Poultry production has a high priority because poultry meat has better energy and protein conversion ratio than many other animals. Traditional poultry is a well-known livestock enterprise in northern Nigeria and women contribute immensely to agricultural production but still their contribution to the country's development remains largely not documented. This study therefore, aimed at assessing the role of rural women, their contribution and constraints to traditional poultry production in Kaura-Namoda local government area, Zamfara State-Nigeria. Sixty (60) women poultry keepers were randomly selected from twelve villages of four districts selected at random and administered with questionnaires to collect relevant data on socio-economic characteristics, management system adopted, output and constraints of poultry production. Data collected were analyzed using descriptive statistics. The result revealed that majority of the respondent were young (26-35 years) and married with no formal schooling whose kept between 11 to 20 bird with ratio of 1:2 of cock to hen. Extensive management system is practicing by the majority of respondent also; recorded more than 40 eggs laid by their hens with farm returns of N2000.00 to N5000.00 ($12.5 to $31.25) per week and sales their produce at market. Majority of the respondents provide local oral leaf and bark extract of mahogany and solanaceous plant for disease control while some uses local trap in controlling rodents, debeaked their birds to avoid cannivalism. Transportation, pest and diseases, weather changes, poor extension services and low capital are some of the constraints of poultry production in the study area.

 Key words: Traditional poultry, women, Kaura-Namoda.


A strong case can be made for developing more flexible and relevant multilingual strategies for teaching and learning within the field of bilingual education. This paper aims to demonstrate how current linguistic and educational practices in countries like Guinea-Bissau, Mozambique and Ethiopia suggest new directions for research and practice. A practical approach is proposed to illuminate the gap between actual language competence on the part of primary students and teachers and the language competence to which their education system aspires. By applying known language and learning principles, policies and practices can be more realistically directed towards reducing this gap in the short, medium and long terms. This involves a reconstruction of multilingual pedagogy to capitalise on the strengths of learners, teachers and linguistic communities. Meanwhile, there is a need for more research on the following: (1) effective ways to assess multiple language competencies on the part of teachers and learners; (2) the relationship between learners' multilingual oral competence and literacy; and (3) methodologies that facilitate transfer of skills and knowledge between languages. The implications are that language-in-education policy should be based on what is possible in each sociolinguistic situation and should be flexible enough to offer equitable opportunities for all.


We described a 30-year old man with Ehlers-Danlos syndrome type VI, manifested by marked kyphoscoliosis and severe myopia, who was admitted to our department because of chest pain. Abnormalities of stature and joint system along with eye changes, occurred starting from the birth and they aggravated gradually. Signs of increased fragility of the skin blood vessels appeared during childhood. At the age of 26 years, the patient suffered from a spontaneous rupture of the right brachial artery. Spirometry revealed marked restrictive ventilatory insufficiency, which at present constitutes the predominant health risk for the patient.


Sequences diverge either because they head off to infinity or because they oscillate. Part 1 \cite{Part1} of this paper laid the pure mathematics groundwork by defining Archimedean classes of infinite numbers as limits of smooth sequences. Part 2 follows that with applied mathematics, showing that general sequences can usually be converted into smooth sequences, and thus have a well-defined limit.
Each general sequence is split into the sum of smooth, periodic (including Lebesgue integrable), chaotic and random components. The mean of each of these components divided by a smooth sequence, or the mean of the mean, will usually be a smooth sequence, and so the oscillatory sequence will have at least a leading term limit. Examples of limits of oscillatory sequences with well-defined limits are given.
Methodologies are included for a way to calculate limits on the reals and on complex numbers, a way to evaluate improper integrals by limit of a Riemann sum, and a way to square the Dirac delta function.


A field experiment was conducted in Syria in 1988 to relate yield of chickpea to soil population densities of the root-lesion nematode, Pratylenchus thornei. The field, infested with 0 to 32 nematodes/cm³ soil, was divided in 100 plots of 6.75 m² each and sown to chickpea on 1 March, 1988. The nematode density in the soil of each plot was determined before sowing and after harvest. In mid April, nematodes were counted in the chickpea roots and root necrosis was assessed. There was a negative correlation between nematode densities at sowing and yield of chickpea. It is estimated that a threshold limit is 0.031 nematodes/cm³ soil and a maximum yield loss of 58% occurs at 2 nematodes/cm³ soil. Numbers of P. thornei/g roots were positively correlated with root necrosis index.


The experience of IRBIS64 Library Automation System implementation into the specialized library for the blind is discussed. The settings and functions of management of users, collections, and events databases are considered. The key dictionaries of setting storage places and user categories are described. At the library, the user cart html-template has been adapted for various user categories. The AVD System union catalog is used for sharing. The optional IRBIS64-based specialized modules are also discussed, namely the adapted catalog and digital record log designed specifically for the users and services of Kaluga N. Ostrovsky Regional Special Library for the Blind. The methods and principles of software for the blind and visually impaired people are examined. The approach under examination combines the two different methods, that compliant with the international WCAG2.0 standards and the other using cloud technologies of Yandex SpeechKit. The research project enables to fulfill the TyphloCatalog project of designing Internet-based catalog for the specialized libraries for the blind.


The Zipf power law and its connection with the inhomogeneity of the system is investigated. We describe the statistical distributions of the domain masses in the Potts model near the temperature-induced phase transition. We found that the statistical distribution near the critical point is described by the power law form with a long tail, while beyond the critical point the power law tail is suppressed.


Purpose: Loneliness and depression are significant challenges for middle-aged and older adults, and are associated with worse overall health. Even before the COVID-19 pandemic, about 43% of adults aged 60 and above reported experiencing loneliness. People with diabetes (DM) are 2 to 3 times more likely to have depression than those without DM. Loneliness and depression often co-exist and each is likely to worsen DM outcomes. The aim of this study was to examine how loneliness and depression affect A1C levels among middle-aged and older adults with DM. Methods: This study is a secondary analysis of data from the Midlife in the United States Refresher (MIDUS-R) survey that included a national sample of U.S. adults aged 25 to 74 years. We conducted correlation analyses and estimated a hierarchical logistic regression to predict people with A1C levels ≤ 7 or > 7 using the following sets of predictors: 1) demographics and physical health (ethnicity, gender, education, age, and comorbidities), 2) family and friends support, and 3) psychological factors (loneliness and depression). Results: The sample was composed of 92 participants with DM and A1C data in the MIDUS-R. Mean age was 57.37±11.83, 51% were male, and 68 % were non-Hispanic Whites; 39.1 % had A1C >7. The average level of depression was low (CES-D mean 9.42) and loneliness was moderate (mean 12.43, range 1-28). Loneliness was correlated with A1C (r= .26, p 7 (OR = 1.18, p Conclusion: Loneliness is more prevalent and had a greater impact than depression on A1C level. Healthcare providers should assess patients for loneliness and reduce adverse health impacts by referring them for psychosocial interventions as needed. Disclosure Y. Huang: None. A. A. Garcia: None. E. S. Cho: None. H. Kuo: None.


In this paper we present a mixed integer programming approach to deterministic dynamic programming. We consider the problem of computing a policy that maximizes the total discounted reward earned over an infinite time horizon. While problems of this form are difficult in general, suboptimal solutions and performance bounds can be computed by approximating the dynamic programming value function. Here we provide a linear programming-based method for approximating the value function, and show how suboptimal policies can be computed through repeated solution of mixed integer programs that directly utilize this approximation. We have applied this approach to problems with states described by binary vectors with dimension as large as several hundred. Although the number of distinct states associated with such a problem is extremely large, we are able to obtain suboptimal policies with surprisingly tight performance guarantees. We illustrate the application of this method on a class of infinite horizon job shop scheduling problems.


Demand for hydrocarbon fuel is predicted to keep increasing in the coming decades in spite of easily accessible alternative fuels due to shifting geopolitical and economic situations. In order to find new hydrocarbon pockets, we need sharper images of earth's subsurface. Also, the exploration of other sources of energy like geothermal will benefit from better models of the what lies underneath the surface. One way to obtain better images is to use superior numerical methods for forward modelling - Finite-element methods (FEM) are one such method, but their accuracy comes at the cost of increased compute expense. This thesis explores means to reduce this cost and adapt FEM to large-scale problems in geophysics. The Finite Difference (FD) method is the most popular numerical approximation scheme used in subsurface imaging problems. Representing the wave as the solution of individual motion and material equations is advantageous in terms of accuracy and stability and leads to the natural inclusion of density variations in the medium. This representation is referred to as the first-order formulation of the wave equation in this document. Finite Element (FE) methods are commonly derived for second-order equations because of the nature of variational formulation. Finite-element discretisations of the acoustic wave equation in the time domain often employ mass lumping to avoid the cost of inverting a large sparse mass matrix. Unfortunately, for a first-order system of equations, mass lumping destroys the superconvergence of numerical dispersion for odd degree polynomials. In chapter 3 of this thesis, we consider defect correction as a means to restore the convergence. We adapt the defect correction method to FEM by solving the consistent mass matrix with the lumped one as preconditioner. For the lowest-degree element, fourth-order accuracy in 1D can be obtained with just a single iteration of defect correction. In this chapter, we analyse the behaviour of the error in eigenvectors as a function of the normalized wavenumber in the form of leading terms in its series expansion and find that this error exceeds the dispersion error, except for the lowest degree where the eigenvector error is zero. We also present results of numerical experiments that confirm this analysis. Chapter 3 concluded that defect correction can improve the convergence property of finite-elements in the first-order system of acoustic equations in 1D; the inexpensive linear elements showed the same performance as a fourth-order scheme. However, for realistic problems we need to ensure that the same improvement holds in higher dimensions. Based on the results of the earlier chapter, we conjecture that defect correction should work for 2D problems. In the first half of chapter 4, we analyze the 2-D case. Theoretical results imply that the lowest-degree polynomial provides fourth-order accuracy with defect correction, if the grid of squares or triangles is highly regular and material properties constant. But numerical results converge more slowly than theoretical predictions. Further investigation demonstrates that this is due to the activation of error-inducing wavenumbers in the delta-source representation. In the second half of the chapter, we provide a solution to this problem in the form of a tapered-sinc source function. In chapter 5, we consider isotropic elastic wave propagation with continuous masslumped finite elements on tetrahedra with explicit time stepping. These elements require higher order polynomials in their interior to preserve accuracy after mass lumping and are recently discovered up to degree 4. Global assembly of the symmetric stiffness matrix is a natural approach but requires large memory. Local assembly on the fly, in the form of matrix-vector products per element at each time step, has a much smaller memory footprint. With dedicated expressions for local assembly, our code ran about 1.3 times faster for degree 2 and 1.9 times for degree 3 on a simple homogeneous test problem, using 24 cores. This is similar to the acoustic case. For a more realistic problem, the gain in efficiency was a factor 2.5 for degree 2 and 3 for degree 3. For the lowest degree, the linear element, the expressions for both the global and local assembly can be further simplified. In that case, global assembly is more efficient than local assembly. Among the three degrees, the element of degree 3 is the most efficient in terms of accuracy at a given cost. In chapter 6, we consider cubic Hermite elements as interpolants in place of Legendre polynomials. By nature of theirC1 continuity, they might offer a solution to the problems of 'spurious' wavenumbers seen in earlier chapters with conventional interpolation schemes. Results show acceptable convergence properties on homogeneous media, but the representation needs to be altered to suit discontinuities in density, which makes interesting future work.


In this paper, we investigate maximum remaining life expectancy, a conditional measure of longevity that combines information about survival improvements and the ages at which they occur. Comparing across countries, we also examine the time trend in record remaining life expectancy and record total expected longevity. A substantial difference between life expectancy at birth and the maximum remaining life expectancy existed throughout most of the 19 th and 20 th centuries both for national and record measures, though the same group of countries holds the various record measures. The rising trend in the maximum and record life expectancy measures during this period shows that in addition to the well-known declines in early-childhood mortality, survival improvements were simultaneously taking place at other ages. The convergence of life expectancy at birth with the maximum life expectancy in the 1960s suggests that mortality selection at younger ages has decreased substantially, allowing the full population to anticipate a longer life. By combining information about mortality reductions and the ages at which they occur, our results present a link between demographic and epidemiologic transitions and highlight the temporal connection between childhood and adult influences on the historical trajectory of rising life expectancy.


Objectives: We investigated the distribution of common allergens in allergic patients in Guangzhou, southern China. Methods: 7,085 patients with allergic symptoms were examined for serum Total IgE (TIgE) sIgE to 15 common allergens in this region, based on the protocol of reversed enzyme allergosorbent test. Results: 3,758 (53.04%) of the subjects tested positive for TIgE and 4640 (65.49%) for sIgE to at least one of the 15 common allergens. There was no statistical difference in the overall rate of positive sIgE detection between males (3081/4602, 66.95%) and females (1674/2483, 67.42%). Der pteronyssinus and Der farinae were the most common aeroallergens, while eggs and cow9s milk the most common food allergens, responsible for higher positive rates of sIgE responses. By age-group analysis, we noted several peaks of sensitization to the certain allergens: Der pteronyssinus , Der farinae , and Blomia tropicalis at age between 9 and 18;cow9s milk before age 3; eggs at age between 3 and 6. Along with older age, there was an ascending tendency in the overall positive rate of sIgE response to house dust mites among subjects who tested positive for sIgE to eggs or cow9s milk. Conclusions: Such a sequence of events may be a result of allergy march. Knowledge on the prevalence of allergen sensitization in different age groups would help early diagnosis and intervention of allergic diseases in this large geographical region.


A case of interatrial septal lipoma, presenting as recurrent pericardial effusion with signs of constrictive pericarditis, was described. The tumor was removed successfully. The case demonstrated that the difficulties in the differential diagnosis between right atrial tumor and any other cardiac disease still exist. Because of its extreme rarity, the interatrial septal lipoma is rarely considered in the differential diagnosis.


The evolution of female multiple mating is still a largely debated field. Among the benefits that have been proposed to explain this risky behaviour is the replenishment of sperm reserves. Apart from an increase in total sperm number, it can be an expression of post–copulatory mate choice or can be directed towards the uptake of fresh sperm. Using fresh sperm for fertilization instead of sperm aged by storage in the female genital tract may avoid a lowered fertilization capacity, an increase in deleterious effects or a skewed offspring sex ratio. We investigated the influence of sperm age on female fitness in the grasshopper Chorthippus parallelus, a species where females mate multiply. After copulation, females store sperm over the course of weeks until fertilization. An average ejaculate of 250 000 spermatozoa exponentially declined with time within the female's spermatheca. The number of days since copulation better explained the variation in actual sperm number than the number of pods or eggs laid. We investigated differences in female fitness parameters in two treatments. In the first, females were mated only once, while in the second, females always had freshly ejaculated sperm available. Although in our experiment, multiply mated females had heavier offspring than singly mated females, egg number per pod, hatching and fertilization success, their composite effects and offspring sex ratio did not vary with respect to season or sperm age. We therefore reject the hypothesis that the reason for remating in females of this species is the uptake of fresh sperm.


A successful means of in vitro propagation of Streptocarpus rexii Lindl. using leaf tissue as the explants is described. Secondary explants were placed on several regeneration media supplemented with various concentrations of indole-acetic acid (IAA) and benzyladenine (BA). Optimal shoot proliferation was obtained on Murashige and Skoog basal media containing 0.1 mg/L IAA in combination with 0.5 mg/L BA. The growth of explants, as quantified by their fresh and dry weights, was significantly higher in the 1 mg/L IAA with 1 mg/L BA treatment as compared with the 0.1 mg/L IAA plus 1.0 mg/L BA. The increasing concentrations of BA reduced the percentage of explants forming roots. From regeneration media, shoots were transferred to Murashige and Skoog medium supplemented with 1 mg/L IAA for root induction. After six weeks, the rooted plantlets were removed from culture and successfully hardened off in the shade house. For the multiplication of S. rexii Lindl., the best combination was the one involving 1 mg/L IAA and BA. This treatment obtained a highest shoot count and had the highest growth rate. This could play a key role in the large scale mass propagation of this plant.

 Key words: Streptocarpus rexii Lindl., initiation, rooting.


Remeeting is a tool that helps you get more out of in-person meetings. Calendar integration and a special email address al-low users to email agenda items prior to a certain meeting. A discrete notification at the time of the meeting reminds the user to start the recording. During the meeting, the user focuses on the conversation, or can add notes and photos if desired. After the meeting, every participant gets notified by an auto-mated email that lists the participants along with automatically extracted keywords, notes and photos. This stimulates collabo-ration, and keeps follow-up contributions at a central place: Just reply to add further notes to the meeting. The resulting meeting "document" can be shared with others and reviewed using a web app that acts as a visual index to the meeting. This makes Remeeting the perfect tool for regular group meetings, standups and interviews, where people typically track progress and fol-low up on. Remeeting is leveraging, promoting and contributing to open source projects including kaldi and docker.


Spring-based actuators in legged locomotion provide energy-efficiency and improved performance, but increase the difficulty of controller design. While previous work has focused on extensive modeling and simulation to find optimal controllers for such systems, we propose to learn model-free controllers directly on the real robot. In our approach, gaits are first synthesized by central pattern generators (CPGs), whose parameters are optimized to quickly obtain an open-loop controller that achieves efficient locomotion. Then, to make this controller more robust and further improve the performance, we use reinforcement learning to close the loop, to learn corrective actions on top of the CPGs. We evaluate the proposed approach on the DLR elastic quadruped bert. Our results in learning trotting and pronking gaits show that exploitation of the spring actuator dynamics emerges naturally from optimizing for dynamic motions, yielding high-performing locomotion, particularly the fastest walking gait recorded on bert, despite being model-free. The whole process takes no more than 1.5 hours on the real robot and results in natural-looking gaits.


: British composers in the latter half of the twentieth century pursued a belated version of musical modernism rebelling against the establishment by 'returning' to little known medieval manuscripts. The contradiction here is an interesting one, and what the author identifies here as modernist medievalism—the contradictory appropriation of the medieval to expressly forward-thinking ends—is explicitly intertextual. This chapter argues that a modernist composer conjuring the medieval is doing something less than the literal representation of an 'authentic' past than they are engaging in a nexus of imaginary (re)representations of a non-contiguous and Other, shared, version of history, one that elides any such reified notions of the 'high' and the 'low' and unites disparate fields of artistic activity. Beginning with a brief summary of twentieth century precedents focussed principally on the 'Tudor medievalism' of, among others, Benjamin Britten, the author turns his attention to the contrasting medievalisms of Peter Maxwell Davies and Harrison Birtwistle. And specifically, their career-long appropriation of the works of earlier composers John Taverner and Guillaume de Machaut (respectively). For the former example, Davies entered into existent intertextual networks incorporating In Nomine and Dies Irae chants; whereas in the latter case, Birtwistle repeatedly rearranges, deforms, and disguises the techniques of the medieval poet-composer.


Cuckoo search (CS) is a new robust swarm intelligence method that is based on the brood parasitism of some cuckoo species. In this paper, an improved hybrid encoding cuckoo search algorithm (ICS) with greedy strategy is put forward for solving 0-1 knapsack problems. First of all, for solving binary optimization problem with ICS, based on the idea of individual hybrid encoding, the cuckoo search over a continuous space is transformed into the synchronous evolution search over discrete space. Subsequently, the concept of confidence interval (CI) is introduced; hence, the new position updating is designed and genetic mutation with a small probability is introduced. The former enables the population to move towards the global best solution rapidly in every generation, and the latter can effectively prevent the ICS from trapping into the local optimum. Furthermore, the greedy transform method is used to repair the infeasible solution and optimize the feasible solution. Experiments with a large number of KP instances show the effectiveness of the proposed algorithm and its ability to achieve good quality solutions.


Preparing future nursing leaders to be successful is important because many current leaders will retire in large numbers in the future. A structured nursing leadership development program utilizing the Essentials of Nurse Manager Orientation online program provided future nursing leaders with content aligned with nursing leadership competencies. Paired with assigned mentors and monthly leadership sessions, the participants increased their perception of leadership competence.


In this paper, the synchronization of complex dynamical networks (CDNs) with system delay and multiple coupling delays is studied via impulsive distributed control. The concept of control topology is introduced to describe the whole controller structure, which consists of some directed connections between nodes. The control topology can be designed either to be the same as the non-delayed coupling topology of the network, or to be independent of the intrinsic network topology. Based on the concept of control topology, an impulsive controller is designed to achieve the exponential synchronization of CDNs, and moreover, the exponential convergence rate can be specified. Illustrated examples have been given to show the effectiveness of the proposed impulsive distributed control strategy.


Ectopic pregnancy is considered as a possible diagnosis in cases in which women experience acute abdominal pain and a urinary human chorionic gonadotropin (hCG) test produces a positive result. However, we present a case of ruptured ectopic pregnancy involving a negative urinary pregnancy test result. A 34-year-old nulliparous woman was admitted to the emergency room of our hospital due to the sudden onset of lower abdominal pain. Rebound pain in the lower abdomen was detected during a physical examination. Since transabdominal ultrasonography showed massive ascites, and a urinary pregnancy test produced a negative result, we performed a contrast-enhanced computed tomography scan and found a 5-cm right-sided ovarian cyst and extravasation around the left adnexa. We diagnosed the patient with left ovarian hemorrhaging and a right ovarian hemorrhagic luteal cyst. Two hours later, hemorrhagic shock occurred, and an emergency laparoscopic operation was carried out. We detected a swollen left fallopian tube, which had ruptured and was bleeding. We performed left salpingectomy. After the operation, the patient's preoperative serum sample was re-examined to re-assess her hCG level. As a result, her serum hCG level was found to be 23.3 mIU/ ml. Pathological examinations showed a very small number of chorionic villi. The final diagnosis was ectopic pregnancy. The patient's postoperative course was uneventful. This case report illustrates the difficulty of diagnosing ectopic pregnancy. Clinicians should include ectopic pregnancy in the differential diagnoses for cases of acute abdominal pain involving women of reproductive age, regardless of the results of urinary pregnancy tests.


Celebrity worship—is it more than just being a casual fan? To explore this question, a number of scales have been developed to assess celebrity adulation. The most prevalent scale of this type in the literature is the Celebrity Attitudes Scale. Using these types of scales, investigators have examined various college-student and community samples. Findings reveal that individuals with high scores on celebrity-worship scales tend to display a number of psychosocial characteristics. For example, these individuals may harbor concerns about body image (particularly young adolescents), be more prone to cosmetic surgery, and have a personality style characterized by sensation-seeking, cognitive rigidity, identity diffusion, and poor interpersonal boundaries. Likewise, celebrity worshippers may exhibit narcissistic features, dissociation, addictive tendencies, stalking behavior, and compulsive buying. Studies also indicate that individuals with high levels of celebrity worship are more likely to have poorer mental health as well as clinical symptoms of depression, anxiety, and social dysfunction. Of note, no study to date has examined celebrity worshippers for bona fide Axis I and II psychiatric disorders. However, given that celebrity worship exists along a continuum, it appears that being on the high end of this continuum is likely to be associated with a number of potential psychological maladies.


It is hypothesized in the present study that when learners are tasked to write a composition in a second language (such as English language for Filipinos), they use specific approaches to learning and eventually undergo self-regulatory processes. The present study tested a model showing the shift from process to outcome in writing (Zimmerman & Kitsantas, 1999) by assessing the path from approaches to learning to self-regulation (using path analysis) as used in composition writing in English. The Academic Self-Regulated Learning Scale (A-SRL-S) and the Revised-Learning Process Questionnaire (R-LPQ-2F) were administered to 294 college students major in English, communication arts, literature, mass communications, and journalism from different universities in Manila, Philippines. The results showed that: (1) Deep approach significantly correlated with the factors of self-regulation except for environmental structuring and seeking assistance while surface approach did not, (2) deep approach and surface approach was also significantly correlated, and (3) deep approach significantly increased the variance in all self-regulation components while surface approach only increased the variance in memory strategy. Further theoretical implications of the path model were explained.


It is the second largest Greek Island after Crete, but Evia - Euboea in Greek mythology, formerly Negropont to the British - remains almost unknown to tourists. Separated from the mainland for much of its seahorse-shaped length by only a narrow channel, it is tantalisingly close yet apart as far as the casual visitor to Greece is concerned. It has led a double life as an island and yet not an island. This is the story of a five-month journey in 1990 from the bottom of Evia to the top, a journey as much about time as place, for Sara Wheeler describes a world that is fading and being replaced ultimately by nothing. The combination of her responsiveness to Evia's present and her awareness of its rich history declares the arrival of a brand new voice in travel writing.


Hanna and Pantanowitz have presented a very wellwritten and informative summary to answer the above question. I have several comments. It is a given that image acquisition from cytopathology glass slides represents a greater challenge because of the distribution of material on multiple focal planes between the glass slide and coverslip. It may be difficult to focus into cell collections on resulting whole-slide imaging (WSI). z-stacking is an option, but can never perfectly match the infinite vertical focus provided by a traditional microscope and glass slide. In addition, the more z-stacks on WSI, the greater the file size and often the more cumbersome the viewing. However, there usually are thousands of cells on a cytology slide; it is unusual to make a diagnosis from just 1 or 2 small foci on the slide. So it may be that we need to reexamine digital cytopathology with a fresh pair of "lenses." A different approach may be required, such as acquiring 2 separate WSI files scanned at different focal depths from the one original glass slide. Alternatively, one may crop and extract adequately scanned areas prior to diagnosis; after all, even with traditional cytopathology, there always is cellular material left behind in the preservative fluid or on the sampling utensil, which the pathologist never actually views. Others have found that digitizing less than the entire glass specimen did not compromise accuracy. Using 2-dimensional WSI to facilitate learning or the diagnosis of cytopathology cases has been found to be comparable to traditional microscopy. Cytopathology WSI with multiple focal planes may even be superior to the equivalent glass slides for diagnostic accuracy. The issue is more our perception. It is almost universally perceived that diagnostic accuracy using WSI does not match the accuracy achieved with a glass slide and a traditional microscope. It takes longer to report WSI compared with a glass slide. However, there also is a definite learning curve when using WSI: increased diagnostic accuracy and increased time efficacy come with increased WSI use and familiarity. Ergonomics for screening cytopathology slides also can be readily addressed. Becoming accustomed to an altered approach may simply be the answer. We need to try it, familiarize ourselves with it, and then validate it (case-by-case to start with). Then, if the technique is not inferior in accuracy and safety for our patients compared with traditional techniques, perhaps we should go with it.


The effect of antiepileptic drug ethosuximide and sodium valproat on fusion of synaptic vesicles with synaptosomal plasma membranes was studied in cell-free system. It was shown that ethosuximide and sodium valproat increases the rate of Ca(2+)-dependent fusion reaction in vitro. We have found that convulsant drugs pentylenetetrazol and picrotoxin did not fuse membrane components of the model system. Ethosuximide- and sodium valproat-provoked fusion of synaptic vesicles and plasma membranes of synaptosomes were suppressed by convulsant drugs pentylenetetrazol and picrotoxin.


The purpose of this study is to present the theoretical basis, various problems, and the development process applied to the development of Korean textbooks for secondary school students in Thailand. In this study, we examined the goals of Thailand's secondary curriculum, Thailand's educational situation, and the characteristics of Thai students and teachers in order to develop Korean textbooks in secondary schools in Thailand. The study is meaningful on two levels, first of all, that Korean textbooks were developed through strong collaboration between Korea and Thailand. The development of this textbook was carried out through cooperation between experts and government officials from the two countries over the entire course of writing. The second is the systematic process of developing Korean language curriculum and writing textbooks on them. Through the systematic process, textbooks could be developed that focused on Thai secondary school students. The study will be meaningful in that it provided basic research for the development of foreign secondary school textbooks by showing the development process of Korean textbooks for secondary school students. (Ewha Womans University, The Academy of Korea Study, Ewha Womans University, Silpakorn University)


The fifth version of the Emission Database for Global Atmospheric Research (EDGAR 5.0) provides an impressive inventory of various pollutants. Pollutants from different emission sectors are available with daily, monthly and yearly temporal profiles at a high global resolution of 0.1°×0.1°. Although this resolution has been sufficient for regional air quality studies, the emissions appeared to be too coarse for local air quality studies in areas with complex topography. With Switzerland as a case study, we present our approach for downscaling EDGAR emission data to a much finer resolution of 0.02°×0.02° with the aim of modelling local air quality.

We downscaled the EDGAR emissions using a combination of GIS tools including QGIS, ArcGIS, and a series of python scripts. We obtained the surface coverage of different land use features within the defined EDGAR emission sectors from Open Street Map (OSM) using the QuickOSM tool in QGIS. With the calculated local surface area coverage of the emissions sectors, we downscaled the EDGAR inventory data within ArcGIS using a set of developed Arcpy script tools.

The outcome was a much finer resolved emission dataset which we fed into the WRF-CHEM air quality model within a pilot project. A comparison of the modelled pollutant concentrations using the two datasets (original EDGAR data and the downscaled data) shows an improved agreement between the downscaled dataset and the measurement data.

Studies investigating the impact of urbanization, land use change or traffic pattern on air quality may benefit from our downscaling solution, which, thanks to the global coverage of OSM, can be globally applied.


The paper is an attempt to study the effect of repeated boosters with Di-Te vaccine in positive children. The efficacy of their administration (vaccinal coverage degree, level of secreted antitoxins, the persistency of the immune response) and their influence upon the subsequent evolution of HIV infection are investigated.


This paper deals with an identification method based on a model with an automatic choosing function (ACF) for nonlinear systems. A full data region or a whole domain is divided into some subdomains and the unknown nonlinear function to be estimated is approximately described by a linear equation on each subdomain. These linear equations are united into a single one by the ACF smoothly, and thus the resulting model becomes linear in the parameters. Hence these parameters are easily evaluated by the linear least squares method. Moreover the structure of the model by the ACF expansion is properly determined by the genetic algorithm, where the AIC by Akaike is utilized as an objective function. Numerical experiments are carried out to demonstrate the effectiveness of this approach.


The relationship between electoral systems can be examined on a number of dimensions. Seat allocation methods are conveniently divided into two groups: those based on largest remainders and those based on highest averages. The single transferable vote has its own distinct characteristics. Focusing on certain elements – the quota, thresholds, paradoxes and the conditions under which a majority of seats can be won – enables comparisons to be drawn between seat allocation methods. Certain seat allocation methods conventionally seen as variants of proportional representation (PR) cannot be regarded as such. PR methods can be rank ordered according to whether, when complete proportionality is not attainable, they display electoral bias towards larger or smaller parties. However, a definitive ordering is elusive, since some methods that are generally more favourable to larger parties can in some circumstances set lower thresholds of representation than methods generally favourable to smaller parties.


The health impact of attending early childhood development programs in developing countries remains largely unknown. In this study, we focus on the health consequences of attending preschool programs in India. Using a unique longitudinal dataset, we allow for heterogeneity in the impact of preschool across the distribution of health outcomes while controlling for time-invariant unobservables. We detect unique temporal variation in the effect of preschool attendance - growth of preschool attendees is slower than non-attendees in various parts of the distributions of several anthropometric measures when evaluated in the early years between ages 1 and 5. This effect is likely to reverse in the longer term at age 8. The early years' adverse effect can be explained in part by over-attendance in the form of long daily hours, excessive attendance days, and early entry. The findings are insensitive to nutritional incentives like free meals provided in public schools. The growth-retarding effect remains robust for weight-for-age z-scores, implying that the impact of preschool attendance is not only heterogeneous, but differs across dimensions of health status. Our study highlights the need for strengthening the delivery of childhood programs in developing countries in order to prevent adverse health effects in the critical years. Copyright © 2016 John Wiley & Sons, Ltd.


The 2nd Regional Conference on Applied and Engineering Mathematics 2012 (RCAEM-II 2012) provides an excellent opportunity of knowledge sharing and research ideas exchange in all areas of mathematics, statistics and engineering for a better quality of life to meet future challenges. Mathematics and statistics play a vital role in solving wide ranges of problems especially in engineering fields and industries. This biannual conference among mathematicians, scientists and engineering will be contributed to the development and collaboration in all areas science and engineering. The 1st Regional Conference on Applied and Engineering Mathematics 2010 (RCAEM-I 2010) was held in June 2010 in Penang, Malaysia. It was organized by Institute of Engineering Mathematics (Universiti Malaysia Perlis) or known as Institut Matematik Kejuruteraan (IMK) as main organizer in collaboration with School of Mathematical Sciences (USM) and Engineering Mathematics Research Group (UKM) as co-organizer.


Shallow lakes often exhibit a macrophyte‐dominated (MD) clear state or a phytoplankton‐dominated (PD) turbid state, each of which has profound impacts on biological communities, including bacterioplankton community composition (BCC). However, the response of microbial functional gene structure (FGS) to regime shift has not been thoroughly elucidated to date. In this study, we used a functional gene array (GeoChip 5.0) in combination with high‐throughput sequencing of the bacterial 16S rRNA gene to investigate the FGS and BCC between the two regimes in Lake Taihu, a large shallow freshwater lake in China. A simultaneous change in the BCC and FGS was observed between the two different regimes. We observed higher numbers of bacterial operational taxonomic units and functional genes detected by the GeoChip 5.0 in the MD samples than in the PD samples. By performing network analyses, we observed stronger microbe‐microbe interactions but weaker functional gene interactions involved in nutrient metabolism in the MD community than in the PD community. We speculate that at higher concentrations of phosphorus, the domination of Microcystis bloom may weaken the interactions among microbial species by releasing more labile dissolved organic carbon, but enhance the selection and interactions of functional genes involved in carbon cycling in the PD community. In contrast, the lower levels of phosphorus may enhance microbe‐microbe interactions but weaken the interactions between the primary nutrients and particular genes. Overall, this study demonstrated contrasting patterns in the BCC and FGS between the MD and PD communities in a large shallow freshwater lake.


e-governance initiative has helped many governmental organizations to carry out their services transparently, efficiently, and democratically. The admission process in many of the universities in Karnataka is usually manual. The process suffers from redundancy of data and workforce and the process itself is expensive. For the first time in any University in Karnataka, in 2009, an automated system for Post Graduate admissions was designed, developed and implemented for Bangalore University. This e-governance admission system has been in use in the University for the last four years. The process was started as a skeleton model and more services were added later in subsequent academic years during admission. It was found that the system was foolproof. It transformed the whole admission process into a single-window system. Admission Approval, Fee Payment, Hostel Admissions, and Issue of Library Cards were thus brought under a single-window system. This paper compares the novel e-governance initiative with that of the pervious system of admission. It also compares the Bangalore University model with other automated admission models in Karnataka. It investigates the performance of the e-governance initiative in reducing workforce and redundancy. It records the find that the e-governance process has helped the University and its stakeholders in rendering the admission system transparent. Many other Universities in Karnataka are now following this model for their admission.


Human mitochondrial transcription termination factor 1 (MTERF1) has been demonstrated to play an important role in mitochondrial gene expression regulation. However, the molecular mechanism of MTERF1 in colorectal cancer (CRC) remains largely unknown. Here, we found that MTERF1 expression was significantly increased in colon cancer tissues compared with normal colorectal tissue by Western blotting, immunohistochemistry, and tissue microarrays (TMA). Overexpression of MTERF1 in the HT29 cell promoted cell proliferation, migration, invasion, and xenograft tumor formation, whereas knockdown of MTERF1 in HCT116 cells appeared to be the opposite phenotype to HT29 cells. Furthermore, MTERF1 can increase mitochondrial DNA (mtDNA) replication, transcription, and protein synthesis in colorectal cancer cells; increase ATP levels, the mitochondrial crista density, mitochondrial membrane potential, and oxygen consumption rate (OCR); and reduce the ROS production in colorectal cancer cells, thereby enhancing mitochondrial oxidative phosphorylation (OXPHOS) activity. Mechanistically, we revealed that MTERF1 regulates the AMPK/mTOR signaling pathway in cancerous cell lines, and we also confirmed the involvement of the AMPK/mTOR signaling pathway in both xenograft tumor tissues and colorectal cancer tissues. In summary, our data reveal an oncogenic role of MTERF1 in CRC progression, indicating that MTERF1 may represent a new therapeutic target in the future.


In the world of higher education, service to students is very much needed, it is very important to maintain the quality of service so that good and disciplined service to students can be realized. This sentiment analysis aims to determine student opinion made using a questionnaire form. In addition, the Decision Support System with the Simple Multi Attribute Rating Technique (SMART) and Simple Additive Weighting (SAW) methods is expected to be a solution in providing an assessment of the FTKI secretariat services. This study uses a questionnaire form to see student assessments and make it an alternative value. The final results are obtained by testing the order analysis technique, which is 82%, proving that by testing these two methods, service assessment can be more expanded. Keywords: Sentiment Analysis, Questionnaire, SAW, Desicion Support System, SMART.


We present the first implementation and applications of non-Dyson algebraic diagrammatic construction theory for charged excitations in three-dimensional periodic solids (EA/IP-ADC). The EA/IP-ADC approach has a computational cost similar to the ground-state Møller-Plesset perturbation theory, enabling efficient calculations of a variety of crystalline excited-state properties (e.g., band structure, band gap, density of states) sampled in the Brillouin zone. We use EA/IP-ADC to compute the quasiparticle band structures and band gaps of several materials (from large-gap atomic and ionic solids to small-gap semiconductors) and analyze the errors of EA/IP-ADC approximations up to the third order in perturbation theory. Our work also reports the first-ever calculations of ground-state properties (equation-of-state and lattice constants) of three-dimensional crystalline systems using a periodic implementation of third-order Møller-Plesset perturbation theory (MP3).


This paper contains data on and insights into the origins of turbulence associated with a partial blockage at the exit of a two-dimensional, laminar, horizontal duct flow. In essence, this is the upstream approach region of the forward-facing step problem. This work was motivated by the need to identify and control unsteady streamwise vortices generated in the headbox (i.e. contraction section) of an industrial paper machine. The duct was 57.2 cm wide × 10.16 cm high, with up to a 50 % blockage. Experiments were scaled to match Reynolds numbers found in paper machines; exit velocities were as large as 200 cm s−1. The goal of the research was to map the flow at the exit and to examine the response of the flat-plate turbulent boundary layer on the opposing wall under the partial blockage. Laser-induced fluorescence (LIF) and digital particle image velocimetry (DPIV) were used to examine flow in three orthogonal planes at various stations upstream of the duct exit. Mean and instantaneous DPIV vector fields clearly show that an unsteady spanwise vortex forms in the corner formed by the top nozzle wall and partial blockage which, in turn, gives rise to turbulent streamwise vortices. A turbulent boundary layer was initiated on the duct wall opposite the blockage, upstream of a two-dimensional contraction. Results show that even though the acceleration parameter, K, exceeded the nominal critical level of 3.0 × 10−6 for relaminarization beneath the blockage, the flow did not reach a quasi-laminar state. In addition, there did not appear to be direct interaction between unsteady vortex formation at the partial blockage on the upper wall and bottom-wall turbulent boundary layer structures.


Proper names are usually key to understanding the information contained in a document. Our work focuses on increasing the vocabulary coverage of a speech transcription system by automatically retrieving new proper names from contemporary diachronic text documents. The idea is to use in-vocabulary proper names as an anchor to collect new linked proper names from the diachronic corpus. Our assumption is that time is an important feature for capturing name-to-context dependencies, that was confirmed by temporal mismatch experiments. We studied a method based on Mutual Information and proposed a new method based on cosine-similarity measure that dynamically augment the automatic speech recognition system vocabulary. Recognition results show a significant reduction of the word error rate using augmented vocabulary for broadcast news transcription.


Background Huntington's disease (HD) is associated with a variety of cognitive deficits, with prominent deficits in working memory (WM). These deficits can occur in the early stage of the disease and undermine quality of life. Currently, there are no established treatments for these symptoms. Aims The feasibility of implementing a home-based, computerised WM training program was examined in HD patients who reported WM difficulties in daily life. A secondary aim was to assess the patient experience with this training program. Methods Nine patients, aged 26–62, with early stage HD underwent a 25-session (5 days/week for 5 weeks) WM training program (Cogmed QM). Training exercises involved the manipulation and storage of verbal and visuospatial information, with difficulty adapted as a function of individual performance. Neuropsychological testing was conducted before and after training, to evaluate changes in performance on criterion WM measures (Digit Span and Spatial Span) and near-transfer WM measures (Symbol Span and Auditory WM). Post-training interviews about patient experience were thematically analysed using NVivo software. Results Seven of nine (77%) patients completed the program within the recommended timeframe (M = 36 ± 12.35 days). Compared to baseline scores, patients showed significant improvement on both measures of verbal WM (Digit Span, p = 0.047; Auditory WM, p = 0.041). Each of these patients reported that they found training helpful, and almost all (n = 6) felt that their memory improved. Conclusions This pilot study provides support for feasibility of computerised WM training in early-stage patients with HD. Results suggest that HD patients can improve WM with intensive training, though a full-scale intervention project is needed to understand the reliability of changes over time.


The aim of this study was to isolate Vibrio parahaemolyticus strains in tiger shrimps, water and sediment samples of aquaculture farms in Kuching, Sarawak. Antimicrobial susceptibility pattern was compared. Shrimp culture is a very important economic activity in the world and one of the fastest growing industry in Malaysia. Problems with diseases are very common. The use of antibiotics and chemicals are thus widely used against these bacteria. There are many concern regarding the use of these chemicals in shrimp farms. Its potential impact on the development of antimicrobial resistance in the environment and human health arises. The bacterial isolation was performed using the disk diffusion method. This method involved the use of selective enrichment with alkaline peptone water and plating of the enrichment culture onto Thiosulfate Citrate Bile Sucrose. A total of 140 V. parahaemolyticus strains isolated from four different farms were examined for their antimicrobial resistance to 9 commonly used antimicrobials: ampicillin, gentamicin, neomycin, cephalothin, tetracycline, nalidixic acid, kanamycin, chloramphenicol and streptomycin. The most frequently encountered form of resistance were resistance to ampicillin (100%), tetracycline (60%) and nalidixic acid (37.5%). The samples were totally susceptible to gentamicin and chloramphenicol. Low levels of resistance of less than 30% were demonstrated in the other antimicrobial agents. The Multiple Antibiotic Resistance (MAR) indices were highest for tiger shrimps isolates (0.27) and low for environmental sources, water samples (0.011). The results in this study confirm that all strains were susceptible to chloramphenicol. However, the resistance towards ampicillin, tetracycline and nalidixic acid suggest that the use of antimicrobials in tiger shrimps should be stopped to overcome future resistance problem. This study revealed useful information on the resistance pattern of V. parahaemolyticus towards antimicrobial agents. Constant monitoring of the antibiotic resistance patterns of V. parahaemolyticus in the study areas should be done


We have studied the pH effect on the S0 and S2 multiline electron paramagnetic resonance (EPR) signals from the water-oxidizing complex of photosystem II. Around pH 6, the maximum signal intensities were detected. On both the acidic and alkaline sides of pH 6, the intensities of the EPR signals decreased. Two pKs were determined for the S0 multiline signal; pK1 = 4.2 ± 0.2 and pK2 = 8.0 ± 0.1, and for the S2 multiline signal the pKs were pK1 = 4.5 ± 0.1 and pK2 = 7.6 ± 0.1. The intensity of the S0-state EPR signal was partly restored when the pH was changed from acidic or alkaline pH back to pH ~ 6. In the S2 state we observed partial recovery of the multiline signal when going from alkaline pH back to pH 6, whereas no significant recovery of the S2 multiline signal was observed when the pH was changed from acidic pH back to pH 6. Several possible explanations for the intensity changes as a function of pH are discussed. Some are ruled out, such as disintegration of the Mn cluster or decay of the S states and formal Cl- and Ca2+ depletion. The altered EPR signal intensities probably reflect the protonation/deprotonation of ligands to the Mn cluster or the oxo bridges between the Mn ions. Also, the possibility of decreased multiline signal intensities at alkaline pH as an effect of changed redox potential of YZ is put forward. (Less)


The growth of the porosity in high-burnup fuel is of particular interest when considering the effect of fission gas retention within the high-burnup structure (HBS). A mechanistic model of porosity growth under annealing conditions for light water reactor (LWR) UO2 fuel with typical stereological parameters of the HBS has been developed. The model takes into account both multipore and surface interactions that lead to fission gas release from the HBS porosity. We have applied the model to an HBS annealing experiment and found that reasonable agreement with the experimental gas release curve can be achieved for a vacancy diffusion enthalpy close to that measured experimentally. A comparison of the model behaviours at different pore growth rates is performed. We found that the model exhibits porosity evolution characteristics independent of the growth rate, specifically the existence of a maximum porosity, a continuous gas release, and a decreasing pore number density. A general comparison between the model results and in-pile data indicates that up to 250 MWd/kgU, most of the gas is retained within the HBS.


Fabrication, morphology evaluation, and permeance/selectivity properties of three asymmetric BTDA-TDI/MDI copolyimide hollow fiber membranes (HFMs) are reported. The asymmetric HFMs were spun using the dry/wet phase inversion process. The effect of one of the major spinning parameters, the air gap, on the permeance/selectivity properties of the produced HFM was investigated. Scanning electron microscopy was used to evaluate the morphological characteristics and the macroscopic structure of the developed HFM. The permeance values of He, H2, CH4, CO2, O2, and N2 gases were measured by the variable pressure method at different feed pressures and temperatures and the permselectivity coefficients were calculated. The higher selectivity values were evaluated for the Μ1 membrane and were found to be 49.33, 2.99, 5.13, 5.57, and 9.61 for H2/CH4, O2/N2, CO2/CH4, CO2/N2, and H2/CO2 gas mixtures, respectively. The selectivity experiments of H2/CH4, CO2/CH4, and O2/N2 mixtures were performed at 25°C. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4490–4499, 2013


Ets is a large family of transcriptional regulators with functions in most biological processes. While the Ets family gene, prostate‐derived epithelial factor (PDEF), is expressed in epithelial tissues, PDEF protein expression has been found to be reduced or lost during cancer progression. The goal of this study was to examine the mechanism for and biologic impact of altered PDEF expression in prostate cancer.


Observations of relativistic electron precipitation events from Earth's inner magnetosphere to the upper atmosphere provide essential information about the source/loss processes and dynamics of Earth's radiation belts. Equatorial electron pitch angle isotropy can be an indicator of electron precipitation into the atmosphere, with isotropic populations resulting in a full bounce loss cone (BLC) and anisotropic populations resulting in an emptier BLC. Here we study electron microbursts, which are ˜100 millisecond duration streams of relativistic electrons thought to be scattered into the BLC by particle‐wave scattering. By measuring the ratios of >1 MeV electron flux across different detector rows in the Heavy Ion Large Telescope (HILT) instrument onboard the Solar, Anomalous, and Magnetospheric Particle Explorer (SAMPEX) satellite, we quantify the pitch angle isotropy of an electron population. Applying this calculation to microburst events, we have determined the dependence of microburst pitch angle distributions on burst magnitude, magnetic local time (MLT), L‐Shell, and storm phase. We found that high flux magnitude microbursts are typically highly isotropic, while lower flux magnitude microbursts have varying degrees of anisotropy. Furthermore, microbursts are most isotropic as compared to the background population in the afternoon/evening sector as well as initial and main phases of geomagnetic storms. These results have important implications for microburst scattering mechanisms as well as quantification of precipitation driven by this process.


The conceptual design of a magnetic system for an experiment to measure the transverse spin effects in semi-inclusive Deep Inelastic Scattering (SIDIS) at 11 GeV with a transversely polarized target using the CLAS12 detector at Jefferson Lab is presented. A proposal has been submitted to study spin azimuthal asymmetries in SIDIS using an 11-GeV polarized electron beam from the upgraded CEBAF facility and the CLAS12 detector equipped with a transversely polarized target. The main focus of the experiment will be the measurement of transverse target single and double spin asymmetries in the reaction ep↑ → ehX, where e is an electron, p↑ is transversely polarized proton, h is a meson (e.g., a pion or a kaon) and X is the undetected final state. The details of the conceptual design of the shielding magnetic system and transverse dipole are reported.


This paper presents a semi-analytic method for computing frequency dependent means, variances, and failure probabilities for arbitrarily large-order closed-loop dynamical systems possessing a single uncertain parameter or with multiple highly correlated uncertain parameters. The approach will be shown to not suffer from the same computational challenges associated with computing failure probabilities using conventional FORM/SORM techniques. The approach is demonstrated by computing the probabilistic frequency domain performance of an optimal feed-forward disturbance rejection scheme.


Background:
 Increased angiotensin II (ANG) levels elicit profibrotic effects which promote ventricular tachyarrhythmias (VT).

 Hypothesis:
 Gene delivery of the matricellular protein CCN5 ameliorates ANG related VT by reversing fibrosis.

 Methods:
 8-10 wk old mice underwent ANG infusion (3mg/Kg/d) for 2wk after which they received 5E11 drp AAV9.CCN5 (ANGII+CCN5, n=8) or empty vector (ANGII, n=8) and were maintained for another 2wk. Optical mapping was performed in hearts that were challenged with right atrial (RA) burst trains (20Hz, 5-20 sec) to determine VT propensity. Fibrosis was assessed using trichrome staining.

 Results:
 VT was induced in 6/8 ANG, 2/8 ANG+CCN5, and 1/3 control hearts. A total of 34 trains elicited 13 VT episodes (38.4% rate) in ANG whereas 150 trains yielded only 6 episodes in ANG+CCN5 (4.0%). ANG increased the transepicardial APD gradient by causing selective APD prolongation on the RV side which was partially reversed by CCN5. No differences in the APD gradient were found between VT (+) and VT (-) hearts. Activation mapping revealed fixed lines of conduction block leading to onset of VT in ANG hearts. In contrast, RA trains caused shifting ventricular activation patterns that were normalized following the train in ANG+CCN5 (Fig). Extensive fibrotic lesions in ANG were reversed by CCN5 (Fig).

 Conclusions:
 Reversal of fibrosis by chronic CCN5 gene therapy suppresses the incidence of ANG related VT.


The DC performance of GaAs/AlAs heterojunction bipolar transistors (HBTs) grown on silicon substrates with buffer layers ranging from 0 to 5 mu m was investigated. Current gain, collector-emitter breakdown voltage, emitter-base and collector-base diode ideality factors, and breakdown voltages were measured as the buffer layer thickness was varied between 0 and 5 mu m. The current gain steadily increases with increasing buffer layer thickness until the layer reaches 3 mu m. However, the other DC parameters are relatively insensitive to the buffer layer thickness. A small-signal current gain of 60 is typically achieved for devices with 6*6- mu m/sup 2/ emitters at a density of 6*10/sup 4/ A/cm/sup 2/ when the buffer layer is >or=3 mu m.<<ETX>>


A study undertaken to discover whether the incidence and types of intrauterine bacterial growth in IUD users differed from those in nonusers is described. The study 1)compared the early development of infection in IUD users and nonusers, and 2) looked for a correlation between known serious pelvic infection and IUD use. Of 235 patients seen for gynecologic examination (131 IUD users and 104 nonusers), 21 users for 6 months or more and 1 user for less than 4 months had foul-smelling leukorrhea, irregular bleeding, or both. Endometrial cultures were positive in 67% of users, and in 62% of the nonusers. 11 long-term IUD users more than 6 months and 1 nonuser had anaerobic organisms (p less than .01). Of 31 patients admitted for tubo-ovarian or pelvic abcesses, 17 were IUD users, of whom 9 required hysterectomy. Earlier recognition of foul-smelling mucoid discharge on the IUD tail, or abnormal bleeding, or both, as a sign of early pelvic infection, followed by removal of the IUD and institution of appropriate antibiotic therapy, might prevent the more serious sequelae of pelvic inflammation.


In this study, the stimulatory effects of application of glyphosate herbicide coupled with manganese sulfate (8%) foliar fertilizer on the production and bromatological characteristics of Brachiaria brizantha 'Marandu' were evaluated. The experiments were performed using randomized complete block design with a 5×4 factorial scheme in plots subdivided over time (across four evaluations) with four repetitions, totaling 100 observations. The effects of sublethal doses of acid equivalent (a.e.) of glyphosate (5.40, 21.60, 64.80, and 108.00 g·a.e.·ha) and control plus manganese sulfate foliar fertilizer (1,000 g ha) were assessed in four successive evaluations at a defoliation frequency of 21 days. Foliage at 20 cm height (to evaluate forage production); leaf/stem ratio (LSR); and contents of crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), and lignin (LIG) were measured in experimental plots with a usable area of 7.5 m. Application of sublethal doses of glyphosate plus manganese sulfate did not increase forage production, increased LSR, reduced LIG content, and did not affect CP content in all four evaluations. NFD and ADF indicated satisfactory qualitative indices for animal feed following the application of sublethal doses of glyphosate plus manganese sulfate in all four evaluations.


This work reports on an optically-pumped vertical external-cavity surface-emitting laser (VECSEL) emitting around 852 nm for Cesium atomic clocks experiments. We describe the design and the characterization of a VECSEL semiconductor structure suitable for these applications. The parameters of the structure have been optimized in order to have a low threshold and a high gain structure emitting around 852 nm. We achieved an output power of 330 mW for 1.1 W of incident pump power. We are able to simulate the laser emission variations with the temperature of the substrate, the pump radius on the semiconductor structure and the losses inside cavity. A compact and robust setup was built to obtain a stable single-frequency emission. We obtained a 17-mW single frequency emission exhibiting broad and fine tunability around the Cesium D2 line.


To what extent do politicians reward voters who are members of their own ethnic or racial group? Using data from large cities in the United States, we study how black employment outcomes are affected by changes in the race of the cities' mayors between 1973 and 2004. We find that black employment and labor force participation rise, and the black unemployment rate falls, during the tenure of black mayors both in absolute terms and relative to whites. Black employment gains in municipal government jobs are particularly large, which suggests that our results capture causal effects of black mayors. We also find that by improving the employment outcomes of blacks, black mayors lead to higher black incomes both in absolute terms and relative to white incomes. We show that our results continue to hold when we compare the treated cities to alternative control groups of cities, explicitly control for changing attitudes towards blacks or use regression discontinuity analysis to compare cities that elected black and white mayors in close elections.


We consider pricing problems when customers choose under the Markov chain choice model. In this choice model, a customer arriving into the system is interested in a certain product with a certain probability. Depending on the price charged for this product, the customer decides whether to purchase the product. If the customer purchases the product, then she leaves the system. Otherwise, the customer transitions to another product or to the no purchase option with certain transition probabilities. In this way, the customer transitions between the products until she purchases a product or reaches the no purchase option. We study three fundamental pricing problems under this choice model. First, for the monopolistic pricing problem, we show how to compute the optimal prices efficiently. Second, for the competitive pricing problem, we show that a Nash equilibrium exists, prove that Nash equilibrium prices are no larger than the prices computed by a central planner controlling all prices and characterize a Nash equilibrium that Pareto dominates all other Nash equilibria. Third, for the dynamic pricing problem with a single resource, we show that the optimal prices decrease as we have more resource capacity or as we get closer to the end of the selling horizon. We also consider a deterministic approximation formulated under the assumption that the demand for each product takes on its expected value. Although the objective function and constraints in this approximation do not have explicit expressions, we develop an equivalent reformulation with explicit expressions for the objective function and constraints.


Background: This narrative type review aimed to address organ toxicity emanating from incense usage. Methods : An online search using the following MeSH terms "Incense smoke,", "adverse effects," "organotoxicity", "oxidative stress" and "inflammation" was done to identify studies directly applicable to adverse effects of incense smoke exposure. Findings: Exposure to incense smoke demonstrated various toxicity changes in the kidney, testes, lungs, liver and heart. Renal effects included a decrease in oxidative stress markers GSH and CAT, increase in MDA, serum creatinine uric acid and blood urea nitrogen (BUN). Testicular toxicityrevealed significant disturbances in spermatogenetic patterns, testicular atrophy, germinal aplasia, hypospermia and damage to the basal seminiferous epithelia tissue. In the cardiac muscle, ultrastructural changes, increased oxidative stress, inflammation, and altered cardiac hypertrophic gene expression was noted. Thenegative impact of incense smoke emanating from free radical (ROS), lipid peroxidation and GSH destabilizes vascular homeostasis and initiates ahyperinflammatory response, warranting the need to understand the conceptual basis of the mode of action linked to incense exposure. Conclusion : We highlight that incense generates ROS which initiates lipid peroxidation through ATP energy depletion and reduction in the natural antioxidants. This subsequently triggers oxidative stress, inflammation and endothelial dysfunction resulting in organotoxicity.


Abstract Renal disease and disorders of fluid homeostasis are common in captive amphibians. Veterinarians treating amphibian patients should be aware of important physiological differences between Amphibia and other vertebrates encountered in the exotic animal veterinary practice. Of particular clinical importance are the role of the integument in osmoregulation and the diversity of physiological adaptations that enables the Amphibia to inhabit a variety of natural environments. This article reviews physiological concepts and provides an overview of common disorders of the amphibian urinary tract and fluid balance, including the common clinical presentation of subcutaneous (lymph sac) edema in anurans (frogs and toads).


The paper is based on a self evaluation of perceived supervisory capabilities of 21 primary school heads attending a UNICEF workshop on the supervision of teachers in training. In their self evaluation, the heads of schools express lack of confidence and expertise in providing in-school instructional leadership in more than half the subjects comprising the primary school curriculum. The paper distinguishes administrative leadership from curriculum and instructional leadership and concludes by highlighting the role and significance of the school head as a curriculum and instructional leader. It is argued that the extent and quality of implementation of any curriculum is heavily dependent upon the amount and quality of training and leadership afforded assistant teachers in curriculum and instruction.


On 14 June 2017, a Headquarters Agreement between Austria and the Organization for Security and Co-operation in Europe (' OSCE ') was signed. This is remarkable in that the OSCE , unlike other international organisations, lacks a generally acknowledged international legal status. This View from Practice charts the history of the multilateral efforts to grant a clear legal status to the OSCE , the recognition by Austria that it considers the OSCE as having obtained international legal personality on the basis of customary international law by offering to conclude a Headquarters Agreement, and the contents of this Agreement.


Competition between different isogenic mutants of Pseudomonas fluorescens unable to carry out the first steps of the denitrification pathway was compared in soil micro-columns non-planted or planted with maize. A new isogenic mutant of P. fluorescens YT101 affected in both nitrate and nitrite respirations was constructed and used as a model of non-denitrifying strain (FM69MS strain). The outcome of the selection exerted by the plant after co-inoculation of FM69MS at the same ratio either with an isogenic denitrifier unable to reduce nitrate (Nar(-) mutant) or with an isogenic NO2 (-) accumulator (Nir(-) mutant) was investigated in non-limiting NO3 (-) conditions. Regardless of the inoculated mixture, both strains were able to grow in both rhizosphere and non-planted soil. The proportion of Nar(-) or Nir(-) strain in the Nar(-)+FM69MS or Nir(-)+FM69MS total introduced population remained stable in non-planted soil. In the rhizosphere, we observed a higher competitiveness of the Nir(-) mutant compared with FM69MS, whereas the latter showed the same competitiveness as the Nar(-) mutant. These results provide the first demonstration that NO3 (-) reduction is the main nitrogen-dissimilating step controlling the competitiveness of P. fluorescens in the rhizosphere.


In the present work, the sensing capability of nitrogen-doped graphene quantum dots (N-GQDs) was explored for the first time toward hazardous heavy metal ions and they were found to be able to selectively detect cadmium ions (Cd(II)). Cd(II) is one of the hazardous heavy metal ions on the World Health Organization's list of 10 chemicals of major public health concern. The wide use of Cd(II) in industrial applications and its acute and chronic effects on living beings make the sensing of Cd(II) critical. The aromatic N-GQDs, synthesized here through a hydrothermal route using the single precursor polyaniline exhibited a 25- and 6-fold increase in the current response compared to that of a glassy carbon electrode (GCE) and GQD/GCE, respectively. It showed an excellent and exemplary selectivity toward Cd(II), with almost a nil current response for other interfering metal ions. The LOD value of 1.0 × 10−5 ppb, i.e., in parts per trillion, by N-GQDs is the lowest value ever reported, which was 3–4 orders of magnitude lower than the previously reported values. The LOD was extended to the ultra-high sensitivity level of 1 × 10−7 ppb, i.e., in parts per quadrillion, using a pre-reduction step. The LDR (0.001–112 000 ppb) and LOD values satisfactorily met the sensitivity requirement for detecting Cd(II) within the safe limit specified by the U.S. Environmental Protection Agency (EPA) of ≤5 ppb. The sensing performance of N-GQD/GCE was tested against real environmental samples spiked with Cd(II), such as groundwater, seawater, and wastewater, and was found to perform efficiently.


Wine is an agricultural product with very high commerce price variation, which is highly affected by quality ratings. Therefore, quality rating is particularly important for both industry and consumers. However, absence of clear concepts on what constitutes wine quality makes the perception of quality highly subjective, and it is usual for tasters to disagree on the quality rating of a specific wine. For this purpose, a Feedforward Neural Network (FNN) could be trained in order to predict wine quality. In this study, a new FNN method was developed to predict the accurate wine quality based on major sensory characteristics as FNN inputs, and to improve the ability of a taster, groups of tasters, or consumers, to rate wine by taking into account previous decisions. Specifically, five principle sensory characteristics of wines were used as inputs (Aging in Barrel, Aroma Intensity, Body, Astringency, and Acidity) in a rating range 1-3. As outputs, the quality ratings of wines in a range 70-100 were considered. The FNN was created in MATLAB with 1 hidden layer, 5 neurons and 1 output layer. For ratings divided in 5 categories the accuracy was 53% with the use of the FNN, as opposed to the accuracy of 36% achieved by Multiple Linear Regression. For ratings divided in 9 categories the accuracy was 90%. This method may allow each individual or group of tasters to introduce their own data to produce a more objective rating by taking into account previous decisions (subjective) that have accumulated in the database.


Medial rectus innervation was always normal, and lateral rectus innervation was always abnormal. Lateral rectus overactivity accompanied deficient adduction. Lateral rectus underactivity accompanied abduction deficiency and was reflected in slowed saccadic abduction movements. Secondary contractures of the medial rectus and lateral rectus were often present. Lateral rectus overactivity with upgaze, downgaze, or both, caused A, V, or X patterns. Retraction on adduction was accompanied by abnormal activity of the superior rectus, inferior rectus, or lateral rectus. Elevation in adduction was usually caused by abnormal superior rectus activity and not abnormal inferior oblique activity. Narrowing of the palpebral fissure only occurred with retraction of the eye. Levator and orbicularis innervations did not change with adduction.


The congenital long QT syndrome is a cardiac disease characterized by an increased susceptibility to ventricular arrhythmias. The clinical hallmark is a prolongation of the QT interval, which reflects a delay in repolarization caused by mutations in cardiac ion channel genes. Mutations in the HERG (human e ther-à-go-go-relatedgene KCNH2 can cause a reduction in IKr, one of the currents responsible for cardiac repolarization. We describe the identification and characterization of a novel missense mutation T65P in the PAS (Per-Arnt-Sim) domain of HERG, resulting in defective trafficking of the protein to the cell membrane. Defective folding of the mutant protein could be restored by decreased cell incubation temperature and pharmacologically by cisapride and E-4031. When trafficking was restored by growing cells at 27 °C, the kinetics of the mutated channel resembled that of wild-type channels although the rate of activation, deactivation, and recovery from inactivation were accelerated. No positive evidence for the formation of heterotetramers was obtained by co-expression of wild-type with mutant subunits at 37 °C. As a consequence the clinical symptoms may be explained rather by haploinsufficiency than by dominant negative effects. This study is the first to relate a PAS domain mutation in HERG to a trafficking deficiency at body temperature, apart from effects on channel deactivation.


Abstract: In an attempt to ascertain whether the presenting features of idiopathic myelofibrosis (IM) have changed in recent years, 2 groups of patients diagnosed with IM in a single institution in different time periods were compared. The first group included 53 patients diagnosed from 1975 to 1986, and the second included 56 patients diagnosed from 1987 to 1997. No significant differences were observed between the two groups with regard to age, gender, delay from first symptoms to disease diagnosis, peripheral blood hematological values and serum biochemical parameters. Patients diagnosed prior to 1987 presented more often with constitutional symptoms (fever, night sweats, weight loss), but the difference did not reach statistical significance. These latter patients had, however, a higher frequency of splenomegaly (91% vs. 73%, p=0.01) and hepatomegaly (79% vs. 48%, p=0.002), and were more often in the osteosclerotic phase at diagnosis (p=0.05) than patients more recently diagnosed. Finally, no significant differences were found between both groups in either the distribution by prognostic scores or survival. The above results seem to indicate a trend towards a less florid clinical picture of IM at presentation in recent years. This, however, does not result in a longer patient survival.


Background Hypoxia and angiogenesis are features of inflamed and injured tissues. The transcription factors Hypoxia inducible factor (HIF)-1α and (HIF)-2α control cellular metabolic response to decreased oxygen tension thereby promoting angiogenesis and having implications on the pathogenesis of RA. Objectives We focused on the effects of HIF-1α and HIF-2α on angiogenesis and developed a human microvascular endothelial cells (HMEC) lentiviral based knockdown system for both transcription factors allowing us to analyze angiogenesis of HMECs under hypoxia in the absence of HIF-1α or HIF-2α, respectively. Methods Specific knockdown of HIF-1α or HIF-2α was achieved using lentiviral-based shRNA technology. The reduction of HIF-1α or HIF-2α was confirmed on transcriptional and translational level by realtime RT-PCR and Western blot. Angiogenesis of transduced HMECs in comparison to scrambled cells was studied by investigating both tubuli and node formation under hypoxia (<1% O2). Expression of hypoxia driven genes HIF1A, HIF2A, VEGFA and IL8 was quantified by realtime RT-PCR. Multiplex suspension array technology was used to measure the concentrations of secreted VEGF and IL8. Results The successful knockdown of HIF-1α and HIF-2α was confirmed by demonstrating considerably reduced gene expression levels of HIF1A and HIF2A by up to 71% (p=0.0222) under normoxic and hypoxic conditions. As a consequence, strongly reduced HIF-1α and HIF-2α protein levels were detected by Western blot. Targeting of HIF-1α led to a significantly decreased node formation (1.6-fold change under hypoxia, p=0.0067) with similar effects by trend on tubuli formation. The HIF-2α knockdown also led to a significantly decreased tubuli formation (1.7-fold change, p=0.0444) with similar effects by trend on node formation. Furthermore, HIF-1α targeted cells did not show any significant decrease in the gene expressions of VEGFA and IL8 but surprisingly raised cytokine levels of IL8 under hypoxia (1.4-fold change, p=0.021) compared to the control. In contrast, targeting of HIF-2α gave rise to reduced levels of secreted VEGF and IL8 with a significant suppression of IL8 gene expression under normoxia (2.1-fold change, p=0.0101). Conclusions Our findings show essential and overlapping functions of HIF-1α and HIF-2α with regard to their regulatory potential of angiogenesis in HMECs. Both transcription factors have the same impact on VEGF but differ in their effects on IL8 expression. These findings provide new insights into basic principles of angiogenesis in inflamed tissues and are therefore considered to be of clinical importance. Disclosure of Interest None Declared


Pregnancy and trypanosomosis are associated with leukocyte changes. The leukocyte response of pregnant Yankasa ewes during experimental Trypanosoma evansi infection was determined using twenty pregnant ewes. They ewes were divided into 3 groups with 6 ewes in group A, while groups B and C were made up of 7 ewes each. The ewes in group A served as control, whereas those in group B and C were infected with approximately 1.0 x106 parasites/mL of T. evansi (Sokoto isolate) per ewe through the jugular vein on days 59 and 110 of pregnancy, respectively. Blood from each ewe was collected weekly and used to monitor leukocyte changes from the time of parasitaemia till the end of the study. There was significant (p


Diabetic ketoacidosis is a common life-threatening complication, which usually occurs in patients with type 1 diabetes, but it may also occur in those with type 2 diabetes during severe concurrent illness, such as sepsis, myocardial infarction or corticosteroid treatment. This article provides an overview of the diagnosis, pathophysiology and management of diabetic ketoacidosis. The differential diagnosis and treatment of hyperosmolar non-ketotic coma is also discussed, as is the nurse's role in promoting and providing health education to patients with diabetic ketoacidosis.


Various electrical standards are reviewed from the viewpoint of the selection and interpretation of ambient temperature values. Equivalent aging temperatures for insulation have been calculated from recorded ambient temperature data for several typical outdoor and indoor locations. From these the suitability of ambient values now used for the establishment of temperature rises for rating purposes is discussed. These values seem to be well chosen, but some clarification in meaning and in methods of using them for rating and application purposes is desirable. For apparatus rated on a 40 degrees centigrade ambient basis, appreciable margins in permissible temperature rise exist under many conditions and for many places of application. Permissible increase in loading for certain motors without exceeding conservative hot-spot temperatures are suggested, subject to the limitations imposed by other operating considerations.


. The effect of fire intensity - both temperature and duration - on the resprouting pattern of the evergreen Mediterranean shrub Erica multiflora in relation to plant size, was experimentally investigated by subjecting plants to the flame of a propane torch, and observing mortality and resprouting after 5 and 20 months.

Pre-treatment plant size was not important in determining post-fire plant survival, but it did influence the resprouting vigour, increasingly so with time. High temperatures induced higher mortality rates within populations, but duration of fire did not effect mortality. Biomass of resprouts was lower following more intense fire treatments, but this effect progressively disappeared over time, except in plants subjected to the most intense fire treatment. This is probably because of the increasing importance of the below-ground organs for the regeneration of the above-ground biomass. Some of the plants which were clipped but not exposed to fire also died 20 months after treatment. The effect of clipping onmortality andresprout-ing response, estimated as biomass of resprouts, was not significantly different from the effect induced by either low or medium temperature treatments, but was significantly different when compared with the effect of high-temperature treatments.

Field observations show that the establishment of seedlings of E. multiflora is rare both after fire and between fires. Thus, our data support the idea that both a single fire or clipping can diminish the population size of a resprouting species. We conclude that fire may have a stochastic effect on E. multiflora populations, due to the variation in fire intensity existing within a single burning stand.


A study of the structural, electrical and optical properties of copper oxide and copper-aluminum oxide thin films deposited by ultrasonic spray pyrolysis is presented in this work. On one hand copper oxide films were deposited at working temperatures in the range from 300 °C to 500 °C. These films present a mixture of Cu2O and CuO phases, CuO phase being more abundant at higher temperatures; all samples present p-type conductivity. On the other hand, copper-aluminum oxide samples were deposited at 350 °C but with different copper-aluminum ratios in the start solution (0, 12.5, 25, 50, 100, and 200 at%). The films present a mixture of Cu2O and Al2O3 phases, being the Cu2O the most abundant and becoming amorphous as aluminum concentration rises. Electrical characterization indicates that electronic conductivity depends on the amount of Cu2O, while ionic conductivity increases with aluminum concentration. Aluminum concentration also provokes a shift in the valence band towards lower binding energies, as well as an increase in the optical band gap (from 2.6 to 3.7 eV). Upon a thermal annealing at 800 °C the samples turned to CuAl2O4 spinel structure.


Nickel(ii) tetrasulfophthalo-cyanine (NiTSPc) could be electrodeposited onto an indium tin oxide (ITO) electrode to form an electropolymerization film of NiTSPc. The electrochemiluminescent (ECL) behavior of bis-[3,4,6-trichloro-2-(pentyloxy-carbonyl)-phenyl] oxalate (BTPPO) on this modified electrode was investigated in detail. The emission of ECL of BTPPO can be greatly enhanced by hydrogen peroxide at this modified electrode. Thus, a new ECL biosensor for uric acid was developed based on the enzymatic reaction of uric acid in the presence of uricase to produce H(2)O(2). The developed sensor has been used to detect uric acid in real serum samples, and the results compared well with those obtained by the routine method.


For construction and classification of the natural integrable systems we propose to use a criterion of separability in Darboux--Nijenhuis coordinates, which can be tested without an a priori explicit knowledge of these coordinates.


Nowadays several researches have implemented various techniques to solve the problem of clustering data. In this paper we present a visual bio-inspired approach to clustering based on the Conepvim model for visual perception of moving objects in the primary visual cortex (V1) of the human brain. This model uses the Gabor-like filters to detect motion, estimates the global speed, direction and trajectory. We have extended this model with a bio-inspired algorithm: the Self-Organization Maps (SOM) to define how many objects in motion there are in the sequence. Our approach is totally bio-inspired and it has been evaluated on natural sequences of images.


MIPS (million instructions per second) has been the most popular measure for computer speed since its inception, and people use it as the primary basis for comparing the speed of different computers. However, the author contends that using the MIPS year as a measurement of the amount of effort needed to break and compare cryptographic keys has led to some very inaccurate estimates. The MIPS year measurements has four basic problems: (i) Not all instructions are equal, so how do you really know the MIPS rating of a machines? (ii) Not all programs use the same instructions, so different programs can give different measures of speed even for the same machine; (iii) The way you measure the MIPS years expended on a single problem by many machines can introduce two possible errors: an inaccurate estimate of machine speed and an inaccurate measurement of time; (iv) If you consider only the number of instructions executed, you cannot accurately measure the difficulty of hard problems.


Electro-thermal annealing (ETA) in a MOSFET utilizes Joule heating. The high-temperature heat effectively cures gate dielectric damages induced by electrical stresses or ionizing radiation. However, even though ETA can be used to improve the reliability of logic and memory devices, applying ETA in state-of-the-art field-effect transistors (FETs) such as nanosheet FETs (NS FETs) has not yet been demonstrated. This paper addresses the heat distribution characteristic of an NS FET considering the application of ETA, using 3D simulations. A vacuum inner spacer is newly proposed to improve annealing effects during ETA. In addition, evaluations of the device scaling and annealing effect were performed with respect to gate length, nanosheet-to-nanosheet vertical space, and inner spacer thickness. Guidelines for ETA in NS FETs can be provided on the basis of the results.


Abstract : Cyclodextrins are ring-shaped molecules containing an apolar cavity with a diameter 4-8 A wide and approximately 8 A deep. Because of the hydrophilic nature of the surface, the materials are readily dispersed in water. However, hydrophobic groups on the inner surface of the nanoporous molecules attract hydrophobic organics that bind noncovalently to the apolar cavity. Recently, polycyclodextrins have been developed as binders for energetic materials and as sorbants for biological materials, and exhibit potential for development as sorbant materials for water filtration. Studies using these polymers have been reported in the literature and show that the polycyclodextrins are very effective scavengers of organic contaminants in water. Our work expands on the use of cyclodextrins in polymers through the synthesis of several organic cyclodextrin-based polymers. These filtering materials have been shown to scavenge several different kinds of contaminants up to parts per million concentrations from water. Some neutron work has been done to try to ascertain the nature of capture of these contaminants.


Currently there are no effective antifibrotic therapies for liver cirrhosis, a major killer worldwide. To obtain a cellular resolution of directly-relevant pathogenesis and to inform therapeutic design, we profile the transcriptomes of over 100,000 primary human single cells, yielding molecular definitions for the major non-parenchymal cell types present in healthy and cirrhotic human liver. We uncover a novel scar-associated TREM2+CD9+ macrophage subpopulation with a fibrogenic phenotype, that has a distinct differentiation trajectory from circulating monocytes. In the endothelial compartment, we show that newly-defined ACKR1+ and PLVAP+ endothelial cells expand in cirrhosis and are topographically located in the fibrotic septae. Multi-lineage ligand-receptor modelling of specific interactions between the novel scar-associated macrophages, endothelial cells and collagen-producing myofibroblasts in the fibrotic niche, reveals intra-scar activity of several major pathways which promote hepatic fibrosis. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides the conceptual framework required to discover rational therapeutic targets in liver cirrhosis.


Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA

The gene encoding Isocitrate dehydrogenase 1 (IDH1) is frequently mutated in gliomas, chondrosarcomas, acute myeloid leukemia and intrahepatic cholangiocarcinomas. As there are few in-vivo model systems for IDH-mutated tumors we have created a transgenic zebrafish (Danio rerio) model expressing mutant IDH1. We have chosen the zebrafish as a model because they are transparent (allowing monitoring of the transgene in-vivo) and drug screening assays are straightforward (they are simply added to the aquarium).

IDH1R132H and IDH1R132C, mutations found in tumors that both produce D-2-hydroxyglutarate (D2HG) instead of alpha ketoglutarate, were cloned into an expression construct that is driven either by the Nestin or GFAP promoter. IDH1G70D (a loss of function mutation), IDH1wildtype and GFP were used as control. All IDH1 constructs were fused to GFP for visualization. These constructs were injected into fertilized zebrafish eggs at the one-cell stage.

All of our transgenic zebrafish lines remain healthy and produce offspring. Transgene expression was detected in the mid/hindbrain of the central nervous system by immunohistochemistry, Western blot and RT-QPCR. A significant increase in the level of D2HG was observed in all transgenic lines expressing IDH1R132C or IDH1R132H, but not in any of the lines expressing control constructs (IDH1wildtype, IDH1G70D or GFP). In contrast to reported, we failed to detect any differences in hydroxymethyl cytosine (the first step in DNA-demethylation) and mature collagen IV levels between wildtype and mutant IDH1 transgenic fish. We also performed microinjections on fertilized eggs to screen for early developmental effects of IDH1R132H and IDH1R132C. Despite of the high expression of the transgene, no developmental effects were found. Our observations therefore suggest that elevated levels of D2HG are insufficient to initiate tumorigenesis or other phenotypic effects in our fish. Treatment of the transgenic zebrafish with an IDH1 mutant inhibitor, AGI-5198, resulted in a reduction in the D2HG level in the mutant zebrafish. The L2HG level was not affected by AGI-5198. As no tumors were formed in our transgenic zebrafish lines, we backcrossed them with Tp53 mutant fish. Analysis of these lines is currently being performed.

In summary, we have generated a transgenic zebrafish model system that expresses mutated IDH1 that can be used to study effects of mutant IDH1 (or elevated levels of D2HG) in vivo and can be used for drug screening.

Citation Format: Ya D. Gao, Maurice de Wit, Eduard A. Struys, Martine L.M. Lamfers, Gajja S. Salomons, Peter A.E. Sillevis Smitt, Pim J. French. A transgenic zebrafish model for gliomas with mutations in isocitrate dehydrogenase 1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4170.