In many collaborative systems it is useful to automatically estimate the quality of new contributions; the estimates can be used for instance to flag contributions for review. To predict the quality of a contribution by a user, it is useful to take into account both the characteristics of the revision itself, and the past history of contributions by that user. In several approaches, the user's history is first summarized into a number of features, such as number of contributions, user reputation, time from previous revision, and so forth. These features are then passed along with features of the current revision to a machine-learning classifier, which outputs a prediction for the user contribution. The summarization step is used because the usual machine learning models, such as neural nets, SVMs, etc. rely on a fixed number of input features. We show in this paper that this manual selection of summarization features can be avoided by adopting machine-learning approaches that are able to cope with temporal sequences of input. In particular, we show that Long-Short Term Memory (LSTM) neural nets are able to process directly the variable-length history of a user's activity in the system, and produce an output that is highly predictive of the quality of the next contribution by the user. Our approach does not eliminate the process of feature selection, which is present in all machine learning. Rather, it eliminates the need for deciding which features from a user's past are most useful for predicting the future: we can simply pass to the machine-learning apparatus all the past, and let it come up with an estimate for the quality of the next contribution. We present models combining LSTM and NN for predicting revision quality and show that the prediction accuracy attained is far superior to the one obtained using the NN alone. More interestingly, we also show that the prediction attained is superior to the one obtained using user reputation as a feature summarizing the quality of a user's past work. This can be explained by noting that the primary function of user reputation is to provide an incentive towards performing useful contributions, rather than to be a feature optimized for prediction of future contribution quality. We also show that the LSTM output changes in a natural way in response to user behavior, increasing when the user performs a sequence of good quality contributions, and decreasing when the user performs a sequence of low-quality work. The LSTM output for a user could thus be usefully shown to other users, alongside the user's reputation and other information.


A protein fraction from the cellular slime mold Dictyostelium discoideum confers Ca2+-sensitivity on the activation of purified myosin adenosinetriphosphatase (ATP phosphohydrolase, EC 188.8.131.52) from Dictyostelium by purified Dictyostelium actin. That is, the fraction inhibits the actomyosin adenosine triphosphatase activity in the absence of Ca+ but not in the presence of Ca2+. This Ca2+-sensitizing factor affects only the actin-activated myosin adenosine triphosphatase and not the enzyme activity of myosin alone. The Ca2+-sensitivity is conserved when muscle actin replaces Dictyostelium actin, but is lost when muscle myosin replaces Dictyostelium myosin. The factor appears to be a protein since it is nondialyzable, is heat labile, and can be precipitated with ammonium sulfate. The factor can be purified 70-fold on an actin-affinity column.


Cypermethrin is a synthetic, pyrethroid insecticide and used for agricultural practices. The leaching of this pesticide through soil is of great concern because of the possibility of contaminating ground and surface water. The mobility of pesticide in soil being the main environmental reservoir varies among soil orders and the concept is still under investigation. Hence, this study was aimed at investigating the sorption capability of Alfisol and Inceptisol at different soil depth when leached with simulated rainwater of different pH values. The leachates were determined for cypermethrin concentration using a new UV/Visible spectrometry method. The CEC, organic matter content of Alfisol were 4.05±0.03 cmol/kg and 1.74±0.02%, while the corresponding characteristics of Inceptisol were 4.45±0.05 cmol/kg and 1.03±0.01%, respectively. pH of Alfisol and Inceptisol soil orders were 5.92 and 6.25, respectively. Simulated rainwater (pH 4) of 50, 100 and 150 mL leached out 37.0±0.1, 43.1±0.1 and 59.4±0.2% of cypermethrin, respectively from Alfisol at soil depth of 10 cm. At pH 6.8, the corresponding volumes of simulated rainwater leached out 31.8±0.1, 35.4±0.1 and 37.4±0.1% of cypermethrin, respectively. For each soil order, these proportions of sorbed cypermethrin decreased progressively as soil depth increased from 10-30 cm. The proportions of cypermethrin sorbed by Inceptisol were more than the corresponding proportions sorbed by Afisol. Afisol has high clay and organic contents, which might be responsible for its surpassing potential to sorb cypermethrin compared to Inceptisol.

 Key words: Pyrethroid insecticide, leaching, Alfisol-Inceptisol soil orders, simulated rainwater, UV/Visible spectrometry.


For studies of the biological effects of bioaerosols, large samples are necessary. To be able to sample enough material and to cover the variations in aerosol content during and between working days, a long sampling time is necessary. Recently, a high-volume transportable electrostatic field sampler for collection of fine particles has been described. The aim of this study was to investigate whether this sampler can be used for collection of high amounts of authentic bioaerosols that can subsequently be used for biological analysis. The investigation was carried out at a biofuel plant in a straw storage room and in a boiler room over two seasons. The sampled dust was quantified in terms of mass and characterized regarding microbial components and compared with dust sampled by Gravikon and GSP samplers. For the electrostatic field sampler, a prefilter was used to remove large objects. The prefilter was characterized for particle penetration and this testing indicated that the prefilter did not remove particles up to 10 mum, and therefore respirable dust was sampled by the electrostatic field sampler. Using the electrostatic field sampler in the straw storage and in the boiler room, 330 and 315 mg dust (net recovery of the lyophilized dust) was sampled during a period of 7 days, respectively. The sampling rates of the electrostatic field samplers were between 1.34 and 1.96 mg dust per hour, the value for the Gravikon was between 0.083 and 0.108 mg dust per hour and the values for the GSP samplers were between 0.0031 and 0.032 mg dust per hour. The standard deviations of replica samplings and the following microbial analysis using the electrostatic field sampler and GSP samplers were at the same levels. The exposure to dust in the straw storage was 7.7 mg m(-3) when measured by the electrostatic field sampler and 11.8 mg m(-3) when measured by the GSP inhalable dust sampler. The quantity (amount per mg dust) of total fungi, Aspergillus fumigatus, total bacteria, endotoxin and mesophilic actinomycetes sampled by the electrostatic field samplers and the Gravikon samplers varied within the same season by a factor smaller than four. The quantities of some microbial components were higher in the dust collected with all samplers in March than in August. In conclusion, by using the electrostatic field sampler, it was possible to sample replicas of large authentic aerosol samples that can be used, e.g. biological analysis.


Efficient sorting is vital for overall performance of the underlying application. This paper presents Butterfly Network Sort (BNS) for sorting large data sets. A minimal version of the algorithm Min-Max Butterfly is also shown for searching minimum and maximum values in data. Both algorithms are implemented on GPUs using OpenCL exploiting data parallelism model. Results obtained on different GPU architectures show better performance of butterfly sorting in terms of sorting time and rate. The comparison of butterfly sorting with other algorithms:bitonic, odd-even and rank sort show significant speedup improvements against all on Nvidia Quadro-6000 GPU with relatively better sorting time and rate


The diversity of culturable bacteria inhabiting the Baltic Sea surface waters was more divergent at a polluted location than at clean areas. The most important members of the family Enterobacteriaceae that are pathogenic to fish are the enteric redmouth disease agent, Yersinia ruckeri and two species of Edwardsiella, E. tarda and E. ictaluri, Serratia, Proteus and Citrobacter have all been implicated as potential fish pathogens. The use of pharmaceutical substances is rather limited in fish compared to mammalian therapeutics. Medicinal herbs play an alternative role to antibiotic therapy in aquaculture. Ficus species (Moraceae) leaves possess great medicinal potential for the therapy of bacterial and fungal infections and may be used as a natural antiseptic and antimicrobial agent in veterinary. Accordingly, these products can be used in aquaculture as therapeutic and prophylactic agents against fish pathogens, with antimicrobial properties. Present study aimed to investigate the in vitro antimicrobial activity of the ethanolic leaf extracts of various Ficus species against fish pathogen, Citrobacter freundii. The antimicrobial susceptibility testing was done on Muller-Hinton agar by disc diffusion method (Kirby-Bauer disk diffusion susceptibility test protocol). Our results demonstrate that various species of Ficus had mild antibacterial in vitro activity against C. freundii isolated locally from infected eel (Anguilla anguilla L.). The results proved that the extracts from F. drupacea, F. septica, F. deltoidea as well as F. hispida, F. mucuso, F. pumila, F. craterostoma exhibit a favorable antibacterial activity against C. freundii. These validate scientifically their inhibitory capacity attributed by their common use in folk medicine and contribute towards the development of new treatment options in aquaculture based on natural products. The chemical analysis of the aforementioned plant extracts should be performed to determinate their chemical composition and identify the exact phytocompounds responsible for antimicrobial activity against C. freundii. In addition, they should be subjected to pharmacological evaluations with the aim of assessing their in vivo efficacy, toxicity, potential adverse effects, interactions and contraindications. Given the increasing rate of resistance development in bacterial pathogens in aquaculture environments, medicinal plants with antibacterial properties are very important as natural resources for new active compounds.
Key words: antibacterial activity, Citrobacter freundii, infected eel (Anguilla anguilla), Ficus spp., ethanolic extracts, zone of growth inhibition


This paper proposes a functional-link-artificial-neural-network-based (FLANN) multichannel nonlinear active noise control (ANC) system trained using a particle swarm optimization (PSO) algorithm suitable for nonlinear noise processes. The use of PSO algorithm in a multichannel ANC environment not only reduces the local minima problem but also removes the requirement of computationally expensive modeling of the secondary-path transfer functions. A decentralized version of a multichannel nonlinear ANC is also developed, which facilitates scaling up of an existing ANC setup without rederiving the learning rules. This is possible as the controller module of each channel is independent of others. Simulation study of the two new multichannel ANC systems demonstrates comparable mitigation performance. However, the decentralized one is preferred to as it possesses the added advantage of scalability.


In dialogues with key thinkers in the area of critical education, this book documents how a tradition of study grew in the United States. Through in-depth interviews, the author asks each of these thinkers to talk about the relationship between their personal experiences and their academic work. The reader will learn, through listening to these intellectual, political and personal biographies, how and why these individual scholars have struggled for more than three decades to expand the borders of critical education studies. Interviews are held with Henry Giroux, Henry Levin, Herbert Gintis, Jeannie Oakes, Martin Carnoy, Maxine Greene, Michael Apple, Samuel Bowles, Paulo Freire, Gloria Lanson-Billings and Geoff Whitty, among others.


Based on ANSYS and Icepak softwares, the numerical analysis method is used to build up the thermal analysis model of the 2.5D package, which contains a high power CPU chip. The focus of the research is on the determination of the contributing factors and their effects on the thermal resistance and heat distribution of the package. The parametric analysis illustrates that the substrate conductivity, TIM conductivity and fin height are more crucial for heat conduction in the package. Furthermore, these major parameters are compared and analyzed by orthogonal tests, and the optimal solution for 2.5D integration is proposed. The factors' influence patterns on thermal resistance, obtained in this article, could be utilized as a thermal design reference.


Stimulation-induced changes in Cl- content and O2 consumption of collagenase-isolated rat parotid acini were measured. In less than 10 s, carbachol caused a net Cl- efflux, corresponding to approximately 50% of the Cl- content, and increased the O2 uptake by 100%. The increase was inhibitable by ouabain and was dependent on the presence of extracellular Ca2+. Furosemide reduced the unstimulated 36Cl- uptake and prevented the reuptake of Cl- after carbachol-induced release. This suggests that a cotransport system is operating in both the unstimulated and stimulated states. Furthermore, furosemide inhibited the stimulated ouabain-sensitive O2 uptake. Raising intracellular Ca2+ by the calcium ionophore A23187 evoked the same pattern of Cl- loss and O2 uptake as carbachol. Our results are compatible with the following hypothesis. Carbachol raises intracellular Ca2+, causing an increased Cl- permeability of the luminal membrane, resulting in a net Cl- efflux. A subsequently enhanced influx of Cl- and Na+ via a furosemide-sensitive cotransport system increases intracellular Na+. This stimulates the Na+-K+-ATPase and thereby the O2 consumption.


Abstract We examine the applicability of the Next Generation Attenuation‐West2 (NGA‐West2) site‐effects model (Seyhan and Stewart, 2014), which is a V S 30 ‐based (time‐averaged shear‐wave velocity in the upper 30 m) model, to sites in central and eastern North America (CENA), using the NGA‐East ground‐motion database. We determine residual site terms by comparing the observed CENA ground‐motion amplitudes, adjusted to B/C site condition ( V S 30 =760 m/s) using the western site‐effects model, to the corresponding predicted amplitudes of a CENA ground‐motion prediction equation for B/C site condition (Yenier and Atkinson, 2015). The CENA prediction model used the same western site model to level the database before model development. Thus, residual trends reveal inadequacies of the western site‐effects model when applied to CENA ground motions. Plotting the residual site terms versus their corresponding site fundamental frequencies ( f peak ) reveals significant f peak ‐dependent trends at all frequencies. Average residual site terms for CENA sites, after the western site amplifications have been removed, can be as large as 0.45 in log10 units (2.8 in nonlog units) around f ≈ f peak . Correlating the site terms with western site‐effects predictions reveals that at f V S 30 in a manner that is similar to the way they behave in the NGA‐West2 database. However, at higher frequencies, the correlation of site amplification with V S 30 decreases markedly in CENA. In contrast, the horizontal‐to‐vertical (H/V) component spectral ratio (as obtained from the NGA‐East ground‐motion data) is a good predictor of the observed f peak ‐dependent site terms, suggesting that H/V spectral ratio is a more reliable predictor of site amplification for the recording stations of the NGA‐East database. The results of this study demonstrate the importance of a well‐calibrated regional site‐effects model for CENA and the importance of f peak as a site indicator.


Subsidence
due to groundwater withdrawal is a complex hydrogeological process affecting numerous cities settled on top of fluviolacustrine deposits. The discrete spatial
variation in the thickness of these deposits, in combination with subsidence
due to groundwater withdrawal, generates differential settlements and
aseismic ground failure (AGF) characterized by a welldefined scarp. In
cities, such AGF causes severe damages to urban infrastructure and considerable
economic impact. With the goal of arriving to a general criterion for evaluating
the economic losses derived from AGF, in the present work we propose the
following equation: ELi = PVi*DFi.
Where PVi is the value of a property "i", and DFi is a
depreciation factor caused by structural damages of a property "i" due to
AGF. The DFi is calculated empirically through:

 . This
last equation is based on the spatial relations of coexistence and proximity
of property polygons and the AGF axis. The coexistence is valued as the
quotient of the affectation area divided by the total area of the involved
property; and the proximity to the AGF axis is expressed as the inverse of the
perpendicular distance from the centroid of the property polygon to the AGF
axis. The sum of these terms is divided by two to determine the percentage that
affects the property value (PVi). These equations are relevant
because it is the first indicator designed for the discrete assessment of the
economic impacts due to AGF, and can be applied to real estate infrastructure
from either urban or rural areas.


This paper argues that states have undergone a shift in how they see and respond to human smuggling. They are now less bound by those land borders that once demarcated the edges of sovereign territory and act more transnationally in response to the transnational practices of human smugglers. The interception of four cargo boats carrying migrants smuggled from Fujian, China, serves as a case study. Central to understanding the struggle between smugglers and States are geography and vision: how each sees the landscape, plays on distance and proximity, and puts geography to work. After explaining the methodology, I locate Canada in the global industries of human smuggling and border enforcement, outline changes to border enforcement that have taken place in the time since these interceptions, and then discuss the main challenges facing nation‐states in their efforts to combat smuggling. The paper then outlines strategies available to curb smuggling and explores some of Canada's particular efforts. I conclude with policy recommendations.


Purpose: Expression of the sodium-iodide (Na+/I-) symporter (NIS) in thyroid cancer accounts for the success of radioactive iodine (131I) ablation of remnants or metastases following thyroidectomy. Breast cancer (BC) is one of the other malignancies that express functional NIS. The aim of the present study was to evaluate the expression and localisation of NIS according to BC subtype.
Materials and methods: Ninety predominantly high grade primary BC were independently evaluated for NIS expression and cellular localization (membranous and/or cytoplasmic) by immuno-histochemistry. mRNA expression of the NIS (SLC5A5) gene was analyzed across 18 publicly available whole genome microarray datasets including 3,091 primary breast tumors. NIS expression was compared with clinical and pathological tumor characteristics.
Results: Cytoplasmic (cNIS) and membrane (mNIS) immunoreactivity was more frequently observed in estrogen receptor (ER) and progesterone receptor (PR) negative (ER-/PR-) tumors (45% mNIS and 67% cNIS) than in ER and PR positive (ER+PR+) tumors (7% mNIS and 20% cNIS) (p<0.001). cNIS staining was not present in only 4% (1/25) of the tumors with mNIS staining.
NIS mRNA expression was higher in ER negative tumors defined by local pathological ER evaluation (p=0.013) or microarray classification (p=0.011).
HER2 status had no influence on NIS expression regardless of the analytical method considered.
Conclusions: NIS expression is increased in ER negative breast cancer. ER negative breast cancer should be targeted for clinical studies evaluating radioactive iodine therapy including strategies to mobilize cytoplasmic NIS to the cell membrane and enhance the activity of 131I in these cancers.


Emerging technologies open the prospect of extraordinary interventions on the human body. These may go beyond what is strictly necessary to sustain health and well-being. While responding to social and ethical challenges of such advances, the Law simultaneously faces the challenge of reflecting on the legitimacy to legislate and on whether the existing legal framework is appropriate to address the various concerns. In order to do so, it is crucial to establish clear legal definitions. Precise distinctions between interventions on the human body are intrinsically difficult to formulate. However, subject-matter definitions are vital legal tools to determine what is currently regulated in established fields of law and whether there is room for a new legal field – Enhancement Law. This paper provides a reflection on the relevance of establishing a legal definition of human enhancement and to what extent different legal fields and jurisdictions may warrant different understandings of such concept. It reviews a number of different and often divergent concepts and taxonomies of human enhancement and concludes with the proposal and analysis of a definition: Use of technological means with the intention to improve, modify or introduce in the human body aesthetic features, physical, emotional or cognitive performance levels and abilities beyond the human species typical standards under the current evolutionary state, and resulting in induced permanent alterations in the human body.


The development of multicellular organisms is characterized by complex processes that progressively transform essentially a single cell into a creature with complicated structures and highly specialized functions. The fruit fly Drosophila melanogaster provides an excellent model system to investigate these principles of life in great detail. Over the past few decades, Drosophila has been used to investigate and elucidate fundamental aspects that underlie the mechanisms described above. Since this research mainly involved large-scale analysis of genes, many principles are now understood at the gene level. However, it is nowadays clear that transcript abundances no not necessarily correlate with protein expression levels and since the latter determine the complexity of cells it is the ultimate goal to investigate and understand these processes directly at the protein level. The maturation of proteomics-based mass spectrometric techniques allows capturing the identity of many proteins in a single experiment. The primary goal of the work described in this thesis focused on gaining insights into the dynamics of early embryonic development of the fruit fly Drosophila melanogaster at the protein level by combining stable isotope labeling with high-accuracy mass spectrometry. We have developed a quantitative proteomic approach utilizing in vivo 15N-labeling of fruit flies with stable isotopes combined with extensive analysis by LC-MS/MS which has permitted the relative quantitation of thousands of proteins during early embryonic development. This provided insight into the production, stability and modification of individual proteins, while discrepancies between transcriptional profiles and protein dynamics indicated novel control mechanisms in genome activation during early fly development. Differential regulation of numerous proteins was observed and allowed the classification of these proteins into specialized classes. Although this approach shows its strength in identifying and quantitating proteins, some drawbacks include suboptimal labeling and lack of appropriate software for data processing. To overcome these issues, alternative objectives were explored in the work described in this thesis and aimed at developing methods to optimize, improve or facilitate the quantitative analysis of multiple proteins in a single experiment. Metabolic labeling with suboptimal (<98%) 15N-enrichments negatively affects protein identification and quantitation which was discovered by the systematic investigation of two independent 15N-labeled datasets. To overcome or compensate these shortcomings we have developed methods that can be applied to qualitative and quantitative 15N-labeled data. Although metabolic labeling produces most accurate quantitative data, it is not always feasible to incorporate an internal standard metabolically into an organism. So-called label-free techniques allow the quantitation of proteins in two or more samples without the need of using an internal standard. By directly comparing protein expression levels obtained by metabolic labeling based on stable isotope 15N-labeling and label-free quantitation based on spectral peak areas we have correlated both approaches and preliminary data suggests that there is a weak positive correlation between these approaches. Taken together, we have presented a powerful comprehensive proteomics approach that we have applied to early embryonic developed of the fruit fly which provided insights into the production, stability and modification of individual proteins during the developing fly.


In this paper we present a statistical method to build three-dimensional gas distribution maps from gas sensor and wind measurements obtained with a mobile robot in uncontrolled environments. The particular contribution of this paper is to introduce and evaluate an algorithm for 3D statistical gas distribution mapping, that takes into account airflow information. 3D-Kernel DM+V/W algorithm uses a multivariate Gaussian weighting function to model the information provided by the gas sensors and an ultrasonic anemometer. The proposed algorithm is evaluated with respect to the ability of the obtained models to predict unseen measurements. The results based on 15 trials with a mobile robot in an indoor environment show improvements in the model performance when using the 3D kernel DM+V/W algorithm. Moreover the model is able to adapt to the dynamical changes of the environment learning the hyper-parameter from the sensors readings.


Social movement scholarship has increasingly sought to understand the relational dynamics of internal movement activity, from investigating the factors that enable movement coalitions to analyzing the trade-offs of organizational hybridity. We bring these and other related phenomena together under the label of boundary-spanning processes. Specifically, we organize research on boundary-spanning in social movements by identifying three types of boundaries that have symbolic significance as categorical demarcations: ( a) issue and identity boundaries, ( b) organizational boundaries, and ( c) tactical boundaries. We then elucidate the tension in work that has examined how each form of boundary-spanning either promotes or hinders the realization of three important movement outcomes: ( a) mobilization, ( b) internal movement solidarity and scope, and ( c) external social and political change. We relate our three types of boundary-spanning to these three types of outcomes in an organizing framework to locate future opportunities for research on boundary-spanning in social movements.


Wave energy has a huge potential compared to other renewable energy resources. The energy of sea wave can be converted into other form of energy like electrical energy using a Buoy wave energy converter. The converted power is collected by a Power take off device. This paper aimed to model a wave energy converter (WEC) and analyze its potential. It's mainly focus is on the construction and operation of point absorber buoy type wave energy converter and the responses of the converter when sea wave appears on it. The simulation is done in MATLAM/Simulink.


In this report, we investigate the problem of applying a range constraint in order to reduce the systematic heading drift in a foot-mounted inertial navigation system (INS) (motion-tracking). We make use of two foot-mounted INS, one on each foot, which are aided with zero-velocity detectors. A novel algorithm is proposed in order to reduce the systematic heading drift. The proposed algorithm is based on the idea that the separation between the two feet at any given instance must always lie within a sphere of radius equal to the maximum possible spatial separation between the two feet. A Kalman filter, getting one measurement update and two observation updates is used in this algorithm.


Conducting polymers have received increasing attention in both fundamental research and various fields of application in recent decades, ranging in use from biomaterials to renewable energy storage devices. Processing of conducting polymers into fibrillar structures through spinning has provided some unique capabilities to their final applications. Compared with non fibrillar forms, conducting polymer fibres are expected to display improved properties arising mainly from their low dimensions, well-oriented polymer chains, light weight and large surface area to volume ratio. Spinning methods have been employed effectively to produce technological conducting fibres from nanoscale to hundreds of micrometre sizes with controlled properties. This review considers the history, categories, the latest research and development, pristine and composite conducting polymer fibres and current/future applications of them while focus on spinning methods related to conducting polymer fibres.


Competition policy is there to promote competition in order to lower prices and enhance economic efficiency. It does so by challenging business conduct deemed anticompetitive. The purpose of this essay is to address two questions. First: Does competition policy really promote competition? Second: Does competition really lower prices and does it enhance efficiency? The problem with competition policy is that it often promotes competition in a narrow sense, but stands in the way of competition in a broader sense. Moreover, after a century of sharpening the pencil its enforcement criteria remain as ambiguous as ever, giving rise to substantial legal uncertainty. The problem with competition itself is that it does not always work the way it should. What makes competition often ineffective is economies of scale, particularly mass production. Unfortunately, mass production is far more effective than competition itself in both lowering prices and enhancing efficiency. What makes it worse is that the main adversary of competition policy, big business, happens to be the main ally of mass production. In that respect, competition policy may be winning some battles now and then, but is waging a lost war.


ABSTRACT Segregation occurs during most particulate materials-related unit operations including mixing, conveying, discharging, filling, and compaction. A redesigned second-generation primary segregation shear cell (PSSC-II) was fabricated to simulate and quantify percolation and sieving mechanisms-based segregation. Several binary mixtures were tested to quantify the effect of size ratios and absolute size. The constituents of binary mixtures studied were spherical glass beads. Three binary size ratios, 4:1, 6:1, and 8:1, were tested. For a given size ratio, three different absolute coarse (710–850, 1000–1200, and 1400–1700 μm) to fine particle sizes were studied. The experimental results showed that the PSSC-II was capable of quantifying segregation potential for various materials. Several physical parameters such as segregation rate (SR), phase of segregation rate (PSR), distribution of segregation rate (DSR), maximum segregation rate (MSR), and normalized segregation rate (NSR) were created to describe the quantity of segregation to a certain level. It was concluded that: (1) Generally, the segregation rates increase with the increase in size ratio. A linear relationship between NSR and size ratio exists for glass beads (R2 = 0.99). (2) Segregation rate also increases with absolute size. NSR increases linearly with absolute size for glass beads (R2 = 0.99). Furthermore, a quantitative relationship exists between certain size ratios and segregation rates, i.e., while size ratio increased two-fold from 4:1 to 8:1, the NSR increased approximately six-fold. (3) The largest magnitude of the NSR occurred where both absolute size and size ratio were at their largest values. (4) The DSR for the binary mixture of glass beads was mainly concentrated in the center region of the shear box for larger size ratios such as 8:1 and 6:1, whereas, for smaller size ratios such as 4:1, the DSR is approximately uniformly distributed. (5) Both duration of lag phase (DLP) and duration of acceleration phase (DAP) decrease with increase in size ratios and in absolute sizes. The smaller the DLP and DAP, the larger the MSR.


Motion estimation is a key problem in video super-resolution (SR). If the estimation is highly accurate then the high resolution (HR) frames reconstructed is better in quality. Otherwise with small errors in estimation, they will create more degradation in the reconstructed HR frames. In many recent studies, the motion estimation is applied on every block of pixels. There is too little input data for estimating process so that it is hard to get high accuracy in results. This paper presents a new method for SR video image reconstruction through two main ideas. First, video frames are separated into two sections, as scene and motive objects. The motions of the scene are the same and uniform. We will have much data for estimating, so that the result can be more accurate. Second, the motion estimation is based on three parameters, rotation and shifts in vertical and horizontal. It presents a perfectly estimating for real motion of camera when capturing video frames. Based on that, an efficient algorithm is proposed by combination of block matching search method and minimum mean square error estimation. The results of the proposed algorithm are more accurate than those of other recent algorithms. It can be easy to see one we visualize the HR video frames reconstructed by other algorithms.


To the Editor.— We published cases of the dystrophic type of epidermolysis bullosa hereditaria congenita in uniovular male twins. 1 In the treatment of these cases we administered vitamin E, 400 mg daily, intramuscularly first, in tablet form later. The treatment was given continually from Oct 14,1974 to Jan 5,1975, without beneficial effect on the lesions. During this treatment, no iron-containing medicaments were given to patients. In another patient with a dystrophic type of epidermolysis bullosa hereditaria congenita, a 15-year-old girl, we gave the same medicament, also without effect. Some effect was observed in all of our cases when we combined vitamin E therapy with low doses of corticosteroids (15 mg of prednisone daily). According to Rook 2 , "corticosteroids in high dosage may be life-saving and may prevent deformity in infancy and early childhood. The dose should be increased until bulla formation is controlled and then progressively reduced." In 1971,


Bond markets have grown mature in many countries; however, the quality of financial integration varies across ASEAN economies. In the case of bond markets in the ASEAN +3, they experienced fast development; however, they are still less integrated. This study attempts to examine the ramifications of the ASEAN bond market integration and past crises to the Philippines' inflation, credit, and growth and identify what impedes the development of the bond market for the period of 1992 to 2017. The study also aims to have a more in-depth analysis on preventing rises from happening and controlling both credit expansions and inflationary pressures. The Ordinary Least Square method (OLS) was used to examine the relationship of inflation, credit, bond market index, real interest rate, and integration to the Philippines' growth. This led to this paper providing empirical insights that credit has a significant positive relationship with GDP growth; while, inflation has a significant negative relationship with GDP growth. However, the bond market index and integration showed insignificant negative results. This study provides possible reasons for the said conclusion and suggests ways not only to develop and grow the debt market in the Philippines but also to sustain long-run economic stability and growth to become on par with other ASEAN economies.


Objectives: To apply and refine conventional and developing cardiac magnetic resonance (CMR) imaging tissue characterisation techniques, with the aim of applying them to better understand cardiac remodelling in health, disease and as an outcome surrogate in clinical trials.

Background: Cardiac structure, function and perfusion are routinely assessed with a range of imaging modalities in both research and clinical practice. Cardiac magnetic resonance (CMR) imaging is emerging as the gold standard tool for many of these assessments. The use of gadolinium containing contrast agents in CMR protocols allows the detection of myocardial scar and focal fibrosis and provides important prognostic information. The developing field of T1 mapping allows measurement of the extracellular volume, a surrogate for fibrosis that offers further insights into diffuse myocardial change not previously possible.

Methods: CMR tissue characterisation techniques were applied in sequential studies of: ischaemic cardiomyopathy, health, athletic cardiac adaptation and in a randomised controlled study examining the effects of spironolactone in heart failure with preserved ejection fraction.

Results & Conclusions: Late gadolinium enhancement (LGE) imaging is of limited application in predicting functional recovery of dysfunctional segments in ischaemic cardiomyopathy (Chapter 3). Modified Look-Locker Inversion recovery (MOLLI) T1 and extracellular mapping techniques can be applied reproducibly in health and following either bolus or split dose gadolinium administration (Chapters 4 & 5). T1 mapping provides important insights into athletic cardiac remodelling that may allow its application in distinguishing between athletic and myopathic change (Chapter 6). Individuals with heart failure with preserved ejection fraction (HF-PEF) have diffuse myocardial fibrosis as measured with T1 mapping. Early results of a randomised controlled study suggest that the beneficial effects of spironolactone in HF-PEF may in part be due to regression of diffuse myocardial fibrosis (Chapter 7).


The increasing domain of service-oriented computing (SOC) and the continued growth of Web services towards globalization create a significant need for the discovery of the most relevant Web services to a business process. As services are abundant, yet scattered, it is unreasonable and impractical to expect an employee to handle the thousands of management tasks desired and/or required on a continual basis. An agent federation might be the best solution for handling the addition of new business processes in a way that would seamlessly integrate the rationality of a human and the speed of a computer. This work introduces an architecture for the communication and collaboration of intelligent agents to enable businesses to share Web services and adjust their systems on the fly. Furthermore, interaction patterns are introduced that define how agents implement this collaborative architecture for the benefit of their human counterparts.


The Great Match, and Other Matches, published anonymously in 1877, appears to be the first American novel whose entire plot involves baseball. The book opens with the Dornfield nine celebrating a victory over their Milltown rivals, and it closes with Dornfield winning the championship match. In between, the author introduces characters and events in both communities that reveal several themes: athletic rivalry, romantic intrigue, and conflicts between old rural tradition and new urban society. While few pages actually describe baseball action, players are key characters in the novel, and the author uses contemporary debates in baseball to support the plot. The story is amusing, and its depictions of the national pastime add much to our understanding of what baseball meant to rural communities in the 1870s. Critical assessments of The Great Match have differed widely because of readers' expectations based on genre. The primary reason for these variations is that the book was published anonymously, and the author's gender and identity have remained a mystery. Readers expecting either traditional nineteenth-century boys' fiction or sentimental romance find The Great Match disappointing. The central character is the young fanette Molly Milton, and most of the baseball discussions filter through her perspective. While the novel includes plenty of action--baseball, fistfights, body building, and scandal--this is not the primary focus. Instead, such details contribute to the heroine's observations as Molly considers which, if any, of the male characters qualifies as a suitable romantic match for her. Meanwhile, the central male character, Dick Softy, considers which woman, if any, would make a suitable match for him. This brings new meaning to the title, since the championship ballgame might be the "Great Match," with other romantic matches integral to the plot; or, the romance between the heroine and her unexpected hero could be the "Great Match," with baseball and other events in the background. While romance is a central theme, the novel is not purely sentimental. Most sentimental fiction is interior, contemplative, and focuses on the workings of the heart. Its heroines are sedentary and spend most of their time in parlors, bay windows, or bedchambers--thinking, reading, talking, and writing about life rather than actively living it. By contrast, the heroine in The Great Match is "a coming woman": Molly moves outdoors, involves herself in the baseball team's business, cheers aggressively at games, and participates as an active member of the community. She knows which players have broad chests, solid shoulders, and strong legs but places greater value on moral strength. The novel's hybrid genre and nontraditional heroine have helped keep its author's identity a mystery. The Great Match was the fifth volume of Roberts Brothers' No Name Series, which the publisher advertised as a series of Original American Novels and Tales, to be published Anonymously. These novels are to be written by eminent authors, and in each case the authorship of the work is to remain an inviolable secret. "No Name" describes the Series perfectly. No name will help the novel, or the story, to success. Its success will depend solely on the writer's ability to catch and retain the reader's interest. Several of the most distinguished writers of American fiction have agreed to contribute to the Series. This announcement originally appeared in the Boston Daily Advertiser during midsummer 1876, and the publisher also included it in the front matter of each new volume. Formed in 1863, Roberts Brothers had originally specialized in juvenile fiction, but then expanded to publish books for adults. Thomas Niles led the firm, and one of his early successes was signing Louisa May Alcott, who published Little Women with Roberts Brothers in 1868. (1) However, when the national economy faltered, the popularity of Alcott's work was not enough to sustain the entire business. …


Published references to homelessness in newspapers of the 1940s include instances of both foreign and local homelessness. International homelessness is frequently stated to be a result of social conditions: poverty and unemployment. Natural disasters figure small. New Zealand accounts vary more widely, but are dominated by Pākehā homelessness resulting from sub-leasing regulations, "native insurgents" - usually in reference to the attack on Kororāreka, and Wellington's 1848 earthquake, whose homeless sheltered with friends who lived in "wooden buildings." Yet, simultaneously, New Zealand was also proposed as a potential home for England's unemployed homeless, and Auckland - "the neglected offspring of avaricious parents ... exhibiting the tokens of permanent prosperity" due to its merchantile, rather than colonial, British settlement - is stated to have accommodated refugee settlers "driven from their homes by acts of violence and destruction which the native insurgents, intoxicated with success, so wantonly committed." In 1840s newspapers there are no references to homelessness in serialised literature, and few abstract uses of the term.
Māori do not figure large in the references to homelessness as being homeless. There is reference though in the late 1840s to Tommy, who is praised because when he "found himself homeless ... [he] did not return to the savage horde from whence he came, but sought and found other employment amongst the Pakeha's [sic]," and there is a heartfelt plea from a father of half-caste children to other fathers: "let not your children fall back to the state of degradation, from whence their mothers sprung." Potential homeless here is tied to prostitution and disease. This paper will examine the reporting of homelessness throughout the 1840s, and will attempt to isolate specifically architectural issues of the decade which emerge from this.


A geometrical fit of the land masses of northern Europe, Canada and Greenland has been constructed by Dr A. G. Smith using the method devised by Sir Edward Bullard and M r J. E. Everett. The method involves taking points of latitude and longitude on the 500 fm. line at intervals of about 30 miles along the two coasts to be fitted. Young features such as oceanic islands are ignored. By a method of successive approximation, the computer 'homes in ' on to the centre of rotation which gives the minimum root mean square misfit between the rotated coastlines j the misfit being measured as the discrepancy of longitude relative to the centre of rotation. In this manner the 500 fm. line along the east coast of Greenland has been fitted to that of northwestern Europe to form one unit. This unit, that is, the 500 fm. line of the west coast of Greenland and the Channel approaches have been fitted on to the 500 fm. line of Canada. Maps of this fit drawn as a conical projection with two standard parallels of latitude will be presented and will show the geochronological patterns across the reconstructed land masses.


The growth hormone (GH) inhibitory effect of CV 205-502 was evaluated during acute and 3-month administration, alone or in combination with octreotide, in 12 therapy-resistant acromegalic patients. Although these patients previously had undergone surgery and received chronic therapy with octreotide at 0.3-0.6 mg/day, they still had high GH and insulin-like growth factor I (IGF-I) levels. CV 205-502 (0.15 mg), octreotide (0.1 mg) and placebo were tested acutely. CV 205-502 at the dose of 0.15 mg caused a decrease of GH level (from 34.9 +/- 15.1 to 2.7 +/- 0.3 micrograms/l) in 4/12 (33.3%) and completely inhibited prolactin (PRL) secretion in all the patients. Octreotide caused a decrease of GH level (from 37 +/- 6.7 to 15.9 +/- 3.0 micrograms/l) without any change of PRL level. The GH and PRL levels were not changed during placebo administration. CV 205-502 at the dose of 0.3 mg/day (chronic test) normalized GH and IGF-I levels in five patients (41.6%: the four responders to the acute test and an additional patient who was a poor responder to acute CV 205-502 administration). The remaining seven patients were subjected to CV 205-502 (0.6 mg/day) and octreotide (0.6 mg/day) in combination for 3 months. In 2/7 patients the combined therapy induced a greater inhibition of GH and IGF-I levels than did each drug when administered alone. The drug was well-tolerated by the 12 patients. In conclusion, CV 205-502 is able to normalize GH and IGF-I levels and to improve clinical symptoms in certain acromegalic patients resistant to other therapeutic approaches.(ABSTRACT TRUNCATED AT 250 WORDS)


This contribution will focus on the facet of International Criminal Justice where the influence of global law is the most apparent, namely the hybrid or internationalized criminal tribunals. Since many of these tribunals have closed their doors or are in the advanced stage of the proceedings, the time is ripe for a preliminary evaluation. Furthermore, the future necessity and viability of hybrid tribunals will be assessed, both for crimes that fall within and without the jurisdictional regime established by the International Criminal Court (ICC).


Purpose
Many companies invest in innovations because of the inherent benefits, and research on innovation has increased over the year. However, the vast majority of research papers deals with purely technical matters. There seem to be growing concerns over ethical issues in adopting innovations in the construction industry. This extant review of literature aims to analyse the interrelations between the concepts of ethics and innovations in construction research to understand the advances of current scientific production and future lines of research.

Design/methodology/approach
Thus, this work presents a bibliometric analysis covering articles obtained from the Web of Science Core Collection Database published between 1995 and May 2021. A sample size of 5,786 research papers relevant to the study was evaluated using VOSviewer software.

Findings
The results of the analysis shed light on the evolution of the connection between the two concepts. The study highlighted Heng Li as the most productive author. The country with the most publications and citations is China. The most productive institution is the Hong Kong Polytechnic University. The results revealed a limited intellectual exchange and lack of cohesion characterising the two concepts (ethics and innovation), resulting in a situation whereby innovation-related researchers tend to follow personal trajectories in isolation from ethics-related researchers in the construction field.

Originality/value
This is probably the most comprehensive scientometric analysis ever conducted to examine the theoretical relationship between ethics and innovation in construction. This study adds to the so far limited knowledge in the field and provides insights for future research. Overall, this review may spur future research on dyad investigation of ethics and innovative related themes in construction such as ethics and sustainability, ethics and sensor-based technology and ethics and innovative safety approach.


Enforcement of competition law affects consumers' economic interests, as part of the public interests EU competition law protects. Therefore, consumers ought to be involved in the respective enforcement procedures. Against this normative background, we analyse consumers' access to the public enforcement by the Commission; we assess whether and how the formal role they are assigned during this procedure and the way access is defined enable consumers to protect their economic interests. We identify outer and inner limits to consumers' access to competition enforcement procedures, arising from the Commission's discretion in handling complaints and in defining access to information. We critically evaluate those limits against the contention that the enforcement of competition law rules, and the way it is pursued by administrative actors, ought to be guided by the public interests inherent in EU competition law.


Background Paclitaxel is an important chemotherapeutic agent for the treatment of breast cancer. Paclitaxel-induced peripheral neuropathy (PIPN) is a major dose-limiting toxicity that can persist into survivorship. While not all survivors develop PIPN, for those who do, it has a substantial negative impact on their functional status and quality of life. No interventions are available to treat PIPN. In our previous studies, we identified that the HIF-1 signaling pathway (H1SP) was perturbed between breast cancer survivors with and without PIPN. Preclinical studies suggest that the H1SP is involved in the development of bortezomib-induced and diabetic peripheral neuropathy, and sciatic nerve injury. The purpose of this study was to identify H1SP genes that have both differential methylation and differential gene expression between breast cancer survivors with and without PIPN. Methods A multi-staged integrated analysis was performed. In peripheral blood, methylation was assayed using microarray and gene expression was assayed using RNA-seq. Candidate genes in the H1SP having both differentially methylation and differential expression were identified between survivors who received paclitaxel and did (n = 25) and did not (n = 25) develop PIPN. Then, candidate genes were evaluated for differential methylation and differential expression in public data sets of preclinical models of PIPN and sciatic nerve injury. Results Eight candidate genes were identified as both differential methylation and differential expression in survivors. Of the eight homologs identified, one was found to be differential expression in both PIPN and "normal" mice dorsal root ganglia; three were differential methylation in sciatic nerve injury versus sham rats in both pre-frontal cortex and T-cells; and two were differential methylation in sciatic nerve injury versus sham rats in the pre-frontal cortex. Conclusions This study is the first to evaluate for methylation in cancer survivors with chronic PIPN. The findings provide evidence that the expression of H1SP genes associated with chronic PIPN in cancer survivors may be regulated by epigenetic mechanisms and suggests genes for validation as potential therapeutic targets.


When a host population is faced with a pathogen it may invest resources in avoiding infection, recovering from infection or developing immune memory against the infection. All of these mechanisms of costly host defence decrease the incidence of infection (in contrast to tolerance) and are therefore known as host resistance. Because investment in resistance lowers the incidence of infection which in turn decreases the advantage of resistance, an evolving population will often come to rest at an intermediate level of investment. Optimal levels of investment in costly resistance reflect a fine balance between epidemiological and evolutionary dynamics. To begin with we demonstrate key qualitative differences in the nature of this balance depending on the combination of host and pathogen types. We then return to some important questions in the study of resistance. Is high investment associated with high incidence of infection or high force of infection? How does optimal investment vary between populations? How are these patterns affected by concurrent pathogens residing in the host population? We show how exact invasion fitness and approximations for optimal investment can be used to answer these questions.


The present study deals with the actual situation of the Hungarian sour cherry production in order to outline the chances of the future and the trends of the development anticipated. The general conclusion accepted that on the long run Hungarian sour cherry production ought to be reorganised. The conditions of keeping the position on the international market are outlined: integration of small farms into large plantations (several times 10 hectares), introduction of mechanical harvest and high (15–20 t/ha) yields. For all that, adequate expertise should be developed on the cooperative farms, where the up to date technology could be applied with innovative initiatives. Small farms (up to 1–2 hectares) and home gardens have no chances to stay on the competitive market. The actual volume of sour cherry of 40–70 thousand tons per year cannot be increased in the future. The sour cherry area was 16 000 ha in 2001, the actual is around 12–13 thousand, and will decline during the following 5 years to less than 10 thousand hectares. International Journal of Horticultural Science 2010, 16 (1): 99–104. Agroinform Publishing House, Budapest, Printed in Hungary ISSN 1585-0404


Introduction/Objective: Stroke is the fifth leading cause of death in the United States and results in significant morbidity and mortality annually. Its wide prevalence and critical nature make it essential to recognize and properly triage patients with symptoms of stroke so that appropriate time-sensitive interventions may be delivered. Many studies have delineated gender differences in risk, diagnosis and treatment of stroke; however, limited information exists on the association between gender and Emergency Department (ED) triage priority. The objective of this study is to determine if there is a gender difference in the assignation of an emergency priority of admission code among Florida stroke patients. Methods: An observational cross-sectional study was performed through secondary analysis of the Florida Stroke Registry, composed of hospital discharge data collected by the Agency for Healthcare Administration (AHCA) on Florida stroke patients from 2012. A descriptive analysis was utilized to profile the study population, calculating measures of centrality and dispersion of demographic variables. We tested associations of our bivariate analysis using chi-square tests, then performed a multivariate analysis using logistic regression to control for confounders. Odds ratios were used to measure associations. Results: Women were 24% more likely to receive an emergency priority of admission code than men. Following adjustment and stratification by primary stroke center designation, it was determined that women remained more likely to receive a priority code of admission than males. This occurred at a higher rate in primary stroke centers (35% more) than in non-certified hospitals (11% more). Independently, the other factors included in the adjusted analysis (age, race, payer, source of admission, day of the week, and stroke center designation) also held statistically significant associations with emergency priority triage. Conclusions: Gender disparity does exist among Florida stroke patient triage and more research should be conducted concerning the factors influencing the assignation of an emergency priority code. Emergency department care providers may need more gender specific protocols on stroke triage and additional training in recognizing gender specific symptoms. Additional studies need to be conducted in order to identify if gender disparities exist in other links of the stroke chain of survival.


Recommender systems rely on user behavior data like ratings and clicks to build personalization model. However, the collected data is observational rather than experimental, causing various biases in the data which significantly affect the learned model. Most existing work for recommendation debiasing, such as the inverse propensity scoring and imputation approaches, focuses on one or two specific biases, lacking the universal capacity that can account for mixed or even unknown biases in the data. Towards this research gap, we first analyze the origin of biases from the perspective of risk discrepancy that represents the difference between the expectation empirical risk and the true risk. Remarkably, we derive a general learning framework that well summarizes most existing debiasing strategies by specifying some parameters of the general framework. This provides a valuable opportunity to develop a universal solution for debiasing, e.g., by learning the debiasing parameters from data. However, the training data lacks important signal of how the data is biased and what the unbiased data looks like. To move this idea forward, we propose AotoDebias that leverages another (small) set of uniform data to optimize the debiasing parameters by solving the bi-level optimization problem with meta-learning. Through theoretical analyses, we derive the generalization bound for AutoDebias and prove its ability to acquire the appropriate debiasing strategy. Extensive experiments on two real datasets and a simulated dataset demonstrated effectiveness of AutoDebias. The code is available at https://github.com/DongHande/AutoDebias.


Colorful traits can vary in response to neural control, hormone levels, reproductive state, or abiotic factors. In birds, colorful plumage traits are generally considered static ornaments that only vary irreversibly due to abrasion, bacterial degradation, or wear. However, in this work it is shown that iridescent feather color varies rapidly and reversibly in response to changes in ambient humidity. Based on optical models and sorption experiments, these changes appear to be caused by a swelling of the outer keratin cortex following water absorption. To our knowledge, this is the first study describing dynamic color changes in any keratinous biophotonic nanostructure.


Purpose: To determine the diagnostic accuracy of mean macular retinal thickness (mRT) and macular ganglion cell layer (mGCL) thickness measured by Spectralis spectral-domain optical coherence tomography (SD-OCT) posterior pole thickness map (PPTM) in differentiating between normal and glaucoma eyes of different severity.Study design: Cross-sectional study.Methods: All subjects were divided into normal and glaucoma groups according to the visual fields-based Glaucoma Staging System. They underwent slit-lamp examination, Humphrey visual field test, and SD-OCT (PPTM) imaging. mRT and mGCL thickness measurements were recorded. Analysis of variance with the least significant difference post hoc test was used for pairwise comparison. Ability to discriminate between normal eyes and those with differing severity of glaucoma was assessed using the area under the receiver operating characteristic curve (AUROC).Results: A total of 201 eyes from 201 subjects were enrolled in this study. The mean glaucoma was 290.2 ± 12.1 μm, 270.1 ± 17.0 μm, and 259.1 ± 15.0 μm, respectively. Mean mGCL thickness for the corresponding three groups was 32.3 ± 2.8 μm, 27.6 ± 3.3 μm and 22.2 ± 3.8μm, respectively. AUROC analysis showed excellent diagnostic discrimination between glaucoma and normal subjects for mRT (AUC: 0.90) and mGCL thickness (AUC: 0.92). The cut-off value of mRT was 274.9 μm (90% sensitivity, 75% specificity) and of mGCL thickness was 27.9 μm (93% sensitivity, 74% specificity). The discrimination ability performance of mRT and mGCL thickness deteriorated with increasing severity of glaucoma with mGCL thickness (AUC: 0.67–0.87) performing slightly better than mRT for all grades (AUC: 0.58–0.71).Conclusions: mRT and mGCL thickness measurement on PPTM showed great sensitivity and specificity to discern between normal and glaucomatous subjects. The discrimination ability of mRT and mGCL thickness, however, decreases with increasing grade of glaucoma. We believe SD-OCT PPTM offers an alternative imaging method to detect early glaucoma.


Introduction Patients with genital dermatology (GD) conditions frequently present to sexual health services. Following service tendering, there are reports of contracts excluding provision of specialist GD services within sexual health. We aimed to review the case load of GD conditions presenting to walk-in sexual health clinics, to reach an understanding of the demand for these services within our specialty. Methods Members of the BASHH GD Specialist Interest Group collected data on the first 30 to 50 new symptomatic patients presenting to their sexual health walk-in service on 5th September. Results 382 patients presented to 9 services across England and Scotland. Of these, 164 (43%) presented with a GD condition. GD STI diagnoses (e.g. warts, herpes simplex) were excluded. 75 patients (20%) presented with non-STI GD conditions. Of these, 59% were male, 91% heterosexual. The modal age range and ethnicity were 18–25 year olds (36%) and white British (67%). GD diagnoses included: candida/tinea 17%, normal variant 11%, eczema 8%, non-specific balanitis 8%, irritant dermatitis 7%, vulvodynia 5%, lichen sclerosus 5%, lichen planus 3%, psoriasis 3%. 17% of cases required senior review. 33% had follow up: 32% by a Genitourinary Medicine consultant; 12% in a Genitourinary Medicine specialist clinic. 4% required skin biopsy. Discussion Our study demonstrates that non-STI GD conditions constitute a high proportion of clinical presentations to walk-in sexual health services. Many cases require in-house senior input. Commissioners must recognise the burden of GD on services and the expertise required to ensure optimal management of GD within sexual health.


The traditional paper manual is losing our attention, while the amount of online instructional videos grows rapidly. Many companies notice this change and produce their own online instructional videos. At the same time, users themselves are making and sharing their own instructional videos on online social platforms such as YouTube. This user-generated content (UGC) is a popular source of information for other users. A combination of the two types of instructional videos also exists: companies co-operating with users through sponsoring. The idea behind this is that users helping users could be more effective than companies helping users. People's perception of source credibility could play a role in this, as no companies with ulterior motives are involved. This study investigates the differences in people's perception of source credibility of instructional videos by different sources, and tries to determine the role of trustworthiness, competence, and goodwill as determinants. It also looks into the effect of the sources on perceived usability of the product and the instructional video. Data was gathered in an experiment with three types of software tutorial videos. Results of the study indicate that there are generally no differences in the outcomes of users' credibility or usability assessments when the source differs, but the content of the instructions is equal. This shows that letting users provide the instructions could still be as effective a letting professionals do so. The only exception is the component goodwill: users do perceive sources of the two user-generated videos as more caring than the company as a source, with the independently produced user-generated video scoring higher on goodwill than the sponsored user-generated video. The outcomes can help organizations in the design process of instructions: they can benefit from co-operation with users, as long as they make sure that the instructional design is sufficient.


In this paper a class of discretized piecewise linear chaotic maps of a very high dimensions are used for communication over a noisy channel. An information payload that is sent over a channel is controlled in the transmitter and is related to the symbolic sequences of chaotic trajectory. Such chaotic systems are used for generating new ensembles of nonlinear codes. The proposed decoding method is based on belief propagation principle, such that a complete link to modern coding theory is established. The transmission of information using chaotic systems, usually showing mediocre performance, here on contrary, have a very good performance with a threshold for a certain level of signal-to-noise ratio (SNR)


While pretrained models such as BERT have shown large gains across natural language understanding tasks, their performance can be improved by further training the model on a data-rich intermediate task, before fine-tuning it on a target task. However, it is still poorly understood when and why intermediate-task training is beneficial for a given target task. To investigate this, we perform a large-scale study on the pretrained RoBERTa model with 110 intermediate-target task combinations. We further evaluate all trained models with 25 probing tasks meant to reveal the specific skills that drive transfer. We observe that intermediate tasks requiring high-level inference and reasoning abilities tend to work best. We also observe that target task performance is strongly correlated with higher-level abilities such as coreference resolution. However, we fail to observe more granular correlations between probing and target task performance, highlighting the need for further work on broad-coverage probing benchmarks. We also observe evidence that the forgetting of knowledge learned during pretraining may limit our analysis, highlighting the need for further work on transfer learning methods in these settings.


The study is set out to examine the private cost of National Certificate in Education, through the distance learning mode as organized by the National Teachers Institute (NTI) Ekiti State branch in Nigeria. This was to open the eyes of the prospective students to know what on the average he has to spend and also to provide data for the state chapters of the institute on how to ease the burden of the students undergoing the course. The study made use of cross-sectional data retrieval format to collect the necessary information needed for the three circles contact period. The data was analyzed using arithmetic mean and percentages. It was found out that tuition fees accounted for the percentages of students' expenditure, followed by examination fees, and mid-day meal. Library, sports and development levy are not relevant for this type of student. The federal Government of Nigeria could subsidize the tuition fees for the prospective grade II teachers so as to ease their problem because majority of them are unemployed.


Background Chronic parasitic infections are associated with active immunomodulation which may include by-stander effects on unrelated antigens. It has been suggested that pre-natal exposure to parasitic infections in the mother impacts immunological development in the fetus and hence the offspring's response to vaccines, and that control of parasitic infection among pregnant women will therefore be beneficial. Methodology/Principal findings We used new data from the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy conducted in Uganda, to further investigate this hypothesis. 2705 mothers were investigated for parasitic infections and then randomised to albendazole (400mg) versus placebo and praziquantel (40mg/kg) during pregnancy in a factorial design. All mothers received sulfadoxine/pyrimethamine for presumptive treatment of malaria. Offspring received Expanded Programme on Immunisation vaccines at birth, six, 10 and 14 weeks. New data on antibody levels to diphtheria toxin, three pertussis antigens, Haemophilus influenzae type B (HiB) and Hepatitis B, measured at one year (April 2004 –May 2007) from 1379 infants were analysed for this report. Additional observational analyses relating maternal infections to infant vaccine responses were also conducted. Helminth infections were highly prevalent amongst mothers (hookworm 43.1%, Mansonella 20.9%, Schistosoma mansoni 17.3%, Strongyloides 11.7%, Trichuris 8.1%) and 9.4% had malaria at enrolment. In the trial analysis we found no overall effect of either anthelminthic intervention on the measured infant vaccine responses. In observational analyses, no species was associated with suppressed responses. Strongyloidiasis was associated with enhanced responses to pertussis toxin, HiB and Hep B vaccine antigens. Conclusions/Significance Our results do not support the hypothesis that routine anthelminthic treatment during pregnancy has a benefit for the infant's vaccine response, or that maternal helminth infection has a net suppressive effect on the offspring's response to vaccines. Trial Registration ISRCTN.com ISRCTN32849447


Drama Managers, a specific type of the more general Experience Manager, have become a common subject of study in the interactive narrative literature. With a range of representational and computational approaches, authors have repeatedly developed techniques that enable computers to generate, reason about, and adapt narratives in an interactive virtual setting. In order to fully realize an experience manager, seven representational and computational problems need to be solved, generally on a case-by-case basis. In other words, the choice to use an Experience Manager is the choice to model the design as, and implement solutions to, seven inter-dependent design problems. We explicitly articulate those design problems and provide a number of examples of methods that both motivate the design problems as well as illustrate a range of approaches to solving them.


The photophysics and charge transport properties of polymer host materials largely determine the resultant electroluminescent (EL) performance of solution-processed phosphorescent organic light-emitting diodes (s-PhOLEDs). Herein, these characteristics of the state-of-the-art polymer host material, i.e. poly(N-vinylcarbazole) (PVK), are manipulated via the choice of the processing solvent by means ofdifferent boiling points. Compared to the control PVK film (toluene as solvent), the PVK film with a high packing density processed with o-dichlorobenzene (ODCB) solvent displays a higher excitonic energy, i.e. the more the "p-PVK" contribution, the lower the content of low energy PVK electromers under EL driving, and also a different hole transport capability. For the PVK:FIrpic doped film, it is confirmed that the host-to-guest energy transfer efficiency is the best for the ODCB based film among these samples. PVK:FIpric doped s-PhOLEDs are comparatively fabricated by using these solvents, and the ODCB based device achieves a high luminous efficiency of 29.0 cd A−1, corresponding to 16% enhancement with respect to 25 cd A−1 of the control TOL device. Such performance promotion is attributed to the satisfied energy transfer process from PVK to FIrpic and also the enhanced charge balance conditions achieved in the ODCB device.


In designing policies to help resolve its energy problems, every country faces a unique set of conditions. Contributors to this volume profile the energy situation in the developing countries, assess the role of energy policy in Third World development, and discuss the global energy situation in relation to these countries' consumption, production, trade, and resource endowment. The rest of the volume provides researchers with different sources of information--statistical and bibliographic--relating to energy policy development in the Third World. Managing the increasing demand for energy is explored in depth.


The effect of VAE latex modification on the physical properties of cement mortar is investigated. The porosity problem in cement mortar modified by vinyl acetate ester-ethylene (VAE) copolymer emulsion was successfully resolved by reasonable defoaming technique. It is shown that the bond strength and water resistance properties of modified cement mortar are better than unmodified cement mortar. When polymer-cement ratios ranged from 0 to 0.25, the bond strength and anti-permeability increased first and then decreased. The best value appeared at 0.1(polymer-cement ratio). SEM shows that the modified sample has compacted structure, polymeric films wrap the cement body and fill in the gap between cement and sand to improve the interfacial bond.


BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually a systemic disease and so requires chemotherapy even when surgical resection is possible. Current agents such as gemcitabine are only effective in a minority of patients and chemoresistance is an important issue faced in pancreatic cancer. There is an urgent need for more effective therapies; Novel agents may offer an avenue for this. The CDK family of protein kinases are pivotal in cell cycle regulation that is often deranged in cancer. HSP90 is a molecular chaperone affecting multiple key cellular signaling pathways of importance in pancreatic cancer. OBJECTIVES: To determine the efficacy of AT7519, a novel CDK inhibitor, and AT13387, a novel HSP90 inhibitor in pancreatic cancer models in vivo and in vitro both as single agents and in combination with gemcitabine. METHODS: Cell proliferation was measured using the EZ4U assay. Cell cycle analysis was performed with flow cytometry. Apoptosis analysis was using the Caspase-Glo 3/7 luminescent assay. Western blotting assessed expression of client proteins and phosphorylation. A murine xenograft model was employed assessing tumour volumes with external calipers. Experiments were performed using AT7519 and AT13387 as single agents and in combination with gemcitabine. RESULTS: AT7519 inhibited proliferation in cell lines including a gemcitabine resistant line (SUIT-2 GR) with IC50 values ranging 5-2000nM. Cell cycle analysis showed actions in line with CDK inhibition. At 24 hours induction of caspase 3/7 was significantly increased in AT7519 treated cells compared with those in control media (p=0.01). Phosphorylation of client proteins were inhibited. Isobolar analysis of AT7519 combined with gemcitabine suggested an additive effect. AT7519 was tolerated as a single agent and in combination with gemcitabine in a xenograft model and resulted in slowed tumour growth compared to control (p = 0.0446). AT13387 inhibited proliferation of all cell-lines with IC50 values of 29nM-325nM including a cell line with acquired gemcitabine resistance. AT13387 treated cells accumulated in G0/G1 and G2/M phases of the cell cycle (p<0.05). Late apoptosis was seen after 40 hours post treatment with At13387. AT13387 treatment resulted in down-regulation of HSP90 client proteins and up-regulation of the HSP70 co-chaperone. AT13387 was tolerated and moderately efficicacous as a singe agent in a murine xenograft model but was poorly tolerated in combination with gemcitabine and conferred no benefit over single agents. CONCLUSIONS: AT7519 is a promising agent for combination therapy in pancreatic cancer, as acquired resistance to gemcitabine does not give AT7519 resistance. AT13387 showed promising effects in vitro but was poorly tolerated in an in vivo combination with standard therapy therefore may offer a therapeutic avenue for non-responders to conventional therapies


Introduction: Multiple sclerosis (MS) is a progressive, neurological condition in which balance difficulties and falls are commonly reported. Measuring balance is important for assessment and to measure outcome of intervention and measures used should have known levels of reliability and validity. This research aimed to identify the measures used by physiotherapists for balance, walking and gait, and to review psychometric testing of commonly used measures for people with MS. Research tested psychometric properties of the measures among patients with MS.
Method: A survey of physiotherapists identified widespread outcome measurement, that reliability and validity of measures was important and that the Berg balance scale (BBS) and 10-metre walking test (10MWT) were commonly used measures. A literature review highlighted limited evidence of psychometric testing of these measures among people with MS. The short form BBS (sfBBS) had not been tested at all. The BBS and sfBBS were tested for reliability and validity among people with MS. The 10MWT and objective force-plate data were also tested as measures of balance.
Results: The national survey of physiotherapists yielded an encouraging 77.5% return rate and showed that therapists valued measurement. The patient-based study recruited a smaller sample than desired leading to caution in interpretation. The sfBBS was strongly related to the BBS and both had acceptable levels of intra-rater reliability. Inter-rater reliability was affected by interpretation of scoring guidelines and the sfBBS had significant measurement error. The 10MWT, especially at maximal pace, may be used as an estimator of balance ability.
Conclusion: There must be clear instructions for scoring the BBS particularly between raters. Caution is required in generalising from a small sample size however analyses demonstrated acceptable levels of intra-rater reliability in MS. The sfBBS and 10MWT, as balance estimates, may save time for patients and clinicians and reduce the burden on patients.


With the recent growth of the local food systems movement, OSU Extension formed a new statewide team. In the process, Extension program delivery systems were explored contrasting traditional program delivery (historically rooted in a teacher-clientele, information transfer, demonstration methodology) vs. a community capacity-building facilitation process. This seemingly marginal distinction raised questions with deeper implications for Extension's outreach and engagement process. In brief, how can Extension fill the gap between community-expressed needs and the traditional framework of delivery? Should Extension help communities fulfill their goals and objectives by acting as facilitators, co-conveners, and true partners, rather than simply as educators?


Recently the first named author defined a 2-parametric family of groups $G_n^k$ \cite{gnk}. Those groups may be regarded as a certain generalisation of braid groups. Study of the connection between the groups $G_n^k$ and dynamical systems led to the discovery of the following fundamental principle: "If dynamical systems describing the motion of $n$ particles possess a nice codimension one property governed by exactly $k$ particles, then these dynamical systems admit a topological invariant valued in $G_{n}^{k}$".
The $G_n^k$ groups have connections to different algebraic structures, Coxeter groups and Kirillov-Fomin algebras, to name just a few. Study of the $G_n^k$ groups led to, in particular, the construction of invariants, valued in free products of cyclic groups.
Later the first and the fourth named authors introduced and studied the second family of groups, denoted by $\Gamma_n^k$, which are closely related to triangulations of manifolds.
The spaces of triangulations of a given manifolds have been widely studied. The celebrated theorem of Pachner \cite{pach} says that any two triangulations of a given manifold can be connected by a sequence of bistellar moves or Pachner moves. See also \cite{GelKapZel,nab}; the $\Gamma_n^k$ naturally appear when considering the set of triangulations with the fixed number of points.
There are two ways of introducing this groups: the geometrical one, which depends on the metric, and the topological one. The second one can be thought of as a "braid group" of the manifold and, by definition, is an invariant of the topological type of manifold; in a similar way, one can construct the smooth version.
In the present paper we give a survey of the ideas lying in the foundation of the $G_n^k$ and $\Gamma_n^k$ theories and give an overview of recent results in the study of those groups, manifolds, dynamical systems, knot and braid theories.


Over the last 60 years, luminescence dating has developed into a robust chronometer for applications in earth sciences and archaeology. The technique is particularly useful for dating materials ranging in age from a few decades to around 100,000–150,000 years. In this chapter, following a brief outline of the historical development of the dating method, basic principles behind the technique are discussed. This is followed by a look at measurement equipment that is employed in determining age and its operation. Luminescence properties of minerals used in dating are then examined after which procedures used in age calculation are looked at. Sample collection methods are also reviewed, as well as types of materials that can be dated. Continuing refinements in both methodology and equipment promise to yield luminescence chronologies with improved accuracy and extended dating range in the future and these are briefly discussed.


The efficiency of Conflict Driven Clause Learning (CDCL) SAT solving depends crucially on finding conflicts at a fast rate. State-of-the-art CDCL branching heuristics such as VSIDS, CHB and LRB conform to this goal. We take a closer look at the way in which conflicts are generated over the course of a CDCL SAT search. Our study of the VSIDS branching heuristic shows that conflicts are typically generated in short bursts, followed by what we call a conflict depression phase in which the search fails to generate any conflicts in a span of decisions. The lack of conflict indicates that the variables that are currently ranked highest by the branching heuristic fail to generate conflicts. Based on this analysis, we propose an exploration strategy, called expSAT, which randomly samples variable selection sequences in order to learn an updated heuristic from the generated conflicts. The goal is to escape from conflict depressions expeditiously. The branching heuristic deployed in expSAT combines these updates with the standard VSIDS activity scores. An extensive empirical evaluation with four state-of-the-art CDCL SAT solvers demonstrates good-to-strong performance gains with the expSAT approach.


To determine the diagnostic values of plasma CD64 and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in children with pneumonia.Sixty children with pneumonia between August 2014 and October 2015 were classified into bacterial pneumonia group (25 cases), viral pneumonia group (17 cases), and Mycoplasma pneumonia group (18 cases) according to their clinical manifestations, pathogen cultures, and X-ray findings. Another 30 healthy children who underwent physical examination during the same period were selected as the control group. The concentrations of CD64 and sTREM-1 in blood samples were determined using ELISA. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic sensitivity and specificity of plasma CD64 and/or sTREM-1 for bacterial pneumonia.The expression of CD64 and sTREM-1 in the bacterial pneumonia group was significantly higher than that in the viral pneumonia, Mycoplasma pneumonia, and control groups (P<0.05). The areas under the ROC curves of CD64, sTREM-1, and a combination of the two markers for diagnosing bacterial pneumonia were 0.878, 0.805, and 0.956, respectively. The sensitivity and specificity of CD64 for diagnosing bacterial pneumonia were 81.30% and 92.32%, respectively, when the cut-off value was 641 pg/mL. The sensitivity and specificity of sTREM-1 for diagnosing bacterial pneumonia were 78.65% and 84.67%, respectively, when the cut-off value was 1 479 pg/mL. The sensitivity and specificity of a combination of the two markers for diagnosing bacterial pneumonia were 93.15% and 91.54%, respectively.Plasma CD64 and sTREM-1 can be used as markers for diagnosing pediatric bacterial pneumonia, and a combination of the two markers results in better diagnosis.


The high property price syndrome in Hong Kong has led to heightened concern about the role of landed capital in property development. Recently, the hegemony of the real estate industry has become a buzzword in local literature, but unfortunately there is neither adequate theoretical articulation nor informed understanding of the concept of hegemony. There is widespread misunderstanding of hegemony, equating it to domination by property tycoons. The local literature has overlooked the government-business collusion in constructing the common sense of society so as to dominate others. Through an empirical investigation of the redevelopment of 'Government/Institution or Community' (G/IC) land in Hong Kong, this article attempts to offer an alternative explanation to the land question of G/IC redevelopment by highlighting that the everyday life of the silent majority and of professionals has in fact perpetuated the hegemony of the real estate industry in Hong Kong. It is argued that the government, property developers, professionals, charitable organisations and the general public have altogether participated, in different ways and to different extents, in the capital accumulation projects of leading developer conglomerates in Hong Kong. A land (re)development regime has thus contributed to the property boom in Hong Kong.


Purpose: The paper challenges agency and stewardship theories' straw person conceptions of human behaviour and discusses how the board of directors can use accounting and control systems to effectively moderate a realistic model of the CEO's behaviour. Design/methodology/approach: The paper uses a pragmatic approach in reconciling agency and stewardship theory. Findings: As well as a framework for implementing strategy, Robert Simons' levers of control can be used to regulate the behaviour of the CEO. Beliefs and interactive control systems encourage pro-organisational behaviour, whereas boundary and diagnostic control systems constrain self-interested (or opportunistic) behaviour. Originality/value: Assuming people are opportunistic leads to accounting and control systems which encourage opportunistic behaviour and discourage pro-organisational behaviour. Assuming people are pro-organisational leads to accounting and control systems which an opportunistic CEO can exploit. This paper shows how, theoretically, organisations can employ the levers of control to resolve this paradox.


This report details the authors' development of a computer controlled spotlight with four actuated degrees-of-freedom for pan, tilt, linear movement, and beam focusing. The authors review the mechanical structure, kinematic model, calibration data, and control algorithm. The resultant system enables the spotlight to maintain constant intensity of the illumination of a surface, while changing the incident angle of the light. In this way, the authors effectively simulate the changing illumination experienced in low earth orbit. The simulation system is currently used to test human and computer inspection of orbital platform mockups for the Space Station freedom.<<ETX>>


The market of imaging and non-imaging sensors offers nowadays a wide range of products, which are constantly improving and growing. Given the recent advances in the miniaturization of devices for metric survey, and the relatively cheap COTS (Commercial Off The Shelf) solutions widely available, it is therefore crucial to optimally exploit, calibrate and evaluate the performance for 3D data acquisition of the new available devices. These issues are part of the latest research addresses of different Geomatics groups, with the aim to analyze and evaluate these new sensors, in order to discover their real potentialities which are not only connected to their interesting design, low price and small dimensions. According to the final objective of the research, which is the realization of 3D metric survey of a Cultural Heritage site using different techniques and methods, one small UAV (Unmanned Aerial Vehicle) and a portable TLS (Terrestrial Laser Scanner) have been employed. The acquisition strategies and the processing methods are discussed, and the quality of the achievable results is analysed, together with an evaluation of the sensors and the outline of the best practices and use cases scenarios.


Buildings can be compared to a bundle of goods sold in a market, where each of the building characteristics combined equate to the expected overall transaction value. By collecting data on many different buildings a regression analysis can be used to determine the correlation (relationship) of each characteristic to the transaction price —e.g. physical characteristics and other external influencing elements that may add or subtract from the building value. Each of these correlations can be measured to determine a degree of confidence (i.e. significance) and then subsequently be used to build a hedonic pricing model. Hedonic pricing models can be useful to determine the intrinsic value of each attribute, as well as to predict transaction prices. This can be particularly useful when traditional discounted cash flow models fall short because of the absence of a market, when no comparable buildings exist, and for nonincome generating buildings.


ABSTRACT Purpose: We assess farm technology adoption in an integrated analysis of social networks and innovation in plantain production in Ghana. The paper explores the strength of social networks in the agricultural innovation systems (AISs) and the effect of AISs on adoption of improved farm technology. Methodology/Approach: The paper uses social network analysis (SNA) tools to identify, map and analyze the AISs and the two-stage Heckman selection model. Combining qualitative and quantitative methods allows testing the differential effects of social networks on technology adoption. Findings: We find weak innovation systems in the study area. Farmers are central in the social networks but have little to no influence in the innovation system perspective. Social network capital plays a critical role in improving adoption of improved farm technology. Practical implication: Focal farmers are important actors disseminating farm technology. They should be supported by policies to interact more effectively with research and extension agents. Strengthening the role of social networking in the innovation system will enhance adoption of improved farm technology. Theoretical implications: The inclusion of SNA indicators in the adoption model is a novel approach for quantifying the effect of the innovation system and contributes to understanding the roles of different actors. Further validation of the SNA indicators is needed for a comprehensive analysis of the innovation system. Originality/value: The innovation system approach is useful for researchers and policy-makers by encouraging them to consider new innovation actors and relationships in technology development and dissemination. Combining quantitative and qualitative methods can help to identify starting points for policies to promote innovations among farmers.


Objective. (a) To describe trends in the number of heart interventions performed over time, (b) to determine the length of waiting lists for elective heart interventions in the Netherlands according to the monthly survey of the Supervisory Committee for Heart Interventions in the Netherlands [Begeleidings-commissie Hartinterventies Nederland (BHN)], (c) to compare the length of the waiting lists with existing standards, and (d) to determine the reliability of the waiting list survey. Design. Prospective. Method. Data were obtained from the monthly waiting list survey of the I3 heart centres in the Netherlands (I January 1999-30 November 2002) and from the intervention registry (I January I999-30 June 200I), which was complete for I0 centres. Both the survey and the maintenance of the registry are carried out by the Supervisory Committee for Heart Interventions in the Netherlands. Results. (a) The number of percutaneous coronary interventions performed in the Netherlands has increased. The number of cardiothoracic interventions remained stable. (b) The number of patients waiting for a percutaneous coronary intervention is increasing by 16% per annum. In November 2002 there were 75I patients on the waiting list. The number of patients waiting for a cardiothoracic intervention increased by 20% per annum until August 200I and since then there has been a decrease of 21% per annum. In November 2002, I557 patients were on the waiting list. (c) The percentage of patients treated within existing standards has fallen to 78% for percutaneous coronary interventions and to 53% for cardiothoracic interventions. (d) The length of the waiting list and the waiting times obtained in the survey concurred with the data taken from the intervention registry. Conclusions. The length of the waiting list for heart interventions has increased and complies increasingly less with existing standards. The monthly waiting-list survey was a reliable method of determining the length of waiting lists for elective heart interventions.


Studies have successfully elucidated the mechanism of action of several effector domains that comprise the MARTX toxins of Vibrio vulnificus. However, the biochemical linkage between the cysteine proteolytic activity of Makes Caterpillars Floppy-like (MCF) effector and its cellular effects remains unknown. In this study, we identify the host cell factors that activate in vivo and in vitro MCF autoprocessing as ADP-Ribosylation Factor 1 (ARF1) and ADP-ribosylation Factor 3 (ARF3). Autoprocessing activity is enhanced when ARF1 is in its active (GTP-bound) form compared to the inactive (GDP-bound) form. Subsequent to auto-cleavage, MCF is acetylated on its exposed N-terminal glycine residue. Acetylation apparently does not dictate subcellular localization, as MCF is found localized throughout the cell. However, the cleaved form of MCF gains the ability to bind to the specialized lipid phosphatidylinositol 5-phosphate enriched in Golgi and other membranes necessary for endocytic trafficking, suggesting a fraction of MCF may be subcellular localized. Traditional thin-section electron microscopy, high-resolution cryoAPEX localization, and fluorescent microscopy show that MCF causes Golgi dispersal resulting in extensive vesiculation. In addition, host mitochondria are disrupted and fragmented. Surprisingly, ARF1 is not itself processed or post-translationally modified by MCF. Further, only catalytically inactive MCF stably associates with ARF1, thus serving as a substrate trap. Our data indicate that ARF1 is a cross-kingdom activator of MCF, but reveal that MCF mediates cytotoxicity likely by directly targeting another yet to be identified protein. This study begins to elucidate the biochemical activity of this important domain and gives insight into how it may promote disease progression.