In Spring 2008, five student teams were put into competition to develop software for a Cambodian client. Each extended team comprised students distributed across a minimum of three locations, drawn from the US, India, Thailand and Cambodia. This paper describes a couple of exercises conducted with students to examine their basic awareness of the countries of their collaborators and competitors, and to assess their knowledge of their own extended team members during the course of the project. The results from these exercises are examined in conjunction with the high-level communication patterns exhibited by the participating teams and provisional findings are drawn with respect to quality, as measured through a final product selection process. Initial implications for practice are discussed.


With both rock art and ochre-stained marine shell ornamentation identified at the four Timor-Leste sites of Jerima-lai, Lene Hara, Matju Kuru 1, and Matja Kuru 2, it should not be surprising that almost one kilogram of colorants were also recovered from these same sites. Pieces displaying clearly identifiable use wear (grinding, scraping, rub-bing) were collected from the earliest levels of Jerimalai dating to around 40,000 cal. BP, and continued up through the deposit to the near present levels. Similar quantities and distributions were also found in Matju Kuru 1 and 2, along with Lene Hara. Alongside these colorant fragments were six stone implements displaying evidence for ochre processing, providing insights into the exact pigment producing tools used in this location. Also found was an artifact dated to >10,200–9909 cal. BP from MK2 which may be a fragment of a mastic including ochre as an in-gredient in its formation. Overall, this Timorese assemblage offers the ideal opportunity to explore ochre process-ing and use over a 40,000 year period in Island Southeast Asia — information which has been previously lacking.


EUCAM, in cooperation with Asian Development Bank, Carnegie Endowment for International Peace and the Wolfensohn Centre for Development (Brookings Institution), organised a conference on Regional Cooperation and Development in Central Asia. The event was hosted by CEPS on March 2-3, 2009. The gathering was marked by a broad range of perspectives on the constellation of interests, capacities and motivations regarding a more integrated Central Asia. Water resource issues that largely define the relationships between the Central Asian states were discussed from various angles by Central Asian and international experts and representatives of major donor agencies (Aga Khan Development Network and UNDP). This Commentary attempts to synthesize the diverse viewpoints and arguments put forward at this important event.


The circadian clock confers temporal regulation in metabolism, and its disruption leads to obesity and insulin resistance. In the current study, we identify that the opposing circadian clock regulators, transcription activator Bmal1 and its repressor Rev-erbα, exert concerted control of the actin cytoskeleton-MRTF/SRF pathway to drive beige adipocyte development, and that this clock regulatory axis is required for beige fat thermogenic capacity. Key components of the MRTF/SRF signaling display circadian oscillations in beige fat, and cistromic analyses revealed Bmal1 and Rev-erbα chromatin occupancy of genes involved in MRTF/SRF regulation. Genetic loss- or gain-of-functions of Bmal1 and Rev-erbα in adipogenic precursors markedly altered actin cytoskeleton organization. Bmal1 silencing inhibits F-actin formation and MRTF/SRF activity whereas its forced expression augments actin cytoskeleton. Notably, Bmal1 and Rev-erbα transcriptional control of the MRTF/SRF signaling modulates beige fat thermogenic capacity in vivo. Prrx1-Cre-mediated subcutaneous beige fat-selective Bmal1 ablation induced browning with augmented mitochondrial metabolism, resulting in resistance to obesity that improved insulin sensitivity. Conversely, overexpression of Bmal1 in beige depot suppressed the thermogenic program with adipose expansion and impaired glucose tolerance. In contrast, Rev-erbα gain-of-function phenocopied that of Bmal1 ablation, leading to browning of beige fat, resistance to obesity and insulin sensitivity. Mechanistically, we show that genetic loss of Bmal1 enhanced beige precursor differentiation and thermogenic induction, whereas Rev-erbα overexpression similarly promoted beige adipogenesis. Collectively, these findings uncover a novel concerted circadian clock control in beige adipocyte development that determines thermogenic capacity via the cytoskeleton-MRTF/SRF signaling cascade.

 X.Xiong: None. W.Li: None. R.Liu: None. V.Yechoor: n/a. K.Ma: None.

 NIH 1R01DK112794 to KM and DK097160 to VY


procedure (30 August, p 618). We fully endorse the recommendation concerning x-ray checks after insertion of the central catheter and also acknowledge that some may prefer to use the internal jugular vein. We note that in the case described where a pneumothorax developed "four passes of the needle" were made to place the line. The use of the Sonicaid probe has proved very effective in localising the vein and more than one attempt is now unusual.


Purpose - – The aim of this study is to analyse the transformation of the Ecuadorian financial system using the regulatory dialectic approach (Kane, 1977). This research examines the initial conditions and motivating factors of the reform process, as well as the interplay between government and bankers during the period 2007-2012. Design/methodology/approach - – Kane's regulatory dialectic suggests that regulation of financial institutions is a series of cyclical interactions between opposing political and economic forces. Three main stages are identified: thesis (measures and regulatory actions), antithesis (avoidance/lobby against those reforms) and synthesis (adaptive reregulation resulting from the interaction between interest groups). Findings - – Since 2007, the government focused on regulating interest rates, developing a liquidity fund for banking emergencies, increasing taxation and restricting international capital flows. These government initiatives took place against a background of conflicting interests. Private bankers opposed the majority regarding them as burdensome new rules, rather than enlightened reforms. Publicly, these reforms as intended by the government were seemingly supported. Finally through the political process, they were approved. To date, these reforms have strengthened the financial system, produced encouraging social policy results and placed the financial sector to serve the government's development strategy. Originality/value - – Using Kane's notion of regulatory dialectic, we explain the process of financial reform in Ecuador as part of a cyclical interaction between opposing forces. Drawing on this framework enabled insight into the nature of government intervention. Hence, we show how that intervention affected the growth, development and structure of the banking system.


with the notion of virtual servers, peers participating in a heterogeneous, structured peer-to-peer (P2P) network may host different numbers of virtual servers, and by migrating virtual servers, peers can balance their loads proportional to their capacities. The existing and decentralized load balance algorithms designed for the heterogeneous, structured P2P networks either explicitly construct auxiliary networks to manipulate global information or implicitly demand the P2P substrates organized in a hierarchical fashion. Without relying on any auxiliary networks and independent of the geometry of the P2P substrates, we present, a novel load balancing algorithm that is unique in that each participating peer is based on the partial knowledge of the system to estimate the probability distributions of the capacities of peers and the loads of virtual servers, resulting in imperfect knowledge of the system state. With the imperfect system state, peers can compute their expected loads and reallocate their loads in parallel. Through extensive simulations, we compare our proposal to prior load balancing algorithms.


Many AI (or ML) systems have been proposed for clinical decision support, providing diagnosis, prognosis or treatment recommendation. It is well known that the impact of these systems varies, with benefits such as improved decision making or time saved set against any potential harm introduced by the AI. The main technique proposed to evaluate impact is an 'Impact Study', a form of trial of a completed system. Vital though such studies are, they require at least a prototype system to be deployed which can be expensive. Meanwhile, the merits of AI predictors are mainly argued using accuracy measures, such as a confusion matrix or an AUC. We argue that the impact of a proposed AI system should be modelled during its development, to justify the expense of an Impact Study. We show that an Influence Diagram can be used for this and provide a small set of models for generic AI systems, with two main findings. First, we show that the way that an AI predictor is used – primarily how it interacts with clinical decision makers – is at least as important as its predictive accuracy. Indeed, we show that different uses of the same predictor vary in impact without any change in its accuracy. Secondly, we show that the proposed use of an AI predictor also determines the information needed to model its potential impact. Some information is always needed on the decision accuracy of existing clinical decision makers, but the form and extent of this varies.


As Subject Guide for Health and Social Care students at the University of South Wales. Mae'r dudalen hon hefyd ar gael yn Gymraeg


'Adjusting Sails' is a narrative inquiry which presents the stories of three secondary teachers who underwent transfer from one school to the other in the Maldives. This metaphoric journey also describes my journey as a narrative researcher, how I sailed into unknown waters with my participants, what I discovered, and the interpretations I drew from their experiences. Semi-structured interviews of teachers and transfer managers and the analysis of official correspondence of the transfer contributed to the richness of the data. The stories of the teachers were analyzed for common themes, partially corroborated by contrasting the data gathered from interviews with two transfer managers, and written in collaboration with the participant storytellers. Trustworthiness of findings was further enforced through member-checking and adhering to reflexive procedures. The findings of this study suggest that the three teachers found the transfer quite stressful and as having impacted negatively on their emotions and professional lives. Communication issues before and after the transfer, personal perceptions associated with the transfer as well as leadership practices in their new environments appeared to have given rise to de-motivation, stress and frustrations. Apart from contributing to existing literature on teacher transfer, this study highlighted factors that made the transfer a negative experience for teachers and provided evidence which may usefully inform school managements and future transfer policies on the impact a transfer can have on the emotional and professional well-being of teachers.


Background— Exercise performed at higher relative intensities has been found to elicit a greater increase in aerobic capacity and greater cardioprotective effects than exercise at moderate intensities. An inverse association has also been detected between the relative intensity of physical activity and the risk of developing coronary heart disease, independent of the total volume of physical activity. Despite that higher levels of physical activity are effective in reducing cardiovascular events, it is also advocated that vigorous exercise could acutely and transiently increase the risk of sudden cardiac death and myocardial infarction in susceptible persons. This issue may affect cardiac rehabilitation. Methods and Results— We examined the risk of cardiovascular events during organized high-intensity interval exercise training and moderate-intensity training among 4846 patients with coronary heart disease in 3 Norwegian cardiac rehabilitation centers. In a total of 175 820 exercise training hours during which all patients performed both types of training, we found 1 fatal cardiac arrest during moderate-intensity exercise (129 456 exercise hours) and 2 nonfatal cardiac arrests during high-intensity interval exercise (46 364 exercise hours). There were no myocardial infarctions in the data material. Because the number of high-intensity training hours was 36% of the number of moderate-intensity hours, the rates of complications to the number of patient-exercise hours were 1 per 129 456 hours of moderate-intensity exercise and 1 per 23 182 hours of high-intensity exercise. Conclusions— The results of the current study indicate that the risk of a cardiovascular event is low after both high-intensity exercise and moderate-intensity exercise in a cardiovascular rehabilitation setting. Considering the significant cardiovascular adaptations associated with high-intensity exercise, such exercise should be considered among patients with coronary heart disease.


In recent years, coulometric analysis has been developed and widely used as a technique for the determination of substances in solution by measuring the quantity of electricity required for the completion of a reaction in an electrolysis cell. Of two coulometric techniques, i. e., coulometric titration with a constant current and coulometric analysis with a controlled potential of a working electrode, the latter is more interesting to the author, because by this method both electrolytic separation and quantitative determination of chemical species can be achieved simultaneously. Especially, the use of a mercury cathode as the working electrode(1)) has an advantage that the optimum control potentials can easily be determinable from
polarographic data. In our laboratory, we took up the coulometry of uranium as one of the interesting themes of researches when we had an opPortunity in studying various kinds of analytical methods for uranium in accordance with the request by Japan Atomic Fuel Corporation. The coulometric determination of uranium (VI) by using
a mercury cathode at a controlled potential was studied by G. L. Booman, W. B. Holbrook and ]. E. Rein(2)). It was found to be very useful for the analysis of uranium in a highly enriched nuclear element which underwent fission to an appreciable
extent. But the instrument used by them(3)) was complicated and expensive. Therefore, a simple counter millicoulometer has been coustructed in our laboratory, a readymade potentiostat (electrical instrument for automatic controlled potential electrolysis) being tried for electrolysis. By these instruments, the author studied the fundam ental conditions of coulometry for uranium and tried the successive determinations of uranium and thallium in mixed solutions.


This paper constructs a reading miscue detection system based on conventional Large Vocabulary Continuous Speech Recognition (LVCSR) framework. In order to incorporate the knowledge of reference (what the reader ought to read) and some error patterns into the decoding process, two methods are proposed: Dynamic Interpolation of Language Model (DILM) and Dynamic Multiple Pronunciation Incorporation (DMPI). DILM dynamically interpolates the general language model based on analysis of reference and so restricts the active paths of decoding not too far away from the reference. It makes the recognition more accurate, which further improve the detection performance. DMPI dynamically adds some pronunciation variations into the search space to predict reading substitutions. It solves the con¿iction between the coverage of error predictions and the perplexity the search space. The experimental results show that the proposed two methods can totally decrease EER by 14% relatively totally, from 46.4% to 39.8%.


This book is unique in its field.

The content explores the chemistry and physics relating to the materials used in the various printing processes, including: inks; their chemistry, composition and rheology; paper; the chemistry and physics of its bulk and surface properties and how these are engineered to influence the behaviour of the paper both during printing and in the printed product; polymers, their chemistry and uses in the many printing applications including subtrates, ink formulations and printing plates; recycled paper, the chemistry of de-inking, flotation and manufacture of recycled papers including newsprints and quality papers; The optics of substrate surfaces including the roles of gloss, scattering, reflection and refraction and their impact on print quality; colour chemistry and the molecular chemistry of dyes and pigments used as colorants in inks; modern digital imaging and platemaking techniques including the science of platemaking for conventional plates and the newer computer to plate material.

The book is aimed to present the reader with a progressive study of chemistry and physics which can take the reader to different levels of complexity. So, the target audiences are at postgraduate as well as undergraduate levels, and industrial research laboratories.

This edition looks closely at the latest developments which have taken place in digital imaging techniques applied to both digital printing and plate making. In digital imaging, developments, proofing technologies and the latest digital printing techniques are explained and compared. New technologies including magnetographic, masterless presses and electrocoagulation are reviewed. Recent developments in ink jet printing systems include tone-jet, flat-jet and multi-drop technologies.

The science and technology behind new materials, including photograde ink jet colorants, microporous and water swellable photopaper substrate media are introduced. The technologies behind the exciting recent innovations of electronic paper (E-paper) and electronic inks (E-inks) are explained.


In this article we examine how partner choice and strategies of social reproduction among the Wampar of northeastern Papua New Guinea are implicated in currently pressing questions about the future of Wampar as a socio-cultural unit. We use long-term qualitative and quantitative data based on fieldwork and census surveys conducted between 1954 and 2013 from the village of Gabsongkeg to analyse temporal and spatial patterns of partner choice. We are especially interested in interethnic marriages and their effects on group boundaries and group identities, given a pre-existing pattern of ethnic endogamy. Our results show that intermarriages between Wampar and non-Wampar have constantly been rising; in younger marriage cohorts some 60% of Wampar individuals are intermarried with partners of other ethnic identities. The data reveal that local and historical particularities inflect partner choices in ways that impact on settlement patterns, modes of engagement with the economic institutions of the modern state and, ultimately, the taken-for-granted nature of the identity inhering in the name "Wampar"; these impacts, in turn, increase the likelihood of interethnic marriage and precipitate questions about the rights attaching to local corporate identities under conditions where land is increasingly related to its commodity values.


ABSTRACT Journalistic branding in the age of social media has been attracting growing academic interest. Self-branding has become an everyday routine among journalists, but the very limited scholarship on journalistic branding on social media has largely focused on national or local journalists in single democracies, ignoring foreign correspondents, who traditionally enjoy more professional autonomy but are going social under the challenges in the age of social media. This study looks at how foreign correspondents in China, with a heavily regulated and censored social media environment, use Twitter for journalistic branding, and examines the dynamics of this branding. The Twitter profiles of 129 China correspondents and 1,249 of their tweets were content analyzed, with the findings suggesting that foreign correspondents in China use Twitter primarily for broadcasting rather than networking. They also emphasize organizational identity much more than personal one. The implications of those findings and the extent to which they might be specific to China are discussed.


Cultural transmission between individuals can take various forms. One-to-many transmission refers to the case when each individual in a population socially acquires cultural traits from one particular individual who occupies a special social status, such as teacher or powerful authority. Researchers have argued that one-to-many transmission accelerates cultural change compared with one-to-one transmission, which occurs between a pair of individuals. In contrast, a recent mathematical analysis has demonstrated that the rate of cultural change is not necessarily higher with one-to-many transmission under the assumption that cultural variants are selectively neutral. Here we analyze models of one-to-one and one-to-many transmission in a situation where cultural variants are not selectively neutral. Our analysis suggests that one-to-many transmission tends to show higher rate of cultural change than one-to-one transmission when cultural variants are selectively disfavored.


Epistemological beliefs about Mathematics are associated with students' cognitive performances and effective responses. This study aims to investigate the epistemological beliefs of students about the Mathematics curriculum and their relationship with academic achievement. In this study, a quantitative research approach through the correlational method was used. 600 students from 20 public secondary schools of the Lahore District were selected through two-stage random sampling. Conceptions of Mathematics Inventory were adapted after ensuring its validity and reliability in our local context. The reliability of the inventory was α = 0.917. It was found that secondary school students had sophisticated epistemological beliefs about Mathematics curriculum beliefs about formulas; which are significant in Mathematics as they represent useful ideas and are based on the certainty of knowledge. Moreover, students' epistemological beliefs were positively correlated with their Mathematics academic achievements. It is recommended that teachers may try to recognize the Mathematics epistemological beliefs of students as they commence a new session of classes and take care of appropriate instructions that enhance students' Mathematics epistemological beliefs.


Understanding population characteristics and residential patterns of recent and long-standing older immigrants is important to ensure that settlement services are adequately supporting a diverse and vulnerable population. This research paper represents a pilot study to fill in the gap found in the already limited scholarship on the characterization, spatial distribution and in-group differences of older immigrants in the Toronto CMA. Firstly, it explores the nuanced differences in population composition of four ethnocultural-specific subgroups representing long-standing (Italian and Portuguese) and recent immigrants (Chinese and South Asian) and secondly, it identifies clusters of recent immigrants that are settling outside of the long-standing ethnocultural enclaves. Despite having higher rates of education than their long-standing counterparts, Chinese and South Asian are characterized by low income prevalence and lack of knowledge of an official language. Hence, determining the multilingual composition of the South Asian and Chinese subgroups can facilitate language-specific settlement services within recent older South Asian and Chinese immigrant clusters.

Key words: older adults, immigration studies, recent immigrants, settlement challenges, low income, hot spot analysis, Toronto Census Metropolitan Area


In this paper we present an application of Constraint Logic Programming to the design and implementation of type inference algorithms for programming languages. We present implementations in Prolog and Constraint Handling Rules (CHR) of several algorithms which belong to the state of the art of type inference for programming languages: the Damas-Milner type system, the Ohory system for labeled records and the Rank-2 Intersection Type system. In our implementation the differences between the general aspects of the type inference algorithms and the constraint resolution modules become more clear, when compared to other implementations of the same systems, usually made in a functional programming language. In the constraint modules, solving equality constraints, here implemented by Prolog unification, is completely separated from constraint simplification, which is made by solvers implemented in CHR for each system. Constraint Logic Programming revealed to be a highly declarative specification and implementation language for type inference algorithms.


Microturbines (MTs) are currently being deployed as small scale on-site distributed generators for microgrids and smart grids. This calls for extensive off-line and real-time research for analyzing the load following performance of MTs under islanded and grid-connected modes of operation at distribution voltage level. This paper presents development and simulation of MT models to analyze its load following performance with general as well as critical priority loads. Load following analysis of the models are carried out through Matlab simulations for both standalone and grid-integrated modes of operations. Two MT models are considered for performance analysis. MT Model-1 comprises speed governor, acceleration control and temperature control blocks. It is assumed that MT is operating under normal operating conditions (neglecting its fast dynamics). Speed control operates on the speed error formed between a reference speed and rotor speed. Speed control is usually modelled by using a lead-lag transfer function or by a PID controller. MT Model-2 is based on the standard GAST model. The real power control is described as conventional PI-control function. The MTgenerator unit consists of the MT coupled to a synchronous generator. The unit is integrated to the utility distribution system at the point of common coupling (PCC). It can be connected/disconnected to distribution system by operating the PCC circuit breaker.


This dissertation examines the extent to which proximity to markets - as measured by market potential, the trade cost-weighted sum of surrounding regions' GDP - can explain late-nineteenth century Europe's regional per capita income differentials. The research questions are: (1) was the spatial distribution of regional income random; (2) how helpful are traditional explanations - coal and institutions - of regional income; (3) how helpful is market potential when controlling for traditional explanations; and (4) did market potential have an effect on other determinants of income? This dissertation finds that: (1) the distribution of regional per capita income increasingly concentrated in the northwest; that there was little tendency to income convergence; and regional inequalities were higher within than between countries; (2) while a measure of regional institutions is correlated with income, simple distance-to-coal and a cost-to-coal measures are not; (3) market potential has a significant effect on income; foreign market potential more so than domestic; and increasing core relative to peripheral market potential results in perpherial income losses; and
(4) changes in literacy rates, a proxy for human capital, responded to changes in market potential. In conclusion, a new economic geography framework with market potential at its core fits the historical experience well. Certain regions performed better than others generally because they had cheaper access to markets. At the start of the period, trade costs were high, and so economic activity - long concentrated in Britain - was spread out more or less evenly across the Continent. By the end of the period, when trade costs dropped dramatically, economic activity concentrated in the northwest of Europe at the cost of the periphery.


Sporadic amyotrophic lateral sclerosis is a motor neuron disease of unknown origin. Autoimmunity against voltage-gated calcium channels is one mechanism hypothesized to be the cause of the disease. In support of this hypothesis, it was previously reported that amyotrophic lateral sclerosis IgG specifically blocked the binding of 8B7 monoclonal antibody to the IX I subunit of voltage-gated calcium channels, suggesting overlapping epitopes of the two antibodies. It is, however, possible that the 8B7 epitope was destroyed by proteases. Data presented here show that the blocking of 8B7 binding to the a1 subunit by diethylaminoethyl cellulose (DEAE)-purified amyotrophic lateral sclerosis IgG was not observed with Fab fragments of amyotrophic lateral sclerosis I&. The blocking was prevented by serine protease inhibitors. Moreover, it was reproduced by plasminogen and urokinase. These observations suggest that raised proteolytic activity in amyotrophic lateral sclerosis IgG preparations may be responsible for the blockade of 8B7 monoclonal antibody demonstrated previously. They also indicate the need to be particularly cautious when interpreting the results of incubation in amyotrophic lateral sclerosis sera or IgG preparations. Furthermore, they suggest that proteases may be partly responsible for some of the effects previously described for amyotrophic lateral sclerosis IgG. However, the proteolytic activity needs to be better defined and its possible role in amyotrophic lateral sclerosis investigated.


Reusable development can promote the productivity of large workflow systems development. However it has not precluded developers from designing workflow system tailoring to users' specific needs, though workflow management coalition standardized the five kinds of abstract interfaces of workflow enactment service in workflow reference model. Specific business process characteristics are still supported by specific workflow system. Method of software reuse is introduced to enhance reusability of the core of workflow system, i.e. workflow engine. In component environment, general functionalities of workflow engine are abstracted from business component, resulting in that the reusability of business component is extended into workflow engine. So two aspects are considered, i.e. component-based business processes development and reusable workflow engine development. The proposed approach is supported by a set of composition methods and reuse strategies. Through application and comparison, we show that different business requirements are met by reusing the


Background There are around 450 rare bone diseases and 10 main types of vasculitis with differing impact on patients and health services. Historically, tests and treatments designed for more common disorders have been applied to both sets of conditions with variable results. Rudy is a recent NIHR funded UK research registry, with strong emphasis on patients' self-reported outcomes, which aims to create a national cohort of patients with rare diseases of the bone, joints and blood vessels. The long term vision is to enable large scale genetics and epidemiology studies and facilitate patient recruitment for clinical trials and biomarker studies. Objectives To analyse the patient self-reported outcome data registered in RUDY up to January 2015. Methods Collaboration between the National Health Service, Academia, Industry and patients' associations was established. Participants with a clinical diagnosis of a rare disorder of the bones, joints or blood vessels with a prevalence of less than 1:5000 were recruited using a web based platform. The diagnosis and demographics were registered and one set of questionnaires was offered for completion to all patients. Results There were 133 patients (71% females) registered; mean age 44.6±18.1 years [3-81] with 10 patients <18 years. Rare bone or joint disorders were more frequent (65%), particularly fibrous dysplasia. The most common diagnosis of vasculitis was granulomatosis with polyangiitis (GPA) (49%) [Table]. On line assessments of general health were performed: EQ5D-5L was completed by 56% of patients with a mean score of 2.2±1.2 in mobility, 1.6±0.9 in self-care, 2.1±1.1 in usual activities, 2.6±0.9 in pain/discomfort and 1.8±0.8 in anxiety/depression (range 0-4, best to worst) and 68.4±19.9 general health (range 0-100, worst to best); SF-36 by 53% of patients with a mean score of 47.1±40.3 in physical functioning, 29.3±45.5 in limitations due to physical health, 58.1±49.3 in limitations due to emotional problems, 40.6±27.3 in energy/ fatigue, 69.2±26.1 in emotional wellbeing, 61.3±29.5 in social functioning, 53.9±28.1 in pain and 40.2±30.0 in general health (range 0-100, worst to best); Nottingham ADL score by 59% of patients with a mean score of 19.1±3.9 (range 0-22, worst to best); and Pittsburgh Sleep Quality Index by 56% of patients with a mean score of 9.8±4.0 (range 0-21, best to worst). Pain was further assessed through the Pain detect and McGill pain questionnaires in 53% of patients. Paediatric participants have recently been asked to fill the Childhood Health Assessment, Paediatric Quality of Life and Wong-Baker faces' questionnaires. Other disease specific questionnaires, prospective evaluation of the outcome measures assessed, and the construction of a bone fracture map and a family tree for relatives to participate in are being developed. Conclusions The RUDY project provides an easy way to collect valuable data and facilitate research on patients with rare diseases of bone and in the vasculitides. A significant proportion of patients reported impairment in several domains of their quality of life and function, highlighting the need for a better understanding of these conditions. Disclosure of Interest None declared


A newborn presented with airway obstruction due to a large nasopharyngeal mass extending into the oropharynx. A diagnosis of teratoma was made by transoral fine needle aspiration (FNA) biopsy and confirmed by subsequent histologic studies. The cytologic features of nasopharyngeal teratoma are presented, and the diagnostic utility of FNA biopsy in evaluating such lesions is discussed.


INTRODUCTION
The epidemiological transition model proposed by Omhran at the beginning of the 1970s (decreased fecundity rate and increased life expectancy), together with modifications in lifestyles and diet, showed increased mortality due to chronically degenerative causes. This essay thus discusses and makes a comparative analysis of some currents of thought, taking as its common thread an analysis of epidemiological change identified in different eras or stages and relationships with some public health models or conceptual frameworks.

DISCUSSION
Discussing public health paradigms leads to a historical recapitulation of conceptual models ranging from magical-religious conceptions to ecological and socio-medical models. M. Susser proposed 3 eras in this discipline's evolution in his speech on the future of the epidemiology.

CONCLUSION
The epidemiological changes analysed through different approaches constitute elements of analysis that all models discussed in this essay include to delimit the contributions and variables so determining them.


Hyperimmune sera against spherules and against arthrospores of Coccidioides immitis were prepared by inoculation of rabbits. The antibody content of these sera was studied by the agar gel diffusion method. It was observed that antispherule pooled sera formed multiple precipitin bands with extracts of spherules and of arthrospores. The antiarthrospore pooled serum, however, failed to precipitate with the spherule extract, and formed a single band in the presence of an arthrospore solution. When the spherule and the arthrospore extracts were tested with a variety of different antisera, it was observed that the spherule preparation formed bands only in combination with anti-purified spherule pooled serum, whereas the arthrospore extract precipitated with anti-purified spherule, antiarthrospore, and anti-Histoplasma capsulatum pooled sera. It was also observed that a spherule culture supernatant solution formed five precipitin bands in combination with anti-spherule pooled sera, formed one band with pooled antiserum from rabbits with coccidioidomycosis, and did not precipitate in the presence of antiarthrospore pooled serum. Coccidioidin, however, formed two bands in the presence of any of these antisera. It was therefore concluded that extracts from the spherule phase of C. immitis differed from solutions obtained from the arthrospore and mycelial phases.


The heterodimeric HU protein, isolated from Escherichia coli, is associated with the bacterial nucleoid and shares some properties with both histones and HMG proteins. It is the prototype of small bacterial DNA binding proteins with a pleiotropic role in the cell. HU participates in several biological processes like cell division, initiation of DNA replication, transposition, and other biochemical functions. We show here that bacteria lacking HU are extremely sensitive to 'y irradiation. Expression of either one of the subunits of HU in the hupAB double mutant nearly restores the normal survival rate. This shows that the sensitivity is due to the absence of HU rather than being the result of a secondary mutation occurring in the hupAB cells or a modification of the SOS repair system, since SOS genes are induced normally in the absence of HU. Finally, in vitro studies give an indication of its potential role: HU protects DNA against cleavage by y-rays.


The SEMARA approach, an integration of the Simplified and Robust Surface Reflectance Estimation (SREM) and Simplified Aerosol Retrieval Algorithm (SARA) methods, was used to retrieve aerosol optical depth (AOD) at 550 nm from a Landsat 8 Operational Land Imager (OLI) at 30 m spatial resolution, a Terra-Moderate Resolution Imaging Spectroradiometer (MODIS) at 500 m resolution, and a Visible Infrared Imaging Radiometer Suite (VIIRS) at 750 m resolution over bright urban surfaces in Beijing. The SEMARA approach coupled (1) the SREM method that is used to estimate the surface reflectance, which does not require information about water vapor, ozone, and aerosol, and (2) the SARA algorithm, which uses the surface reflectance estimated by SREM and AOD measurements obtained from the Aerosol Robotic NETwork (AERONET) site (or other high-quality AOD) as the input to estimate AOD without prior information on the aerosol optical and microphysical properties usually obtained from a look-up table constructed from long-term AERONET data. In the present study, AOD measurements were obtained from the Beijing AERONET site. The SEMARA AOD retrievals were validated against AOD measurements obtained from two other AERONET sites located at urban locations in Beijing, i.e., Beijing_RADI and Beijing_CAMS, over bright surfaces. The accuracy and uncertainties/errors in the AOD retrievals were assessed using Pearson's correlation coefficient (r), root mean squared error (RMSE), relative mean bias (RMB), and expected error (EE = ± 0.05 ± 20%). EE is the envelope encompassing both absolute and relative errors and contains 68% (±1σ) of the good quality retrievals based on global validation. Here, the EE of the MODIS Dark Target algorithm at 3 km resolution is used to report the good quality SEMARA AOD retrievals. The validation results show that AOD from SEMARA correlates well with AERONET AOD measurements with high correlation coefficients (r) of 0.988, 0.980, and 0.981; small RMSE of 0.08, 0.09, and 0.08; and small RMB of 4.33%, 1.28%, and -0.54%. High percentages of retrievals, i.e., 85.71%, 91.53%, and 90.16%, were within the EE for Landsat 8 OLI, MODIS, and VIIRS, respectively. The results suggest that the SEMARA approach is capable of retrieving AOD over urban areas with high accuracy and small errors using high to medium spatial resolution satellite remote sensing data. This approach can be used for aerosol monitoring over bright urban surfaces such as in Beijing, which is frequently affected by severe dust storms and haze pollution, to evaluate their effects on public health.


Electronics to be used in space must often perform in high temperature or radiation hard environments that render conventional solid‐state technologies unable to meet mission requirements. As a result, microscale and nanoscale field emission devices are being explored as fundamental components of electronics capable of operating in these harsh environments. Wide scale implementation of these devices is hindered by the difficulty of fabricating large, mechanically stable, uniform arrays of sharp emitting tips. This work presents a scalable method to produce uniform arrays of field emitting tips. Polystyrene spheres are applied as a template for electrochemical deposition. An electrochemical etching process is developed to sharpen tips to a radius of curvature of 5–10 nm, optimizing them for field emission applications. The flexibility of the fabrication process allows for device optimization in terms of tip geometry, density, and constituent material to achieve high field enhancement factors, exceeding 100. Miniaturized field emitting diode and gated triode devices are fabricated. Finally, the electrochemically deposited material is used as a scaffold for the deposition of a refractory, low work function emitting layer, and the hybrid cathode is characterized as a field emitter at temperatures up to 300 ºC.


ABSTRACT Political ideology is often characterized along a liberal–conservative continuum in the United States and the left–right continuum in Europe. However, no study has examined what this characterization means to young Turkish voters or whether it predicts their approach to morality. In Study 1, we investigated in two separate samples the relation between young Turkish participants' responses to the one-item left-to-right political orientation question and their self-reported political ideologies (conservative, socialist, etc.). In Study 2, we investigated the relation of moral dimensions as defined by Moral Foundations Theory to political party affiliation and political ideology. Results revealed that CHP, MHP, and AKP voters display a typical right-wing profile distinct from HDP voters. Findings regarding political ideology measures were consistent with party affiliations. Taken together, the findings reveal the distinctive nature of young Turkish people's political orientations while supporting the predictive power of the one-item political orientation question.


This study was carried to determine the best seed mixture of vetch and triticale for East Mediterranean rainfed conditions of Turkey. The experiments were conducted in two locations, Adana and Kozan, during the years of 2003 - 2005. The field trials were arranged in a randomised block design with three replications. In the research, pure stands of vetch and triticale and their seed mixtures (80% vetch + 20% triticale, 60% vetch + 40% triticale, 40% vetch + 60% triticale, 20% vetch + 80% triticale) were studied. Crude protein concentrations, hay and crude protein yields of pure stands and the mixtures and the percentage of vetch in the dry matter yield were determined. In addition to these, relative yield total (RYT) values were calculated for the mixtures. The study showed that the characters studied were significantly influenced by years, locations and mixtures. According to the averaged values of two years, the seed mixture containing 20% vetch and 80% triticale gave highest dry matter yield with an average vetch content of 23.5% under Adana conditions, while the seed mixture of 40% Vetch + 60% triticale gave the highest dry matter yield with an average vetch content of 10% under Kozan conditions. RYT values for the mentioned mixtures were 1.12 and 1.20, respectively. It was concluded that the above mixtures of vetch and triticale could be recommended for the locations in Adana and Kozan, respectively.


ABSTRACT The Lyme disease-associated spirochete, Borrelia burgdorferi, is maintained in enzootic cycles involvingIxodes ticks and small mammals. Previous studies demonstrated that B. burgdorferi expresses outer surface protein A (OspA) but not OspC when residing in the midgut of unfed ticks. However, after ticks feed on blood, some spirochetes stop making OspA and express OspC. Our current work examined the timing and frequency of OspA and OspC expression by B. burgdorferi in infected Ixodes scapularis nymphs as they fed on uninfected mice and in uninfected I. scapularis larvae and nymphs as they first acquired spirochetes from infected mice. Smears of midguts from previously infected ticks were prepared at 12- or 24-h intervals following attachment through repletion at 96 h, and spirochetes were stained for immunofluorescence for detection of antibodies to OspA and OspC. As shown previously, prior to feeding spirochetes in nymphs expressed OspA but not OspC. During nymphal feeding, however, the proportion of spirochetes expressing OspA decreased, while spirochetes expressing OspC became detectable. In fact, spirochetes rapidly began to express OspC, with the greatest proportion of spirochetes having this protein at 48 h of attachment and then with the proportion decreasing significantly by the time that the ticks had completed feeding. In vitro cultivation of the spirochete at different temperatures showed OspC to be most abundant when the spirochetes were grown at 37°C. Yet, the synthesis of this protein waned with continuous passage at this temperature. Immunofluorescence staining of spirochetes in smears of midguts from larvae and nymphs still attached or having completed feeding on infected mice demonstrated that OspA but not OspC was produced by these spirochetes recently acquired from mice. Therefore, the temporal synthesis of OspC by spirochetes only in feeding ticks that were infected prior to the blood meal suggests that this surface protein is involved in transmission from tick to mammal but not from mammal to tick.


When assessing the reliability of tubular offshore structures a major source of uncertainty is the magnitude of the fluid loading. This is usually estimated using Morison's equation which in turn requires estimates of the water particle kinematics, the size of the tubular members and the magnitude of the empirical force coefficients. This paper addresses the last two aspects both of which are greatly effected by the presence of marine growth. The paper begins by considering the a prior prediction of the type of marine growth which will occur on a North Sea structure and the way in which various types of growth tend to spread over the structure and overlay one another. Data is presented on the mean and variance of the final thickness of the growth and the size of individual species. A review of all the know laboratory and other experiments to estimate the effects of marine growth on the fluid loading of circular cylinders has been undertaken. From these data estimated of the mean and variance of the force coefficients associated with the various types of marine growth are presented and discussed.


Marine energy, especially tidal current and ocean wave resources, bear immense potential for generating renewable power toward meeting global electricity needs. A number of conversion technologies have been successfully demonstrated worldwide and precommercial/commercial deployments are expected to appear in the near future. While electric power utilities foresee renewable technologies as a viable alternative to fossil fuels, marine energy technologies are generally excluded in their energy planning processes. Lack of technological preparedness and unavailability of device information are two major obstacles in that regard. This article provides an insight on how such novel schemes of power generation can be analyzed under conventional network planning exercises using generic information. The first study focuses on wave power integration along the coasts of Oregon, USA for the year 2019 and analyzes the Northwest electrical network. The second study considers both tidal current and ocean wave resources in South Korea for the years 2017 and 2022. The primary objective of these high-level grid scenario analysis is to identify the practical potential for longer term large-scale wave and/or tidal power generation, particularly focusing on the transmission networks. Steady-state (overloading and voltage deviations/collapses), time-domain (angular stability and dynamic voltage recovery characteristics), and small-signal (eigenvalue) stability analysis are carried out for these systems. Subsequent to establishing a number of study scenarios, N-1 contingencies and various suitable violation criteria are prepared, which are used in identifying the underlying network bottlenecks, especially within the coastal areas. Simplified generic dynamic models of tidal current and ocean wave devices are developed for the time-domain analysis. It is expected that similar studies, once conducted by the interested utilities, will equip them better toward considering marine energy in their future portfolios. In addition, device manufacturers and project developers will have greater confidence in the emerging marine energy market.


Intraocular (i.o.) infection of mice with scrapie produces strain-specific targeting of replication and subsequent pathology within the visual system projection areas in the CNS, but also initiates an extraneural infection. Following i.o. infection with ME7 scrapie, infectivity was detected 24 h later in the Harderian gland, the superficial cervical lymph nodes (SCLNs) and the spleen, but not until 20 days in Peyer's patches and inguinal lymph nodes (ILNs). Persistent low levels of infectivity were found in the Harderian gland (which lies within the orbit), but the presence of PrP could not be confirmed by immunolabelling or Western blotting. SCLNs contained maximal amounts of infectivity by 20 days post-infection and remained at this level throughout the incubation period. ILNs reached a similar plateau at 60 days, as did Peyer's patches at 80 days and spleen at 100 days. Further investigation of the role of the spleen in pathogenesis showed that in contrast to ME7 scrapie, mice infected with 79A scrapie had high levels of infectivity in the spleen by 20 days post-infection, irrespective of the route of infection. In addition, the disease developed more rapidly following direct intrasplenic infection with ME7 scrapie than with intraperitoneal infection. Splenectomy at 7 days either before or after i.o. infection had no effect on the incubation period. These results indicate that the rate of replication of infectivity is both tissue and scrapie-strain dependent, and that extraneural spread of infection can occur via the lymphatic system.


The spectral induced polarization (SIP) method is a promising method for many near surface applications, including characterization of contaminated soil. In this study, SIP measurements, high-resolution X-ray tomography and image analysis are combined to investigate clean and tetrachloroethylene (PCE) contaminated sand. This is the first known combination of these methods and the aim of this paper is to demonstrate some powerful possibilities of using X-ray tomography in SIP research. X-ray tomography enables a direct visual control of the sample conditions and quantification of relevant sample properties via image analysis techniques. The image stacks from were processed with image analysis techniques, so that individual grains and PCE phases could be extracted from the sample volume. This enabled calculations of relevant sample properties such as PCE blob volumes, grain diameter, -surface area and –eccentricity as well as bulk porosity, specific surface area to pore volume and proportion of high-density grains. We conclude that the combination of SIP measurements and X-ray tomography have a great potential of increasing the understanding of SIP mechanisms in geological materials. The tomography results can be used both to calculate properties relevant for SIP interpretation as well as 3D modelling of the pore space.


The amine regenerator of acid removal unit in South Pars Gas Complex, Assalouyeh, Iran was modeled. This model was fitted to assess the large scale columns and allow application of solar thermal energy for production of low pressure steam. Heat transfer fluids including Therminol oil, sulfur, or salt melt could be applied to yield thermal energy from a solar collector and to store and transfer it to the reboiler of columns. The Angstrom model was adopted here to simulate solar irradiance. Solar irradiance data for the city of Assalouyeh, during the years of 2009-2014, were collected and applied. The results indicated that based on a reboiler duty of around 21.8 MW, a solar collector area of 148,000 m2 was required with a mass of heat transfer and storage medium of 1247255 kg oil, 1787732 kg salt melt and 3803686 kg sulfur, respectively. This model was applied as an analytical tool to explore and describe the following two problems encountered during real plant operation: fouling in the amine heat exchangers and increasing regenerator pressure.


Curie temperatures of R2Fe17 and RTiFe11 (R=rare earths) can be raised drastically by addition of interstitial nitrogen. Can one see similar effects in Nd2Fe14B? This question is particularly interesting because Nd2Fe14B's relatively low Curie temperature has limited its applications in high temperature operations. Nitrogen additions by heat treating Nd2Fe14B in flowing N2 at different temperatures have been reported to raise its Curie temperature by 20–50 °C. We report an attempt of nitriding Nd2Fe14B by mechanical alloying it with Li3N. Our attempt resulted in the formation of a rare form of neodymium nitride, NdN2. The original goal to nitride Nd2Fe14B by mechanical alloying it with Li3N seems to be inapplicable.


A package, named VLSI array architectures synthesizer (VAAS), to synthesize VLSI array architectures for DSP applications is presented. VAAS has been imbedded with the systematical synthesis method for systolic arrays, two-level pipelined systolic arrays, and multiple-array architectures. It provides a design environment with an algorithm description language, 3D graphical representations, performance evaluation, array simulation, a library of systolic algorithms, etc. Based on the environment, feasible VLSI array architectures for a DSP application can be exploited quickly. Two design examples are used to demonstrate the package.<<ETX>>


Information is limited on the influence of range condition on cattle diets in the Chihuahuan desert. Botanical composition of cattle diets on Chihuahuan desert ranges in excellent and good condition was studied by microhistological analysis. Cattle feces were analyzed seasonally from fall 1991 through fall 1992. Excellent condition and good condition ranges supported 86% and 72% of the climax vegetation, respectively. Key species in cattle diets on the excellent condition range were black grama (Bouteloua eripoda Torr.) and threeawns (Aristida spp.). On the good condition range the key species were dropseeds (Sporobolus spp.), threeawns and black grama. Total grass and black grama content of cattle diets were greater on the excellent condition range. Seasonal trends occurred in cattle diets on good condition but not on excellent condition range. Low availability of forbs and shrubs explained the high diets similarities among seasons on the excellent condition range. Cattle on good condition range readily used forbs and shrubs when green grass was unavailable. Nitrogen and phosphorus analyses of fecal samples indicated diets were nutritionally superior on the good compared to the excellent condition range. Our research and other studies show consumption of forbs and shrubs permits cattle to maximize their nutritional welfare when grasses are dormant. The excellent condition range in our study had a different(P<0.05) mean grass standing crop (999 kg/ha) across periods compared to on the good condition range (659 kg/ha). Based on our research and other studies excellent condition Chihuahuan desert range maximizes forage quantity for cattle but good condition range appears better from a nutritional standpoint in the spring and early summer. Our research and other studies indicate Chihuahuan desert ranges dominated by black grama are most effectively used in winter while ranges with a high dropseed component are best suited for use in summer and early fall.


Olive oil contains polyphenols, vitamin E, and other natural antioxidants that are the oil's own natural preservatives. Antioxidants dampen the autogeneration of peroxides, delaying the onset of oxidation and rancidity. As a result, antioxidants increase the oil's shelf life. Among the antioxidants, there are compounds that have been associated with human health benefits. They absorb free radicals and appear to have a positive impact on cardiovascular and cancer ailments, as attributed to the Mediterranean diet. The main objectives of this chapter were to investigate the phytochemical profile such as phenolic compounds and tocopherols, and in vitro, to study the biological potential (antioxidant capacity) of the olive oil. Furthermore, the relationship and correlations between phytochemical and antioxidant capacity have been highlighted. The investigation of these compounds supported by verifi-able evidence may explain their role in the quality and authenticity of olive oil as well as their contribution to human health.


Objective: In recent decades, the prevalence of atopic diseases has risen. Genetic factors and environmental factors are accused for this increase. The studies examining risk factors for asymptomatic atopy are limited, although many studies have investigated environmental risk factors in atopic diseases. The aim of study, to determine the prevalence of atopic sensitization among asymptomatic health workers and to examine the effects of active smoking and latent tuberculosis for atopic sensitization. Materials and Methods: Healthy participants with no described positive history of atopy and history of familial atopy were selected. Sixty participant aged 22-37 years were tested using tuberculin skin test (TST) and the skin prick tests (SPT) with 13 allergen extracts were performed. TST was accepted as latent tuberculosis if it was 15 mm or over. Results: At least one SPT response was found in (26.7%) 16 of 60 subjects. The most common sensitization was to Dermatophagoides pteronyssinuss. SPT results were compared and it was found that 5 (16.7%) people had positive SPT in smoker groups and 11 (36.7%) people in non-smoker groups (p> 0.05). TST was found over 10 mm in all subjects. TST was found over 15 mm in 65% of the subjects.No case had active or history of tuberculosis. In atopic and non-atopic groups, rates of TST positivity were 43.7% and 72.7% respectively (p= 0.03). Conclusion: Atopy was found in a quarter of healthy workers who no described positive history of atopy and history of familial atopy. It was thought that there was an inverse association between atopy and latent tuberculosis and that latent tuberculosis reduced development of atopy. We found no relationship between active smoking and atopy.


Study objectives were to assess the efficacy, safety, and tolerability of AFQ056 in Parkinson's disease patients with levodopa-induced dyskinesia. Two randomized, double-blind, placebocontrolled, parallel-group, in-patient studies for Parkinson's disease patients with moderate to severe levodopa-induced dyskinesia (study 1) and severe levodopa-induced dyskinesia (study 2) on stable dopaminergic therapy were performed. Patients received 25–150 mg AFQ056 or placebo twice daily for 16 days (both studies). Study 2 included a 4-day down-titration. Primary outcomes were the Lang-Fahn Activities of Daily Living Dyskinesia Scale (study 1), the modified Abnormal Involuntary Movement Scale (study 2), and the Unified Parkinson's Disease Rating Scale–part III (both studies). Secondary outcomes included the Unified Parkinson's Disease Rating Scale–part IV items 32–33. The primary analysis was change from baseline to day 16 on all outcomes. Treatment differences were assessed. Fifteen patients were randomized to AFQ056 and 16 to placebo in study 1; 14 patients were randomized to each group in study 2. AFQ056treated patients showed significant improvements in dyskinesias on day 16 versus placebo (eg, Lang-Fahn Activities of Daily Living Dyskinesia Scale, P 5 .021 [study 1]; modified Abnormal Involuntary Movement Scale, P 5 .032 [study 2]). No significant changes were seen from baseline on day 16 on the Unified Parkinson's Disease Rating Scale-part III in either study. Adverse events were reported in both studies, -----------------------------------------------------------------------------------------------------------------------------Daniela Berg, Jana Godau, Claudia Trenkwalder, Karla Eggert, IIona Csoti, Alexander Storch, Heiko Huber, Monica Morelli-Canelo, Maria Stamelou, Vincent Ries, Martin Wolz, and Christine Schneider are members of the German Parkinson Study Group. *Correspondence: Dr. Baltazar Gomez-Mancilla, Neuroscience Discovery, Novartis Pharma AG, CH-4002 Basel, Switzerland; baltazar.gomezmancilla@ novartis.com Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Funding agencies: This study was funded by Novartis Pharma AG, Basel, Switzerland, which provided the study drugs. These studies are registered: NCT00582673 and NCT00888004. Daniela Berg has received financial contributions from Novartis Pharma AG for taking part in an expert meeting, for giving a talk at its Community Health Day, and for being on an advisory board. Jana Godau received honoraria for lectures from Novartis Pharma AG. Ilona Csoti has received financial contributions from Novartis Pharma AG for being on an advisory board. Alexander Storch has received honoraria for presentations and advisory board meetings from Novartis Pharma AG. Thérèse Di Paolo has received honoraria for presentations and contracts from Novartis Pharma AG. Heiko Huber has received travel grants from Novartis Pharma AG. Fabrizio Gasparini, Sam Hariry, Marc Vandemeulebroecke, Walid Abi-Saab, Donald Johns, and Baltazar Gomez-Mancilla are employees of Novartis Pharma AG. Katy Cooke is a full-time employee of Alpha-Plus Medical Communications Ltd. (UK), which received support from Novartis Pharma AG for the time spent on the production of this manuscript. Received: 24 September 2010; Revised: 17 November 2010; Accepted: 1 December 2010 Published online 11 April 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.23616 R E S E A R C H A R T I C L E Movement Disorders, Vol. 26, No. 7, 2011 1243 including dizziness. Serious adverse events (most commonly worsening of dyskinesias, apparently associated with stopping treatment) were reported by 4 AFQ056-treated patients in study 1, and 3 patients (2 AFQ056-treated patient and 1 in the placebo group) in study 2. AFQ056 showed a clinically relevant and significant antidyskinetic effect without changing the antiparkinsonian effects of dopaminergic therapy. VC 2010 Movement Disorder Society


The use of radiolabeled anticancer antibodies to detect cancer sites by external scintigraphy has had a relatively long history. With the advent of monoclonal antibodies (MAbs), which precluded the need for purifying the antibodies by laborious purification steps, there was a surge of interest and efforts to develop these reagents for both imaging and therapy applications (1). Today, many thousands of patients have received different forms and doses of MAbs for various purposes, and four MAb-based products have been licensed for manufacture and sale in the U.S. (2,3). This article describes the most recent MAb product to be approved in the U.S. for colorectal cancer imaging, including discussions of using this agent and its therapeutic counterpart in several cancer types.


Vehicular networks promise features such as traffic management, route scheduling, data exchange, entertainment, and much more. With any large-scale technological integration comes the challenge of providing security. Blockchain technology has been a popular choice of many studies for making the vehicular network more secure. Its characteristics meet some of the essential security requirements such as decentralization, transparency, tamper-proof nature, and public audit. This study catalogues some of the notable efforts in this direction over the last few years. We analyze around 75 blockchain-based security schemes for vehicular networks from an application, security, and blockchain perspective. The application perspective focuses on various applications which use secure blockchain-based vehicular networks such as transportation, parking, data sharing/ trading, and resource sharing. The security perspective focuses on security requirements and attacks. The blockchain perspective focuses on blockchain platforms, blockchain types, and consensus mechanisms used in blockchain implementation. We also compile the popular simulation tools used for simulating blockchain and for simulating vehicular networks. Additionally, to give the readers a broader perspective of the research area, we discuss the role of various state-of-the-art emerging technologies in blockchain-based vehicular networks. Finally, we summarize the survey by listing out some common challenges and future research directions in this field.


1. Of the five sesquiterpene antibiotics tested and found to inhibit protein synthesis in yeast spheroplasts, trichothecin, trichodermol or trichodermin stabilized polyribosomes whereas, in contrast, verrucarin A or T-2 toxin induced 'run off' of polyribosomes with a corresponding increase in 80S monoribosomes. The effect of fusarenon X on the system could not be determined as the drug failed to enter the cells. 2. [acetyl-14C]Trichodermin bound to yeast polyribosomes with a dissociation constant of 2.10 muM and to yeast 'run off' ribosomes with a dissociation constant of 0.72 muM. 3. Trichothecin, trichodermol, fusarenon X, T-2 toxin and verrucarin A competed with [acetyl-14C]trichodermin for binding to its receptor site on 'run off' ribosomes. The observed competition was quantitatively similar for all drugs tested. In contrast, the five drugs competed to different extents with trichodermin for binding to its receptor site on polyribosomes. Thus trichothecin competed with relative efficiency, whereas verrucarin A competed poorly, and the other drugs occupied intermediate positions between these two extremes. 4. Studies were also carried out with yeast 'run off' ribosomes prepared from both a wild-type strain and a strain resistant to trichodermin. Competition experiments between verrucarin A and [3H]anisomycin indicated that verrucarin A bound to 'run off' ribosomes from the mutant strain less efficiently than to those from the wild-type.


The development of strategies for actively stimulating immunological rejection of tumors, previously an elusive goal, has been accelerated by recent improved understanding of the molecular basis of immune recognition and immune regulation of cancer cells. This has led to the identification of several tumor antigens with immunogenic potential. The translation of these advances into the clinic as cancer vaccines requires carefully conducted, well-coordinated but discovery-oriented research in the form of clinical trials that can quickly assess alternative vaccine strategies for each tumor type, immuno-monitoring, and tumor escape mechanisms. In this regard, the Cancer Vaccine Collaborative (CVC), an innovative partnership between Ludwig Institute for Cancer Research (LICR) and the Cancer Research Institute (CRI), is a promising paradigm for the advancement of cancer vaccines. The CVC utilizes a unique academic structure that plans, sponsors, and conducts early-phase cancer vaccine trials. The standardized monitoring employed by the CVC enables the comparison of single vaccine variables such as the constitution of an antigen (protein, peptide, viral vectors, or DNA), the method, frequency, and intensity of antigen delivery, and the addition of different adjuvants. In the first part of my talk, I will give an overview of progress made by the CVC in the last few years. In the second part of my talk, I will illustrate the activities of the CVC by using our ovarian cancer program. The long-range goal of our studies is to harness the potential of cellular immune responses for improving the outcome for patients with epithelial ovarian cancer (EOC). Although most patients with EOC initially demonstrate excellent response to frontline therapies, the relapse rate is approximately 85%. Within 2 years of surgery and systemic chemotherapy, tumors usually reoccur and once relapse occurs, there is no known curative therapy. A proposed strategy for minimizing the risk of recurrent disease is immunotherapy. Patients who demonstrate complete response to frontline therapies could be considered for immunotherapy, with the presumption that the majority do in fact have micrometastases. This approach necessitates the identification of targets with tissue-restricted expression and immunogenic potential, and the development of strategies to improve the immunogenicity of these antigens. Based on these considerations, in collaboration with the NY Branch of the LICR (1, 2, 3, 4), we have characterized the repertoire of "cancer-testis" (CT) antigens expressed in EOC (including NY-ESO-1, LAGE-1, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7, CT10, CT16, CT17, BAGE, OY-TES-1, SCP-1, AKAP3, SSX-1, SSX-2 and SSX-4). The results demonstrate that most EOC express at least one of these CT antigens and there is some inter-relationship in the pattern of expression. In addition, we have determined the relationship between immune cell infiltration, CT antigen expression and clinical outcome in EOC. Our study indicates that the prognostic significance of TILs is attributable to intraepithelial CD8+ TILs, while overall T-TIL (CD3+ TIL), CD20+ TIL and CD4+ TIL subtypes were not significantly prognostic. Further, a high intraepithelial CD8+/CD4+ T-cell ratio is a favorable prognostic variable in EOC suggesting that the amount of CD4+ TILs may play a role in determining the prognostic significance of CD8+ TILs in EOC. Since this effect may be attributed to the CD4+ CD25+ regulatory T (Treg) cells, we have also characterized the phenotype and effector functions of NY-ESO-1 specific T cells in the tumor microenvironment, and examined the interaction of these cells with autologous tumor derived CD4+ CD25+ T cells. In the final part of the talk, preliminary results from a phase 1 clinical trial of NY-ESO-1DP4 p157-170 (NY-ESO-1DP4), a peptide of potentially dual MHC class I and class II specificities, in patients with EOC will be presented. This abstract was published in Cancer Immunity, a Cancer Research Institute journal that ceased publication in 2013 and is now provided online in association with Cancer Immunology Research.


A non-contact galvanometer-based optical scanning system for diffuse correlation tomography was developed for monitoring bone graft healing in a murine femur model. A linear image reconstruction algorithm for diffuse correlation tomography was tested using finite-element method based simulated data and experimental data from a femur or a tube suspended in a homogeneous liquid phantom. Finally, the non-contact system was utilized to monitor in vivo blood flow changes prior to and one week after bone graft transplantation within murine femurs. Localized blood flow changes were observed in three mice, demonstrating a potential for quantification of longitudinal blood flow associated with bone graft healing.


Je n'ai fait cette lettre-ci plus longue que parce que je n'ai pas eu le loisir de la faire plus courte. Blaise Pascal The characterization of the electronic response of nanostructures to external electromagnetic fields is of great importance, both from the theoretical and technological points of view. In contrast to light elements, new physical processes and phenomena appear in heavy elements, where relativistic effects, like spin-orbit coupling cannot be ignored. In this work we develop the theoretical framework and the numerical tools needed to address those processes within time-dependent density functional theory (TDDFT). We first apply this methodology to the study of the photoabsorption cross-section of small cationic xenon clusters. Overall, we find our results to be in good agreement with experiment, except for the incorrect prediction of the relative intensities of the peaks. As a second application, we investigate the effect of spin-orbit coupling in the optical response of small gold clusters. We find that this effect is always noticeable, but its importance depends on the dimensionalities of the clusters (the effect is larger for wires than for 2D and 3D structures) and on the size of the clusters (the effect is "quenched" with increasing cluster size). Finally, we study the role of spin noncollinearity in the excited state properties of small chromium and iron clusters and its interplay with spin-orbit coupling. In particular, we compare the dipole and spin-dipole responses of clusters with collinear and noncollinear spin arrangements. We find that, in all cases, the different electronic structure of collinear and noncollinear configurations are reflected to some extent in the spectra. On the contrary, no direct evidence of spin-orbit coupling can be found in the spectra.


Evolutionary game theory is extended to models of two-species interactions where fitnesses are based on individual characteristics (strategies) rather than on a population dynamic that assumes homogeneous species. It is shown that the coevolutionary theories in the literature that combine ecology with genetic viability selection are part of this extended theory and that the dynamic stability resulting from a separation of ecological and evolutionary processes actually follows from game-theoretic solution concepts. The main focus of the paper is to investigate the application of the ESS (evolutionarily stable strategy) solution concept to dynamic stability when fitnesses are given by random interactions between individuals as opposed to viability selection. For two-species frequency-dependent interactions, the ESS criterion that implies stability asserts that, in any system near the ESS, at least one of the species is better off (i.e., more fit) if it evolves towards the ESS. The global stability of a polymorphic two-species ESS that is shown for two-species matrix games gives a powerful tool to predict the course of evolution through static fitness comparisons.


With coverage of the major theories and concepts alongside diagnostic tools and a practical framework for implementation, Leading Cultural Change will help the reader analyse and diagnose their current organizational culture, become aware of the key challenges and how to overcome them and learn how to adapt their leadership style, ensuring they are fit to lead a cultural change programme. Taking in core topics such as change context, language and dialogue as a key cultural process and the change team process, it uses a longitudinal case study of Cordia, a public sector organization transitioning into an LLP, to enhance learning and understanding. Leading Cultural Change is a unique text, rooted in behavioural sciences, which explores the topic as an organizational necessity to achieving sustained competitive advantage.


Our previous study demonstrated that compounds in indoor dusts strongly inhibit thyroxine (T4) binding to the human thyroid hormone transport protein transthyretin (TTR) in vitro. Exposure assessment indicated that house dust is an important medium of exposure of children to TTR-binding compounds when binding potency and dust ingestion rates are high. Here, we used chemical fractionation with in vitro competitive human TTR-binding assay and GC-MS to analyze the TTR-binding compounds in a sulfuric-acid-treated dust extract. 2,4,6-Tribromophenol (TriBPh) and 2,3,4,5,6-pentachlorophenol (PeCPh) were potent TTR-binding compounds in all dust samples. 2,4,6-TriBPh- and 2,3,4,5,6-PeCPh-derived theoretical T4 equivalents (T4EQs), calculated arithmetically from the concentrations and relative potencies, accounted for about 40-70% of experimental T4EQs detected in indoor dusts, indicating that these compounds contributed strongly to the TTR-binding potency of indoor dust. Indoor sources of 2,4,6-TriBPh might be brominated flame retardants currently used in household materials such as electrical appliances. In contrast, the 2,3,4,5,6-PeCPh might be trace evidence of past use in agricultural chemicals and preservatives in indoor or outdoor environments, because its use has been banned since 1990 in Japan. 2,4,6-TriBPh and 2,3,4,5,6-PeCPh are ubiquitous potential thyroid-disrupting compounds in the home and work environments of Japan and other countries.


This study aims to understand how people engage with art in the era of selfies, digital devices, and social media. It examines the audience experience of an art exhibition, where visitors are encouraged to use social media to share their art experience, to understand how such an approach might change the nature of visitor engagement with art. Arguably, selfies taken in the art space enrich the visitor's experience and engagement with art and function as co-creational, empowering, and authentic marketing tools for museums. Data for this research were collected through non-participant observation (ethnography) and netnography at the National Gallery of Victoria, in Melbourne, Australia. The results show that rather than promoting disengagement from the art piece, selfies in the art space become "networked material-discursive entanglements" empowering art consumers to co-create value and arts organizations to reduce their distance from consumers and reproduce the iconic authenticity of the artwork in the virtual space. The article contributes to selfie theory by overcoming the traditional view of selfies as manifestation of narcissistic self-expression. Instead, it promotes an interpretation of selfies as an empowering and democratizing means used by art consumers to develop narratives and identity projects in a context such as the museum where traditionally the development of the narrative is apanage of an elite. A further contribution provided by this research stems from the identification of clusters of visitors (i.e., reality escapers, art lovers, photoholics, and selfie lovers), placed on a continuum of value co-creation, which arts administrators need to be conscious of as they enter a more dynamic era of art consumption. By outlining managerial implications, this study provides an initial reflection on how arts managers can navigate the emerging era of the selfie in the museum context.


OBJECTIVE
There have been significant changes to the management of COVID-19 in recent months, including protocols and guidelines designed to prevent, diagnose, and treat the Novel Coronavirus (COVID-19). Several management options have been suggested and have since gained popularity, though we expect additional modifications to be made, as well as more new cases in the coming months, given a lack of definitive treatment and well-controlled experiments. This review highlights the available and potential treatments, along with the challenges associated with each.

MATERIALS AND METHODS
We conducted a comprehensive overview of all peer-reviewed studies, editorial comments, and letters to the editor based on a search in PubMed, Google Scholar, Web of Science, and Scopus. The following terms were used: "COVID-19," "SARS-CoV-2," "drug," "treatment," "medication," and "management." All searches were done between March and May 20, 2020.

RESULTS
There are several potential medications available for COVID-19, such as Interferon α (IFN-α), Teicoplanin, Ribavirin, Galidesivir, Lopinavir/Ritonavir, Chloroquine phosphate, Arbidol, Velpatasvir, Favipiravir, Ledipasvir, Remdesivir, Sofosbuvir, Darunavir, Qingfei Paidu Decoction (QPD), and Imatinib. However, we do not have a definitive and specific treatment yet.

CONCLUSIONS
We are expecting to have more cases in the coming weeks/months. Therefore, further research is needed to characterize the disease behavior, to find the absolute drug, and to refine the treatment.


This paper discusses the problem of adaptive estimation of a univariate object like the value of a regression function at a given point or a linear functional in a linear inverse problem. We consider an adaptive procedure originated from Lepski [Theory Probab. Appl. 35 (1990) 454-466.] that selects in a data-driven way one estimate out of a given class of estimates ordered by their variability. A serious problem with using this and similar procedures is the choice of some tuning parameters like thresholds. Numerical results show that the theoretically recommended proposals appear to be too conservative and lead to a strong oversmoothing effect. A careful choice of the parameters of the procedure is extremely important for getting the reasonable quality of estimation. The main contribution of this paper is the new approach for choosing the parameters of the procedure by providing the prescribed behavior of the resulting estimate in the simple parametric situation. We establish a non-asymptotical "oracle" bound, which shows that the estimation risk is, up to a logarithmic multiplier, equal to the risk of the "oracle" estimate that is optimally selected from the given family. A numerical study demonstrates a good performance of the resulting procedure in a number of simulated examples.


The deterioration of air quality in China has resulted in many people looking for remedies to counteract the impact that air pollution is perceived to be having on their health. As the importance of diet on immune health is becoming increasingly well recognised, a narrative literature review was undertaken to elucidate Chinese consumers' acceptance of functional food products designed to help the immune system recover from pollution-driven impact and to assess their market potential. Consumers' attitude towards immune-boosting functional foods were mainly positive, with scientific validation being important in determining the credibility of a product. This was despite the fact that the effectiveness of the functional food products currently in the market that purported to be remedies for pollution-driven impacts on the lung did not appear to be supported by scientific evidence. Numerous studies have reported functional foods could provide a wide range of benefits to immune health, including helping pollution-driven immune issues. This review highlights the market demand for effective and scientifically-proven functional food products that help Chinese consumers' immune system recover from the impact of air pollution.


Glycoprotein H (gH) homologues are found in all members of the herpes virus family, and gH is one of the virion envelope glycoproteins that is essential for virus entry. In this study, a recombinant soluble form of Herpes simplex virus type 1 (HSV-1) gH, in which the ectodomain is fused to the Fc-binding region of IgG, has been generated. This was expressed in mammalian cells together with gL and the resulting gHFc-gL heterodimer was purified using Protein A Sepharose. Low-affinity cell binding assays showed that gHFc-gL bound specifically to Vero cells and mutation of a potential integrin-binding motif, Arg-Gly-Asp (RGD), in gH abolished binding. CHO cells failed to bind in this assay. However, CHO cells expressing the human alphavbeta3 integrin bound efficiently to gHFc-gL, suggesting that HSV-1 gH can bind to cells using alphavbeta3 integrins and that this binding is mediated by the RGD motif in the gH ectodomain.


The mass migration of Italians to Anglo-Saxon countries, such as the USA and Australia, caused a great amount of discontent in religious circles, so much so that Italian migrants have been considered a religious "problem". One of the greatest contributors to the Italian "problem" was the folk religion of the new arrivals. They had very little or no instruction in the doctrines of the Catholic Church and their folk religion was considered a "syncretic melding of ancient pagan beliefs, magical practices and Christian liturgy". 1 This paper will examine the Italian "problem" in Australia. It will establish that the "problem" did exist in Australia before the Second World War, a period that has been considered by scholars to be a period of non-activity and has consequently been neglected. Quite often it is believed that, due to small numbers and remote settlement patterns, Italian migrants did not pose a "real challenge" to the Catholic Church in Australia before the Second World War. 2 This paper will look at the attitudes of the Australian Catholic hierarchy to Italian migrants in Australia during the inter-war years and how the Australian bishops attempted to care for Italian migrants by providing them with Italian-speaking Irish priests who, in some cases, sufficed, but were not a complete answer to the "problem". The Italian priests who worked among Italian migrants in Australia during the 1920s were Fr Vincenzo de Francesco, Fr Severino Mambrini and Bishop Coppo. This paper will examine the methods used by these priests to bring Italian migrants back to the Church.


In this study, we investigated the impact of elevated atmospheric CO2 (ambient + 350 μmol mol–1) on fine root production and respiration in Scots pine (Pinus sylvestris L.) seedlings. After six months exposure to elevated CO2, root production measured by root in‐growth bags, showed significant increases in mean total root length and biomass, which were more than 100% greater compared to the ambient treatment. This increased root length may have lead to a more intensive soil exploration. Chemical analysis of the roots showed that the roots in the elevated treatment accumulated more starch and had a lower C/N‐ratio. Specific root respiration rates were significantly higher in the elevated treatment and this was probably attributed to increased nitrogen concentrations in the roots. Rhizospheric respiration and soil CO2 efflux were also enhanced in the elevated treatment. These results clearly indicate that under elevated atmospheric CO2 root production and development in Scots pine seedlings is altered and respiratory carbon losses through the root system are increased.


A pattern database (PDB) for a planning task is a heuristic function in the form of a lookup table that contains optimal solution costs of a simplified version of the task. In this paper we introduce a method that sequentially creates multiple PDBs which are later combined into a single heuristic function. At a given iteration, our method uses estimates of the A* running time to create a PDB that complements the strengths of the PDBs created in previous iterations. We evaluate our algorithm using explicit and symbolic PDBs. Our results show that the heuristics produced by our approach are able to outperform existing schemes, and that our method is able to create PDBs that complement the strengths of other existing heuristics such as a symbolic perimeter heuristic.


PCOS affect approximately 6-10% of women of child bearing age. Insulin resistance & compensatory hyperinsulinemia play a central role in PCOS. It is characterized by chronic anovulation & infertility with either oligomennorhea or amenorrhoea & hyperandrogenism. The ovary does not make the hormones needed for the eggs to fully mature. Follicles may start to grow and build up fluid but none of the follicle becomes large enough. Instead some follicles may remain as cysts. Since no follicle becomes large enough and no egg matures or is released, ovulation does not occur and the hormone progesterone is not made. Without progesterone, a woman's menstrual cycle becomes irregular or ceases. The cysts so produced make male hormones, which also prevent ovulation. The action of stradiol on the hypothalamic pituitary axis and on the endometrium is unopposed because of a lack of cyclical progesterone secretion. Insulin sensitizers like metformin is thus a rationalized therapeutic approach for women having primary infertility due to PCOS. Metformin pecifically targets not only insulin resistance but several other aspects of the syndrome including reproductive abnormalities


We report on the ability of holographic light fields to alter the normal growth patterns of filamentous fungi. The light fields are produced on a microscopic scale by borrowing methods from the field of optical tweezers, but without the aim of directly trapping or manipulating objects. Extended light fields are shown to redirect and constrict hyphal tip growth, and induce hyphal branching in a highly reproducible manner. The merits of using discrete and continuous light fields produced using a spatial light modulator are discussed and the use of three-dimensional 'pseudowalls' of light to control the growth patterns is reported. We also demonstrate the dependence of hyphal tip growth on the wavelength of light, finding that less power is needed at shorter wavelengths to effect changes in the growth dynamics of fungal hyphae.


According to requirements of online steel ball surface defect inspection, the automatic detection method of spherical surface defect on the track has been posed. To ensure photographing of the whole steel ball surface, the six CCD video cameras are used in this system. To overcome steel ball surface reflection, the red LED light source is used, and then the real and clear images are got. The steel ball surface defect is recognized accurately by means of image recognition technology and image reconstruction technology etc. This method provides theoretical basis and technical support for ball defection and quality classification.


We report on enhanced detection of strain waves in gold gratings, using a probe laser pulse tuned at and close to the surface plasmon-polariton (SPP) resonance of the gratings. The enhancement, of up to twenty times, is observed in the strain-wave-induced reaction changes and depends on the type of acoustic wave. For the surface acoustic wave, the enhancement of the optical reaction is greatest at the peak of the resonance, while strain-wave-induced reaction changes of other types of strain waves show their strongest enhancement when the probe pulse is tuned to the wings of the SPP resonance.


Biological response modifiers such as pro and prebiotics have been recently used in aquaculture showing abilities as immunostimulants, enhancing resistance to different fungal, bacterial and parasitic pathogens and tolerance to environmental stress. This experiment evaluated three different concentrations (0.05, 0.1 and 0.5 %) of β-1,3/1,6 glucans on nonspecific immune parameters of channel catfish ( Ictalurus punctatus ). Results showed that intake supplementation with 0.05 % of β-1,3/1,6 glucans provides a greater immunostimulation over the fourth treatment week. Significant higher differences ( p < 0.05) were obtained on parameters related to phagocytic activity on blood cells, also other assays showed more reactive cells to nitroblue tetrazolium (NbT) stain on spleen and head kidney analysis. We conclude that the use of 0.05 % of β-1,3/1,6 glucans added to a commercial diet improves nonspecific immune system of channel catfish ( I. punctatus ).


The lure of practice beyond disciplinary ordinance lies in potential for
thinking beyond established paradigms. Belgian philosopher of science,
Isabelle Stengers claims that things already impinge across disciplinary
boundaries; that an "ecology of practices" is possible in the "event" of
interdisciplinary transaction. This paper investigates insights from one art
practice that links to other practices for particular durations. It thereby
enters zones dependent on temporal aggregation and attentive
dialogues, enunciating a chain of potentially generative and sustaining
production for those involved.


Background: To treat the joint pain arial part of Asparagus officinalis (asparagus) has historically been used. However, its efficacy for rheumatoid arthritis has not been pharmaceutically evaluated. We explore the phytochemical analysis anti-inflammatory, analgesic and anti-arthritic activity of petroleum ether, ethanol and aqueous extracts of Asparagus officinalis aerial part. Materials and Methods: Tail-flick method was used to evaluate the analgesic activity anti-inflammatory activity was carried out using paw oedema induced with carrageenan and CFA induced arthritic model was used to evaluate the potential in anti-arthritic activity in rats. The Petroleum ether, ethanolic and aqueous extracts were dosed orally in three divided doses (75, 150 and 300 mg/ kg). For anti-inflammatory and analgesic activity diclofenac sodium at 10 mg/kg was used as standard, whereas in anti-arthritic model prednisolone at 5 mg/kg and methotrexate at 0.5 mg/ kg were used as standard. One-way ANOVA followed by Dunnett's multiple range test were used to analyse statistical significance between means. Results: The results revealed a dose-controlled anti-inflammatory, anti-arthritic effect with different extracts whereas at some extent analgesic activity was observed. Four compounds were present and confirmed by LCMS/MS. The CFA model's findings showed improved defence against arthritic lesions and changes in body weight. Additionally, Asparagus officinalis significantly improved rheumatoid factor, changed WBCs, and favourably altered radiographic and histological alterations. Conclusion: The findings indicate that Asparagus officinalis is a strong anti-arthritic and anti-inflammatory compound that may be suggested for the treatment of both chronic and acute inflammation.


In the age of e-commerce, many logistic companies must operate in large road networks without accurate knowledge of travel times for their specific fleet of vehicles. Moreover, millions of dollars are spent on routing services that do not accurately cap-ture the specific characteristics of the companies' drivers and the types of vehicles they must use. In this work, we consider a logistic operator that has limited information about travel times in a network, and who seeks to find the optimal expected shortest path of origin-destination pairs. We model this problem as an Online Shortest Path Problem, common to many last mile routing settings: given a graph whose arcs' travel times are stochastic and follow an unknown distribution, the planner seeks to find a vehicle route of minimum travel time from an origin to a destination. We assume the planner progressively collects information on the travel conditions as the drivers keep serving requests. Inspired by combinatorial multi-armed bandit and Kriging literature, we propose three methods with different characteristics that effectively learn the optimal shortest path and illustrate the practical advantages of incorporating spatial correlation in the learning process. Our approach balances the trade-off of exploration (better estimates for unexplored arcs) vs exploitation (executing the minimum expected time path) by using the Thompson Sampling algorithm. In each iteration, our algorithm executes the path minimizing the expected time with data from a posterior distribution of the arcs' speeds. We carry out a computational study comprising two settings: a set of four artificial instances and a real-life case study. The case study uses empirical data of taxis in the 17km-radius area of the center of Beijing, completely en-veloping Beijing's "5th Ring Road". In both settings, we observe that our algorithms efficiently and effectively balance the exploration-exploitation trade-off.


The proto-oncogene RET encodes a transmembrane growth neurotrophic receptor with tyrosine kinase (TK) activity. RET mutations are associated with several human neoplastic and nonneoplastic diseases, including thyroid papillary carcinoma, multiple endocrine neoplasia type 2 syndromes, and Hirschsprung's disease. Activation of receptor TKs results in the binding and activation of downstream signaling proteins, among which are nonreceptor TKs of the Src family. To test the involvement of c-Src in Ret-mediated signaling, we measured the levels of c-Src activity in NIH3T3 cells coexpressing Ret and the accessory GFR alpha-1 receptor or an epidermal growth factor receptor/Ret chimeric receptor when the cells were stimulated by glial cell line-derived neurotrophic factor or epidermal growth factor, respectively. Ret stimulation resulted in the activation of c-Src. We also measured the levels of Src kinase activity in cell lines expressing isoforms of the Ret receptor activated by different mutations. These cells showed higher Src kinase activity than the normal counterpart. Furthermore, we show that Ret is able to associate with the SH2 domain of Src in a phosphotyrosine-dependent fashion. Microinjection of a kinase inactive mutant of c-Src blocked Ret-mediated mitogenic effect. These experiments demonstrate that activated Ret is able to bind and stimulate c-Src kinase and that Src activation is essential for the mitogenic activity of Ret.


In this paper, we study the problem of user clustering in the context of their published short text streams. Clustering users by short text streams is more challenging than in the case of long documents associated with them as it is difficult to track users' dynamic interests in streaming sparse data. To obtain better user clustering performance, we propose a user collaborative interest tracking model (UCIT) that aims at tracking changes of each user's dynamic topic distributions in collaboration with their followees', based both on the content of current short texts and the previously estimated distributions. We evaluate our proposed method via a benchmark dataset consisting of Twitter users and their tweets. Experimental results validate the effectiveness of our proposed UCIT model that integrates both users' and their collaborative interests for user clustering by short text streams.