ABSTRACT Armored mud balls similar to ones previously studied on marine and lacustrine shorelines are now forming on Sapelo and Cabretta Islands, Georgia. This report constitutes the first study of armored-mud-ball formation in a harrier-island environment. Small, 0.3-1.5-m-high sea cliffs of Pleistocene marsh deposits in the lower foreshore erode to form the mud-ball cores. During transport to the upper foreshore, beach sediment partially armors the surface of the mud cores. Predominance of sand-size armor and rootbound cores set these samples apart from earlier studies. Intermittent rolling in the swash zone on the gently sloping beach flattens the core and concentrates armor on opposing sides. No evenly armored, very highly spherical mud halls, common to fluvial environments, were found in his study area. Because several armored mud balls were found buried in sand on the backshore, it is likely that some will be preserved. Such lithified, armored mud balls may be especially useful in determining seaward facies of ancient barrier-island deposits.


Cross-disciplinary i?½happiness researchi?½ has made big progress in the measurement of individual welfare. This development makes it tempting to pursue the old dream of maximizing aggregate happiness as a social welfare function. However, we postulate that the appropriate approach is not to maximize aggregate happiness in seeking to improve outcomes by direct policy interventions. The goal of happiness research should rather be to improve the nature of the processes through which individuals can express their preferences. Individuals should become better able to advance their idea of the good life, both individually and collectively.


This chapter introduces some key concepts: what international regimes are; how to measure their effectiveness (the dependent variable); how this can be explained (independent variable); and the severe methodological challenges associated with answering these questions. Two main explanatory perspectives are introduced: the nature of the problem dealt with by the regime and its problem-solving ability. The chapter then surveys some key general findings that have emerged from the study of the effectiveness of international environmental regimes. Perhaps the most important finding is that although most international regimes that have been studied have had some effect on the problems they address, they have very rarely been able—if at all—to solve them fully. Another important observation is the sizeable variation among regimes in their problem-solving ability. The chapter presents empirical examples to illustrate how effectiveness can be measured and explained in practice. Most attention is given to the global climate regime, given its prominence on the international agenda. Viewed from a problem-solving perspective, however, the climate regime emerges as a low-effectiveness regime. This is briefly contrasted with the highly successful international ozone regime, as well as a regime that is very hard to measure in terms of effectiveness due to the deep and divisive conflicts over values, namely, the international whaling regime.


To fhe Editor-There is a growing consensus among clinicians and researchers that Alzheimer's disease is a complex phenomenon and probably does not represent a single clinical entity. Rather, the syndrome represents multiple disease processes, the precise nature of which remain to be defined. The unknown causes may include infectious mechanisms, genetic influences, and environmental causes. This case report involves a husband and wife who presented for comprehensive assessment of dementing disease in January 1985. Both were age 75 and had been experiencing symptoms of progressive cognitive impairment for 4 years. Records of their primary-care physician corroborate the impression of the family that they had functioned normally until that time. Additional shared history includes an episode in late spring of 1980 of severe diarrhea, nausea, and vomiting that lasted 7 to 10 days, approximately 12 months before the onset of memory loss. Evaluation of well water at that time revealed contamination with coliforms. The well is shallow (approximately 20 feet), taken from surface aquifers draining corn fields. At the time of initial assessment their degree of cognitive impairment was moderate and both scored in the mid-teens on the Folstein Mini-Mental State Examination. The following 11 months were characterized by rapid deterioration of cognition and function. The family decided at this point to institutionalize them. They remained there until they died 14 months later, within 7 days of each other. Autopsy revealed changes in both brains compatible with the diagnosis of Alzheimer's disease. In addition, both had congophilic angiopathy and the husband had a healed microinfard in the right lateral parietal cortex. The clinical course of these cases raises many questions. The statistical probability of husband and wife simultaneously becoming ill with Alzheimer's disease is remote. The possibility of a common causal mechanism is only conjecture but does pique one's curiosity. Were there substances other than bacteria in the well water? A growing body of literature implicates casual exposure to organophosphate compounds with Parkinson's and Alzheimer's diseases,',Z an interesting supposition that is impossible to c o n k after the fact.


Therapies that lower blood pressure or lipid levels slow the progression of atherosclerosis, and reduce morbidity and mortality in patients with hypertension or atherosclerotic disease. A combination tablet containing both amlodipine besylate and atorvastatin calcium has recently been approved for the treatment of hypertension and dyslipidemia in a growing number of countries. We decided to undertake a thorough literature search to evaluate the effects of amlodipine and atorvastatin in hypertensive hypercholesterolemic patients on blood pressure values, lipid profile values and, when available, data on small- and large-artery compliance, left ventricular mass index, and inflammatory parameters. From the data collected, it emerged that in hypertensive and hypercholesterolemic patients, the combination of amlodipine plus atorvastatin is more effective than the single drugs alone in reducing blood pressure and in improving lipid profile. Furthermore the combination of amlodipine plus atorvastatin also improved small-artery compliance, inflammatory markers, left ventricular hypertrophy and reduced uric acid faster and more effectively than the single drugs taken alone. For these reasons, the combination of amlodipine plus atorvastatin could be the treatment of choice in hypertensive and hypercholesterolemic patients.


While networks between research, industry and the public sector are regarded as prerequisites for innovation and regional development, establishing these structures is not trivial and their success is far from given. To deepen our knowledge of these networks, a dynamic model describing the coordinating functions and their drivers within such constellations is presented and empirically examined by means of an explorative case study. The model illustrates the challenges of cooperation in cross-sector constellations, which stem from different logics and expectations, and how different actors' degree of commitment varies over time. In successful cross-sector collaboration, actors fulfil different functions during different phases, and leadership shifts over time. A greater understanding of these dynamics can enhance public policy initiatives aimed at sustaining cooperation for innovation and regional growth.


The patterns that appear in exchanges between researchers, scientific journal publications and the demand for scientific articles often intersect, but the logic behind each type of activity is not necessarily the same. Analyses of requests for scientific articles from document suppliers may help to interpret current developments in electronic publishing. This study of article requests to the Institut de l'information scientifique et technique (INIST) shows that, in France, document supply customers fall into three main categories : business, academic libraries and public research organisations, in descending order. Demand focuses mainly on medicine, pharmacology, biology and chemistry, and the distribution of articles is entirely in accordance with the laws of bibliometrics. A further comparative analysis shows a high reciprocal correlation (except in the physical sciences) between the 50 journals most frequently requested from INIST, and the 50 most frequently cited journals according to ISI (Institute for Scientific Information). The titles which did not appear in either one list or the other show that the most frequently cited physics journals are not necessarily requested from the document supplier, and that, conversely, some frequently requested journals are not often cited. It may therefore be assumed that a trade in electronic articles is likely to develop quite rapidly in disciplines which are common to both lists, although this would focus on reputed titles only, but that a different pattern of electronic document exchange would emerge for scientific literature in other disciplines.


A new linear sparse array based on the nested array is proposed, which enjoys all the good properties of the two-level nested array, and can provide more degrees of freedom (DOF). The new array is constructed by two uniform linear arrays (ULAs) and an additional sensor. The sensor locations, the array aperture, and the achievable DOF from its difference co-array (DCA) are all benefited for closed-form expressions. Furthermore, the resulting DCA is kept as a hole-free ULA. The optimal numbers of sensors in the two ULAs provided the total number of physical sensors are derived. This new array can resolve more sources and achieve better angle estimation performance than the two-level nested array. Simulation results validate these conclusions.


Sharing knowledge is one of important elements in academic libraries. The activity uses ICT to inform one another. Most academic libraries in Indonesia, supporting infrastructures and reward are the main factor to conduct the activity. The implementation of such activity, especially in academic libraries, has resulted some beneficial both for librarians and its users. Motivation is considered as one of important aspects in sharing knowledge. By having supporting facilities or infrastructures, the activity can run smoothly and properly .


We investigated preliminarily whether methylenetetrahydrofolate reductase (MTHFR) 677C/T or reduced folate carrier 1 (RFC1) 80G/A polymorphisms were associated with toxicities during maintenance chemotherapy with mercaptopurine (6MP) and methotrexate (MTX) in children with acute lymphoblastic leukemia or lymphoblastic lymphoma. The clinical records of 20 children (2 to 15-y old) who had received maintenance chemotherapy were reviewed retrospectively and their genomic DNA was genotyped to identify polymorphisms at MTHFR 677C/T, RFC1 80G/A, and thiopurine methyltransferase 719A/G. Maintenance chemotherapy with 6MP and MTX was repeated on a weekly basis, and any week during which 6MP and/or MTX dosing was withheld was counted as an interrupted episode. Associations between the risk of interruptions and polymorphisms were studied using a generalized estimating equation analysis. Patients with an increasing number of T alleles at MTHFR 677C/T experienced interruptions in both 6MP (P<0.01) and MTX (P=0.03) more frequently. Patients with an increasing number of A alleles at RFC1 80G/A experienced interruptions in 6MP (P=0.04) more frequently. This preliminary study does not prove but suggests that MTHFR 677C/T and RFC1 80G/A polymorphisms may serve as predictors of toxicity during maintenance chemotherapy.


In the recent past, innovation and technological activities have been recognized as
major sources of economic growth and have been prioritizing with a greater
attention in academia and public policy. The advantage of innovation has become a
critical ingredient in achieving the higher growth rates (Solow, 1956; Romer, 1994;
and Aghion and Howittt, 1998). Innovation is a buzz word in Indian context, and
national innovation council of India has declared 2010-2020 as the roadmap to
decade of innovations. Make in India program was launched by the Government of
India to further emphasize on the importance of innovation, particularly for
manufacturing sector in India. In this backdrop, this thesis has made an attempt to
examine the following objectives. First, this study examines the linkage between
innovation and total factor productivity growth, both for aggregate economy and
manufacturing firms. Second, the key determinants that affect the innovation in
manufacturing sector are identified. Lastly, this study examines the major obstacles
for pursuing innovation activities in manufacturing firms.
To examine these objectives, this thesis collected the data from both primary and
secondary sources. For macro level analysis, the annual data of India is collected
from the World Development Indicators (WDI) and for micro analysis, apart from
the primary survey (from Bengaluru and Hyderabad), the PROWESS data base, ASI
and annual reports and publications of the companies included in the sample are
used.
The first objective of the thesis intended to examine the effects of innovation at both
macro and micro levels on the TFP growth of India. First, at the macro level ARDL
bound testing co-integration approach was used, wherein the results indicated a cointegrating relationship between innovation (such as patents, scientific journal
articles, trade mark applications and the share of high technology exports of
manufacturing sector) and TFP growth. The estimated results indicate a
cointegrating relationship between innovation and TFP growth; but the openness has
a detrimental effect on the TFP growth, which is largely generating from the excess
import activities. Further, coefficients of long-run elasticities show that the rise in
overall innovation activities improves the TFP growth, which also holds true in the
short run along with human capital variable. Also, the results are consistent and
stable that stood against several diagnostic tests. In the next level, this thesis
explored the same research question by focusing on the relationship between
innovation and growth at firm level productivity by taking a closer look at different
types of innovations (product, process, marketing and organizational innovations) in
case of Indian manufacturing sector. The empirical results based on random effect
model found that the productivity of firms involved in innovation is more as
compared to non-innovative firms. Finally, we examined the effects of various types
of innovation on TFP growth, and found that the process and marketing innovations
are the significant facilitators of the TFP growth of Indian manufacturing sector.
The Second objective of the study explores the factors that determine the innovation
activities in Indian manufacturing firms. After applying the panel probit models, it
was revealed that the exports and R&D expenditure have a positive and significant
effect on determining the innovation in case of manufacturing sector. Other key
factors such as import intensity, manager's prior experience, and conducting training
sessions for the employees at firm level have a positive impact on the innovation
activities. However, firm age and capital intensity affect negatively to innovation.
To check the robustness of our results, this study further examined the determinants
of innovation by considering capital intensive firms and found similar results. The
findings of our results suggest that the policymakers need to concentrate more on
export orientation policies and invest in R&D through subsidizing or create more
R&D incentive projects, which would significantly boost innovations in India.
Further, by using the same firm level data, the study carried out the primary analysis
on the factors that actually slowed down or hampered innovations in Indian firms.
The survey revealed that the factors such as uncertain outcomes from the future
innovations, cost of innovation (R&D expenditure), lack of qualified labor, and lack
of appropriate source of finance were largely noticed while attempting innovations.
Based on different models, we treated obstacles to innovation as dependent variables
(considered major three obstacles and run three separate probit equations). In all the
models, it is observed that the negative sign of the marginal effects suggests that
export oriented firms are more likely to reduce the obstacles as compared to nonexport oriented firms by around 2%. This implies that such export oriented firms
might be able to generate high profits or would gain other beneficial effects from
international markets. In contrary to this, the import oriented firms suggests that
these firms are likely to face more obstacles than that of non-import oriented firms.
However, the firm age and size of the firm are not significant, but export and import
variables have some effect on influencing the factors that negatively effects
innovation activities in Indian firms.
The overall findings of the study is a wakeup call for the policy makers to not only
plan for investing in R&D projects but also provide avenue to manufacturing firms
for accessing finance. Apart from the R&D constraints and lack of skilled labor, we
must not ignore the role of government/ academic institutions for directly helping
the manufacturing firms, particularly medium and small firms, by providing them
with support. The present study suggest the policymakers to concentrate more on
export orientation policies and invest in R&D through subsidizing or creating more
R&D incentive projects, which would significantly boost innovations in India.


Young children's writing activity in English Reception classrooms is framed by a rigid developmental model whereby children are conceived of as 'becoming' writers. However, recent postSstructuralist research suggests that writing activity, as an assemblage of objects, bodies, expressions and territories, involves constant change rather than being fixed to particular frameworks.

This ethnographic enquiry focussed on six children in one Reception class during one school year. Deleuzoguattarian ideas were 'plugged into' a sociocultural, multimodal understanding of young children's writing and the children were reSconceptualised as 'becoming': creating and disrupting multiple connections and relations through their actions as writers and research participants. Narrative observations, field notes, photographs, video and artefacts were analysed rhizomatically and vignettes of data were formed into discursive assemblages.

The findings indicate that children's writing within openSended play in the classroom was a moving, overlapping and connective ensemble, utilising many different modes of expression (drawing, text making, map making, copying, etc.). The writing materials used in these encounters 'mattered' to children: their sensorial qualities, the histories associated with them, and the potential they had to be adapted. Writing activity, however, was often organised by adults into regular discreet phonics sessions where the children's opportunities for material intraSaction, social interaction and links to other writing experiences, were limited. Alongside this, discourses surrounding writing in the classroom were reflective of the curriculum 'ideal', and certain modes of expression were privileged.

The conclusions suggest that containing young children's writing within representative acts driven by external outcomes limits the potential of writing to be a sensory, embodied, material, and connected activity. Adults in schools should foster children's playful writing encounters where these elements exist. Effective practices are needed to encourage young children's multiple modes of expression, enabling them to build the language associations needed for their writing to be meaningful and desirous.


Aptamer biosensors have been immobilized on beads, introduced into micromachined chips on the electronic tongue sensor array, and used for the detection and quantitation of proteins. Aptamer chips could detect proteins in both capture and sandwich assay formats. Unlike most protein-based arrays, the aptamer chips could be stripped and reused multiple times. The aptamer chips proved to be useful for screening aptamers from in vitro selection experiments and for sensitively quantitating the biothreat agent ricin.


Studying inter-individual variation in foraging by top predators is key for understanding the ecology of their populations, while knowledge of seasonal variability in foraging helps explain temporal changes in habitat use and ecological role. We investigated the inter-individual and seasonal differences in stable isotope ratios of sperm whales Physeter macrocephalus in the temperate foraging ground of the Kaikóura Canyon, New Zealand. Isotope ratios of carbon and nitrogen were measured in 107 samples of sloughed skin from 37 individual males with a wide range of residency patterns and body lengths, sampled over 4 summers and 3 winters. Variability in individual isotope ratios was analysed with generalised additive mixed models. The whales' residency patterns, but not body size, accounted for most heterogeneity of δ13C and δ15N. Specifically, whales that visited Kaikóura occasionally had more diverse and lower isotope ratios than more frequent visitors (by ca. -1‰ δ13C and -2‰ δ15N), likely reflecting a range of foraging habitats further offshore and/or south of Kaikóura Canyon. We suggest that these patterns reflect differences in large-scale foraging patterns within the population. In addition, whales sampled in winter had significantly lower values of δ13C than whales sampled in summer (by ca. -0.5‰), indicating seasonal differences in the use of food resources. Our results provide new insights into foraging patterns of sperm whales, and highlight the value of accounting for individual differences in the ecology of top predators.


Link-slabs made of Ultra-High Performance Concrete (UHPC) connecting individual spans in a bridge can be used to eliminate joints. Due to the deck continuity, the distribution of forces and displacements at the supports is different than the distribution from a structural system composed of multiple single spans. This is of importance in rehabilitation or retrofit projects, where many times the original structural system consists of multiple single spans with a line of expansion bearings or a line of fixed bearings at each end of the spans. The NY State Department of Transportation is using UHPC link-slabs as a way of eliminating joints in several rehabilitation and maintenance projects. Methods to evaluate and distribute lateral loads to the substructure, like those created by temperature, wind, braking, and seismic effects, have been developed. This presentation will address the challenges in global design of UHPC link-slab systems due to combining multiple spans into a contiguous superstructure system. Computational methods, code compliance issues, and methods of dealing with insufficient structural capacity of existing substructures when that problem arises will be covered.


The interest for higher quality in higher education targets and respects the ethical standards of writing and presenting academic papers by both teachers and students. In the context of public discussions over copyright over the last few years and a self-plagiarism, universities in Romania have made efforts to align with the standards of European universities for knowledge and enforcement in this area. Thus, specific procedures and work platforms have been created and developed (eg the webstudentase.ro platform, the use of the Semplag program at the University of Pite?ti, accessing www.sistemantiplagiat.ro at the "Carol Davila" University of Medicine and Pharmacy in Bucharest).
 Although in the last years, in the course of seminars, laboratories, practical activities and courses on academic writing norms, according to the legal provisions in force, a study among the students of the Faculty of Psychology and Education Sciences reveals the insufficient understanding of the meaning of the term plagiarism, the incomplete knowledge of the modalities the plagiarism, the self-plagiarism, the possibilities of avoidance, as well as the sanctions for violation of the legislation. The study also shows a knowledge and use of plagiarism detection programs for a small number of surveyed students.
 Familiarizing with academic writing rules, author citation, use of translators in other languages for each first year of study, attention to compliance with these standards throughout the course of all faculty work, constant application of ethical rules to prevent plagiarism can prevent the risk of non-compliance with academic standards and the improvement of business activities in universities.


In this paper, a two-stage scheme for the recognition of Persian handwritten isolated characters is proposed. In the first stage, similar shaped characters are categorized into groups and as a result, 8 groups are obtained from 32 Persian basic characters. In the second stage, the groups containing more than one similar shape characters are considered further for the final recognition. Feature extraction is based on under sampled bitmaps technique and modified chain-code direction frequencies. For the first stage features, we compute 49-dimension features based on under sampled bitmaps from 49 non-overlapping 7×7 window-maps. 196-dimension chain-code direction frequencies from 49 overlapping 9×9 window-maps are computed and used as features for the second stage of the proposed scheme. Classifiers are one-against-other support vector machines (SVM). We evaluated our scheme on a standard dataset of Persian handwritten characters. Using 36682 samples for training, we tested our scheme on other 15338 samples and obtained 98.10% and 96.68% correct recognition rates when considered 8-class and 32-class problems, respectively.


The Science of Proof traces the rise of forensic medicine in late eighteenth- and nineteenth-century France and examines its implications for our understanding of expert authority. Tying real life cases to broader debates, the book analyzes how new forms of medical and scientific knowledge, many of which were pioneered in France, were contested, but ultimately accepted, and applied to legal problems and the administration of justice. The growing authority of medical experts in the French legal arena was nonetheless subject to sharp criticism and scepticism. The professional development of medicolegal expertise and its influence in criminal courts sparked debates about the extent to which it could reveal truth, furnish legal proof, and serve justice. Drawing on a wide base of archival and printed sources, Claire Cage reveals tensions between uncertainty about the reliability of forensic evidence and a new confidence in the power of scientific inquiry to establish guilt, innocence, and legal responsibility.


BACKGROUND
Atopic dermatitis (AD) is an early and important step in the propagation of the allergic march, enhancing food and respiratory allergies via epicutaneous sensitisation to allergens.

OBJECTIVES
To determine the prevalence and patterns of aeroallergen sensitisation, asthma and allergic rhinitis in South African (SA) children with AD.

METHODS
This was a prospective, observational study in a paediatric university hospital in Cape Town, SA. Children with moderate to severe AD, aged 6 months - 10 years, were recruited randomly and investigated for food sensitisation and allergy. They were assessed for sensitisation to aeroallergens by the immuno solid-phase allergen chip test. House-dust mite DerP and DerF, dust mite Eur m, Timothy grass, Bermuda grass, tree pollen, mould (Alternaria), cat and dog sensitisation patterns were analysed. Symptoms of asthma and allergic rhinitis were elicited using a questionnaire modified from the International Study of Asthma and Allergies in Childhood study questions.

RESULTS
One hundred participants (59 black Africans and 41 of mixed ethnicity) were enrolled (median age 42 months). Of the participants, 39% had symptoms of asthma and 53% symptoms of allergic rhinitis; 89% tested positive to at least one aeroallergen, most commonly house-dust mite DerP or DerF (81%), dust mite Eur m (51%), Timothy grass (36%) and cat (35%). Asthma, allergic rhinitis and aeroallergen sensitisation all increased with increasing age, while food allergy decreased with age. Food allergy was not an independent risk factor for respiratory allergies. Children were sensitised to indoor allergens (house-dust mite, pets) from an early age, while pollen allergies increased with age.

CONCLUSIONS
In this cohort of SA children with moderate to severe AD, comorbidity with respiratory allergies was high. The prevalence of respiratory allergies increased with age while food allergy decreased with age, in keeping with the pattern of the allergic march. Seasonal allergies increased with age, while house-dust mite and pet allergy peaked in younger children, in keeping with early exposure via a defective skin barrier. Early and effective restoration of the skin barrier in AD may be a target for reducing aeroallergen-related diseases.


Background: There is a dearth of research focusing on identifying the social complexities impacting on oncology and palliative care (PC), and no study has explored how the health-care system in Nigeria or other African contexts may be influencing utilization of these services. Aim: This study explored how social complexities and the organization of health-care influenced the decision-making process for the utilization of oncology and PC in a Nigerian hospital. Methods: This qualitative study used an interpretive descriptive design. Data were collected using semistructured interview guides with 40 participants, comprising health-care professionals, patients, and their families. Thematic analysis was conducted to generate and analyze patterns within the data. Findings: Three themes were identified: dysfunctional structural organization of the health-care delivery system, service-users' economic status, and the influence of social networks. The interrelationship between the themes result in patients and their family members decisions either to present late to the hospital, miss their clinical appointments, or not to seek oncological health care and PC. Conclusion: This article offers insights into the role of the health-care system, as organized currently in Nigeria, as "autoinhibitory" and not adequately prepared to address the increasing burden of cancer. We therefore argue that there is a need to restructure the Nigerian health-care system to better meet the needs of patients with cancer and their families as failure to do so will strengthen the existing inequalities, discourage usage, and increase mortality.


This paper presents research work relating to design method and mechanical properties of functionally-graded composite (FGC) beams, in which a kind of strain hardening material UHTCC is used as a replacement for the concrete material that surrounds the longitudinal reinforcements. According to mechanical models of materials and a series of assumptions, a simplified design method of such FGC beams is proposed. On the basis of superposition, the determination and the influencing factors of the thickness of UHTCC layer in FGC beams is discussed. Compared with theoretical and experimental results, simplified method shows conservation and guarantees the safety of structures. During the whole flexural loading process, it is found that the opening of cracks in flexural members can be greatly restricted by the introduction of UHTCC. The possibility of steel corrosion therefore can be evidently reduced.


Neuropeptide Y (NPY), a 36 amino‐acid peptide found within the hypothalamus, is thought to be an important regulator of food intake. Hypothalamic NPY gene expression, synthesis and secretion are all known to be increased in models of increased metabolic demand in which serum glucocorticoids are also elevated. The present studies were designed to test the hypothesis that glucocorticoids are required for increased hypothalamic preproNPY mRNA levels induced by food deprivation (FD). First, animals underwent bilateral sham‐adrenalectomy (sham) or not (control), and were subjected to 72 h FD, or not. Total RNA was isolated from hypothalamic tissue blocks and the content of preproNPY mRNA was measured by solution hybridization/RNase protection analysis. This study revealed that there was no significant difference in hypothalamic preproNPY mRNA content between shamfed and control‐fed groups, or between sham‐FD and control‐FD groups. In the second experiment, animals underwent bilateral adrenalectomy (ADX), were allowed to feed ad libitum and were sacrificed 1 day, 4 days and 7 days after ADX. Nuclease protection analysis revealed no significant effect of ADX on hypothalamic preproNPY mRNA levels over this time‐course. Finally, we examined the role of glucocorticoids in regulating NPY gene expression following FD. Animals underwent bilateral ADX, or not. At the time of surgery, ADX animals received placebo, or corticosterone (B) replacement in the form of constant release pellets, at one of two doses. Food was removed from half of the animals in each group 24 h after surgery; all animals were sacrificed 72 h thereafter. There was no difference in preproNPY mRNA content between the ADX‐FD and ADX‐fed groups, relative to the fed controls. Replacement with corticosterone [ADX(B)] did not alter preproNPY mRNA content in fed animals, however preproNPY mRNA content in FD animals was increased 2.5‐fold. These studies demonstrate that glucocorticoids are necessary and serve a stimulatory role in the increase in hypothalamic preproNPY mRNA levels observed under conditions of FD, and suggest that hypothalamic NPY gene expression may be directly responsive to peripheral metabolic and hormonal signals.


To enhance the ability and reliability of product variant design, an object-oriented framework was constructed using an extensible module/product class for setting up a modular design model. A module/product in a class was identified as an object by encapsulating the involved information as properties and the transforming or interaction activities as operations. This extensible object was gradually optimized through communications with other objects and integrations of design knowledge in five domains. These include Customer, Functional, Physical, Process and Engineering, which is a new domain introduced in this paper. The programmatic framework was implemented and successfully demonstrated using some typical machine tool products.


Peer behaviors may significantly influence personal behavior yet individuals may not accurately estimate their peers' actions. Overestimations of peer substance use may encourage initiation or exacerbate extant problems. The present study examines misperceptions of peer pharmaceutical misuse and explores the relationship between reported misuse and perceptions of misuse for four categories of prescription drugs. Data collected from 2,349 college students in the Southeastern United States were analyzed and results indicated that overall perceptions of misuse were significantly higher than actual misuse. These findings suggest that intervention efforts may benefit from addressing misperceptions of pharmaceutical misuse. Study limitations and implications are addressed.


Snore related signals (SRS) have been found to carry important information about the snore source and obstruction site in the upper airway of an Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS) patient. An overnight audio recording of an individual subject is the preliminary and essential material for further study and diagnosis. Automatic detection, segmentation and classification of SRS from overnight audio recordings are significant in establishing a personal health database and in researching the area on a large scale. In this study, the authors focused on how to implement this intelligent method by combining acoustic signal processing with machine learning techniques. The authors proposed a systematic solution includes SRS events detection, classifier training, automatic segmentation and classification. An overnight audio recording of a severe OSAHS patient is taken as an example to demonstrate the feasibility of their method. Both the experimental data testing and subjective testing of 25 volunteers (17 males and 8 females) demonstrated that their method could be effective in automatic detection, segmentation and classification of the SRS from original audio recordings.


In the middle of the 13th century the Crown of Aragon conquered by military means the Muslim Mediterranean Coast of the Iberian Peninsula, incorporating it into the European feudal world; this resulted in the destruction of the Andalusi
state and part of its society as well as in a redistribution of towns, villages, houses and lands among Christians. The historiography of some years ago emphasized the role of trade and urban burgesses in these new societies, but present opinion is more related to a long expansion of feudal society as well as the creation in Majorca and Valencia of a colonial society. Logically, the consequences of this process had also an effect in Catalonia and Aragon where the movement had its origins, and its effects can be verified on the re-settlers' migrations, the changes in agrarian structures due to the redistribution, the expansion of commercial towns, and the political changes that resulted from the participation of the urban patrician class in the new power structures: townships and parliaments.


We show here that VHF signals scattered from the 150 km region above Jicamaca exhibit two distinct types of features. In one type (type A), the Doppler spectral width increases with the echo strength and the corresponding signal‐to‐noise ratio (SNR). A second type (type B) of higher SNR echoes exhibits SNR‐independent Doppler spectral widths that are much narrower than those observed in the first type. The type A echo population is by far the dominant population. Comparisons with earlier data sets collected at Jicamarca and elsewhere suggest that the type A and type B are likely to be associated with a naturally enhanced incoherent scattering (NEIS) process and the unstable growth of field‐aligned irregularities (FAIs), respectively. We conjecture that small radar systems operated near the geomagnetic equator that have reported 150 km echo observations detected FAI echoes and that the NEIS echoes can only be seen by high sensitivity systems.


Abstract Nanoscale titanium dioxide (nanoTiO2) is a commercially important nanomaterial. Animal studies have documented lung injury and inflammation, oxidative stress, cytotoxicity and genotoxicity. Yet, human health data are scarce and quantitative risk assessments and biomonitoring of exposure are lacking. NanoTiO2 is classified by IARC as a group 2B, possible human carcinogen. In our earlier studies we documented an increase in markers of inflammation, as well as DNA and protein oxidative damage, in exhaled breath condensate (EBC) of workers exposed nanoTiO2. This study focuses on biomarkers of lipid oxidation. Several established lipid oxidative markers (malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxy-trans-nonenal, 8-isoProstaglandin F2α and aldehydes C6–C12) were studied in EBC and urine of 34 workers and 45 comparable controls. The median particle number concentration in the production line ranged from 1.98 × 104 to 2.32 × 104 particles/cm3 with ∼80% of the particles <100 nm in diameter. Mass concentration varied between 0.40 and 0.65 mg/m3. All 11 markers of lipid oxidation were elevated in production workers relative to the controls (p < 0.001). A significant dose-dependent association was found between exposure to TiO2 and markers of lipid oxidation in the EBC. These markers were not elevated in the urine samples. Lipid oxidation in the EBC of workers exposed to (nano)TiO2 complements our earlier findings on DNA and protein damage. These results are consistent with the oxidative stress hypothesis and suggest lung injury at the molecular level. Further studies should focus on clinical markers of potential disease progression. EBC has reemerged as a sensitive technique for noninvasive monitoring of workers exposed to engineered nanoparticles.


Nowadays, social networks become popular with the emerging of web-based social networking services. Recently, several mobile services are developed to connect users to their favourite social networks such as Facebook, Twitter, Flickr, etc. However, these services depends upon the existing web-based social networks. In this paper, we present a mobile service for joining groups across communities. The originality of the work is that the framework of the service allows creating and joining social networks that are self-contained for mobile company servers. The service consists of several sub-services such as users invitation, group finding and others. Users, regardless of their disability, can use the service and its sub-services without the need to create their own accounts on social web sites and thus their own groups. We also propose a privacy control policy for mobile social networks.


Purpose: The RetinOpTIC project performs mass screening of color fundus images and assesses image quality and Diabetic Retinopathy (DR) grade. Algorithm performance is evaluated on the Messidor-2 image database.

Methods: Based on artificial intelligence (AI) solutions, referable DR is detected using convolutional neural networks (CNNs). The solution includes first the automatic assessment of the quality of the photography, and then the DR grade


scientific theories (perhaps with a few exceptions such as string theory), which can be comprehended given enough (laborious) training. In addition, science is cumulative and increasingly collaborative, which means that the cognitive burden is being divided both synchronically and diachronically between humans and recently with machines, which have taken up an enormous part of that burden. Although this does not make science any more intuitive, it does make it more secure. McCauley's book is about the cognitive foundations of religion and science. It is the most precise and comprehensive exposition that I have come across on both accounts. The author chose to see these accounts from one possible perspective; in this commentary, I chose another. The two are not mutually exclusive, but the choice of perspective does influence the overall implications, and I have chosen to present a more optimistic conclusion. In my view, science is more secure than it has ever been and its position will only become stronger. While the cognitive proclivities for scientific thought are just as strong as those for religious thought, institutionalized science today plays a more central role in global economy and politics than institutionalized religion. Furthermore, science is growing exponentially; religion is not growing at all*religiosity has been and still is ubiquitous, although institutionalized religion with all its might has never been less influential on the global sociopolitical arena. Science has*more than anything else*immense direct impact on the quality of our lives and increasingly on our very existence. Although McCauley's claim that ''nothing about human nature would ever prevent the loss of science again'' (p. 286) is logically sound, I am convinced that science will only go away, along with religion, with the end of


This article presents the results of the seismological evaluation of the first 18 months (January 1995 to June 1996) of the Group of Scientific Experts third Technical Test (GSETT-3). Performance measures such as completeness, estimates of detection thresholds, and equivalent circle areas as an estimate of location accuracies are obtained by comparing the REB (Reviewed Event Bulletin) of GSETT-3 to global and regional reference bulletins, and also by intrinsic methods. Incremental detection thresholds are stated on the PDE (Preliminary Determination of Epicenter) m b scale: magnitude conversion formulae are derived to convert REB m b and other reference bulletin magnitudes to this scale. At the 90% confidence level, an incremental detection threshold of about m b (PDE) 3.5 or better is attained in northwest Europe and parts of North America, Central Asia, and Australia. Apart from these areas, the threshold is generally around 4.0 in the Northern Hemisphere. In the Southern Hemisphere it is 4.2 or better in most of South America and northern and equatorial Africa, and between 4.2 and 4.6 in other regions with the highest values being attained in some remote parts of the southern oceans. Still at the 90% confidence level, equivalent circle areas for the m b (PDE) 4–4.5 magnitude range come close to 1,000 km 2 in northern Europe. The global average is about 8,000 km 2 . At the 50% level (the median of all detected events), most northern hemisphere regions have equivalent circle areas at or below 1,000 km 2 , and even in the southern hemisphere 5,000 km 2 are not exceeded. Observed performance is used to calibrate network simulation codes, which allow to interpolate system capabilities over aseismic regions and to extrapolate for the capabilities of the future International Monitoring System (IMS) seismic network. It is concluded that at the 90% confidence level, except in remote ocean areas, a global incremental detection threshold of m b (PDE) 4 and a location accuracy of the order of 1,000 km 2 are attainable with the IMS seismic network. However this will require a full calibration of the network and an optimized usage of the auxiliary station network. New computational methods as well as calibration will help to improve the depth determination.


12-O-Tetradecanoylphorbol-13-acetate (TPA) and 4 beta-phorbol 12, 13-dibutyrate (PDBU) are potent tumor promoters and share several biological activities of epidermal growth factor (EGF). We have shown previously that EGF stimulates DNA synthesis and proliferation and inhibits TSH-induced markers of differentiation in dog thyroid follicle-derived primary cultures. Using this system, we have examined the biological action of TPA and PDBU in reference to that of EGF. Low concentrations (1.6-16 nM) and to a lesser extent higher concentrations (greater than 1.6 microM) of TPA and PDBU stimulated cell proliferation in a 1% serum, hormone-supplemented medium and triggered the DNA synthesis revealed by autoradiography in cells which were quiescent before stimulation in serum-free conditions. EGF, TSH, and dibutyryl cyclic adenosine 3':5'-monophosphate separately also induce DNA synthesis, but they produce little if any effects additive to those of TPA. In fact, TPA appeared to inhibit the mitogenic effects of EGF. Moreover like EGF, phorbol esters strongly inhibited in 2 days the morphological effects of TSH and basal and TSH-stimulated iodide transport capacity and thyroglobulin messenger RNA accumulation, two markers of thyroid differentiation. TPA also inhibited the expression of differentiation stimulated by dibutyryl cyclic adenosine 3':5'-monophosphate indicating a post-cyclic adenosine 3':5'-monophosphate site of action. TPA and EGF shared long-term morphological effects such as the induction of an elongated fusiform shape, but not acute effects. The thyroid cells progressively and spontaneously escaped both the mitogenic and differentiation-inhibiting effects of TPA and PDBU, while, as shown previously, these parameters are stably modified by continuous culture with EGF. This suggests specific desensitization processes to phorbol esters. As evidence is accumulating that phorbol esters act at least partly by stimulating the calcium-activated, phospholipid-dependent protein kinase C, our results shed light on the possible key role of this kinase in carcinogenesis and in the normal control of proliferation and expression of differentiation in the thyroid gland. Additionally they suggest that complex interactions occur between the mechanisms of action of EGF and of phorbol esters in the thyroid cell.


Biomagnetic signals, mostly due to the electrical activity in the body, are very weak and they can only be detected by the most sensitive magnetometers, such as Superconducting Quantum Interference Devices (SQUIDs). We report here biomagnetic recordings with hybrid sensors based on Giant MagnetoResistance (GMR). We recorded magnetic signatures of the electric activity of the human heart (magnetocardiography) in healthy volunteers. The P-wave and QRS complex, known from the corresponding electric recordings, are clearly visible in the recordings after an averaging time of about 1 min. Multiple recordings at different locations over the chest yielded a dipolar magnetic field map and allowed localizing the underlying current sources. The sensitivity of the GMR-based sensors is now approaching that of SQUIDs and paves way for spin electronics devices for functional imaging of the body.


The abundance of proteins expressed in a particular environment are primary determinants of an organism's phenotypic and fitness properties. However, protein synthesis is costly and proteome size is limited; thus, the benefit of expressing proteins also comes with costs. In this thesis, I interrogate the evolutionary and regulatory trade-offs resulting from these proteome allocation constraints. Throughout the thesis I employ a genome-scale model of metabolism and protein synthesis for Escherichia coli, which can compute condition-specific proteome allocation requirements and limitations. First, I show that microbial growth rates are quantitatively determined by the expression of unused protein. Rather than supporting growth in the current environment, large fractions of the expressed proteome enable readiness for environmental change and stress. The expression of these different proteome segments is regulated by global transcription factors and results in fitness trade-offs. Second, I show that after selecting for growth through experimental evolution, several adaptive regulatory mutations increase fitness through proteome and energy resource re-allocation. These pleiotropic mutations in the RNA Polymerase systematically re-allocate the proteome towards growth and away from stress resistance, showing that fitness trade-offs are readily modulated by global regulators during evolution. Finally, I show that the diversity present in evolving populations is predictable and due to proteome allocation trade-offs. Rather than evolving to a unique optimum, a range of near-optimal proteomic and metabolic phenotypes is apparent when strains are independently evolved in the same environment. The diversity of alternative phenotypes reflects a rate-yield trade-off due to the varying protein cost of metabolic pathways in central carbon metabolism. Thus, proteome allocation constraints have a pervasive and predictable effect on bacterial ecology, regulation, and evolution.


The identification of women with their physical bodies is the root cause of their oppression in a patriarchal culture and society like India. Most often women are denied the rights to emotional, mental, psychological and physical spaces. The fact that the female body is constantly under pressure to conform and mould into prescribed social and cultural roles brings into question the spaces that need to be protected as well rights that need to be claimed so that women's bodily integrity is respected. This paper highlights the struggles and spaces that Indian women have negotiated in their quest for empowerment.


The aim of this paper is to discuss the nature and status of distance education in the age of globalization, i.e. how best it fits for the present educational scenario. In this connection, we will discuss how Blended Learning (hence after, BL) is one among the other learning strategies mostly helpful for the learners. Keeping this view in mind, this paper is divided into three sections. The first section aims to discuss the nature of distance education in the age of globalization. The second section devotes a discussion on why we need blended learning in ODL system and in which way it plays a vital role for maximizing the benefit of the learners, tutors, and the institutions. The third section explains the pros and cons of blended learning to evaluate how successfully it can be implemented in the ODL system. The paper concludes with an established view that blended learning is a globalized approach to the distance education.


Shadow IT coexists with mandated information systems. Developed and applied by nonIT domain experts, it is as a rule, but not exclusively, used for resolving nonroutine issues, for which mandated IS does not have appropriate functions. Shadow IT solutions are not supported or controlled by IT departments. The aim of the paper is to show to which extent shadow IT has been researched, as this area has not yet received the necessary attention from both academia and business. A systematic literature review was conducted in order to find the papers covering the topic of shadow IT. The following electronic databases were searched: Web of Science (Thomson Reuters), Scopus (Elsevier), and AIS Electronic Library (The Association for Information Systems (AIS)).  More than half of the analysed papers are case studies in one or more organizations. The papers were published mostly in scientific conferences and in scientific journals. Based on the literature review, the reasons for shadow IT occurrence, the possibility of its management, as well as its advantages and disadvantages are presented. The most important conclusions and views regarding shadow IT, according to the authors' opinion, are indicated at the end. The limitation of a systematic literature review is that only papers published in English are analysed. Besides identifying papers covering the shadow IT topics, the reasons for the emergence of shadow IT, the possibilities of its management and its advantages and disadvantages are systematized.


InGaN/GaN-based solar cells with vertical-conduction feature on silicon substrates were fabricated by wafer bonding technique. The vertical solar cells with a metal reflector sandwiched between the GaN-based epitaxial layers and the Si substrate could increase the effective thickness of the absorption layer. Given that the thermally resistive sapphire substrates were replaced by the Si substrate with high thermal conductivity, the solar cells did not show degradation in power conversion efficiency (PCE) even when the solar concentrations were increased to 300 suns. The open circuit voltage increased from 1.90 V to 2.15 V and the fill factor increased from 0.55 to 0.58 when the concentrations were increased from 1 sun to 300 suns. With the 300-sun illumination, the PCE was enhanced by approximately 33% compared with the 1-sun illumination.


Real-world decision problems often involve multiple competing objectives or a complex reward structure that violate Markov assumption. However, the existing research on sequential decision making under uncertainty primarily focused on Markov Decision Processes (MDPs) with scalar Markovian reward signals. My thesis considers settings where scalar Markovian rewards are not sufficient to produce desired behaviors. The first part of my thesis develops algorithms to optimize lexicographically ordered objectives. The second part considers autonomous agents which incorporate the perspective of their observer. As the perspective of the observer can depend on how the agents behaved so far, rewards in this setting can depend on histories (non-Markovian). In the final part of my thesis, I hope to characterize when rewards beyond scalar Markovian signals are needed from the decision theoretic perspective


To study the potentialities of CT in the diagnosis of recurrent cancer of the large bowel, 325 patients underwent various surgical interventions for colorectal carcinoma were examined. The surgery-CT study interval ranged from 2,5 months to 11 years. It was found that CT might detect various intra- and extraintestinal relapses and generalize a tumorous process. With this, the efficiency of CT is higher than that of other diagnostic tools in the detection of extraintestinal relapses and generalizing the tumorous process. To timely reveal a relapse the CT interval should exceed 4-5 months.


ARUZ is a large scale, massively parallel, FPGA-based reconfigurable computational system dedicated primarily to molecular analysis. This paper presents a methodology for ARUZ firmware development that simplifies the process, offers low-level optimization, and facilitates verification. According to this methodology, firstly an expanded, generic, all-in-one VHDL description of variable Processing Elements (PEs) is developed manually. GCC preprocessing is then used to extract only the desired target functionality. A dedicated software instantiates and connects PEs in form of a scalable network, divides it into subsets for chips and generates its HDL description. As a result, individual HDL-coded specification, optimized for certain analysis, is provided for the synthesis tool. Code reuse and automated generation of up to 81% of the code economizes the workload. Using well-optimized VHDL for core description rather than High Level Synthesis eliminates unnecessary overhead. The PE network can be scaled inversely proportional to PEs complexity, in order to efficiently utilize available resources. Moreover, downscaling the problem makes verification during HDL simulations and testing the prototype systems easier.


The report describes the activities and plans of the Climate Change Science Program (CCSP), which incorporates the U.S. Global Change Research Program established under the Global Change Research Act of 1990, and the Climate Change Research Initiative that was established by the President in 2001. CCSP coordinates and integrates scientific research on climate and global change supported by 13 participating departments and agencies of the U.S. Government. The document highlights recent advances and progress supported by CCSP-participating agencies in each of the program's research and observational elements, as called for in the Strategic Plan for the U.S. Climate Change Science Program released in July 2003, and later modified in the 2008 CCSP Revised Research Plan. The document also describes how observational and predictive capabilities are being improved and used to create tools to support decisionmaking at local, regional, and national scales to cope with environmental variability and change.


OBJECTIVES: Right ventricular failure after left ventricular assist device (LVAD) insertion is associated with significant mortality and morbidity. Mechanical support options include right ventricular assist devices, venoarterial extracorporeal membrane oxygenation (ECMO) and venopulmonary artery ECMO, the latter often involving central cannulation. We sought to evaluate the feasibility and early outcomes of a truly percutaneous venopulmonary artery (pVPA) ECMO strategy, with the potential advantage of bedside removal once weaned. METHODS: Data from a single tertiary centre were reviewed retrospectively from January 2014 to January 2019. During this time, 54 patients underwent LVAD insertion, with 19 requiring mechanical support for right ventricular failure. Among them, 10 patients received pVPA ECMO. Implantation of the pVPA ECMO was performed under transoesophageal echocardiography and fluoroscopy guidance, with an inflow cannula placed in the right atrium via the right femoral vein and an outflow cannula placed in the left pulmonary artery (PA) via the right internal jugular vein. RESULTS: Cannula insertion was 100% successful with no need for repositioning. Eight patients (80%) were able to be successfully weaned (at the bedside); 6 were discharged from the hospital and there were no cases of early sepsis, mediastinitis or thromboembolism. At follow-up, 5 patients had received transplants (50%), with 1 on LVAD support as destination therapy (10%). Survival was 60 ± 15% and 50 ± 16% at 6 and 12 months, respectively. CONCLUSIONS: pVPA ECMO is 100% technically feasible and is an efficient method for temporary right ventricular support after LVAD insertion with the advantage of simple bedside removal and avoidance of a PA graft remnant in the chest cavity.


We identify and characterize a gene cluster in El Tor Vibrio cholerae that encodes a cytotoxic activity for HEp-2 cells in vitro. This gene cluster contains four genes and is physically linked to the cholera toxin (CTX) element in the V. cholerae genome. We demonstrate by using insertional mutagenesis that this gene cluster is required for the cytotoxic activity. The toxin, RtxA, resembles members of the RTX (repeats in toxin) toxin family in that it contains a GD-rich repeated motif. Like other RTX toxins, its activity depends on an activator, RtxC, and an associated ABC transporter system, RtxB and RtxD. In V. cholerae strains of the classical biotype, a deletion within the gene cluster removes rtxC and eliminates cytotoxic activity. Other strains, including those of the current cholera pandemic, contain a functional gene cluster and display cytotoxic activity. Thus, the RTX gene cluster in El Tor O1 and O139 strains might have contributed significantly to their emergence. Furthermore, the RTX toxin of V. cholerae may be associated with residual adverse properties displayed by certain live, attenuated cholera vaccines.


Dr. A. H. Hickman writes: Dr J. L. Roberts (1976, this Journal 132,139–54) admits that he has not established the existence of the Ballachulish Syncline (Bailey 1934). Roberts accepts Bailey's stratigraphy, confirms the outcrop pattern and the D3 Stob Ban Synform but finds no evidence that the central outcrop of the Ballachulish Limestone Formation occupies the refolded inverted limb of a major recumbent fold. Bailey (1910) first postulated the Ballachulish Syncline to explain a vertical repetition of limestone, slate and schist which did not correspond to his concept of the area's stratigraphic succession. However, it is now known that the Ballachulish Limestone Formation contains thick intercalations of black slate and, less commonly, phyllite (Hickman 1975, p. 126) so that no structural repetition need be envisaged at Callert. Bailey's sections through the Ballachulish Syncline (e.g. Bailey & Maufe 1960, fig. 7) show that over large areas its core consists of a remarkably uniform thickness (about 100 m) of Ballachulish Limestone Formation underlain and overlain by Leven Schist Formation. From Glencoe to Coire Mhorair (2185 7585), Coire an Easain (2250 7495) and the 'Windows of Etive' the length: thickness ratio of this core is about 100:1. Bailey (Bailey & Maufe 1960, p. 83) suggests that the core may even extend farther SE to Beinn Doirean (but see Thomas & Treagus 1968) and NE to Kinlochlaggan. The writer considers that these various isolated outcrops of limestone are probably local intercalations within the Lochaber Group. Dr Roberts does not mention that to the


The Late Permian Shaiwa Group of the Ziyun area of Guizhou, South China is a deep-water facies succession characterized by deep-water assemblages of pelagic radiolarians, foraminifers, bivalves, ammonoids and brachiopods. Here we report 20 brachiopod species in 18 genera from the uppermost Shaiwa Group. This brachiopod fauna is latest Changhsingian in age and dominated by productides. The palaeoecologic and taphonomic analysis reveals that the brachiopod fauna is preserved in situ. The attachment modes and substratum preference demonstrate that the Shaiwa brachiopod fauna comprises admixed elements of deep-water and shallow-water assemblages. The presence of the shallow-water brachiopods in the Shaiwa faunas indicates the involuntary settlement of shallow-water brachiopods. The stressed ecologic pressure, triggered by warming surface waters, restricted ecospace and short food sources, may have forced some shallow-water elements to move to hospitable deep-water settings and others to modify their habiting behaviours and exploit new ecospace in deep-water environments. We infer that the end-Permian global warming and subsequent transgression event may have accounted for the stressed environmental pressure in the shallow-water communities prior to the end-Permian mass extinction.


The role of Atlantic Meridional Overturning Circulation (AMOC) as the driver of Dansgaard-Oeschger (DO) variability that characterized Marine Isotope Stage 3 (MIS 3) has long been hypothesized. Although there is ample proxy evidence suggesting that DO events were robust features of glacial climate, there is little data supporting a link with AMOC. Recently, modeling studies and subsurface temperature reconstructions have suggested that subsurface warming across the tropical North Atlantic can be used to fingerprint a weakened AMOC during the deglacial because a reduction in the strength of the western boundary current allows warm salinity maximum water of the subtropical gyre to enter the deep tropics. To determine if AMOC variability played a role during the DO cycles of MIS 3, we present new, high-resolution Mg/Ca and δ18O records spanning 24–52 kyr from the near-surface dwelling planktonic foraminifera Globigerinoides ruber and the lower thermocline dwelling planktonic foraminifera Globorotalia truncatulinoides in Southern Caribbean core VM12-107 (11.33°N, 66.63°W, 1079 m depth). Our subsurface Mg/Ca record reveals abrupt increases in Mg/Ca ratios (the largest equal to a 4°C warming) during the interstadial-stadial transition of most DO events during this period. This change is consistent with reconstructions of subsurface warming events associated with cold events across the deglacial using the same core. Additionally, our data support the conclusion reached by a recently published study from the Florida Straits that AMOC did not undergo significant reductions during Heinrich events 2 and 3. This record presents some of the first high-resolution marine sediment derived evidence for variable AMOC during MIS 3.


This qualitative study is an investigation into teacher's perceptions about using restorative practice based programs in schools. A grounded theory approach was used to understand teachers' individual experiences, identifying both the positive features and limitations of restorative processes. Participants completed a survey with guiding questions that explored three main areas: (a) strengths, (b) limitations, and (c) overall teacher perceptions of using school based restorative programs. Analysis revealed that teachers support using restorative programs in schools but are concerned about limitations including funding, time commitment, and training. An emergent theory is presented along with a discussion of the research implications and suggestions for future research. Keywords: restorative practices, restorative justice, teachers perceptions, school programs, school counseling TEACHERS' PERCEPTIONS ABOUT USING RESTORATIVE PRACTICE BASED PROGRAMS


Maintaining self-sustaining populations of zoo and aquarium collections can be challenged when natural reproduction fails within mixed-sex populations; however, reproductive success can sometimes be restored with the application of reproductive technologies. Among a population of three female and one male Zebra Sharks (Stegostoma tigrinum), production of young failed despite constant male presence with two of the females. To determine if assisted techniques could be used to rescue sexual reproduction, artificial insemination was performed in a singleton female twice over a three-year period using freshly collected semen. Hatching success for eggs laid by all three females was monitored to compare natural and artificial insemination modes. After the first insemination (December 15th, 2011), 143 yolked eggs resulted in no sexually produced offspring and four genetically-confirmed, parthenogenetic offspring. After the second insemination (September 24th, 2013), 62 yolked eggs resulted in two sexually produced offspring, 18 and 33 days after insemination, and three parthenogenetic offspring > 213 days post-insemination. For the two females housed with the male, no sexual offspring resulted. All females produced at least one hatched parthenote. This study successfully employed artificial insemination to circumvent barriers to natural reproduction in Zebra Sharks. With further development, artificial insemination represents a powerful tool that could be used for maintaining genetic diversity for animals housed in aquaria and conservation-based breeding programs for elasmobranchs.


In some cases early intervention and multiphase orthodontic treatment are insufficient to correct the skeletal and soft-tissue disharmonies present in cleft lip and palate patients. Commonly, midface deficiency with skeletal and dental Class III malocclusion is present in combination with other dental anomalies. In cleft lip and palate patients, orthognathic surgery may involve maxillary advancement with a LeFort surgical procedure, maxillary distraction osteogenesis, and mandibular setback in combination with maxillary advancement, and, on rare occasions, isolated mandibular setback. The selection of the optimal treatment for a specific patient depends on the patient's age, amount of needed advancement, severity of the maxillomandibular discrepancy, impact of the surgery on the speech, relapse/stability relationship, esthetic outcome, and the consideration of the possible complications. The need for multidisciplinary treatment planning and sequentially staged treatment is essential for successful patient outcomes. The purpose of this article is to outline multidisciplinary strategies in cleft lip and palate patient care.


Slip vectors of multiple orientations on a single fault surface may be explained by the interaction of crustal-scale faults in response to nearby earthquakes. Field observations of at least five sets of striae on a single planar fault surface can be reproduced in numerical experiments. These experimental results suggest that slip vectors having variable orientations may reflect a highly transient local stress state in an otherwise constant regional stress field. Our results suggest that stress-inversion techniques should be applied with caution to areas with complex regional-scale fault patterns.


Background
The West German pavilion for the 1970 World's Fair in Osaka is remembered mainly for the great success of its spherical pavilion inside which the music of Karlheinz Stockhausen was performed daily for six months in front of over a million people. The auditorium was designed in collaboration between Stockhausen and the architect Bornemann, and represented the pinnacle of performance spaces for spatial audio, with fully controllable 360 degree sound and light.

Research questions
What was the relationship between the architectural and electronic spatial technologies and the performance practice of the musicians inside the spherical auditorium? How did the spherical space live up to expectations? It always sounds like such an amazing project, but what was it really like? Was there any other music played at the West German pavilion? What made the Stockhausen Ensemble split up halfway through the Expo?

Aims
Through ethnographic, archival, and some practical reconstruction work, I aim to provide a number of different perspectives on the nature of the project, getting past the marketing splendour and glossy public relations image of this iconic project.

Summary of content
Interviews with performers who spent six months performing Stockhausen's music in Osaka, including Rolf Gehlhaar, Peter Eotvos, Michael Vetter, David Johnson, and Mesias Maiguashca, are used to give a sense of the day to day experience of the conditions of performing in the spherical auditorium. Communications between the technical team from the TU Berlin also help build a picture of the conditions in the auditorium. Archival research in the Siemens archive, TU Berlin, and the Stockhausen archives has allowed me to form a detailed picture of the technology designed for the auditorium, and correspondence between engineers and technicians has exposed all kinds of problems with the technology and the architecture, and some responses and solutions to mitigate their effects on the performance practice.

I have found significant details about the other five exhibition spaces, and the range of music by other composers played across all of these halls in the West German pavilion, including some interesting feedback from visitors.

The interview and archival materials paint a rather different picture of the conditions, technology, and practices and underlying all of this is the major differences of opinion between three core members of Stockhausen's ensemble which led them to split from him in the middle of the Expo.

Significance
The Expo 70 spherical pavilion stands as what we might nowadays call an historically significant "impact case study", and has certainly been presented as such over the years. I have been able to separate some of the public narrative (and myth) from what actually took place, and this paper presents a much more nuanced picture of the event from the perspective of the performers, and their interactions together, with the electronic performance technology, and with the space.


The paper aims to discuss the world of fast-paced technology from a Darwinian standpoint and examines the technological choices made by countries and the impact of such choices on their economic growth. The paper explores how a country's economic growth is dependent on the strategic technological choices they make. By clubbing together the fate of countries and companies, we intend to simplify the narrative and explore a few key aspects such as the diminishing relevance of competitive behavior and ways of adapting to and adopting new technologies to become an evolutionary driver in a technology-centric world. This review highlights the need for exploring technological advancements at the periphery in delivering sustained future growth for countries like India. Historical evidence shows that adapting to newer technologies is more important than competing in legacy industries and sectors for a country to boost its economy. Adaptability is more essential for sustained economic growth than competing. The vision for India's technological future should be to make strategic technological choices that have significant growth vectors working in its favor. Rapid technological changes mean that a country can pursue industries without having to go through the learning curve many other countries went through previously in their developmental history. In this fast-paced, techno-centric world, technological choices that are made today determine the quantum of associated economic growth in the future.


There have been thousands of Madonnas with the Child but few more beautiful than the one shown in the illustration, which is known as the Madonna Litta and is in the Hermitage Collection in Leningrad, U. S. S. R. The clothing is of particular interest, the head dress, the gown and the cloak being fine examples of the beautiful garments of the period. The painting is by Leonardo da Vinci, who, despite some authorities to the contrary, produced some of the most glorious art which has been seen in the artistic country of Italy. From a pediatric standpoint, the thing of especial interest is the nursing gown with the openings to permit the use of the breast without undressing or opening the clothing. A sensible design unfortunately rarely used today. Maybe if it were made the fashion more American mothers would nurse their babies.


Background: In-vitro model systems provide an important tool in breast cancer research and, over recent years, there have been considerable advances in their construction. However, despite these advances, the majority of models still employ a narrow range of established cell lines, which frequently are not appropriate for the in-vivo cell type they are representing 1 . Method: As part of the Breast Cancer Campaign Tissue Bank, we have developed a cell culture programme which feeds into the main tissue collection and involves the systematic generation of materials from normal, high-risk, cancer-containing and malignant breast tissue in order to make available a breadth of material to the research community. Following informed patient consent, fresh tissue is retrieved and, using tissue digestion and magnetic bead technology 2 , purified cell populations are isolated, characterized and frozen down, or further processed for DNA and RNA isolation. Results: We have isolated purified populations of luminal epithelial, myoepithelial and fibroblast cells from normal breast, risk-reduction (BRCA1 and BRCA2 mutated) breast and from morphologically normal breast tissue surrounding breast cancer. We have generated matched surround and tumour-associated fibroblasts, as well as matched tumour epithelial and tumour-associated fibroblast cell isolates. These cells have been incorporated into 2- and 3-D culture models and we have demonstrated successful genetic manipulation, with siRNA gene knockdown and gene over-expression through retroviral transduction. Immortalisation of selected cell populations is currently underway. Intact organoids and tissue explants have also been generated for in-vitro experimentation. Matched frozen and FFPE samples are available, together with full clinicopathological data. The research community can access these biomaterials via a web-based search portal, with full user support. Conclusion: Through this cell culture programme we aim to make available a wider and more appropriate range of materials for breast research, which should allow more clinically relevant model systems to be developed and add value to breast cancer biobanking. References: 1. Thompson A., et al. Evaluation of the current knowledge limitations in breast cancer research: a gap analysis. Breast Cancer Research 2008; 10: R26. 2. Gomm J.J. et al. Isolation of pure populations of epithelial and myoepithelial cells from the normal human mammary gland using immunomagnetic separation with Dynabeads. Analytical Biochemistry 1995; 226: 91-99. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-19-05.


This paper examines the effects of agglomeration economies (AE) on the sensitivity of firm location to tax differentials. An initial reading of the story suggests that, with AE, when a firm moves into a community attracted by a tax reduction, other firms may decide to move in as well. This suggests that AE increase the sensitivity of firm location to local taxes. However, a second version of the story reads that, if economic activities are highly concentrated in space, AE might offset any tax differential, hence suggesting a reduction in this sensitivity. This paper provides a theoretical model of intraregional firm location with Marshallian AE that is able to generate both hypotheses: AE increase (decrease) the effect of taxes when locations are (are not) of a similar size. We then use Spanish municipal data for the period 1995-2002 to test these hypotheses, analyzing the combined effect of local business taxes and Marshallian AE on the intraregional location of employment. In line with the theory, a municipality with stronger AE experiences lower (higher) tax effects if it is sufficiently dissimilar (similar) to its neighbors in terms of size.


The present study is aimed to provide information on the abundance of natural foods of Salmo trutta macrostigma (T., 1954). Fish were captured from Uzungol Stream in Trabzon, Turkey between March 2009 and May 2010. It was investigated whether the dietary preferences of trout (S. t. macrostigma) change on account of seasons. Captured fish were measured 17.11 ± 4.65 cm (S.D.) (range 5 to 30 cm), 60.38 ± 48.52 g (S.D.) (range 2.34 to 250.84) (n = 163), respectively. The condition factor of trout calculated 1.00 ± 0.5 (S.D.) (range 0.57 to 1.58) (n = 163). The age range was between 0 and 8 years old. Stomach contents were analyzed using two methods, the frequency of occurrence and numerical method. A total of 11 prey groups were identified in the diets of brown trout living in Uzungol Stream. Prey groups were consisted of Trichoptera, Clitellata, unidentified Insecta, Coleoptera, Ephemeroptera, Haplotaxidae, Diptera, Verenoide, Plecoptera, Hymenoptera and Arachnidae. Analyses of stomach contents showed that the trout feed basically on Arthropoda and Annelidae. Seasonal variation of different food items showed that a high percentage of occurrence of Clitellata were recorded during both winter and autumn, while the highest percent of Coleoptera occurred during summer.

 Key words: Uzungol stream, Salmo trutta macrostigma, stomach contents, frequency of occurrence, numerical method, seasonal variations.


Many hormones circulate bound to serum proteins that modulate ligand bioactivity and bioavailability. To understand the biology of leptin action, we investigated the presence of leptin binding proteins in serum. 125I-labeled leptin binds competitively to at least three serum macromolecules with molecular masses of ∼ 85, ∼ 176, and ∼240 kDa in rodents and ∼176 and ∼240 kDa in humans. The ability to bind appears to involve sulfhydryl/disulfide interactions because it is inhibited under reducing conditions. When serum is added to recombinant 125I-leptin, there is a shift in sedimentation of 125I-leptin as analyzed by sucrose gradient centrifugation from ∼ S1.9 to ∼ S4.3. This shift is markedly attenuated in serum from obese mice (ob/ob, db/db, brown-fat ablated, gold-thioglucose treated, high-fat fed) compared with that from nonobese controls. The size distribution of endogenous serum leptin as determined by radioimmunoassay (RIA) after sucrose gradient centrifugation is also consistent with saturation of binding in hyperleptinemic obesity. In humans, free leptin increases with BMI. Thus, in lean rodents and humans a large proportion of leptin circulates bound to several serum proteins. Free leptin is increased in serum of obese subjects, which may alter leptin bioactivity, transport, and/or clearance.


In recent years, Sweden has promoted prefabricated buildings supporting the increasing of prefabricated rates in buildings with precast components, in order to reduce the environmental problems caused by the construction sector. This study, focusing on the construction activities, examines how the increasing prefabricated rate could influence the environmental impacts of the construction sector. This study conducts a cradle-to-gate life cycle assessment (LCA) of a reference building with a prefabricated rate of 26% in the Stockholm Royal Seaport, and compares nine scenarios with prefabricated rates, ranging from 6% to 96%. The results indicate the water footprint decreases, but the total energy footprint and carbon footprint increase as the prefabricated rate increases. Among other impacts, terrestrial ecotoxicity shows the biggest increase with an increase of the prefabricated rate. This study reveals that material extraction is the largest influencing factor, causing a water footprint when the prefabricated rate increases. The impact changes in the energy footprint, carbon footprint, and terrestrial ecotoxicity, and are primarily determined by transport and are sensitive to transport distance and vehicle types.


Ferroresonance in five-legged, grounded wye-wye transformers is investigated through computer simulation. The transformer model is based on a novel approach and is able to simulate transient and steady-state behaviors of modern low-loss transformers with severely nonlinear cores. Published waveforms from field tests of transformer ferroresonance are successfully reproduced. Simulations suggest a simple method for suppressing ferroresonance overvoltages. The physics of grounded wye-wye transformer ferroresonance is explained and verified by simulation. >


The dynamic equilibrium among the condensation, evaporation and shear flow of the lubricant on a slider has been modeled by solving a continuum-based partial differential equation, with temperatures obtained from a finite element model. Zero-flux and specified-flux boundary conditions were used to study the trailing pad of a slider. The results show that the average lubricant thickness on the trailing pad gradually approaches a steady state, and the steady-state value increases with increasing disk lubricant thickness. A reduction of the flying height leads to a reduced steady-state slider lubricant thickness. The temperature rise of the disk surface tends to promote the lubricant transfer to the slider in a region close to the trailing edge. However, this effect may be locally suppressed by the laser-induced local thinning of the lubricant film on the disk.


Relationships between agents can be conveniently represented by graphs. When these relationships have different modalities, they are better modelled by multilayer graphs in which each layer is associated with one modality. Such graphs arise naturally in many contexts including biological and social networks. Clustering is a fundamental problem in network analysis where the goal is to regroup nodes with similar connectivity profiles. In the past decade, various clustering methods have been extended from the unilayer setting to multilayer graphs in order to incorporate the information provided by each layer. While most existing works assume – rather restrictively that all layers share the same set of nodes, we propose a new framework that allows for layers to be defined on different sets of nodes. In particular, the nodes not recorded in a layer are treated as missing. Within this paradigm, we investigate several generalizations of well-known clustering methods in the complete setting to the incomplete one and prove some consistency results under the Multi-Layer Stochastic Block Model assumption. Our theoretical results are complemented by thorough numerical comparisons between our proposed algorithms on synthetic data, and also on real datasets, thus highlighting the promising behaviour of our methods in various settings.


Background The ICD-based Injury Severity Score (ICISS) provides a criterion for selecting severe injuries, useful when reporting trends in injury incidence because less affected by extraneous factors than total hospitalised cases. We assessed the relative performance of some variants of ICISS. Method Records from the Australian National Hospital Morbidity Database were included if Principal Diagnosis was S00-T89 (ICD10AM), the episode ended in the 2 years to 30 June 2007 and the mode of separation was not transfer to another acute-care hospital or statistical discharge. The ICISS variants studied were: multiplicative; worst injury; treating comorbidity as a covariate (instead of and as well as age); hybrid (precoordinating multiple injury codes within each body region); and omitting same-day cases. Survival proportions specific to each injury diagnosis code (Osler's 'SRR') were used to calculate ICISS, the method differing between variants. Performance of each variant in predicting survival was assessed by logistic regression modelling. Findings Multiplicative and worst injury approaches had similar discrimination and calibration (H-L statistic). Replacing age with comorbidity improved discrimination in multiplicative and worst injury models but calibration deteriorated. Including both comorbidity and age improved discrimination (multiplicative and worst injury); calibration did not change in the former, and deteriorated slightly in the latter. The hybrid approaches did not improve the models. Excluding same-day cases had little effect. Conclusion In this setting (all hospitalised injuries; ICD10AM coding) the best overall performance was for the multiplicative approach with both age and comorbidity as covariates.


After the coup d'etat came to power in May 2014, the military government had been exercising their ideologies through the educational policies and curriculum planning which have been actively responded by the Ministry of Education. Contemporary curriculum reform is employed as a mechanism for maintaining the status quo of elites group who have held privileged positions among the Thais. Looking through the social studies curriculum, it becomes the centerpiece of public schools' efforts to cultivate younger generations into what it means to be " Thainess ". However, Thainess becomes inevitably hybrid to certain extents in the era of globalization. By looking into the contemporary context of education from the postcolonial theory, I learn that if educationalists are to educate young Thais for global citizenship in today's pluralistic society, the social studies curriculum must go beyond the Siamese colonization of knowledge construction, and also provides pedagogical spaces of the experiences, knowledge and perspectives of diverse people in Thai society.


This is the story behind a photo of Fanny Cochrane Smith singing traditional Tasmanian songs, and being recorded by Horace Watson, in 1903. Fanny Cochrane was the first Aboriginal child born on Flinders Island in 1834, in the settlement established for Tasmania's Aboriginal people. She claimed to be the last Tasmanian. Tasmania's and Australia's history reverberate through this image: cultural contact, genocide and reconciliation, tradition and modernity. The image is of the act of folklore collection at its most poignant. The article explores the life of two individuals and how they came together to create an invaluable record of Tasmanian Aboriginal culture. The reverberations continue to this day as their descendents' lives are changed through their connection to this story and their continuation of its themes.For sound files, go to Supplementary Files in tool bar, right


In 65 patient suffering from podagra, liver function was found to depend on a number of aggravating factors (alcoholic drink use, obesity). Liver function disorders were detected in 1/4 of the patients examined. Alterations in enzymic activity were recorded in 44% of podagra patients, using alcohol. The level of AlAT was 0.78 +/- 0.21 mumol/l versus 0.54 +/- 0.02 in the control group (p less than 0.05), that of AcAT 0.60 +/- 0.13 mumol/l versus 0.41 +/- 0.01 in the control group, and that of xanthine oxidase 110.9 +/- 3.89 units versus 87.4 +/- 1.4 in the control group. In 22.2% of podagra in the disease history, alterations in liver function were also detectable, which was likely to be due to the podagra process itself. On scanning of 36 patients suffering from podagra, 23 persons manifested diffuse and 6 focal liver injury.


The aim of this thesis was the creation of a mobile applications for the Android operating system, which would allow the users using supported smart mobile devices to remotely control a digital single-lens reflex camera from the camera manufacturer Canon. The application was named Upravljalnik fotoaparata. The primary objective, which we followed in the thesis, was to produce a application with a basic functionality of taking a photo or the triggering of the camera aperture. We discussed both the infrared remote controlling for devices with a built-in infrared transmitter, wired cable remote control for use in combination with a device's audio-output and a corresponding generated sound signals as well as control via the USB connection. In the first part of the thesis, we briefly introduce the camera that we want to remotely operate and we also describe the Android operating system and the development environment. In the second part, we describe the making of the mobile applications. For each of the controlling modes, we first analyzed the issue and searched for its possible solutions, which were then also practically built within the application. In doing so, we also sometimes expanded the basic operation with additional functionalities such as capturing a photo with a timed delay or shooting in Bulb mode. As an extension of the operation we also presented the intervalometer functionality and support for interval imaging .


The negative impact of a sedentary lifestyle and poor diet on health is evident across the lifespan, but particularly during the university period. Usually, the diet of university students is rich in sweetened drinks and processed foods and low in fruits, vegetables and legumes. Although there is an association between maintaining a healthy diet and the frequency of cooking at home, the time currently spent on cooking or learning how to cook is decreasing globally. The main aim of this study was to explore university students' perceptions about healthy cooking and barriers to eating healthily. A group of 26 students participated in four focus groups. Content analysis was conducted using Atlas.ti v.8. Students perceived cooking healthily as a more complicated and time-consuming process than cooking in general. Individual and environmental factors were the most reported barriers. Costs and time, among others, were the main barriers pointed out by students with regard to healthy eating. This study highlights the need to develop interventions that modify these false perceptions about cooking healthily, and to train students so that they are able to cook healthy meals in a quick, easy, and cost-effective way. Further, specific actions are required in the university setting to minimize access to unhealthy options and to promote those linked to healthy eating.


This paper proposes a risk scoring model to assess the performance of 27 US companies listed online by applying Data Envelopment Analysis (DEA) and comparing with the traditional financial measure Return on Equity (ROE). The DEA evaluation process involves two processes: (1) computation of operating efficiency and effectiveness to measure a company's operating performance, and (2) measurement of the return level per unit of risk to provide guidance for their investors. The risk scoring model is useful for both investors and company managers. For investors, it yields a new stock selecting strategy. For managers, it provides a risk-adjusted performance evaluation process. Empirical results show that for the Internet industry, the effectiveness of a company is more important than operating efficiency. Investors investing in efficient online companies yield higher returns.


OBJECTIVE: To establish method for determining the contents of alpha-pinene and octyl acetate in Boswellia serrata, in order to provide preference for making quality standards for B. serrata and processed B. serrata. METHOD: Application of orthogonal design was employed to optimize the solvent, solvent quantity and extraction time. The GC-MS analysis was performed on a Rxi-5ms silica capillary column, running in the electron impact (EI) mode, with ion trap and injector temperature of 200 degrees C and 250 degrees C, respectively. The column oven was initially 50 degrees C and was held for 1 min after injection, followed by temperature ramping at 5 degrees C x min(-1) up to 130 degrees C, holding for 1 min. 1 microL of samples solution were injected in the split mode (1:60). Helium was the carrier gas. The mass spectrometer was set to scan m/z 45450 with an ionizing voltage at 70 eV. RESULT: Sample solutions were prepared for 50-fold dose by ultrasonic extraction with hexane for 30 min. The content of alpha-pinene and octyl acetate in 10 batches of B. serrata were 0.021 3-0.149 5, 2.519 6-9.098 0 mg x g(-1), respectively. And, those of alpha-pinene and octyl acetate in processed B. serrata were 0.015 9-0.065 9, 0.801 0-12.812 2 mg x g(-1). CONCLUSION: The method is a stable and reliable for determining the contents of alpha-pinene and octyl acetate in B. serrata.


A controller design method for Petri net with uncontrollable and unobservable transitions that enforces the conjunction of a set of linear inequalities on the Parikh vector is proposed. The method is based on the theory that each place can be described with a Parikh vector inequality. Constraints are classified into admissible and inadmissible constraints. An inadmissible constraint cannot be directly enforced on a plant because of the uncontrollability or unobservability of certain transitions. Construct the controller though transforming the inadmissible constraint into admissible one. The method eases the design of controller, because it is based on part net design, and it only considers the direct or indirect transitions related to the constraints. So the computation required to find the Petri net controller is quite simple. Finally, the method is proved to be simple and efficient through one example.


ABSTRACT Animal models of human disease provide an in vivo system that can reveal molecular mechanisms by which mutations cause pathology, and, moreover, have the potential to provide a valuable tool for drug development. Here, we have developed a zebrafish model of Parkinson's disease (PD) together with a novel method to screen for movement disorders in adult fish, pioneering a more efficient drug-testing route. Mutation of the PARK7 gene (which encodes DJ-1) is known to cause monogenic autosomal recessive PD in humans, and, using CRISPR/Cas9 gene editing, we generated a Dj-1 loss-of-function zebrafish with molecular hallmarks of PD. To establish whether there is a human-relevant parkinsonian phenotype in our model, we adapted proven tools used to diagnose PD in clinics and developed a novel and unbiased computational method to classify movement disorders in adult zebrafish. Using high-resolution video capture and machine learning, we extracted novel features of movement from continuous data streams and used an evolutionary algorithm to classify parkinsonian fish. This method will be widely applicable for assessing zebrafish models of human motor diseases and provide a valuable asset for the therapeutics pipeline. In addition, interrogation of RNA-seq data indicate metabolic reprogramming of brains in the absence of Dj-1, adding to growing evidence that disruption of bioenergetics is a key feature of neurodegeneration. This article has an associated First Person interview with the first author of the paper. Summary: Using computational analyses to harness artificial intelligence, we have tested a genetic model of Parkinson's disease and reveal a distinct movement phenotype in adult zebrafish lacking Dj-1.