medicago sativa L.), less research has evaluated these factors in warm-season grasses, specifically bermudagrass [Cynodon dactylon (L.) Pers.]. In this study, Greenfield' bermudagrass was grown on a Pickwick silt loam soil (fine-silty, mixed, semiactive, thermic Typic Paleudult) and packaged in conventional rectangular bales at five concentrations of moisture (178, 208, 248, 287, and 325 g kg ') and at high and medium bale densities (overall means = 208 and 186 kg m 3 , respectively). Bale density had little effect on forage nutritive value after storage. Furthermore, hale density had no effect (P > 0.05) on indices of spontaneous heating (heating degree days 35°C, maximum temperature, and 30-d average temperature), visual evalualion of mold, and dry matter (DM) recovery. Positive linear relationships occurred between concentrations of fibrous forage components and indices of spontaneous heating; coefficients of determination (r 2 ) statistics were similar for each index of spontaneous heating that was used as the independent variable in these linear regressions. Concentrations of acid detergent insoluble N and neutral detergent insoluble N expressed on a DM basis were positively related to measures of spontaneous heating in close linear relationships (r 2 ≥ 0.80). Regressions of other N fractions on measures of spontaneous heating exhibited lower coefficients of determination, but generally had significant slopes. Results of this study indicate that N in bermudagrass is very susceptible to reductions in bioavailability through heat damage during bale storage, and that this damage is increased with increases in initial bale moisture.


—The goal of online active learning is to learn predictive models from a sequence of unlabeled data given limited label query budget. Unlike conventional online learning tasks, online active learning is considerably more challenging because of two reasons. Firstly, it is difficult to design an effective query strategy to decide when is appropriate to query the label of an incoming instance given limited query budget. Secondly, it is also challenging to decide how to update the predictive models effectively whenever the true label of an instance is queried. Most existing approaches for online active learning are often based on a family of first-order online learning algorithms, which are simple and efficient but fall short in the slow convergence and sub-optimal solution in exploiting the labeled training data. To solve these issues, this paper presents a novel framework of Second-order Online Active Learning (SOAL) by fully exploiting both the first-order and second-order information. The proposed algorithms are able to achieve effective online learning efficacy, maximize the predictive accuracy and minimize the labeling cost. To make SOAL more practical for real-world applications, especially for class-imbalanced online classification tasks (e.g., malicious web detection), we extend the SOAL framework by proposing the Cost-sensitive Second-order Online Active Learning algorithm named "SOAL CS ", which is devised by maximizing the sum of weighted sensitivity and specificity or minimizing the cost of weighted mistakes of different classes. We conducted both theoretical analysis and empirical studies, including an extensive set of experiments on a variety of large-scale real-world datasets, in which the promising empirical results validate the efficacy and scalability of the proposed algorithms towards large-scale online learning tasks.


Sexual assault is a pervasive form of violence associated with many detrimental physical, mental, emotional health outcomes as well as having profound public health effects. Preventing sexual violence is a formidable task, and evaluating the work being carried out by sexual violence prevention programs also proves to be challenging. The focus of this thesis project was to partner with the Pittsburgh Action Against Rape (PAAR) to conduct an evaluation of how they implement the Community Readiness Assessment Model (CRAM) as part of their sexual violence prevention programming. What follows is a process evaluation of PAAR's implementation of the CRAM process, assessing how closely PAAR's implementation aligns with the original Level 1 activities of the CRAM logic model. Using an exit interview of my own design, I conducted follow-up interviews with the PAAR staff and community partners who were involved in the CRAM process. I held these interviews in person, recording the interviews with verbal consent from the participants. To analyze the results, I transcribed and coded the exit interviews, using a thematic analysis method to identify themes that emerged from the transcripts. After coding, transcribing, and performing the thematic analysis, the following themes were identified from the community partner interviews: the interview design was unfit for the community, the interview questions were confusing, and that the interviewees felt comfortable during the interview. Here are the themes that surfaced from the PAAR staff interviews: more preparation was needed for the interviews, the interview questions were challenging, and there were positive aspects of the interview process that should be retained. The proposed process evaluation is of great public health significance as it not only improves the CRAM process for PAAR, but also provides a community assessment process evaluation that rape crisis centers nationwide can model. After reviewing the literature, it is to my knowledge that this is the first process evaluation of a sexual violence readiness assessment.


Facts concerning the evaluation of the influence of E. coli M17 exometabolites and fructooligosaccharides (FOS) on the growth and antagonistic activity of lactobacilli are presented. As revealed by these facts, preparation "Aktoflor" accelerates the growth of lactobacillary cultures, increases the final yield of biomass and antagonistic activity. E. coli M17 exometabolites contained in "Aktoflor" have been shown to be more active in comparison with FOS. The character of their influence on lactobacilli is discussed and the conclusion is made that the restoration and maintenance of eubiosis is greatly determined by the pool of metabolites excreted by the bacteria.


We present photometric parameters of the galaxies in the direction of the galaxy cluster LCDCS-S001 and improved kinematic parameters from new spectroscopic observations. From GMOS multi-object spectroscopy, we have been able to confirm a new set of 10 cluster members, resulting in a total 22 objects from previous observations. With these data, a dispersion velocity of σ= 887 ± 249 km s−1, a virial radius R200= 0.98 ± 0.22 Mpc and a mass of M200= (5.4 ± 2.8) × 1014 M⊙ have been derived. From GMOS i′ and r′ images, we have extracted the individual sources and derived their magnitudes, relative positions and the bulge+disc brightness profile decomposition. We show that the cluster has an elongated morphology along the north–south direction, with ellipticity ɛ= 0.49 ± 0.14, well represented by a King model with a core radius RC= 283 ± 66 kpc, above the typical core radii of regular clusters. It shows at least one local overdensity, north-west from the cluster centre, very compact and with a very high central density. The i′ luminosity function of LCDCS-S001 has an almost flat faint-end, α=−1.16 ± 0.18. As for the constituent galaxies, we have found that a large fraction of the cluster galaxies are late-type systems. Extensive simulations were made in order to verify the validity of our conclusions. We discuss the implication of these results for the evolutionary status of LCDCS-S001 and conclude that this cluster is still dynamically young.


DESIGN OF DRY CASK STORAGE FOR SERPONG MULTI PURPOSE REACTOR SPENT NUCLEAR FUEL. The spent nuclear fuel (SNF) from Serpong Multipurpose Reactor, after 100 days storing in the reactor pond, is transferred to water pool interim storage for spent fuel (ISFSF). At present there are a remaining of 245 elements of SNF on the ISSF,198 element of which have been re-exported to the USA. The dry-cask storage allows the SNF, which has already been cooled in the ISSF, to lower its radiation exposure and heat decayat a very low level. Design of the dry cask storage for SNF has been done. Dual purpose of unventilated vertical dry cask was selected among other choices of metal cask, horizontal concrete modules, and modular vaults by taking into account of technical and economical advantages. The designed structure of cask consists of SNF rack canister, inner steel liner, concrete shielding of cask, and outer steel liner. To avoid bimetallic corrosion, the construction material for canister and inner steel liner follows the same material construction of fuel cladding, i.e. the alloy of AlMg2. The construction material of outer steel liner is copper to facilitate the heat transfer from the cask to the atmosphere. The total decay heat is transferred from SNF elements bundle to the atmosphere by a serial of heat transfer resistance for canister wall, inner steel liner, concrete shielding, and outer steel liner respectedly. The rack canister optimum capacity of 34 fuel elements was designed by geometric similarity method basedon SNF position arrangement of 7 x 6 triangular pitch array of fuel elements for prohibiting criticality by spontaneous neutron. The SNF elements are stored vertically on the rack canister.  The thickness of concrete wall shielding was calculated by trial and error to give air temperature of 30 o C and radiation dose on the wall surface of outer liner of 200 mrem/h. The SNF elements bundles originate from the existing racks of wet storage, i.e. rack canister no 3, 8 and 10. The value of I 0 from the rack no 3, 8 and 10 are 434.307; 446.344; and 442.375 mrem/h respectively. The total heat decay from rack canister no 3,8 and 10 are 179.640 ; 335.2; and 298.551 watts. The result of the trial and error calculation indicates that the rack canister no 3, 8 and 10 need the thickness of concrete shielding of 0.1912, 0.1954 and 0.1940 m respectively. Keywords: heat and radiation decay, spent fuel , storage cask.


Electrically conductive composites were made from short glass fibre (GF) and carbon black (CB) blended with high-density polyethylene (HDPE) using a single screw extruder. The Young's modulus, tensile and impact strengths were improved with the addition of GF, and the surface conductivity in the static dissipative range of 10-6 to 10-9 S was achieved at CB content as low as 1 wt%, significantly lower than that in the unreinforced CB/HDPE. Addition of a coupling agent (MAPE) improved bonding between fibres and the polymer matrix and increased the stiffness and fracture resistance.


Introduction: Lower respiratory tract infections (LRTIs) continue to be a major health problem in children. Increasingly "atypical" agents such as Chlamydophila pneumoniae are being recognized as a significant cause of LRTI. The current study evaluated serological and molecular methods in detection of LRTI due to C. pneumoniae in young children. Materials and Methods: Serum and nasopharyngeal aspirate (NPA) were collected from 53 treatment-naïve children (6 months–6 years) with LRTI. Immunoglobulin M (IgM) and IgG antibodies to C. pneumoniae were detected in serum by enzyme-linked immunosorbent assay (ELISA) and microimmunofluorescence (MIF) test. Nonnested polymerase chain reaction (PCR) to detect a 183-bp fragment of the 60-kDa outer membrane protein 2 of C. pneumoniae was performed on DNA extracted from the NPA samples. Results: Of the 53 children tested, 14 (26.4%) children were diagnosed to have acute C. pneumoniae infection according to CDC guidelines. When compared with IgM MIF (reference test), PCR and IgM ELISA showed a sensitivity of 36% and 71%, respectively, and a specificity of 100%. IgG antibodies were positive in an additional 8 cases, by both MIF and ELISA, suggesting "possible" reinfection. Conclusion: This study despite its drawbacks provides evidence that C. pneumoniae is a significant cause of LRTI in young children.


Subject
 Passive and active fund management.

 Significance
 Active investment, actively buying and selling assets to try and outperform the market, was already under fire because of poor performance, high fees and passive funds (tracking a specific index) performing well due to the surge in global equity markets. Exacerbating this, the decision on June 2 by Neil Woodford, one of the United Kingdom's best-known fund managers, to suspend withdrawals from his flagship Equity Income Fund is triggering a scandal in UK asset management.

 Impacts
 Passive funds performing well fuels asset price bubble fears as they tend to lead to more money being directed to larger firms and sectors.
 Exchange Traded Funds, popular passively run vehicles, have momentum, holding almost 5.5 trillion dollars, six times as much as in 2009.
 The dollar may rise as geopolitical uncertainty will drive 'safe haven' interest but doubts over US growth and policy will cap the trend.


OBJECTIVES
Neuroendocrine neoplasms (NENs) are an extremely heterogeneous medical entity, representing a diagnostic and therapeutic challenge. Chronic inflammation, as is the case with other malignancies, plays a crucial role in NEN carcinogenesis.

DESIGN
The complete blood count (CBC) is a reliable tool for monitoring patients with cancer. Quantifying the absolute count of neutrophils (N), lymphocytes (L), platelets (P), and the ratios that derive from these parameters (neutrophil-to-lymphocyte ratio - NLR, platelet-to-lymphocyte ratio - PLR, and inflammatory systemic index - SII calculated as N×P/L) proved their prognostic and predictive value in numerous malignancies.

MATERIALS AND METHODS
We aimed to investigate the utility of these hematological parameters in 31 patients with NENs of various locations. Our study included the comparative analysis of pre-treatment hematological markers in NEN patients versus 21 age and gender matched healthy individuals. Additionally, for 26 out of the 31 patients included we analyzed and compared the inflammatory markers before and after treatment initiation.

RESULTS
The results revealed a statistically significant higher median value of N, NLR, PLR and SII in the NENs group in comparison with the values obtained in the control group and higher values of N, NLR and SII in the pretreatment group. Furthermore, we observed a higher mean value of the post-treatment P in the pancreatic NENs as opposed to the values obtained for other tumor locations.

CONCLUSIONS
The current study emphasizes the importance of the evaluation of CBC in the NENs setting thus adding value to prognostic models that can be useful for risk stratification and medical decision-making.


The present solutions of well cementing are mostly designed by designers' experience and calculation which can not predict the engineering quality after application of the designs. Meanwhile some questions in the designs can not be solved before construction. On the basis of detailed evaluation of every influential factor according to construction and environmental conditions, this article provides cementing fuzzy neural network model by means of 2nsoftEditor neural network modeling tools, and the stable software systems with the combination of artificial neural network and fuzzy logic rules are expected to improve the credibility of cementing quality prediction. Construction practice shows that cementing quality prediction with application of fuzzy neural network system before cementing can greatly reduce the cementing costs and improve the cementing success ratio.


Abstract. Surface analytical methods are applied to examine the environmental status of seawaters. The present overview emphasizes advantages of combining surface analytical methods, applied to a hazardous situation in the Adriatic Sea, such as monitoring of the first aggregation phases of dissolved organic matter in order to potentially predict the massive mucilage formation and testing of oil spill cleanup. Such an approach, based on fast and direct characterization of organic matter and its high-resolution visualization, sets a continuous-scale description of organic matter from micro- to nanometre scales. Electrochemical method of chronoamperometry at the dropping mercury electrode meets the requirements for monitoring purposes due to the simple and fast analysis of a large number of natural seawater samples enabling simultaneous differentiation of organic constituents. In contrast, atomic force microscopy allows direct visualization of biotic and abiotic particles and provides an insight into structural organization of marine organic matter at micro- and nanometre scales. In the future, merging data at different spatial scales, taking into account experimental input on micrometre scale, observations on metre scale and modelling on kilometre scale, will be important for developing sophisticated technological platforms for knowledge transfer, reports and maps applicable for the marine environmental protection and management of the coastal area, especially for tourism, fishery and cruiser trafficking.


Background and Objectives:
Different studies carried out mainly in young
non-consuming children of alcoholics show an association of P300 abnormalities with
alcoholism and with the
T
aqI-
A1 allele. Since the relationship between P300 and the
T
aqI-
A1 allele has not been specifically studied in alcoholic patients, our objective was to
investigate whether the association exits in this population.
Methods:
Our sample consisted of 176 recently detoxified male alcohol-dependent
patients. These patients had been alcohol dependent from a mean age of 22.6 years and
consumed on average 164.63 (± 142.99) cm
3
of alcohol daily. P300 was studied using an
auditory paradigm.
T
aqI
-A polymorphism genotyping was performed. The association
between P300 and
T
aqI-
A, and correlation with age and alcohol consumption, was studied.
Results:
The
T
aqI-
A1 allele was found in 38.6% of our patients (n = 68). The latency and
amplitude of P300 were 361.64 milliseconds and 17.53 microvolts, respectively. P300 wave
latency in alcoholic patients was longer than the reference value obtained from a sample of
healthy men of the Event-Related Potentials Unit (p < 0.001). Alcoholic patients who carried
the
T
aqI
-A1 allele showed more prolonged P300 latency than non-carriers, and these in turn
more than the control subjects. P300 characteristics varied according to age, but an associa-
tion with amount of alcohol or number of years consuming was not found.
Conclusions:
There is a relationship between the
T
aqI
-A polymorphism and P300 wave
characteristics in alcoholic patients. Further investigations need to be carried out in non-
consuming alcoholic patients and in healthy control subjects to confirm this association and
to clarify the possible influence of the neurotoxic effects of alcohol on P300 physiology.


Balance dysfunction has been recognised as a key marker of concussion for many years. Whilst this measure has been exploited within concussion assessments, current balance procedures are expensive, and laboratory-constrained or inexpensive, but subjective. The present study focused on developing an objective, inexpensive tool to assess balance utilizing Virtual Reality (VR) to induce a perturbation and a Wii Balance Board (WBB) to measure the response. The first part of this thesis focused on constructing a VR-WBB system to determine its validity when assessing balance. Notably, piloting confined the VR component of the system was effective in inducing perturbation and further, the WBB could adequately quantify the response by obtaining sensitive centre of pressure (COP) data. The second prut of this thesis focused on refining this prototype, assessing how an individual's balance would be affected by speed-manipulated and axismanipulated perturbations. Current studies highlighted that manipulating axes and speed of perturbation significantly affected the COP response, which has profound implications when developing the optimal VR-WBB tool. Overall this thesis confirms that the VR- WBB prototype is an effective system to induce a perturbation and obtain quantifiable balance responses. With further parameter refinement, this tool could be revolutionary for pitchside assessment of concussion.


This paper describes the research status of the warm stamping at home and abroad. The status of aluminum alloy and magnesium alloy is introduced in warm stamping respectively, using the tensile test, the drawing test, and bending experiments to prove the temperature and other factors have effect on the formability of materials. It also presents the status that using warm forming to solve the spring-back problem of the high strength steels. In addition, the mold and lubrication are also the key problems in warm stamping; they have a corresponding development with the development of warm forming though there are a few scholars specializing in the content.


Two aspects of the hydrological change in Tokyo are analyzed in this paper. The first is the changes in river courses, canals and open aqueducts from ca. 1890 to ca. 1985. The position of surface waters were traced from the topographical maps. Average stream density in the 23 special wards area except for three wards in the eastern lowland was 1.4 km-1 during a period from 1890 to 1910, while it reduced to 0.49 km -1 in 1985. In several wards, the density reduced to less than 10 % during this 100 years. The diminution of small rivers and canals began as early as 1920's, and many of them disappeared by 1985.The reduction of surface waters is closely related to the diffusion of municipal water supply and sewerage system, therefore, the water balance caused by the man-induced water transport was estimated for the recent about 40 years. The water balance was calculated for each ward and city for each 10 years interval. Data were taken from several kinds of statistics on waterworks and "Statistic Yearbook of Tokyo". The total water supply includes the municipal water and the industrial water. The annual amount of total supply expressed by water depth (height) was about 6 m during 1960's and 1970's in the central district of Tokyo, that is, about four times of the annual rainfall in Tokyo. The depth of total water supply exceeded the annual rainfall in all the 23 special wards in 1970's. The consumption and supply of water have been reduced since 1980's according to the establishment of recycling system. Because of the high supply rate, the depth of seepage from underground pipes of the waterworks amounted to 1 my-1 in 1975 in the central wards.The first sewerage system was established in 1920's, but the coverage for all the areas in Tokyo was not completed until the recent. Therefore, more than 1 my -1 of the untreated water had been discharged from several wards before 1980 causing the high pollution of rivers. Historical changes in surface waters and their pollution can be explained in connection with the changes in man-induced water balance. It must be emphasized, that the artificial water transport is a crucial element in understanding the urban hydrology.


Three-dimensional (3-D) video has only recently become a buzzword. It offers a high quality and immersive multimedia experience on consumer electronic platforms. The year 2009 was a seminal year for 3-D video with the first successful
film Avatar illustrated its use to a wide audience. As a result of advances in capturing, signal processing, transmission, and display technologies, both industry
and academia are now focused on delivering 3-D media to home systems and to mobile devices. Wireless transmission of 3-D video content is expected to be the next big revolution in consumer multimedia applications. It faces many challenges in the processing chain from capture to display. Because of these challenges, this thesis investigates and presents a number of novel techniques for error resilience 3-D video transmission.
Four error resilience techniques for 3-D video transmission over wireless networks were proposed. The recent H.264/AVC standard and the video-plus-depth 3-D video format were adopted to assist in implementing these techniques. The pro-
posed methods could also be applied to other video coding standards and to different 3-D video formats.
This thesis begins by investigating the standard error resilience source coding of H.246/AVC I-frame and of JPLW for still image transmission. Standard error resilience techniques are reviewed and compared. The experimental results show that H.264/AVC is much more robust in reducing transmission errors than JPWL. The second part of the thesis proposes a new hierarchical 16-Quadrature amplitude modulation (QAM) based unequal error protection (UEP) scheme for 3-D video with depth image based rendering (DIBR). The video-plus-depth format is partitioned into two sequences, i.e., a colour sequence and a depth sequence,
according to their respective importance to the overall quality of the 3-D video. In this approach, the highly important colour sequence is better protected with the
most significant bits (MSBs) of 16-QAM, while the less important depth sequence uses the less significant bits (LSBs). The third part of the thesis investigates the use of cooperative diversity to enhance the performance of high data rate communication over wireless fading channels. Although cooperative diversity has received much research attention recently, it has not yet been investigated in the context of unique characteristics of 3-D video transmission. In this part, the performance of a cooperative 3-D video system, with amplify-and-forward (AF) relaying, for UEP 3-D video transmission through best relay selection is investigated. In particular, closed-form
expressions for outage probability and bit error probability (BEP) were developed. The results of the BEP, outage probability, and peak signal-to-noise ratio (PSNR) were presented to demonstrate the proposed UEP scheme in terms of the received quality of 3-D video.
Finally, for more effi�cient 3-D video transmission, relay selection and hierarchical quadrature amplitude modulation (HQAM) were joined because they help address the problems of diversity and robustness. This part is concerned with the use of hybrid relay networks and HQAM for improved UEP transmission of colour-plus-depth 3-D representation. Hybrid relay selection along with HQAM was proposed as a method to overcome the decreases in video quality of high SNR values when HQAM was used alone. It has the advantages of both techniques at different SNR regions. Analytical expressions of the BER and outage probability of the SNR
were given in closed-form. The proposed techniques offer the opportunity for significant improvements over the existing techniques for 3-D video transmission. It is expected that these methods will �find wide applications in future 3-D video systems and wireless networks such as 4G networks.


Synthesis of a series of novel iminophosphorane derivatives of piperazine was accomplished through Staudinger reaction in high yields (70-80%). In the first step, 1-(4-fluorophenyl) piperazine (1) and 1-(2-pyrimidyl) piperazine (6) were reacted with chlorodiphenylphosphine (2) in the presence of triethylamine (TEA) in dry THF at low temperature under N2 atmosphere to form the compounds (3) and (8). These on further reaction with a series of alkyl azides (4a-k) gave the corresponding iminophosphorane derivatives (5a-k). Their chemical structures were established by IR, 1H, 13C, 31P-NMR, mass spectral studies and elemental analyses. All the titled compounds (5a-k) showed promising anti-microbial activity.


Though northern peatlands cover only 3 % of the land surface they count as one of the largest terrestrial organic C pools. This huge C pool is threatened by increasing temperatures, related microbial degradation and indirect effects of climate change leading to vascular plant dominance over sphagnum mosses and a shift from graminoids to shrubs. Effects of these changes in vegetation on peat degradation are unknown. Dissolved organic matter (DOM) as an important component of the C cycle in peatlands might be used as a sensitive indicator of enhanced peat degradation. Furthermore, peatlands are the major source of DOM in many surface waters and understanding the mechanisms of peat degradation will help to elucidate the reasons for the ongoing trends of increasing concentrations of dissolved organic carbon (DOC) in surface waters. In this study we aimed to determine effects of temperature and plant functional types (PFT: graminoids, shrubs) on amounts and composition of DOM allowing conclusions about ongoing changes in peat degradation. We selected two ombrotrophic peatlands in the Italian Alps, reflecting a temperature gradient where we manipulated the vascular plant cover by selective clipping. On the established plant functional type plots we collected DOM directly after plant removal and during the following seasons over a period of one year. Besides DOC concentrations we determined DOM composition by C-13 of DOC and UV and fluorescence spectroscopy. The short term response (2-24h) of DOM to the plant clipping enabled us to estimate the C input of vascular plants via roots. The medium to long term data showed a clear relation of DOM to the temperature gradient and the PFT. All in all our results indicated a substantial contribution of the roots from vascular plants to DOM in peatlands. The release of DOM from peat clearly increased with temperature and vascular plant biomass. The difference between graminoids and shrubs seems to be marginal. We conclude that higher temperatures and greater vascular plant biomass result in increasing peat degradation as one likely reason for increasing DOC concentrations in many surface waters across Europe and North America.


Twenty-first century teacher educators need to design learning experiences integrating technology for transformative learning. Bringing together the power of deep content knowledge, pedagogical knowledge and technological knowledge in an integrated manner is critical in the design of today's learning experience. The TPACK framework assists educators to gain competency and confidence to design technology-enhanced learning in ways that transform the learning experience for both students and teachers. This paper describes the TPACK findings of secondary pre-service teachers who have just completed their second professional experience placement in conjunction with a curriculum and pedagogy course. Pre-service teachers reported that they were developing the necessary confidence in working with the technology and designing learning using a TPACK framework. From the data, it was apparent that teacher educators are able use the framework to design, model and explore innovative teaching with technology to design TPACK learning experiences that are mindful and thoughtful


In the past 50 years a relevant increase in the inclusion of word-formation data in Italian dictionaries has taken place. This development has proved very important to Italian users: in other words it has increased their linguistic awareness. Dictionary users are convinced to investigate WF mechanisms. What looking-up strategies are necessary in order to achieve this goal? This paper analyzes the development of the treatment of word-formation issues in Italian monolingual dictionaries published since the mid-1960s. A short profile of the dictionaries analysed will introduce the topic. The paper aims to find the different selections of affixes and components listed as headwords in the dictionaries analysed and the selections of items included in each entry (neologisms or 'traditional' words), in order to compare the different lexicographical techniques used.


OBJECTIVE
To estimate total cost of atrial fibrillation (AF) management concerning acute coronary syndrome, heart failure, stroke and drug related adverse events with respect to clinical practice and available guidelines.

METHODS
This cost analysis study was based on identification of total costs related to management of acute coronary syndrome, heart failure, stroke and the drug related adverse events in patients with AF based on standardized questionnaire forms filled by experts according to their daily clinical practice and also to ACCF/AHA/ESC guidelines. Total cost included cost items related to treatment, healthcare resources utilization, and diagnostic test and consultations.

RESULTS
The yearly cost of acute coronary syndrome per patient was 5.478.43 TL according to expert's view reflecting real clinical practice whereas it was 11.319.44 TL when calculation was based on recommendations in the guidelines. The average total cost of heart failure was 4.523.74 TL according to expert's view whereas it was 2.925.86 TL based on guidelines. The average total cost of stroke was 5.719.25 TL according to expert's view but 7.931.18 TL based on guidelines. Among drug related adverse events, only those related to cardiac adverse events were estimated to be higher according to expert view as compared to guideline recommendations (288.65 vs. 150.99 TL).

CONCLUSIONS
Reflecting the treatment algorithms in the management of AF and related adverse events, our findings seem to emphasize the extra burden on health economics posed by patients suffering from the uncontrolled disease.


Sixty-four climbers participated in a randomized clinical trial of acetazolamide prophylaxis for acute mountain sickness (AMS) during rapid, active ascent of MT Rainier. Twenty-nine (93.6%) of 31 climbers receiving acetazolamide and 25 (75.8%) of 33 receiving placebo attained the summit. Time spent ascending from sea level to the summit (4,394 m) averaged 33.5 hours (range, 23 to 48 hours). On the summit AMS was less common in climbers receiving acetazolamide, and they experienced less headache, nausea, drowsiness, shortness of breath, and dizziness and a greater sense of satisfaction and psychological well-being. Minute ventilation on the summit was significantly greater in subjects taking acetazolamide (24.9 +/- 2.0 L/min compared with 16.9 +/- 3.8 L/min). Expired vital capacity was also greater on the summit in the acetazolamide group (6.9 +/- 0.4 L compared with 5.8 +/- 0.4 L). We conclude that acetazolamide is effective in the prophylaxis of AMS for climbers attempting rapid, active ascent. Increased ventilation at altitude, producing an increased alveolar oxygen tension, may be related to the observed amelioration of symptoms.


Our purpose is to provide end-users with a means to query ontology based knowledge bases using natural language queries and thus hide the complexity of formulating a query expressed in a graph query language such as SPARQL. The main originality of our approach lies in the use of query patterns. In this article we justify the postulate supporting our work which claims that queries issued by real life end-users are variations of a few typical query families. We also explain how our approach is designed to be adaptable to different user languages. Evaluations on the QALD-3 data set have shown the relevancy of the approach.


ABSTRACT Aim: A is an irreversible ErbB family blocker that has shown promising clinical activity in pts with SCC of the head/neck and lung. Here, we report results of LL8, a phase III trial that prospectively compared A and E in pts with SCC of the lung following failure of first-line chemotherapy. Methods: Eligible pts with stage IIIB/IV SCC were randomized 1:1 to receive A (40 mg/day; 50 mg/day from Cycle 2 for pts meeting AE criteria) or E (150 mg/day) until disease progression. All pts had progressed after ≥4 cycles of platinum-based doublet chemotherapy and had not received prior EGFR TKIs. Pts were stratified based on race (eastern Asian vs other). The trial was powered for PFS and OS. The primary endpoint was PFS (RECIST 1.1) as assessed by independent radiological review (IRR). Secondary endpoints included overall survival (OS; planned at 632 events), objective response rate (ORR), disease control rate (DCR) and safety. Overall 795 pts were recruited between March 2012 and January 2014. Planned primary analysis was based on 414 PFS events by IRR in the first 669 patients randomized (A: 335, E: 334) while recruitment was ongoing. Results: Baseline characteristics were well balanced between arms: median age 65y; male 85%; eastern Asian 22%; never smoker 5%. Median PFS was significantly higher for A than E, both by IRR (2.4 vs 1.9 months; HR [95% CI]: 0.82 [0.68–1.00]; p = 0.043) and investigator review (2.7 vs 1.9 months; HR [95% CI]: 0.78 [0.65–0.93]; p = 0.005). Furthermore, ORR (4.8% vs 3.0%; p = 0.233) and DCR (45.7% vs 36.8%; p = 0.020) were higher with A vs E. Overall AE profile was comparable (pts with ≥G3 AEs: 50.2 and 49.1% for A and E) with higher incidence of drug-related ≥G3 diarrhoea (9.7 vs 2.4%) and G3 stomatitis (3.3 vs 0.0%) with A and higher incidence of G3 rash/acne with E (5.5 vs 9.0%). Conclusions: LL8 is the largest prospective trial to compare EGFR TKIs in pts with relapsed/refractory SCC. PFS and DCR were significantly better for A than E. AEs were comparable and consistent with the mechanistic profile of EGFR inhibition. Disclosure: G. Goss: Advisory board for Boehringer Ingelheim prior to initiation of study; E. Felip: Advisory Boards for: Boehringer Ingelheim, Novartis, Roche and Bristol Myers Squibb; S. Lu: Advisory Boards for: AstraZeneca and Boehringer Ingelheim; K.N. Syrigos: Advisory boards for Roche, Novartis and Leo; A. Morabito: Advisory Boards for: Lilly and Italfarmaco; A. Ardizzoni: Advisory Boards for: Boehringer Ingelheim, MSD, BMS, Lilly, GSK, Daiichi, Pierre Fabre, Pfizer; S. Gadgeel: Advisory Boards for: BI, Novartis and Genentech; J. Love: Employee of Boehringer Ingelheim; V. Chand: Employee of Boehringer Inhelheim J. Soria: Advisory Boards for: Boehringer Inhelheim. All other authors have declared no conflicts of interest.


BIRD LEGEND AND LIFE. By Margaret Coulson Walker. New York: The Baker-Taylor Company. Cloth. (6x9.) Price, 'l.2ll, net. Margaret Coulson Walker won a permanent, place among bird lovers throngh "Birds andTllelr''NestIDg,'· and this dellghttul book wtllbut Intenslfy thelr,appreetatlon. Tbe tI1lrty-flve illustrations are all tulI-pap Photograp!Ja neatly !DBerte4." The real' chUm' of:the book. bowever. Is In, the critical and . Uterary,' avian legends and superstJtIon of birds. Birds exercl8ed tt strong Influence on preblstllrtc re1fg!on, baymgj 1IeeD~ worshiped aa gods In. tbelong Biro, and·Jater·..·'U~ representatives ot the higher powers, tb4lG~.''IOJq''.' BO tar aatoattrlOOtethe origin of the woi'ld'ltIe1ttotbe ' egg ot 8Omemysterlous bird. The;Aztee8:beIleY~9tllat all good people 118.a reward otmerlt ''IVel'em,etainOl'o phOBed at the close ot lite Into .fe8tbered eoupterB,fand as ncb were privUeged to ~ their time In'tie'1lea'DtI" tu1 groves· of l'aradlse•. To.•the.Nortb'YAmertl!all'IIldIanB tbunc1erwas the clOUd.blrd f1applng'hls mighty: wings. wbUe tbe UgbtnlDgwaa tbeflaBbot bill eye. ,In all lande birds .had prophetic power. bavIDg beeJi:tw1ce' born, once as an egg andtben·as the bIrd.TIIe 70Wt;" the raven. and the woodpecker were the chief b~'ot portent... and. as ncb receive especial attention In tIIese fascinating pages.' -"


Organophosphates are a known danger to human health with an array of biochemical targets and complex toxic effects. Phenyl saligenin phosphate (PSP) is an organophosphate and related phenoxy substituted organophosphates irreversibly bind to a variety of important enzymes causing the condition known as organophosphate induced delayed neuropathy (OPIDN). These compounds also potentially cause cardiac muscle damage but little is known about how this class of compounds effect cardiomyocytes. The identification of proteins targeted by these toxins is of interest.

This study investigates the synthesis and application of novel fluorescently labelled organophosphates to investigate organophosphate interaction with H9c2 cardiomyoblasts. The synthesis of probes with BODIPY, pyrene and rhodamine fluorescent component is explored with success in preparation of pyrene and rhodamine probes. The fluorescent behaviour of three rhodamine labelled phenyl saligenin phosphates probes with alkyl and PEG linkers is examined and the cytotoxicity of the probes assessed by monitoring MTT reduction, and LDH release from exposed H9c2 cardiomyoblasts. All three analogues showed cytotoxicity (4 h exposure; 100 μM). These probes were found to bind to proteins within mitochondria and spots from 2D-gel electrophoresis experiments, visualised at 532 nm, which are undergoing MS analysis.

This project also describes progress towards a photoreactive-fluorescent probe to identify the site of action of the potassium channel opener, diazoxide, which activates cardioprotective pathways. The drug is believed to target mitochondrial KATP channels, but the protein structure of these channels has yet to be elucidated. The fluorescence labelling of whole cardiac cells with a dansyl fluorescent -benzophnone-photoreactoive diazoxide probe has been demonstrated and the progress toward a rhodamine fluorescent analogue is presented.


Introduction: Knowledge of patient priorities is important to select appropriate treatment. Discrete choice experiment (DCE) methodology involves making trade-offs which indicate patients' preferences. Aim: To determine the relative importance to participants in the PRACTICAL study, a 12-month open-label RCT of symptom-driven budesonide-formoterol versus regular budesonide plus as-needed terbutaline, of attributes distinguishing these regimens. Methods: Regimen attributes were identified using focus groups. Participants finishing the PRACTICAL study after 26 March 2018 at 6/14 sites completed one of two DCEs based on their stated preference for as-needed combined preventer/reliever therapy or regular preventer and as needed reliever. 1000minds software and the PAPRIKA method were used for the DCEs. Results: The DCEs were completed by 296 of 407 (73%) eligible participants. Figure 1 shows preference weights representing the relative importance of the attributes in the DCEs. Frequency of breathlessness had a stronger influence on choice than risk of flare up, type of regimen or steroid dose. Within each DCE, attribute weights were not affected by the patient's randomisation group. Conclusions: In these DCEs, participant's preferences were influenced by several attributes in addition to as-needed versus regular treatment. The relative importance of such attributes should be considered during shared decision-making with patients.


Nowadays human-created systems are increasing in complexity due to the interaction of humans and technology. Especially road traffic systems are composed of multitudinous resources (e.g. personnel, vehicles, organizations, etc.), which make it even harder to anticipate the positive and negative effects on safety. One key in achieving a significant reduction of fatalities is seen in driver assistant systems counterbalancing the lack of drivers' capabilities. But the actual outcome of implementing these sophisticated technologies especially on influencing driver's capabilities are yet unknown. Latest research exemplifies an increase of reaction times of drivers in case of dysfunctional driver assistant systems. This research paper applies STAMP/STPA (STAMP = systems-theoretic accident model and processes; STPA = systems-theoretic process analysis) to the German automobile traffic system focusing on the effects of driver assistant systems on drivers. By doing so, the potential hazards caused by technology can be identified. (A) Paper to the session "Aspects of Driver Assistant Systems" of the 5th International Conference on ESAR "Expert Symposium on Accident Research", 7th to 8th September 2012 in Hannover.


The United States antitrust approach to intellectual property has evolved over time. The same antitrust analysis now applies to conduct involving IP as to conduct involving other forms of property, taking into account the specific characteristics of the particular property right.

However, there have been significant calls recently for presumptions that infringements suits and licensing conduct by patent assertion entities (PAEs) labeled "patent trolls" and holders of standard essential patents (SEPs) are monopolization or attempts to monopolize that violate Sherman Act §2, 15 U.S.C. §2. This paper argues that the basic principles of keeping in mind history and context, and general antitrust principles, apply equally to SEPs and PAEs as to other economic phenomena, and there is no need for any special presumptions.


A lack of competence in crisis management has been shown to be a causal factor in a number of recent maritime accidents. In safety critical industries other than commercial shipping, such as civil aviation, nuclear and petrochemical, research is being undertaken to identify behavioural markers that can be used to assess competence in crisis management. Although there is now a general acceptance of the core concepts for the non-technical or resource management skills required for competence in crisis management, there is also an acceptance that the behaviours associated with these skills are context specific. This research programme improves the understanding of how a behavioural marker system can be used to assess the competence in crisis management of merchant marine engineering officers within the context of a merchant vessel engine control room.

This research reviews the current practice in using behavioural markers for the assessment of competence in crisis management within safety critical industries and the military. The differences between the assessment frameworks and environments in which behavioural markers are currently being used for this assessment of competence are discussed. The influences of these differences on the use of behavioural markers for the assessment of competence in crisis management within the context of a merchant vessel engine room control room are investigated.

Through the use of ethnographic study, the research presents a set of behavioural markers that can be used to assess competence in crisis management within the context of a simulated merchant vessel's engine room control room. The research concludes that these behavioural markers can be used as a valid objective assessment framework for the assessment of ocompetence in crisis management of merchant navy engineering officers.


A shift in practice towards a process-orientated and collaborative art practice within the strands of art practice in the public realm raises the question, what is the practical contribution artists make to society' which can only be answered by first understanding how artists work. Introducing the concepts of ˜context, ˜artist-led and ˜residency with reference to the Artists Placement Group, the problematics of assessing the social contribution of context-specific art practices are presented as resting upon two difficulties, the conceptual gulf between the artworld and the public realm and the assumption that artists can or should not articulate their intentions for an artwork. Combining questions raised from practice with the problems outlined by Suzanne Lacy, the need for research into the generative process of public artists is established. The purpose of the research is to investigate and develop artists understanding of the generative process by examining the interaction of artists in contexts in the public realm and to make that information explicit. An appropriate methodology and theoretical framework is found by critically reviewing recent related practice-based research projects in Art and Design with special attention to the work of Ian Hunter on immersion strategies in rural contexts. The model of the artistic process as problem-solving, developed by J. Getzels and M. Csikszentmihalyi , is also examined against current theories in scientific research into creativity and theories of social policy problem-setting of Donald Schon and the pattern of inquiry by John Dewey and subsequently extended. Data was generated by recording the decisions and reflections of three artists carrying out an actual artist-led context-specific project in the public realm (˜Taming Goliath). Data gathered by using a specially adapted method (˜Sweatbox) were analysed by using the Generative Process Model. The results produced narratives which describe each artists experience and information on the methods artists use to interact with a context in the public realm, their intentions. The significance of the findings and the experience are discussed in relation to the work of Suzanne Lacy and Allan Kaprow with recommendations for further research. In conclusion, four areas contributing to knowledge are proposed: the extension of the Generative Process Model, the development of an methodology of analysis, the usage of the Sweatbox method and contributions to the body of knowledge of artists processes in the public realm.


We characterized the bone disease of transilial biopsy specimens from children with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) and genetically related asymptomatic hypercalciuric subjects. All HHRH patients showed irregular mineralization fronts, markedly elevated osteoid surface and seam width, increased number of osteoid lamellae, and prolonged mineralization lag time. These findings are consistent with a mineralization defect and indicate unambiguously that the bone disease in HHRH is osteomalacia. The only abnormality seen in the asymptomatic hypercalciuric subjects was slightly extended osteoid surface. Parametric and nonparametric statistical analyses performed on a pooled sample of HHRH patients and asymptomatic hypercalciuric subjects revealed a very high inverse correlation and a tight linear relationship between serum phosphorus and osteoid parameters. Serum 1,25-dihydroxyvitamin D, which is low in other forms of hereditary hypophosphatemia and osteomalacia, is elevated in HHRH and correlated positively with osteoid parameters and the mineralization lag time. Serum alkaline phosphatase showed similar relationships. These results as well as the clinical, biochemical, and radiological remission of bone disease consequent to phosphate therapy strongly suggest that in HHRH 1) hypophosphatemia alone is sufficient to cause osteomalacia; and 2) the elevation of 1,25-dihydroxyvitamin D reflects the degree of the primary renal phosphate leak, but is not involved in the pathogenesis of the bone disease.


INTRODUCTION Recent litigation brought against cigarette manufacturers,(1) software companies over potential year 2000 computer problems,(2) and a fast food restaurant for serving coffee that was allegedly too hot(3) reminds us of the importance and dynamic nature of tort law in the United States. Judging from ongoing coverage by newspapers and television, tort law is newsworthy. Yet, as with other legal issues, it is within the covers of law reviews and specialty journals in economics that much of the debate over the social utility of various tort rules and their reform takes place. In that debate law and economics exercises great influence. "Ever since the 1970s, the modern movement in economic analysis has been in full swing. That analysis has highlighted the deterrence function of tort law. Indeed, even in the works of mainstream scholars, deterrence has now assumed the role of a primary rationale for tort liability rules."(4) One example of this influence is the impact of economic analysis of tort law on the revision of the Restatement of Torts (Second) sections on products liability.(5) In spite of the significance of tort law and the economic analysis of it, the general public, practicing attorneys, and legislators often know little about the findings and informed opinions of those scholars specializing in law and economics. The purpose of this Article is neither to review contemporary issues surrounding tort law(6) nor to gauge the extent of the influence of specialists in law and economics; our purpose is to address whether a consensus exists among these scholars about a few fundamental doctrines of tort law. Because efficiency is a major concern in the field of law and economics, each proposition raises an issue of efficiency about a tort rule. We thus framed ten propositions about how efficiently tort rules achieve their purposes. In the following section we present our results as a whole. Next we discuss the results individually, offering brief resumes of the debates that inspired the particular questions. Finally, we offer some general conclusions based on the results taken together. DISCUSSION As part of a larger survey conducted during the summer of 1996,(7) we sent questionnaires to members of the American Law and Economics Association (ALEA).(8) We received useable responses to 16.2% of the 389 surveys we mailed out. Respondents were asked to classify themselves as legal scholars (on the basis of their having a law degree), as economists (on the basis of their having a Ph.D. in economics), or as both (on the basis of their having a law degree and a Ph.D. in economics). Next they were asked to note whether they agreed with each of ten propositions about tort law, using a five point scale in which i equals "strongly disagree" and 5 equals "strongly agree."(9) The percentage of those surveyed who responded to each proposition and the total distribution of responses for each proposition are reported. In addition, we calculated the average numerical scores for each of the three groups of scholars: legal scholars (Law), economists (Econ), and those with training in both (Law/Econ), for each proposition. We estimated t-statistics for each statement, to test for statistically significant differences in the mean scores of the three groups, and chi-square tests, to determine if there are statistically significant differences in the distribution of responses for each proposition within each group.(10) The results are presented in the Table. TABLE Responses(12) 1. No fault automobile insurance is efficient. Strongly Disagree 21% 32% 20% 23% 4% Strongly Agree Percent Responding: 89% Average: 2.55 Law(13): 2.51 Econ(14): 2.67 Law/Econ(15): 2.40 2. Contributory negligence is more efficient at producing optimal behavior than comparative negligence. Strongly Disagree 7% 32% 37% 19% 6% Strongly Agree Percent Responding: 86% Average: 2. …


Herbomineral formulations have been used worldwide against various chronic and degenerative diseases due to its fewer side effects. A new proprietary herbomineral formulation was formulated consisted of an ashwagandha root extract and minerals (zinc, magnesium, and selenium). The present study was aimed to evaluate the impact of the Biofield Energy Treated herbomineral formulation in male Sprague Dawley (SD) rats for immune biomarkers modulation. The test formulation was divided into two parts. One part was denoted as the control without any Biofield Energy Treatment, while the other part was defined as the Biofield Energy Treated sample, which received the Biofield Energy Healing Treatment remotely from twenty renowned Biofield Energy Healers. Biomarkers like immunoglobulins (IgG, IgM), cluster differentiation (CD4+), CD8+, superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO) were monitored. The level of IgM was increased by 4.76% in the Biofield Energy Treated test formulation (G4) compared to the disease control group (G2). The levels of CD4+ and CD8+counts were significantly (p≤0.01) increased by 222.22% and 355.36% in the G4 group compared to the G2 group. The level of lymphocyte was increased by 5% and eosinophil count was significantly decreased by 75% in the G4 group compared to the G2 group. The lipid biomarkers such as total cholesterol (TC), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) were significantly lowered by 9.70%, 6.67%, and 23.54%, respectively in the G4 group compared to the G2 group. The expression of SOD was reduced by 9.96% in the G4 group compared to the G2 group. Further, LPO expression was significantly reduced by 33.38% and 16.88% in the G4 and untreated test formulation (G5) groups, respectively compared to the G2 group. Therefore, it can be concluded that the Biofield Energy Treated test formulation showed significantly improved the cellular and humoral immunity, hematological and biochemical profile compared with the untreated test formulation. As a result, it can be established that The Trivedi Effect®-Biofield Energy Healing has the significant capacity for immunomodulatory effect, which may also be useful in organ transplants, anti-aging, and stress management by improving overall health and quality of life.


With the demand for the high performance, the vehicle handling stability is more and more attractive and becomes one main service performance of modern car. At the same time, traditional calculation method can not meet the requirement of modern automobile research on the analysis of varied performances. The virtual simulation software increases greatly and it is possible to do the vehicle simulation trial. In this paper, a vehicle model of 10-DOF is built by using the dynamics simulation software ADAMS. Through the dynamic simulation test, the vehicle handling stability is studied with emphasis when the S.M. (Static Margin) is positive,zero or negative.The result is a reference in design of the vehicle, so the purpose of saving test funds and shortening design time is achieved.


: It is shown that preliminary taurine treatment prevents the disturbances of energy metabolism in the brain, heart and liver tissues of Wistar rats with acute hypoxic hypoxia. Administration of taurine restored to normal the parameters of adenine pool: the concentration of ATP increased within the cytoplasm, while that of ADP and AMP diminished; mitochondrial respiration proceeded more rapidly; the concentrations of pyruvate and malate decreased; isocitrate dehydrogenase activity, P/O and NAD/NADH ratios increased. Taurine treatment resulted in a decreased level of lipid peroxides in the rat tissues with hypoxia. The role of intracellular calcium content and biomembranes structure changes as the mechanisms of taurine action on energy metabolism and lipid peroxidation is discussed.


Borrelia persica (Bp) is the most prevalent species causing tick-borne relapsing fever (TBRF) in Central Asia and the Middle Eastern countries whilst B. burgdorferi sensu stricto (Bbss) is an endemic genospecies causing Lyme borreliosis (LB) in North America and Europe. TBRF patients commonly suffer from recurrent fever attacks due to spirochete proliferation and antibody-mediated killing of these organisms in the blood, whereas during the early stage of infection LB patients commonly show skin lesions (erythema migrans). If left untreated, LB patients may develop to a chronic phase with Lyme arthritis or other tissue lesion due to inflammatory responses (e.g., acrodermatitis chronica atrophicans). Despite a severe debate over the exact dissemination pathways employed by borrelia organisms, little is known how Bp and Bbss disseminate in the body of mammalian hosts. Hence, a murine model with a novel and precise infection approach was established to explore the dissemination route of host-adapted Bp and Bbss organisms post intradermal (ID) and intravenous (IV) inoculation in immunocompetent C3H/HeOuJ mice.
Since borreliae are able to express differentially outer surface proteins (Osps) in vitro and in vivo, it was necessary to generate the host-adapted bacteria from immunodeficient NOD-SCID mice. An ID inoculation of 1.0 x 10^5 culture-derived Bp organisms per animal resulted in the peak of spirochetemia with 8.8 x 10^6 cells per ml blood of NOD-SCID mouse. However, 1.0 x 10^6 and 1.0 x 10^8 cultured Bbss caused spirochetemia with a low load resulting in up to 4.9 x 10^4 and 7.2 x 10^4 organisms per ml blood, respectively. Interestingly, hematogenous Bp spirochetes were detectable by both qPCR and cultivation at least one day earlier when compared to Bbss. It seems that Bp is more efficient in entering the bloodstream and multiplying in the circulation of the immunodeficient mice than Bbss.
Compared to the ID injection the strict IV inoculation via the jugular vein in C3H/HeOuJ mice was the most critical step to clarify whether host-adapted Bp and Bbss organisms are capable of leaving the bloodstream for further colonization in mammalian tissues. After either ID or IV inoculation of 7.2 x 10^5 host-adapted Bp organisms, these spirochetes were detectable up to day 24 in C3H/HeOuJ mice. Bp counts reached up to 1.9 x 10^6 and 4.1 x 10^6 per ml blood sampled at day 12 post ID and IV challenge, respectively. Correspondingly, antibody detection with collected plasma and serum samples showed that specific antibodies to Bp were induced. Notably, all brain tissue samples from both ID and IV inoculated C3H/HeOuJ mice were positive for Bp when tested with molecular methods and cultivation. In contrast, neither the Bbss ospA gene nor viable spirochetes were found in the blood of any C3H/HeOuJ mouse inoculated either ID or IV with approx. 3 x 10^3 host-adapted Bbss spirochetes. Interestingly, on day 49/50 after ID injection, Bbss spirochetes were re-isolated from most tissue samples collected from the ears, skins (injection areal), tibiotarsal joints, urinary bladders, and hearts. Strong antibody responses against Bbss were detected in all ID inoculated animals. In contrast, after IV injection of host-derived Bbss organisms, neither borrelial DNA nor viable spirochetes were present in any tissue sample collected from these animals. In addition, they did not produce specific antibodies against Bbss.
In summary, 1) Bp is excellently capable of adapting to and surviving in the bloodstream. The spirochete disseminates predominantly via hematogenous route to distant organs (e.g., brain) to establish a persistent infection; 2) Bbss is a tissue-bound spirochete that migrates primarily via non-hematogenous routes. Intradermal deposition will cause a successful persistent infection while the blood vessel system is an impasse for this bacterium. The animal model applied in this study mimics the natural infection conditions of tick bite as closely as possible. Borreliae were used in an inoculum dose expected to be deposited by ticks in the skin of mammal hosts or in a development phase (host-adapted) they most likely express in blood. The detailed characterization of the spirochetes' dissemination pathways provides an advanced understanding of the pathogenicity mechanism of TBRF and LB species, and can help to improve diagnostic approaches or therapeutic strategies. Notably, blood transfusion of Bp may poses a high risk of infection to recipients whereas the risk to become infected with Bbss is nonexistent.


BACKGROUND
Array-based comparative genomic hybridization (aCGH) is a reference high-throughput technology for detecting large pathogenic or polymorphic copy-number variations in the human genome; however, a number of quantitative monogenic mutations, such as smaller heterozygous deletions or duplications, are usually missed in most disease genes when proper multiplex ligation-dependent probe assays are not performed.

METHODS
We developed the Motor Chip, a customized CGH array with exonic coverage of 245 genes involved in neuromuscular disorders (NMDs), as well as 180 candidate disease genes. We analyzed DNA samples from 26 patients with known deletions or duplications in NMDs, 11 patients with partial molecular diagnoses, and 19 patients with a clinical diagnosis alone.

RESULTS
The Motor Chip efficiently confirmed and refined the copy-number mutations in all of the characterized patients, even when only a single exon was involved. In noncharacterized or partially characterized patients, we found deletions in the SETX (senataxin), SGCG [sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein)], and LAMA2 (laminin, alpha 2) genes, as well as duplications involving LAMA2 and the DYSF [dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive)] locus.

CONCLUSIONS
The combination of exon-specific gene coverage and optimized platform and probe selection makes the Motor Chip a complementary tool for molecular diagnosis and gene investigation in neuromuscular diseases.