This paper demonstrates the influence of extreme wet winter weather on pore water pressures within clay fill railway embankments, using field monitoring data and numerical modelling. Piezometer readings taken across the London Underground Ltd network following the wet winter of 2000/2001 were examined, and showed occurrences of hydrostatic pore water pressure within embankments but also many readings below this. A correlation was found between the maximum pore water pressures and the permeability of the embankment foundation soil, with high permeability foundation soils (of Chalk or river terrace deposits) providing underdrainage and maintaining low pore water pressures within the overlying clay embankment fill. Numerical modelling of transient water flow in response to a climate boundary condition supports this conclusion and has been used to demonstrate the influence of clay fill and underlying foundation permeability on transient pore water pressures during extreme (c. 1 in 100 year) and intermediate (c. 1 in 10 year) wet winter rainfall. For clay founded embankments, extreme wet winter conditions increased pore water pressures significantly compared with an intermediate winter, while for embankments underlain by a permeable stratum pore water pressures were less sensitive to the extreme winter rainfall.


n a rapidly changing world, we need to know which areas warrant protection from current and forthcoming threats. This is hard to do objectively in the vast Southern Ocean. However, identifying where predators go also tells us where their prey can be found. If multiple predator species and their diverse prey are found in the same place, then this indicates an area of high ecological significance. We assembled Southern Ocean predator tracking data to produce a database of over 4000 individual animal tracks from 17 species. Statistical spatial models used these data to project the at-sea movements for all known colonies of each predator species across the entire Southern Ocean. These projections were combined across all species to provide an integrated map of those areas important to many different predators. These areas of ecological significance were scattered around the Antarctic continental shelf and in two oceanic regions, one extending from the Antarctic Peninsula into the Scotia Arc, and another surrounding the sub-Antarctic islands in the Southern Indian Ocean. Existing and proposed marine protected areas (MPAs) are mostly within these important habitats, suggesting they are currently in the right places. Yet, when using IPCC climate model projections to account for how areas of important habitat are likely to move by 2100, the same MPAs may not remain perfectly aligned with important predator habitats. Dynamic MPAs are therefore needed to ensure continued protection of Southern Ocean ecosystems and their resources in the face of growing demand by the current and future generations.


Background Food access is an important aspect of health promotion for the elderly. The aim of this study was to investigate the relationship between distance to the nearest food store and diet variety in rural community-dwelling elderly Japanese. Methods This cross-sectional study analyzed data from 1,103 elderly participants surveyed by mail in rural areas of Japan. Diversity of food intake was assessed using the diet variety score (DVS). Street network distance from home to food store was calculated and categorized by quartile using a geographic information system and analyzed in relation to diet using multivariable regression with the primary outcome as low DVS. Sub-analysis of the association with DVS was conducted for each food store category (convenience store, supermarket, and small food store). The association between intake frequency of each food group and distance was also analyzed. Results Participants in the fourth quartile of distance to food store had significantly higher prevalence ratio (1.15; 95% CI, 1.01–1.32) for low DVS than those in the first quartile. There was a significant tendency between greater distance to food store and lower DVS (P for trend = 0.033). Supermarkets and convenience stores, in particular, showed significant associations. Greater distance was significantly associated with lower frequency of meat and fruit intake. Conclusion There was significant association between distance to nearest food store and diet variety in rural Japanese elderly. These findings suggest the importance of interventions for areas at high risk of low diet variety, such as places far away from food stores.


Ultra high frequency (UHF) partial discharge sensors are widely used for condition monitoring and defect location in the insulation systems of high voltage equipment. Designing sensors for specific applications often requires an iterative process of manufacture, test, and mechanical modifications. This paper demonstrates the use of finite-difference time-domain (FDTD) simulation as a tool to predict the frequency response of a UHF sensor design. Using this approach, the design process can be simplified and parametric studies can be conducted in order to assess the influence of component dimensions and material properties on the sensor response. The modeling approach is validated using a broadband UHF sensor calibration system, which uses the step response of the sensor to determine its frequency-domain transfer function. The use of a transient excitation source is particularly suitable for modeling using FDTD, which is able to simulate the step response output voltage of the sensor, from which the frequency response is obtained using the same post-processing applied to the physical measurement. Comparisons between simulation and measurement are made for three different sensors, demonstrating sensitivity agreement to within about 10%. Some examples of simple parametric studies carried out using the FDTD model are also presented.


The beam extracted from cyclotron is of Gaussian distribution, but in many applications the uniformly distributed beam is needed. There are some methods to achieve uniform beam, but the uniformity is less than expected. This paper introduces the process of the wobbling magnet design which can get the high uniform beam. On the base of the design theory and the measurement to the wobbling magnet, we can confirm that there has high uniform beam on the target under the wobbling magnet effect. It is the first time to design and manufacture the wobbling magnet by ourselves in our country, and the measurement results show that the magnetic field in the wobbling magnet are satisfied the requirement of the storage wobbling magnet.


Academic literacy development within the secondary schooling system in South Africa has reached crisis proportions, with a large number of students exiting the system unable to function adequately within the tertiary sector or labour market. Attempts to remedy this crisis by introducing curriculum reform over the past few years have yielded little success, with universities having to take on the literacy problem by offering a variety of remedial programmes to ensure that students are equipped to access learning and succeed at their studies. Research shows that most literacy intervention programs at universities appear to favour a more traditional approach to English academic language development by focusing on grammatical rules, sentence structure, spelling and punctuation. This bottom-up approach does not necessarily equip students with the skills needed to write coherent and cohesive extended pieces of writing as required by university assessment processes. For this reason, the Reading to Learn (RtL) methodology was chosen to be implemented within a writing module at the University of KwaZulu-Natal and within selected Grade 11 classes in the Winelands District in an attempt to find an alternative approach to academic literacy development. The purpose of this article is to offer a comprehensive synthesis of some of the theoretical assumptions of RtL as well as its practical implementation before embarking on an evaluative study of this methodology in future papers. In doing so, this article offers a brief discussion on academic literacy pedagogies and situates RtL within these frameworks. This is followed by a synthesis of the practical implementation of RtL and a discussion of the works of Halliday (1989, 1996), Vygotsky (1978) and Bernstein (1990, 1996) which have had an influence on the development of RtL.


In domains where users are exposed to large variations in visuo-spatial features among designs, they often spend excess time searching for common elements (features) on an interface. This article contributes individualised predictive models of visual search, and a computational approach to restructure graphical layouts for an individual user such that features on a new, unvisited interface can be found quicker. It explores four technical principles inspired by the human visual system (HVS) to predict expected positions of features and create individualised layout templates: (I) the interface with highest frequency is chosen as the template; (II) the interface with highest predicted recall probability (serial position curve) is chosen as the template; (III) the most probable locations for features across interfaces are chosen (visual statistical learning) to generate the template; (IV) based on a generative cognitive model, the most likely visual search locations for features are chosen (visual sampling modelling) to generate the template. Given a history of previously seen interfaces, we restructure the spatial layout of a new (unseen) interface with the goal of making its features more easily findable. The four HVS principles are implemented in Familiariser, a web browser that automatically restructures webpage layouts based on the visual history of the user. Evaluation of Familiariser (using visual statistical learning) with users provides first evidence that our approach reduces visual search time by over 10%, and number of eye-gaze fixations by over 20%, during web browsing tasks.


Guest Editors' IntroductionNotebook interfaces – documents combining executable code with output and notes – first became popular as part of computational mathematics software such as Mathematica and Maple. The Jupyter Notebook, which began as part of the IPython project in 2012, is an open source notebook that can be used with a wide range of general-purpose programming languages.Before notebooks, a scientist working with Python code, for instance, might have used a mixture of script files and code typed into an interactive shell. The shell is good for rapid experimentation, but the code and results are typically transient, and a linear record of everything that was tried would be long and not very clear. The notebook interface combines the convenience of the shell with some of the benefits of saving and editing code in a file, while also incorporating results, including rich output such as plots, in a document that can be shared with others.The Jupyter Notebook is used through a web browser. Although it is often run locally, on a desktop or a laptop, this design means that it can also be used remotely, so the computation occurs, and the notebook files are saved, on an institutional server, a high performance computing facility or in the cloud. This simplifies access to data and computational power, while also allowing researchers to work without installing any special software on their own computer: specialized research software environments can be provided on the server, and the researcher can access those with a standard web browser from their computer.These advantages have led to the rapid uptake of Jupyter notebooks in many kinds of research. The articles in this special issue highlight this breadth, with the authors representing various scientific fields. But more importantly, they describe different aspects of using notebooks in practice, in ways that are applicable beyond a single field.We open this special issue with an invited article by Brian Granger and Fernando Perez – two of the co-founders and leaders of Project Jupyter. Starting from the origins of the project, they introduce the main ideas behind Jupyter notebooks, and explore the question of why Jupyter notebooks have been so useful to such a wide range of users. They have three key messages. The first is that Notebooks are centered around the humans using them and building knowledge with them. Next, notebooks provide a write-eval-think loop that lets the user have a conversation with the computer and the system under study, which can be turned into a persistent narrative of computational exploration. The third idea is that Project Jupyter is more than software: it is a community that is nourished deliberately by its members and leaders.The following five articles in this special issue illustrate the key features of Project Jupyter effectively. They show us a small sample of where researchers can go when empowered by the tool, and represent a range of scientific domains.Stephanie Juneau et al. describe how Jupyter has been used to 'bring the compute to the data' in astrophysics, allowing geographically distributed teams to work efficiently on large datasets. Their platform is also used for education & training, including giving school students a realistic taste of modern science.Ryan Abernathey et al. , of the Pangeo project, present a similar scenario with a focus on data from the geosciences. They have enabled analysis of big datasets on public cloud platforms, facilitating a more widely accessible 'pay as you go' style of analysis without the high fixed costs of buying and setting up powerful computing and storage hardware. Their discussion of best practices includes details of the different data formats required for efficient access to data in cloud object stores rather than local filesystems.Marijan Beg et al. describe features of Jupyter notebooks and Project Jupyter that help scientists make their research reproducible. In particular, the work focuses on the use of computer simulation and mathematical experiments for research. The self-documenting qualities of the notebook—where the response to a code cell can be archived in the notebook—is an important aspect. The paper addresses wider questions, including use of legacy computational tools, exploitation of HPC resources, and creation of executable notebooks to accompany publications.Blaine Mooers describes the use of a snippet library in the context of molecular structure visualization. Using a Python interface, the PyMOL visualization application can be driven through commands to visualize molecular structures such as proteins and nucleic acids. By using those commands from the Jupyter notebook, a reproducible record of analysis and visualizations can be created. The paper focuses on making this process more user-friendly and efficient by developing a snippet library, which provides a wide selection of pre-composed and commonly used PyMOL commands, as a JupyterLab extension. These commands can be selected via hierarchical pull-down menus rather than having to be typed from memory. The article discusses the benefits of this approach more generally.Aaron Watters describes a widget that can display 3D objects using webGL, while the back-end processes the scene using a data visualization pipeline. In this case, the front-end takes advantage of the client GPU for visualization of the widget, while the back-end takes advantage of whatever computing resources are accessible to Python.The articles for this special issue were all invited submissions, in most cases from selected presentations given at JupyterCon in October 2020. Each article was reviewed by three independent reviewers. The guest editors are grateful to Ryan Abernathey, Luca de Alfaro, Hannah Bruce MacDonald, Christopher Cave-Ayland, Mike Croucher, Marco Della Vedova, Michael Donahue, Vidar Fauske, Jeremy Frey, Konrad Hinsen, Alistair Miles, Arik Mitschang, Blaine Mooers, Samual Munday, Chelsea Parlett, Prabhu Ramachandran, John Readey, Petr Skoda and James Tocknell for their work as reviewers, along with other reviewers who preferred not to be named. The article by Brian Granger and Fernando Perez was invited by the editor in chief, and reviewed by the editors of this special issue.Hans Fangohr is currently heading the Computational Science group at the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and is a Professor of Computational Modelling at the University of Southampton, UK. A physicist by training, he received his PhD in Computer Science in 2002. He authored more than 150 scientific articles in computational science and materials modelling, several open source software projects, and a text book on Python for Computational Science and Engineering. Contact him at firstname.lastname@example.com Kluyver is currently a software engineer at European XFEL. Since gaining a PhD in plant sciences from the University of Sheffield in 2013, he has been involved in various parts of the open source & scientific computing ecosystems, including the Jupyter & IPython projects. Contact him at firstname.lastname@example.com Di Pierro is a Professor of Computer Science at DePaul University. He has a PhD in Theoretical Physics from the University of Southampton and is an expert in Numerical Algorithms, High Performance Computing, and Machine Learning. Massimo is the lead developer of many open source projects including web2py, py4web, and pydal. He has authored more than 70 articles in Physics, Computer Science, and Finance and has published three books. Contact him at firstname.lastname@example.com


This practical step-by-step guide - designed for use at your computer - gives clear, compact instructions and self-test exercises to help you learn 2-D drawing using AutoCAD. The text is written for use on all AutoCAD releases from 2000 to 2008. Computer-aided drawing is a skill that every student in architecture, engineering, the trades and construction must learn and ideally at the computer, actually drawing things. AutoCAD is the most widely used package in the industry but existing teaching books tend to be too wordy and focus more on technical wizardry than on how to deliver actual finished drawings using industry drafting protocols.AutoCAD Workbook gives you the skills you need for the full range of drawing types using a wide variety of commands and sequences. Each chapter - or teaching module contains a brief introduction to the commands, explaining exactly how each one can be used, and plenty of exercises to demonstrate how to produce everything from working drawings to presentation drawings; and orthographic projection to pictorial views. Examples include residential and commercial buildings for architects and designers; steel and concrete details for civil and structural engineering; mechanical parts and assemblies for mechanical engineering; and millwork and cabinet-making for woodworking applications.


Public bike system for proximity travel is widely used in urban cities all over the world. Main reasons for launching public bike program is to reduce carbon footprint so as to prevent greenhouse effect and to solve Last-Mile problem in order to make convenient for citizens. However, we may encounter awkward cases in peak hours (from 7:00 to 9:00 and 17:00 to 19:00) that no bike is available at some stations or no vacant place is left to put bikes. The actual solution in most cities is in a traditional way based on call centers. A personnel taking charge of bikes in a certain zone reallocates bikes among bike stations based on notification of bike users by telephone call when bike stations are full or empty. This inefficient solution will reduce bike utilization and even annoy bike users. In this paper, we propose a system & methodology to intelligently guide personnel to reallocate bikes among stations, aiming at overcoming the above awkward cases and maximizing bike utilization.


FMS-like tyrosine kinase 3-targeted (FLT3-targeted) therapies have shown initial promise for the treatment of acute myeloid leukemia (AML) expressing FLT3-activating mutations; however, resistance emerges rapidly. Furthermore, limited options exist for the treatment of FLT3-independent AML, demonstrating the need for novel therapies that reduce toxicity and improve survival. MERTK receptor tyrosine kinase is overexpressed in 80% to 90% of AMLs and contributes to leukemogenesis. Here, we describe MRX-2843, a type 1 small-molecule tyrosine kinase inhibitor that abrogates activation of both MERTK and FLT3 and their downstream effectors. MRX-2843 treatment induces apoptosis and inhibits colony formation in AML cell lines and primary patient samples expressing MERTK and/or FLT3-ITD, with a wide therapeutic window compared with that of normal human cord blood cells. In murine orthotopic xenograft models, once-daily oral therapy prolonged survival 2- to 3-fold over that of vehicle-treated controls. Additionally, MRX-2843 retained activity against quizartinib-resistant FLT3-ITD-mutant proteins with clinically relevant alterations at the D835 or F691 loci and prolonged survival in xenograft models of quizartinib-resistant AML. Together, these observations validate MRX-2843 as a translational agent and support its clinical development for the treatment of AML.


Heat treated pipeline fittings (principally elbows, tees, and reducers) require careful process control. For example, furnace temperature, placement of the fittings in the furnace, transfer time to quenching tank, adequacy of quench or tempering time can all impact the fittings' mechanical properties if not done properly.
 In recent years, the National Energy Board (NEB) became aware of instances of quenched and tempered (Q&T) pipe and fittings having mechanical properties that did not meet Canadian Standards Association (CSA) or similar standards, being installed on pipeline systems under NEB and other regulatory bodies' jurisdiction. In 2013, a pipeline rupture occurred on an NEB-regulated pipeline. Although failure to meet mechanical specifications was not the cause of the incident, the investigations revealed that there were fittings installed on the pipeline with yield strength of less than Specified Minimum Yield Strength (SMYS). The NEB undertook further investigations to determine if this low yield issue might indicate a systemic problem. In the cases examined, contrary to the recorded information in the Material Test Reports (MTRs), not all fittings met the specified mechanical properties requirements, and this was due to inadequate controls in the Quality Assurance Programs (QAPs) of different stakeholders. It is also important to note that MTR results based on a coupon test may not always reflect the properties of each fitting produced following that process.
 The NEB has taken several actions in order to address this potential issue including:
 - Issuing industry-wide Safety Advisories
 - Issuing Orders to all companies under its jurisdiction
 - Commissioning a third party to investigate and write a technical paper on this issue
 - Hosting a technical workshop to facilitate broad dialogue between various stakeholders (using the technical paper as a seed document)
 In this paper, the authors first review the manufacturing process of Q&T fittings. Then case studies are discussed involving four instances of nonconforming fittings. Lastly the authors propose solutions for different stakeholders to effect improvement in Quality Assurance (QA) of pipeline fittings. The authors also recommended enhancement of applicable clauses in related standards and initiation of several research and development (R&D) projects.


Objectives Influence of meteorological variables on the transmission of bacillary dysentery (BD) is under investigated topic and effective forecasting models as public health tool are lacking. This paper aimed to quantify the relationship between meteorological variables and BD cases in Beijing and to establish an effective forecasting model. Methods A time series analysis was conducted in the Beijing area based upon monthly data on weather variables (i.e. temperature, rainfall, relative humidity, vapor pressure, and wind speed) and on the number of BD cases during the period 1970–2012. Autoregressive integrated moving average models with explanatory variables (ARIMAX) were built based on the data from 1970 to 2004. Prediction of monthly BD cases from 2005 to 2012 was made using the established models. The prediction accuracy was evaluated by the mean square error (MSE). Results Firstly, temperature with 2-month and 7-month lags and rainfall with 12-month lag were found positively correlated with the number of BD cases in Beijing. Secondly, ARIMAX model with covariates of temperature with 7-month lag (β = 0.021, 95% confidence interval(CI): 0.004–0.038) and rainfall with 12-month lag (β = 0.023, 95% CI: 0.009–0.037) displayed the highest prediction accuracy. Conclusions The ARIMAX model developed in this study showed an accurate goodness of fit and precise prediction accuracy in the short term, which would be beneficial for government departments to take early public health measures to prevent and control possible BD popularity.


DNA is the blueprint of life. It contains all the information necessary for the synthesis of proteins – the building blocks and workhorses of the cell. Maintenance of DNA in an unchanged state is therefore of utmost importance, since any mutations or loss of the information it holds may lead to catastrophic events, such as cell death or tumorigenesis. DNA needs to be faithfully copied with every cell division, which is an enormous task, given its size and importance. DNA replication is constantly challenged by endogenous and exogenous factors, which have the potential to stall or stop replication – such a circumstance is called replication stress. While cells have evolved a number of mechanisms to deal with replication stress, e.g. checkpoint signaling that halts the cell cycle, DNA repair pathways that remove obstacles or factors that stabilise stalled replication forks, persisting replication stress inevitably leads to genomic instability and tumorigenesis. Interestingly, cancer cells, due to their unrestricted proliferation, have elevated level of replication stress, which makes them more susceptible to anti-cancer therapies that exacerbate genomic instability. It is thus obvious that dissecting the events and mechanisms leading to and following replication stress is important from a basic science and clinical research point of view. Among the many aspects of replication stress, one that is gaining an increasing amount of attention is replication fork stability. Over the last years it was shown that a stalled replication fork is rapidly remodeled into a 4-way structure, an event that is believed to contribute to its stabilisation. However, such a structure needs to be carefully maintained, since lack of its protection may cause an unscheduled processing by nucleases, leading to genomic instability. Interestingly, among the factors that protect stalled replication forks are many proteins previously associated with other DNA repair pathways, such as homologous recombination or Fanconi anaemia. The most recent member of the 'protectosome' group is WRNIP1 (Werner helicase interacting protein 1), but its mode of action is unclear. In this project, we attempted to characterise WRNIP1's biochemical activities and investigate further its cellular function. We have found that the protein exerts its protective function downstream of replication fork reversal, challenging the current model. Our in vitro data show that WRNIP1 binds specifically to 4-way DNA junctions, a structure resembling a reversed replication fork. We have also found that WRNIP1 interacts directly with the replication fork remodeler ZRANB3 and that it is able to limit its replication fork reversal activity in vitro. Combined with published data, our data led us to propose a mechanism in which WRNIP1 binds to reversed replication forks immediately after their generation, thus protecting them against unscheduled MRE11-dependent degradation. Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-151889 Dissertation Published Version Originally published at: Porebski, Bartlomiej. Elucidating the role of WRNIP1 in the protection of stalled replication forks. 2018, University of Zurich, Faculty of Science.


INTRODUCTION AND OBJECTIVES: Calcium oxalate (CaOx) is the most common stone type in the United States. Current AUA guidelines suggest that a 24-hour urine collections should be obtained in high-risk, interested first-time and recurrent stone formers. While these tests can add information to the patient's clinical picture and help guide a stone prevention plan, there may be situations in which a stone analysis alone can drive preventative management. Prior work has suggested that urine chemistries can influence the morphology of CaOx stone toward varying concentrations of the monohydrate (COM) or dihydrate (COD) crystal structure. METHODS: We retrospectively reviewed stone analyses from Beck Analysis laboratories database from Jan 1 2002- Jul 1 2018. We identified 1001 patients with pure COM ( pCOM=791) and pure COD (pCOD=210) who received care from our institution. 123 pCOM and 70 pCOD patients had 24-hour urinalyses completed by Litholink laboratories that could be paired with their stone analysis. Patients younger than 18 or with mixed or non-CaOx stone analyses were excluded. RESULTS: Patient characteristics and 24-hour urine characteristics are included in Table 1. Primary hyperparathyroidism [2 COM; 3 COD], malabsorption syndromes[24 COM; 2 COD] including: surgical bowel resection/diversion, bariatric surgery or Crohn's disease, medullary sponge kidney [4 COM; 0 COD], and anatomical anomalies[9 COM; 2 COD] such as horseshoe, solitary, bifid collecting system, ectopic kidney was noted in the cohort. Comparison of pCOM and pCOD patients (Figure 1) showed correlation with hyperoxaluria (51.2% vs 31.4% p < 0.01) and hypercalciuria (23.6% vs 72.9% p < 0.0001) respectively. CONCLUSIONS: Our results align with prior studies suggesting that a stone analysis represents an aggregate of crystal deposition over a prolonged period and may be representative of underlying urinary derangements. In patients with predominant or pure COD, in whom a 24-hr urinalysis is not available, treatment of underlying hypercalciuria will likely aid in the prevention of further stone events. Table. No title available. Source of Funding: None


Large band instruments and GPS-GIS (global position system-geographic information systems) systems installed on a vehicle in motion are used to measure the electromagnetic field (EMF) present at the ground in a kinematics way. This procedure allows to constantly monitor a wide part of the territory very quickly and cutting the prices. Using a vehicle in motion equipped with a GPS-GIS system synchronized with an electric field probe, it is possible to measure continuously at the same time the position of the probe and the correspondent EMF value. However, many factors as vehicle presence, probe position and field frequency affect the results. To measure high frequency EMF, we suggest to use a metallic shield with known geometric and dielectric properties. This new set-up can be easily simulated and reproduced in laboratory. Comparing laboratory measurements and theoretical calculations, it is possible to determine the suitable measurements conditions.


With the August 1910 annexation of Korea, the Japanese initiated efforts to redefine their relationship with their new colonial subjects. To this end Seoul's trilingual media served as an indispensible agency to inform the peninsula's residents of Japan's colonial policy and to suggest ways for its development. From the start the Japanese administration clearly advertised its policy as assimilation and used the media to market a new Japanese-Korean relationship to the residents of the peninsula. The messages that appeared in these presses varied and even contradicted each other. Articles carried in the English-language Seoul Press often advertised the Japanese-Korean relationship as amicable and predicted that the two people's assimilation would be accomplished with relative ease. The Koreanlanguage Maeil sinbo emphasized the changes that Koreans would have to make to attain a level of civilization that qualified them as Japanese imperial subjects. Contrary to the English-language press, it saw assimilation's success emerging after the people engaged in a long, gradual effort to modernize. Finally, the Japanese-language Keijō shinpō, also aware of the difficulties that historically accompanied assimilation efforts, warned that for assimilation to have a chance at success the Japanese settler would have to adopt a positive image of the Korean people and a cooperative stance toward Japanese administrative efforts. The contradictions found in these messages accented a fundamental problem that Japan's assimilation policy would face in Korea: the anti-Korean attitudes harbored by Japanese residents in Korea and the discriminative practices evident in Japanese administrative policies neutralized efforts by those Japanese and Koreans who accepted Japan's colonial rhetoric and strove to advance this new relationship.


Current multiple-removal algorithms in seismic processing use either differential moveout or predictability. If the differential moveout between primaries and multiples is small, prediction is the only option available. In the last decade, multidimensional prediction-error filtering by weighted convolution, such as surface-related multiple elimination (SRME), have proved to be very successful in practice. So far, multiples have been considered as noise and have been discarded after the removal process. In this paper, we argue that multiple reflections contain a wealth of information that can be used in seismic processing to improve the resolution of reservoir images beyond current capability. In the near future, one may expect that the so-called weighted-crosscorrelation (WCC) concept may offer an attractive alternative in approaching the multiple problem. WCC creates an option to avoid the adaptive subtraction process as applied in prediction-error algorithms. Moreover, it allows the transformation of multiples into primaries. The latter means that seismic imaging with primaries and multiples (nonlinear process) can be implemented by a sequence of linear processes, including the transformation of multiples into primaries and the imaging of primaries.


These Earth's climate is getting warmer, and the signs are everywhere. Abnormal river discharge is one of the impacts that can be found in local scale. This endangering condition leads to the necessary attention on river basin in Sarawak, Malaysia and hence gives birth to this study. The objective of this study is to examine the existence of climate change on Sungai Sarawak River Basin through a hydrologic analysis of river discharge of three water level stations: Station Rayu, Station Git and Station Buan Bidi. The methods applied are mass-curve coupled with Gumbel's graphical statistical method and annual hydrograph. Mass curve plotted shows the deviation of cumulative peak discharge from its original trend with Stations Rayu, Git and Buan Bidi started straying since years 1998, 2001 and 2004 respectively. After breakpoint, Gumbel's graphical statistical method for chance percent evaluation clearly implies the chance percent for all (exception for Station Buan Bidi) discharges has decreased throughout the years. Whereas Gumbel's graphical statistical method for return period evaluation suggested an extension of return period after the transition year (exception for Station Rayu). Two graphical methods pointed to the same direction – rate of decline shifting is greater for high flow as compared to low flow. Broadly speaking, precipitation has not much effect on the discharge variation according to annual hydrographs plotted. However, an obvious decrease in monthly average discharge throughout 18 years was found after change at Station Rayu. This support the climate change fact of "dry getting drier". Water shrinkage in Sarawak River Basin is expected to be experienced frequently in the future.


Multiple treatment guidelines and practice standards have been developed regarding the management of patients with breast carcinoma. Few evaluations of the penetration and utility of these practice standards have been performed. In 1992, the American College of Surgeons (ACOS), the American College of Radiology, the College of American Pathologists, and the Society of Surgical Oncology collaborated in establishing standards for breast‐conservation treatment (BCT). The authors sought to determine whether practice patterns for patients with breast carcinoma who underwent BCT were consistent with these standards 2 years after their dissemination and to establish whether compliance varied by the same patient and hospital variables that predicted for the amount of BCT performed.


Exploiting mobile elements to conduct data collection in wireless sensor networks offers a new approach to reducing and balancing the energy consumption of sensor nodes; however, the resultant data collection latency may be large due to the limited travel speed. Many research efforts have been made on reducing the data collection latency with the scenario where a single mobile element is available. A potential problem with this scenario is the scalability, and a straightforward solution is to employ multiple mobile elements to collect data collaboratively. In this paper, the network where multiple homogeneous mobile elements are available is modeled as an M/G/c queuing system, and insights on the data collection performance are obtained through theoretically analyzing the measures of the queue. In addition, a heuristic formula to determine the optimal number of mobile elements is proposed based on this model. The accuracy of our modeling and analysis, along with the performance evaluation of the proposed heuristic formula, is verified through extensive simulation.


This study aims to generate a risk evaluation methodology for the aged dam structure by coupling the micro and macro models created by hydraulic computation and discontinuous deformation analysis (DDA) with numerical manifold method (NMM), respectively. For the macro analysis, DDA+NMM is an energy-convergence algorithm and can be utilized to estimate critical loading based on the potential joints existing within the discontinuous block system. Due to the micro view, the relationship of groundwater level and precipitation can be studied by using hydraulic computation based on the groundwater flow equations. The proposed method presents an evaluation procedure for modeling an aged earth dam with efficient and economic open-source programs. As the result, the simulation can help determining the criterion of risk factors and the prevention strategy.


The end surface angle of workpece is one of key factors that affect burr sizes and shapes. In this paper, the burr formation process of different end surface angle is simulated with elastic plastic nonlinear element method based on ABAQUS. The influence of end surface angle of workpiece on burr formation processes in high-speed machining 2024 Aluminum alloy is analyzed. The influence of end surface angle on burr sizes and shapes is studied based on equivalent shear strain and negative shear angle. The results have investigated the mechanisms of burr formation fundamentally, which is the basis of burr minimization.


The aim of the study was to investigate the major changes in the indications, culture success and abnormality rate for conventional cytogenetic prenatal diagnosis on amniotic fluid samples between the period of January 1998 and December 2001 in Izmir. The cytogenetic laboratory provides a prenatal service to obstetrics-gynecology departments of different hospitals in Izmir. A limited number of patients (6-8 per week) is randomly accepted for prenatal cytogenetic study. Over the 4 years period 1190 prenatal cytogenetic tests were performed in our center. The most common indication was advanced maternal age for each year. However its rate has increased significantly within the years (35.68% in 1998, 61.38% in 2001), while the rate of both triple test and ultrasound scanning indications decreased. Culture success rates have improved (97.97% in 1998, 99.74% in 2001). Comparing the first two years to the last two years the rate of abnormal cytogenetic results decreased significantly (3.83% in 1998-99, 2.48% in 2000-01). The major reason for this decrease is probably related to the changes in indications throughout the years.


The objective of the research was to determine the effect of pre harvest CaCI2 application on quality changes of tomato fruits. Experiment consisted of 5 treatments: control, application of 0.1 M CaCI2 at 18 ± 2 days after anthesis (DAA), 0.1 M CaCI2 at 25 ± 2 DAA, 0.2 M CaCI2 at 18.t2 DAA and 0:2 M CaCI2 at 25 ± 2 DAA. Tomato fruits cv. Ratna harvested at breaker stage were used throughout the experiment. Variables to be observed were peel color, weight loss, fruit firmness. total soluble solids, titratable acidity, and respiration. Result of the experiment showed that application , of CaCl2 could not maintain quality and extend shelf life. Application of 0.1 M CaCl2 at 25 ± 2 DAA inhibited peel color . development at 9. 12, and 21 days after harvest. Key words: Pre harvest, CaCI2, Tomato, Storage


Regenerated fiber Bragg grating (RFBG) is a temperature-resistant grating fabricated from a standard fiber Bragg grating using high temperature annealing treatment. It is well known for its economic production and high temperature sustainability in which the operating temperature of the developed RFBG can be as high as the maximum annealing temperature. It is believed that stress relaxation is one of the contributing factors to the thermal regeneration process. Exploiting the benefits of CO2 laser in terms of dynamic temperature control and focused heating zone, thermal regeneration of RFBG based on CO2 laser annealing has been successfully demonstrated for the first time. The ensuing cooling process after the post-fabrication annealing treatment is the controlling parameter for the modification of thermal stress in the fiber. After an isothermal annealing treatment followed by a slow cooling process, the Bragg wavelength of the RFBG was red-shifted. This modification is reversible by repeating the annealing treatment followed by a rapid cooling process. It is repeatable with different cooling processes in the subsequent annealing treatments. This phenomenon can be attributed to the thermal stress modification in the fiber core by means of manipulation of glass transition temperature with different cooling rates. This finding is important for accurate temperature measurement of RFBG in dynamic environment. Furthermore, the thermal stress relaxation study was extended to birefringence modification in regenerated grating in polarisation maintaining fiber (RGPMF) by using a CO2 laser annealing technique. After conducting a post-fabrication isothermal annealing procedure followed by a slow cooling process, the birefringence of the RGPMF has been increased. This phenomenon can be explained by the changes in the thermal expansion coefficient and glass transition temperature of the stress applying part at different cooling rates. The birefringence modification is reversible by re-annealing with a subsequent rapid cooling process. This finding is useful for the study of the birefringence modification, operation range, sensitivity, and accuracy of PMF or PMF-related fiber components. The finding of this thesis has opened up a new avenue of research on the application of CO2 laser annealing in thermal regeneration, stress relaxation and birefringence modification in FBG components.


In a short article submitted to ArXiv [1], Maddamsetti et al. argue that the variation in the neutral mutation rate among genes in Escherichia coli that we recently reported [2] might be explained by horizontal gene transfer (HGT). To support their argument they present a reanalysis of synonymous diversity in 10 E.coli strains together with an analysis of a collection of 1,069 synonymous mutations found in repair-deficient strains in a long-term in vitro evolution experiment. Here we respond to this communication. Briefly, we explain that HGT was carefully accounted for in our study by multiple independent phylogenetic and population genetic approaches, and we show that there is no new evidence of HGT affecting our results. We also argue that caution must be exercised when comparing mutations from repair deficient strains to data from wild-type strains, as these conditions are dominated by different mutational processes. Finally, we reanalyse Maddamsetti's collection of mutations from a long-term in vitro experiment and we report preliminary evidence of non-random variation of the mutation rate in these repair deficient strains.


The analysis of the interdependence between international equity markets has been a key issue in international finance as it has important practical implications for asset allocations, risk management, and economic policy. The objective of this thesis is to re-examine the interdependence amongst international equity markets at the industry sector level. In particular, the thesis investigates time varying, long run and short run dynamic relationships between industry sectors of the United States of America and three leading emerging markets/countries: Brazil, Malaysia, and South Africa between January, 2000 and December, 2009. The thesis advances previous studies on international industry sector relationships in three specific aspects. Firstly, it examines a large number of heterogeneous industry sectors from the global economy. Secondly, existing empirical studies in this area need to be updated to include the recent turbulent global economic and financial crisis period. Thirdly, the thesis offers a deeper analysis into the intra-industry sector interdependence than previously presented. Such analysis has important implications for international diversification strategies. A crucial empirical contribution of the study is by applying liner and non liner econometric time series techniques for the evaluation for long run global relationships and causality linkages, including testing for asymmetric causality relations both in linear and nonlinear settings. This thesis also represents [to the best of my knowledge] the first study that extensively considers time-varying relationships amongst international industry sectors by examining time varying correlations and beta stability, as well as time varying cointegration and causality relationships. Another empirical motivation of this thesis is the need to extend existing empirical studies on industry sectors by examining the impact of the recent economic and financial crisis period. Specifically, the thesis investigates the shifts in cross correlations and the dynamic causality linkages between the US and emerging markets' industry sectors before and during the 2007-2009 economic and financial crisis. The initial exploratory analysis of the return cross-correlations indicate that, though small or in a moderate range, the existence of co-movements amongst international industry sectors as all correlations coefficients are positive and significant at the one per cent level. The results for long run relationships provided by linear (without seasonal dummies) and nonlinear cointegration tests show no significant evidence of cointegration relations between the US and the emerging markets industrial sectors. Similarly, the results of the dynamic causality linkages, between the US and emerging markets industrial sectors indicate, there exist some significant short-run causal linkages (linear and nonlinear) between these markets' industry sectors, weak linkages. Overall, the results of time varying analysis indicate unstable relationships between the returns of US and the emerging economies' industry sectors over the sample period. The empirical results of crisis suggest increased cross correlations and causality relationships among the industry sectors of US and the emerging markets under study during the crisis of the sample period than pre-crisis period of the same sample. In summary, the empirical results of the research indicate relatively weak interdependence between the US and the emerging markets industry sectors, which suggest potential diversification benefits for US investors in diversifying their portfolio investment across industrial sectors of the emerging markets.


Blood management strategies are integral to successful outcomes in many types of orthopaedic surgery. These strategies minimize blood loss and transfusion requirements, ultimately decreasing complications, improving outcomes, and potentially eliminating risks associated with allogeneic transfusion. Practices to achieve these goals include preoperative evaluation and optimization of hemoglobin, the use of pharmacologic agents or anesthetic methods, intraoperative techniques to improve hemostasis and cell salvage, and the use of predonated autologous blood. Guidelines can also help manage allogeneic transfusions in the perioperative period. Although the literature on blood management has focused primarily on arthroplasty and adult spine surgery, pediatric spinal fusion for scoliosis involves a large group of patients with a specific set of risk factors for transfusion and distinct perioperative considerations. A thorough understanding of blood management techniques will improve surgical planning, limit transfusion-associated risks, maintain hemostasis, and optimize outcomes in this pediatric population.


The core tools of science (data, software, and computers) are undergoing a rapid and historic evolution, changing what questions scientists ask and how they find answers. Earth science data are being transformed into new formats optimized for cloud storage that enable rapid analysis of multi‐petabyte data sets. Data sets are moving from archive centers to vast cloud data storage, adjacent to massive server farms. Open source cloud‐based data science platforms, accessed through a web‐browser window, are enabling advanced, collaborative, interdisciplinary science to be performed wherever scientists can connect to the internet. Specialized software and hardware for machine learning and artificial intelligence are being integrated into data science platforms, making them more accessible to average scientists. Increasing amounts of data and computational power in the cloud are unlocking new approaches for data‐driven discovery. For the first time, it is truly feasible for scientists to bring their analysis to data in the cloud without specialized cloud computing knowledge. This shift in paradigm has the potential to lower the threshold for entry, expand the science community, and increase opportunities for collaboration while promoting scientific innovation, transparency, and reproducibility. Yet, we have all witnessed promising new tools which seem harmless and beneficial at the outset become damaging or limiting. What do we need to consider as this new way of doing science is evolving?


Purpose: To characterize the localization of interictal spikes by magnetoencephalography (MEG) in patients with mesial temporal lobe epilepsy (TLE). Methods: We studied 5 patients with mesial TLE who had convergent localization information based on presurgical evaluation and became seizure free after anterior temporal lobectomy (ATL). Simultaneous MEG and scalp EEG were recorded before and 6-12 months after surgery using a whole-scalp neuromagnetometer. We visually searched interictal spikes simultaneously occurring on both MEG and EEG channels and analyzed the spikes by MEG dipole modeling. Results: Spikes were localized in anterior temporal region, although most spikes were not exactly located in mesial temporal structure. The dipole orientation was horizontal for 86% (83-94%) of interictal spikes in 4 patients and vertical for 86% of interictal spikes in 1 patient. According to the postoperative MR images with superimposed spike coordinates, 91% (68-100%) of preoperative spike dipoles were situated within the resection demarcation of ATL. Conclusions: In patients with mesial TLE, most interictal spikes were localized in anterior temporal lobe within the resection demarcation of ATL. The dipole orientation can be either horizontal or vertical.


Alternative cathode materials were investigated for application to high voltage lithium ion batteries. Manganese based materials were considered due to the low cost and environmentally sustainable impact. Layer-structured oxide and phospho-olivine materials were prepared by a sol-gel method to obtain mesoscopic particles. The particle size of the layered Li1.15Mn0.545Ni0.245Al0.06O2 material was 200 nm. A ball-milling process reduced the particle size to 60 nm. Doping with Ni and Al in the layered Li1.15Mn0.545Ni0.245Al0.06O2 material provided a redox potential at 4.1 V vs. Li+/Li. The specific capacities of 60 and 200 nm particle sized materials were 150 and 125 mAh/g, respectively at C/10. The 60 nm sized material showed a higher lithium intercalation rate than the 200 nm sized material. Particularly, at high charge-discharge rates (1C and 5C), 127 and 85 mAh/g, respectively compared to 95 and 10 mAh/g at 1C and 5C, respectively of 200 nm material. However, the 60 nm sized material degraded faster upon cycling after 80 cycles. The increased impedance indicates a large resistance associated with the interface reaction in the cycled 60 nm particlels. Two types of electrolytes were investigated in the same cathode material. 3-methoxypropionitrile (MPN) with 1M LiN(SO2CF3)2 electrolyte showed faster Li intercalation than ethylene carbonate/dimethyl carbonate (EC/DMC) with 1M LiPF6 at 1C and 5C in complete cells. LiMnPO4 was synthesized by a sol-gel method using glycolic acid. The decomposition temperature was lower in the dried gel prepared under strong acid conditions. Finally, highly ordered crystallites were formed between 520 and 570°C with particle sizes in the range of 140 to 160 nm. Subsequent dry ballmilling reduced the diameter to 130 ± 10 nm and also improved the carbon coating on the active material. LiMnPO4 material provided a redox potential of 4.1 V vs. Li+/Li. Reversible capacities of 156 mAh/g at C/100 and 134 mAh/g at C/10 were measured. At 92 and 79 % of the theoretical value, respectively, these are the highest values reported to date for this material. At faster charging rates, the electrochemical performance was found to be improved when smaller LiMnPO4 particles were used. The LiMnPO4 material showed an excellent capacity retention upon cycling as phosphate framwork is chemically and thermodynamically stable.


Aim: Currently, in connection with the deterioration of the epizootic situation of rabies in the world, the question of improving the means of routine laboratory diagnostics of rabies remains highly controversial to obtain results of a high degree of reliability. Especially in demand diagnostic rapid test systems based on enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IFA) methods, the sensitivity and specificity of which depend on the degree of purification of antigenic components. Materials and Methods: In this article, a method is given for obtaining a rabies antigen and the results of an experimental study of the activity of its highly purified fractions were obtained by separation in a stepwise gradient of sucrose (20–60%) by ultracentrifugation at 30,000 g. Results: The study of electrophoretic profiles of antigenic fractions in 12.5% polyacrylamide gel showed that the major polypeptide fractions are located in the range of 44.6–70.0 kDa. According to the results of the tests in ELISA and IFA, Fraction 1 was the most active. We optimized the conditions for the formulation of the reactions, and the o-ptimal working concentrations were determined. Conclusion: The revealed immunochemical characteristics of this fraction will allow using it not only as an antigenic component for diagnostic test systems but also as an immunizing material for obtaining highly specific rabies immunoglobulins.


Latin America and the Caribbean (LAC) contain more tropical high-biodiversity forest than the remaining areas of the planet combined, yet experienced more than a third of global deforestation during the first decade of the 21st century. While drivers of forest change occur at multiple scales, we examined forest change at the municipal and national scales integrated with global processes such as capital, commodity, and labor flows. We modeled multi-scale socioeconomic, demographic, and environmental drivers of local forest cover change. Consistent with LAC's global leadership in soy and beef exports, primarily to China, Russia, the US, and the EU, national-level beef and soy production were the primary land use drivers of decreased forest cover. National level GDPs, migrant worker remittances, and foreign investment, along with municipal-level temperature and area, were also significantly related to reduced forest cover. This challenges forest transition frameworks, which theorize that rising GDP and intensified agricultural production should be increasingly associated with forest regrowth. Instead, LAC forest change was linked to local, national, and global demographic, dietary and economic transitions, resulting in massive net forest cover loss. This suggests an urgent need to reconcile forest conservation with mounting global demand for animal protein.


Existing theories consistently predict that relationship banking enhances credit availability for new firms. To put more concretely, these theories predict that soft information acquisition about borrowers' creditworthiness and the resulting incumbent lender's profit-improving and relation-specific consulting ability yield a monopolistic rent for the incumbent lender, and that this expected rent encourages a bank to lend to younger firms to pre-empt an exclusive relationship ahead of rival banks. The present study tries to provide evidence for this hypothesis using a dataset collected from the 2003 Survey of the Financial Environment of Enterprises in Japan. Our statistical analysis shows that the time interval from start-up to the first loan approval for a firm is shorter if a bank intends to undertake relationship banking, even after controlling fund-demand and creditworthiness factors of each firm. This result provides evidence to support the above hypothesis. Our logit analysis shows that the probability for banks to undertake relationship banking is decreasing or hump-shaped against the number of competing banks. Thus, the increase in the number of competing banks is more likely to discourage these banks from providing relationship banking, and this in turn diminishes credit availability for new firms. Besides such an effect arising from relationship banking, the data shows evidence suggesting the statistical significance of another mechanism generating a negative correlation between the number of competing banks and credit availability for new firms, which may be explained by the theory of winner's curse. As a whole, credit availability for new firms was higher in more concentrated local credit markets in the last fifteen years in Japan.


Choosing the correct strategy is crucial for the success of any business ventures, and this is even more so for small firms that have limited resources. Thus, this study involved empirical analysis of the growth strategy adopted by firms within the food processing industry which mainly consist of small & medium sized enterprises. The food industry was selected because of its importance to the Malaysia's economy and also because of its dynamic internal and external environment. For instance, in 2011, processed foods from Malaysia are exported to more than 200 countries, producing an annual export value of more than RM13billion (Malaysian Investment Development Authority, 2012).A representative sample consisting of fifteen firms located in Kuching, Sarawak was used for this study. Results indicated that majority of the firms adopted market penetration strategy due to its perceived low-risks and ease of implementation that do not overstrain organizational resources. Notwithstanding the type of strategies adopted, the most crucial success factors was found to be firm's ability to respond to market signals, personal networking and systematic operational management of the firm.


Computed tomographic (CT) data for 213 cases of various soft tissue tumors of the trunk and extremities were analysed to assess the role of the method in evaluating local extension of tumor. CT allowed to reliably identify the degree of tumor interaction with adjacent major vessels. Its data was fully confirmed by surgery in 88.5% of cases. Moreover, CT gave an opportunity to diagnose occult metastases in adjacent anatomic areas and to assess relationship between tumor and adjacent bones, partly by diagnosing X-ray-negative lesions in the latter. To summarize, CT is instrumental in taking decision to operate and planning the extent of surgery.


Through a qualitative case study of the organising/strategising practices of a small British e-commerce retailer, this paper examines the relationship between routine and organisational change. The study takes as its starting point Josef Schumpeter's notion of creative destruction that suggests that a break from the routine is indeed a necessary characteristic of innovation and organisational change, resulting in a new combination of resources. The findings of the study suggest that strategising is itself an activity that is distributed over a heterogeneous network. On the one hand, it is about stabilising matters of concern in order to ensure the smooth running of the ongoing performance of the assemblage (of routines, humans and artefacts) while on the other hand it is also about seeking and recognising opportunities for productivity gains by turning routines into artefacts.


Lithium (Li) metal anodes have shown a huge potential for next-generation energy storage because of the high theoretical specific capacity and negative potential. Nevertheless, due to the change in the volume and the existence of Li dendrites, the application of the Li metal anode is significantly limited. For the purpose of developing a stable Li metal anode to avoid Li dendrite formation, we introduced a stable artificial solid electrolyte interphase (SEI) film, which was prepared by polyvinyl alcohol (PVA) cementing a metal organic framework (Zn-MOF). The environment-friendly and non-toxic PVA acted as a "glue" to cement the rigid Zn-MOF. The artificial SEI film had high Li ion conductivity and excellent flexibility, which is beneficial for uniform lithium flux, inhibiting dendrite growth and easing the volume change. Consequently, benefitting from the safeguard of the Zn-MOF/PVA artificial SEI film, the anode delivered high coulombic efficiency above 97.7% beyond 250 cycles at a current density of 3 mA cm−2.


As impacted permanent maxillary cuspids occur in 1-2% of the population, the general dentist should know the signs and symptoms of this condition and the interceptive treatment. Features of buccal or palatal cuspid impaction include lack of canine bulges in the buccal sulcus indicating a lingual eruption path and possible impaction; lack of symmetry between the exfoliation and eruption of cuspids that may indicate palatal or lingual impaction; and abnormal mesiodistal location and angulation of the developing maxillary permanent cuspids on radiographs. Diagnosis of impacted cuspid teeth at age 8-10 years can significantly reduce serious ramifications, including surgical exposure and orthodontic alignment as well as root resorption of the lateral incisors. In specific cases, extraction of the primary maxillary cuspids can prevent impaction of the permanent maxillary cuspids and additional sequelae.


Lead tin telluride based alloys are known p-type materials for thermoelectric applications, in the 50-600oC temperature range. These alloys combine desired features of mechanical and thermoelectric properties. The electronic transport properties of PbTe and Pb1-xSnxTe materials may be strongly dependent on the preparation technique. Powder metallurgy process is known to introduce defects and strains, that may alter carrier concentration. Under such non-equilibrium conditions the thermoelectric properties are instable at the operating temperature. An appropriate annealing treatment can eliminate this effect.. The present communication describes the annealing treatment applied to cold compacted and sintered Pb1-xSnxTe materials.


Large forest fires are very hazardous and often cause greater losses. However, due to the vast coverage of forests and the environmental complexity, monitoring which relies on sensor detection of direct contact almost cannot achieve its monitoring function. In this paper, the author proposes that long-range images will first be acquired and so do the images of a larger dynamic range of the observed region, then an embedded video monitoring system will be formed realizing a dynamic monitoring. With the techniques of dynamic image analysis and processing, dynamic image alarms and control signals can be obtained and such videos will be transmitted over the Internet in real-time. Experiments shows this system respond to fires with a fast speed of less than 20ms and the control of fire is highly accurate with a dynamic image area that is less than 1% of the background area.


In the course of a search for chemotherapeutic agents inhibiting suspected peridontitis bacteria, extracted and purified substances from lotus leaf were identified by antimicrobial and Anti-inflammation activity tests with use of the broth micro-dilution methods on 96-microwell plate and ELISA assay. The antimicrobial activity of extracts was tested against four microorganisms, namely: Streptococcus mutans , Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Candida albicans. The Anti-inflammation activity of extracts was tested for inhibition of inflammatory cytokines IL-8 and IL-6 in macrophage BF24. And one pure component was subjected to spectroscopic analysis using UV, IR, EMI-MS, EIMS, 1H-NMR, 13C-NMR, 1H-COSY and HMQC. Our data showed that the minimum inhibitory concentrations of the pour component was less than 5mg/ml for all four microorganisms and the minimum concentration with anti-inflammation was 0.2mg/ml for both IL-8 and IL-6. The component was determined to be Lysicamine. Thus, we conclude that Lysicamine extracted from lotus leaves may be a potential antibacterial and Anti-inflammation agent for oral infection .


New aromatic polyamideimides (PAI) were synthesized by high temperature polycondensation from diamidedianhydrides (formerly prepared by us) and diamines: 1,5-diaminonaphthalene, 4,4'-(hexafluoro-isopropylidene)-dianiline or 2,6-diamineanthraquinone. Chemical structures of PAI obtained (Fig. 1) were confirmed by FTIR (Fig. 2) and NMR (Fig. 3) methods and by elemental analysis. Polyamideimides studied showed high thermal stability both in nitrogen or air atmosphere as well as high glass transition temperature in the range 220-265 °C (Table 1). An evaluation of optical and photoluminescent properties of PAI in NMP solutions (Fig. 4 and 5) showed that they emit the light of wavelength in the range 405-572 nm, dependently on the structure.


Embedding Lean Construction (LC) in an organisation typically requires many changes and is a challenging endeavour. In particular when transformations take place it becomes crucial to measure the current state of the maturation process. Hence there is a requirement for organisations to be able to demonstrate where they are in their LC journey. It has been widely acknowledged that maturity models (MM) provide organisations with such an assessment of the current state. Further benefits of MMs are the guidance and support when implementing a change or improvement strategy. The research presented aims to integrate both LC and MM to enable organisations to measure their current maturity in LC. A qualitative mixed method design was used including focus groups and interviews to explore the phenomenon of LC maturity from key informants. The major findings of the research are: MM can be integrated with LC, and a proposed validated framework can assess the current state of LC maturity within an organisation. The proposed LC maturity assessment framework labelled (LCMM) comprises five maturity levels, 11 Key Attributes, and 60 defined Behaviours, Goals & Practices with 75 Ideal Statements to measure the maturity within organisations embedding LC. This framework provides important support and guidance in the organisational LC maturation process.


This business history analyzes the connections between private business, disarmament, and re-armament as they affected arms procurement and military technology transfers in Eastern Europe from 1919 to 1939. Rather than focusing on the negotiations or the political problems involved with the Disarmament Conferences, this study concerns itself with the business effects of the disarmament discussions. Accordingly, Schneider-Creusot, Skoda, Vickers, and their respective business activities in Eastern European markets serve as the chief subjects for this book, and the core primary sources relied upon include their unpublished corporate archival documents. Shifting the scope of analysis to consider the business dimension allows for a fresh appraisal of the linkages between the arms trade, disarmament, and re-armament. The business approach also explodes the myth of the 'merchants of death' from the inside. It concludes by tracing the armaments business between 1939 and 1941 as it transitioned from peacetime to war.


Abstract:The concept of the commons is central to an argument that connects indigenous people and their struggles both to global politics and to radical reconceptualizations of the relationships among knowledges, resources, and human communities. This article considers the use of the idea of a commons in water and atmosphere in the 2016 protest on the Standing Rock Sioux Reservation against the construction of the Dakota Access Pipeline. It also contextualizes the concept of the commons in relation to the historical expropriation of land from native peoples in North America.


This study introduces a framework to model moderate-to-high poverty
transition in urban neighborhoods using their relative competitive positions
within metropolitan areas. Relative competitive position is measured by a
variety of neighborhood attributes, including resident and neighborhood
characteristics, locational attributes, among others. The model was estimated
using the decennial census, using tracts from 1990 and 2000 as proxies for
neighborhoods. Results indicate that the competitive model works well as a
method to evaluate neighborhood poverty transition. Neighborhoods with
relatively unfavorable competitive positions within a metropolitan area
experience more poverty growth and therefore are likely to have more
concentrated poverty in the future. Based on the results, several
recommendations are made to intervene. These include promoting public transit,
immigrant assimilation programs, among others.


We explore empirically whether earnings uncertainty and borrowing constraints deter households from the stock market, consistent with the predictions of theoretical studies of portfolio choice in the presence of uninsurable earnings. Since recent extensions highlight the importance of the correlation between earnings and financial risks, here we use a self-assessed proxy from the DELTA-TNS 2002 cross-sectional survey to empirically assess the impact. Although income risk does not affect the participation decision of households' reporting a negative correlation, it does lower the participation of those who report a non-negative sign, consistent with economic theory predictions.


Systematic inventive thinking is an innovative topic in the syllabus of science and technology studies in Junior High School in Israel (Ministry of Education, 1996). The project reported in this thesis deals with the development, implementation and evaluation of a curriculum for this topic. The outcomes of this project provide the necessary background for teaching the topic in classrooms and in-service teacher courses (INSET) throughout Israel. The principle findings of the curriculum implementation and evaluation show that it can be successfully learned and taught. Teachers can be trained in the topic by using the learning materials and the teaching methods developed in the project. The curriculum provided ninth-grade students structured and systematic thinking modes for problem-solving and contributed to improving their creative thinking skills. Moreover, the model was received with great enthusiasm and interest by students and teachers alike, and generated a creative atmosphere in the classroom. The study is based on the premise that inventive thinking can be acquired in a systematic manner. Our approach was developed on the basis of various methods in the domain of problem-solving and creativity, especially the work of Altshuller (Altshuller, 1985). The project builds on previous developments carried out for adults in the Open University of Israel (Helfman,1990). The approach that was developed enables learners to conduct the thinking process in a controlled, organized, and conscious manner. The inventive ideas are developed on two levels: An abstract level (development of models and solution concepts) and a concrete level (development of specific solutions). The search for solutions consists of a three-stage method: The first stage consists of applying the imagination in a divergent thinking mode, leading to possible thought directions that may lead to the desired solution. This stage culminates in a large number of models and solution concepts. In the second stage logical considerations are applied to proposed abstract solutions in order to sort them out by examining relevant conditions, constraints and properties. As a result a subset of solution concepts are chosen for further consideration (convergent thinking). In the third stage the abstract solutions chosen in the second stage are transformed into concrete solutions by identifying actual resources that have the characteristics outlined by the abstract solution. In the process, materials, artifacts and procedures are found for solving the problem in several alternative and usually inventive ways. The method of "inventive thinking" provides the problem solver with well defined thinking tools that accompany each of the stages described above. For instance, the "amazing dwarfs" are often used in the solution process as a useful thinking tool enabling the problem-solver to view systems microscopically. These "dwarfs" are not constrained by physical reality and thus enable the problem-solver to use the imagination without prohibition. The use of these dwarfs together with a method for analyzing the relevant systems functionally lead to many alterative solution concepts of problems. These solution concepts are then transformed into actual solutions. In the dissertation 23 creative thinking tools are described. Each tool has a specific role in the design of the solution. The general heuristics offered by the method of "inventive thinking" together with the well defined thinking tools form the basis for the systematic nature of the solution process. The project yielded the following outcomes:  Two textbooks were written for students, two for teachers and s training guide for INSET (Helfman,2000).  A formative evaluation of the learning materials and teaching methods was carried out, leading to the changes and improvements in the model's contents, learning methods, and teaching methods.  The learning materials were used in studies held over two consecutive years – 1994 and 1995 – and were studied in seven ninth-grade classes (N=169). The detailed results are presented in the dissertation.  Thirty-two INSET courses were held throughout Israel, following which the model was applied (fully or partially) in dozens of 7th , 8th and 9th grade classrooms from 1996 to 2000. Since no previos research has been performed on the topic, we attempted to address the following questions: 1. How, and to what extent, does studying the "systematic inventive thinking" method contribute to ninth-graders' ability to solve problems in science and technology? 2. What are the attitudes of ninth-graders, and of teachers attending INSET courses, towards learning the topic of "systematic inventive thinking?" 3. Which problems are entailed in implementing "systematic inventive thinking" in science and technology curricula in Junior High Schools? The study was carried out in two parts. 1. A detailed study was carried out with 103 ninth grade students from 5 classes who studied the topic for an average of 50 hours during the school year. The performance of these students (experimental group) was compared with that of 117 students from 5 classes from the same school with similar background who did not study the topic (comparison group.) 2. A study focused on students' and teachers' views and attitudes was carried out by using questionnaires, interviews and informal observations. Following is a summary of the research results: 1. The detailed study of the students in the experimental group shows that they learned to organize their thinking in a systematic and conscious manner, and improved their ability to solve technological-scientific problems in a creativemethodical way. The process of searching for and discovering solutions generally took place at two levels: the abstract level (developing thought directions), followed by the concrete level (discovering specific solutions.) 2. Performance of the experimental group was compared with that of the comparison group, using three criteria (Guilford, 1959, 1967): thinking fluency, flexibility and originality. In order to evaluate hundreds of solutions, a methodology was developed for characterizing them according to the identity of the subsystems treated in the solution and the specific actions leading to the desired results. The choice of a given set of subsystems and specific actions lead to a well defined "thought direction" for solving the problem. This analysis led to three different measures associated with the previously mentioned criteria: a) The overall number of solutions that were proposed for the problem (thinking fluency) b) the number of thought directions that were developed for solving the problem (thinking flexibility) c) the number of abundant, original and unique solutions (thinking originality) The methodology was also used for diagnosis, enabling students and teachers to receive individual feedback about the thinking process and its outcomes. The students in both groups solved many problems in the course of the study. To gauge the effect of teaching method, three central problems (case-studies) were analyzed in detail. Each problem was solved both by individual students, and by teams. The analysis shows that the performance of the experimental students was significantly higher than that of the comparison students, in the criteria examined. In each of three problems, both in individual work and team work, the experimental group developed dozens of thought directions and dozens of unique solutions, which students in the comparison group had no considered. This fact indicates that students in the experimental group expressed more openness and flexibility of


Abstract Spatial distribution and habitat preferences of 55 river corridor plant species were analyzed on a local scale in the valley of a medium-size regulated river. The analysis was based on the results of a detailed mapping on a 50 km-long section of the Lower San River valley (366 cartogram cells of 1 square km). Selected species were divided into two groups: (1) strictly and (2) loosely confined to river corridors. River corridor plants were found throughout the valley (river channel, active and historical floodplain, older terraces, slopes); however, their frequency was diverse in particular areas. The highest concentrations were observed on the floodplain. Their number decreased towards the border areas of the valley. Species which were less confined to rivers were found more frequently in the valley (one species occupied, on average, 12.9% of grid cells), than plants strictly confined to the river system (one species occupied, on average, 5.9% of grid cells); however, the ranges of species of the second group were more restricted to the Holocene part of the valley, especially to the floodplain. River corridor plants were, ecologically, a highly diversified group. In the San river valley, they were found in riparian forests, pioneer ephemeral communities on the banks of water bodies, dry grasslands, meadows and old river beds; a lot of them grew in ruderal habitats.


Radial turbine featuring a Multi-channel Casing (MC) is a new design under investigation for enhancing the turbine controllability. The idea behind this new design is to replace the traditional spiral casing with a MC, which allows controlling the mass flow by means of opening and closing control valves in each channel. The arrangement of the closed and opened channel is called the admission configuration, while the ratio between the counts of the open channels to the total number of channels is called the admission percentage.
 Among several aspects, when applying different admission configurations, the aerodynamic damping during resonant excitation is considered during the design of the turbine. The present study aims at investigating the effect of different MC admission configurations on the aerodynamic damping as an extension to an aerodynamic forcing study, which already assessed the different forcing patterns associated with these different admission configurations.
 Due to the asymmetry of the flow in circumferential direction resulting from the different partial admission configurations, the computational model is solved as full 3D time-marching, unsteady flow using ANSYS CFX in a one-way fluid-structure analysis. Two different modeling approaches have been considered in this study to investigate their capability of predicting the damping ratio for different MC admission configurations: a) the conventional isolated rotor approach and b) a full model consisting of the rotor and its casing. The results show that the casing affects the aerodynamic damping behavior, which can only be captured by the full model. Furthermore, the damping ratios for all different admission configurations have been calculated using the full stage model.


In a modern system-on-chip design, hundreds of cores and intellectual properties can be integrated into a single chip. To be suitable for high-performance interconnects, designers increasingly adopt advanced interconnect protocols that support novel mechanisms of parallel accessing, including outstanding transactions and out-of-order completion of transactions. To implement those novel mechanisms, a master tags an ID to each transaction to decide in-order or out-of-order properties. However, these advanced protocols may lead to transaction deadlocks that do not occur in traditional protocols. To prevent the deadlock problem, current solutions stall suspicious transactions and in certain cases, many such stalls can incur serious performance penalty. In this brief, we propose a novel ID assignment mechanism that guarantees the issued transactions to be deadlock-free and results in significant reduction in the number of transaction stalls issued by masters. Our experimental results show encouraging performance improvements compared with previous works with little hardware and power overheads.


Spline functions that interpolate data given on the sphere are developed in a weighted Sobolev space setting. The flexibility of the weights makes possible the choice of the approximating function in a way which emphasizes attributes desirable for the particular application area. Examples show that certain choices of the weight sequences yield known methods. A pointwise convergence theorem containing explicit constants yields a useable error bound.


The antifouling properties of poly(ethylene oxide) (PEO)-silane amphiphiles as surface-modifying additives (SMAs) in a condensation cure silicone have been previously demonstrated against simple protein solutions. Comprising an oligo(dimethylsiloxane) tether (m = 13 or 30) and PEO segment (n = 8), sustained protein resistance was achieved even in the absence of a cross-linkable triethoxysilane group, particularly when comprising the longer tether. To probe their potential for thromboresistance, PEO-silane amphiphile SMAs were used to bulk-modify silicones and evaluated for adhesion resistance against whole human blood under both static and dynamic conditions. Both a cross-linkable (XL diblock, m = 13) and a non-cross-linkable (Diblock, m = 30) SMA were evaluated at various concentrations (5-50 μmol SMA/g silicone) in a condensation cure silicone. Under static conditions, silicones modified with either SMA at concentrations of 10 μmol/g or greater were effective in reducing adhesion of human fibrinogen and platelets. Dynamic testing further showed that modified silicones were able to reduce protein adsorption and thrombus formation. This occurred at 5 and 10 μmol/g for silicones modified with XL diblock, m = 13 and Diblock, m = 30 SMAs, respectively. Combined, these results indicate the effectiveness of PEO-silane amphiphiles as SMAs in silicone for improved thromboresistance.


Modern e-Learning Systems have reached an impressive level of complexity, and while the number of features has ever increased, the methods of interaction with students have remained mostly unchanged (chat, forum, internal messaging, e-mail). A rather habitual tool within e-Learning systems is the forum, through which members can have conversations that can be read later on in a logical order.
Within a classic e-Learning system, a student can post questions or answer somebody else's, but the posted messages themselves can be more or less to the point. Thus it is necessary for the teacher to follow the conversations and step in where applicable, but at the same time it would be ideal if the teacher could rate and review the posts, to point out how relevant or valuable they are, while providing feedback at the same time.
 The forum of an e-Learning system should provide additional features besides those commonly met in such a tool; it should be a forum that is adapted to e-Learning, with features for giving feedback to students, emphasizing valuable posts, and rewarding students.
 The current article offers a mechanism that can help fulfill the features mentioned above, by extending the classic forum of an e-Learning system with in-place elements that can be easily used by teachers and students altogether. It only takes a couple of clicks to give feedback, but it has a very high educational value within the e-learning process.
 The mechanism is part of an e-Learning system model MEM (Metacognitive E-Learning system Model), which was introduced in a previous paper, and it can be extrapolated to all types of forums.


Fifty-nine isolates of Salmonella enterica subsp. enterica (S. enterica) isolated from indigenous vegetables, 'selom' (Oenanthe stolonifera) associated with 13 different serovars were obtained from Chemistry Department of Malaysia. The isolates encompass the common serovar, Salmonella enterica subsp. enterica serovar Weltevreden (S. Weltevreden) (39%) and Salmonella enterica subsp. enterica serovar Agona (S. Agona) (8.5%). Frequencies of the other 11 Salmonella serovars were ranged from 1.7% to 5.1%. All isolates were characterized by Enterobacterial Repetitive Intergenic Consensus-Polymerase Chain Reaction (ERIC-PCR), random amplified polymorphic DNA (RAPD), plasmid profiling and antimicrobial susceptibility testing. The results demonstrated ERIC-PCR, RAPD and composite analysis of both are suitable typing methods for S.
enterica by demonstrating good discriminative ability and can be utilize as a rapid approach of comparing S.
enterica isolates for epidemiological investigation. From this study, ERIC-PCR is exhibited lower discriminatory
power when compare with RAPD. On the other hand, plasmid profiles yielded 32 profiles with molecular size ranging from 1129 bp to 17911 bp. Thirteen antimicrobial agents were included in this study and all isolates showed 100% (59/59) resistant to erythromycin and showed Multiple Antimicrobial Resistance (MAR) indexes ranging from 0.08 to 0.68. Dendrogram generated from antimicrobial resistance profiling exhibited poor discriminatory capability at serovar level. Although poultry still remain as the common reservoir for multidrug resistant (MDR) Salmonella. The isolation of 13 Salmonella serovars from selom that showed high MDR in this study is alarming. These results supported the notion that indigenous vegetable (selom) are gaining more antimicrobial resistance and could be potential health hazards.


Understanding the behavioral and neurocognitive relation between mind wandering and learning Judy Xu In the last decade, tremendous advances have been made in the effort to understand mind wandering, yet many questions remain unanswered. Chief among them is how mind wandering relates to learning. Insofar as mind wandering has been linked to poor learning, finding ways to reduce the propensity to mind wander could potentially improve learning. Two experiments were conducted to examine this. The first experiment evaluated how difficulty of the to-be-learned materials affected one's tendency to mind wander and revealed that people mind wandered when there was a mismatch between their level of expertise and the difficulty of materials studied. The second experiment compared whether participants were more likely to mind wander in blocked or interleaved conditions and showed that participants were more likely to mind wander when materials were presented in a blocked fashion. Together, these results indicate that techniques such as studying materials specific to one's own level of mastery or changing the way in which one studies might reduce mind wandering and improve learning. Of equal importance is the question of what happens on in the brain when a person mind wanders. While the effect of mind wandering on early sensory processing is known, the impact it has on learning-related processing is not. In two event-related potential (ERP) experiments, participants were asked to report whether they were mind wandering or not while studying materials they were later tested on. Analyses revealed that elaborative semantic processing – indexed by a late, sustained slow wave that was maximal at posterior parietal electrode sites – was attenuated when participants mind wandered. Crucially, the pattern when people were on task rather than mind wandering was similar to the subsequent memory effect previously reported by other memory researchers, suggesting that mind wandering disrupts the deep level of processing required for learning.


Background: Tobacco is the green leaf that was grown in warm climates. However,
cigarette is the most common method of consuming tobacco and contains many
different chemicals. Cigarette smoking was such a strong addition that was very
difficult to break. Therefore, a study is constructed to determine which chemical
constituents in tobacco leaf had a most significant influence on the rate of cigarettes
burn.

Main Methods: The multiple regression analysis was introduced in this study,
because the dependent variable was single quantitative dependent variable.
Preliminary, the data was filtered by running through the factor analysis and data
transformation. The filtered data then was divided into three partitions: model building
approach, verification by using MAPE and estimating the missing values. To obtain
the best model, in estimating the 4 phases would be carried out in model building
procedure, where NPC test, multicollinearity test based on VIF test and coefficient
test would be carried out in Phase2.

Main Findings: Eight selection criteria test had been explored and introduced in the
process of getting the best model, where the best model is found when it satisfied all
of the minimum values of the eight selection criteria. From the best model, there
were 3 variables emerged which had been included one single independent variable
of calcium and two first-order interaction variables such as, calcium interact with
potassium and chlorine interact with potassium. Moreover, based on the result in
second partition, P2, the MAPE value for the best model is 7.73%.

Conclusion: Calcium, potassium and chlorine were found to be the most significant
factors in estimating the rate of cigarettes burn. While, the estimation efficiency
(MAPE) results tend to signify that model is accepted.


2,6-Diacetylenyl- and 2,6-bis(arylacetylenyl)-functionalized pentamethyl-difluoroborondipyrromethene (BODIPY) derivatives, namely, PBDP1 and PBDP2–4 (aryl = phenyl, 4-methoxyphenyl, or 4-cyanophenyl), respectively, which exhibit extended π-conjugation, were synthesized and characterized by various spectroscopic methods. Significant bathochromic shifts in both absorption and emission were observed upon modifying the structure of the BODIPY core via the strategy of extending its π-conjugation. The derivatives displayed efficient emission in the yellow-to-red spectral region, with a high fluorescence quantum yield and a relatively large Stokes shift. Under conditions of transverse pumping in a cuvette, PBDP1 and PBDP2 exhibited highly efficient and stable laser activity for up to 180 and 110 minutes of continuous irradiation, respectively. Amplified spontaneous emission (FWHM of ca. 2.5 nm) with an efficiency of 41% and 36% was achieved for PBDP1 and PBDP2, respectively, in toluene, which had tunable ranges of 561 to 580 nm and 602 to 617 nm, respectively, on irradiation with a Q-switched Nd:YAG laser at 532 nm. The lasing properties of PBDP3 and PBDP4, which contain electron-donating (–OMe) and electron-withdrawing (–CN) arylacetylenyl moieties, respectively, were also investigated. A corresponding digold(I) diacetylide organometallic complex, namely, (PPh3)Au–CC–BODIPY–CC–Au(PPh3) (PBDP5) was also synthesized and characterized to study the effect of Au(I). PBDP5 exhibited phosphorescence in the vis-NIR region centered at 751 nm at 77 K owing to heavy-atom-induced intersystem crossing.


This report focuses on the relationship between walking and its contributing factors by applying spatial regression methods. Using the Vermont data from the New England Transportation Survey (NETS), walking variables as well as 170 independent variables are derived including some through spatial analysis with Geographic Information Systems (GIS). Among those independent variables, people's lifestyle and perception of the built environment variables are included. A linear regression model is first established to serve as a base model for comparisons with spatial regression models. The results reveal that people's lifestyle and perception of the built environment are significant variables explaining Vermonters' walking behavior. Methodologically, the results reveal that no spatial effect is found and that there are no significant differences between the linear and spatial regression models. Therefore, the study concludes that it may be appropriate to apply traditional non-spatial statistical tools to analyze the relationship between walking and its contributing factors. However, the study suggests that researchers examine whether spatial effect exists in these inherently spatial behaviors before using only traditional statistics. This caution is particularly relevant as methods to estimate spatial models become more commonplace and easily available. The two spatial methods used in this report both reveal small but different challenges.


Giacomo Boni (Venice, 1859-Rome 1925) was one of the international leading figures of Roman archaeology in the 20th century. Within the vast scientific literature concerning him and his work, the analysis of his meaningful relationship with the Japanese culture based on surviving historical sources has never been tempted. Indeed, since his youth Boni got in touch in Venice with Japanese artists destined for success in the coming decades. Once mature, the Venetian became also well known among Japanese archaeologists, even because he had been in 1921 the tour guide of the prince Hirohito at the Forum and the Palatine Hill. The paper tries to offer an overview on Boni's large network in Japanese artistic and political elites, broadly examining unpublished historical sources traced in public and private archives. The article also focuses on the influence of Boni's thought in the development of the discipline of archaeology in Japan.


BACKGROUND
Benznidazole is the drug of choice for Chagas disease. The major drawback of this drug is the high adverse events rate, being cutaneous reactions the most frequent one, leading to definitive withdrawal of treatment in 15%-30% of patients.

METHODS
Prospective observational study where adult Chagas disease patients accepting to receive benznidazole (100 mg/8 hours for 60 days) were included. The objective was to characterize the skin toxicity of benznidazole in patients with Chagas disease, determine the serum cytokine profile, and evaluate the potential association with specific HLA alleles and benznidazole concentration. Serum cytokine levels were measured at day 0, 15, and 60 of treatment. Class I and II HLA alleles were determined. When cutaneous reaction was detected, a skin biopsy was performed. Serum benznidazole concentration was determined at the time of cutaneous reaction, or at day 15 of treatment.

RESULTS
Fifty-two patients were included, 20(38.5%) had cutaneous reaction, and median time of appearance was 9 days. Skin biopsies showed histopathological findings consistent with drug eruption. Patients with cutaneous drug-reaction had higher proportion of eosinophilia during treatment, and higher interleukin (IL)-5 and IL-10 serum concentrations at day 15 of treatment than those without cutaneous reaction. Treatment interruption (that included moderate-severe cutaneous reactions) was more frequent in patients carrying HLA-B*3505 allele (45.5% vs 15.4%, P = .033). No differences in benznidazole serum concentration were found.

CONCLUSIONS
Benznidazole related cutaneous reaction rate is high, and it was produced by a delayed hypersensitivity reaction with a Th2 response. Carrying HLA-B*3505 allele could be associated with moderate-severe cutaneous reaction.