We have cloned two DNA fragments containing 5'-GATC-3' sites at which the adenine is methylated in the macronucleus of the ciliate Tetrahymena thermophila. Using these cloned fragments as molecular probes, we analyzed the maintenance of methylation patterns at two partially and two uniformly methylated sites. Our results suggest that a semiconservative copying model for maintenance of methylation is not sufficient to account for the methylation patterns we found during somatic growth of Tetrahymena. Although we detected hemimethylated molecules in macronuclear DNA, they were present in both replicating and nonreplicating DNA. In addition, we observed that a complex methylation pattern including partially methylated sites was maintained during vegetative growth. This required the activity of a methylase capable of recognizing and modifying sites specified by something other than hemimethylation. We suggest that a eucaryotic maintenance methylase may be capable of discriminating between potential methylation sites to ensure the inheritance of methylation patterns.


My scientific interest is focused on the field of cellular electrical activity, ranging from the study of intracellular enzymatic processes to the characterization of new generation of drugs. For this purpose I also used the most powerful techniques of investigation, including patch-clamp technique, fluorescence imaging, and surface plasmon resonance (SPR) spectroscopy. Moreover, to shed light on complex molecular mechanisms, unconventional strategies were employed, requiring sometimes the realization of specific devices not commercially available.
In particular my PhD thesis includes two different scientific projects: the biophysical characterization of antimicrobial peptides and the modulation of visual phototransduction in vertebrate cones.
In the first project, the patch-clamp technique was employed to study the pore forming properties of synthetic cecropin-melittin hybrid peptide (CM15), alamethicin F50/5 and its synthetic analog [L-Glu(OMe)7,18,19] under strict physiological conditions. These short peptides selectively permeabilize the bacteria plasma membrane leading to their lyses and death: they are therefore a source of antibacterial molecules, and inspiration for novel and more selective drugs. I pursued this study by recording the ion current through the channels formed by these peptides, once inserted in the membrane of photoreceptor rod outer segment membrane (OS) isolated from frog retinae. The peptides were applied to (and removed from) the extracellular OS side in ~50 ms with a computer-controlled microperfusion system, so that the ion channel characteristics (as its selectivity, blockade and gating) and the dynamics of pore formation could be precisely assessed. On the basis of the electrophysiological recordings obtained, it was demonstrated that, different than alamethicins, CM15 produced voltage-independent membrane permeabilisation, repetitive peptide application caused a progressive permeabilisation increase, and no single-channel events were detected at low peptide concentrations. Collectively, these results indicate that CM15 form pores according to a toroidal model. Moreover, in order to understand the divalent-cation dependency of [L-Glu(OMe)7,18,19] binding to the lipid bilayer at the molecular level, the electrophysiological experiments were paralleled with experiments employing SPR spectroscopy. Results indicate the presence of Ca2+ in the external solution increases the probability of formation of smaller and more stable [L-Glu(OMe)7,18,19] pores. The second project of this thesis concerns the investigation of the physiological role of the neuronal calcium sensor zGCAP3 in the photrasduction cascade. This study was pursued through the simulation of an over expression and a knock-down of this protein, by delivering it, or its monoclonal antibody, into zebrafish cone cytosol, while recording their photoresponses with the patch-clamp technique. The intracellular protein delivery was attained via the patch pipette, by ejecting the proteins out of a tube inserted into the pipette lumen. A microperfusion system was employed to apply the desired exogenous molecules with a precise timing. However, the long tapered shape of the pipette shank make it very difficult to perfuse efficiently the cell with this strategy. For this reason a pressure polishing setup was assembled to enlarge the patch pipette shank, through the calibrated combination of heat and air pressure. This allowed to insert quartz or plastic tubes in the pipette lumen very close to its tip. In order to obtain a substantial and specific silencing of the zGCAP3s in zebrafish cones, surface plasmon resonance experiments were performed to allow the selection of a monoclonal antibody with strong affinity for zGCAP3 and low cross interaction with other components of the phototransduction cascade. Results showed that the perfusion with GCAP3 did not altered significantly the light response, while he anti-zGCAP3 incorporation in the cytosol caused the progressive photoresponse fall, followed by the progressive fall of saturating flash response amplitude, probably due to the progressive GC inhibition. The unexpected lack of an effect of zGCAP3 incorporation in the cone cytosol, suggests that the endogenous number of zGCAP3 is saturating, i.e. their number is equal or above the number of their target molecules (guanylate cyclase), therefore any further increase of zGAP3 in the cytosol is uneffective.


Indian languages are broadly classified as Indo-Aryan or Dravidian. The basic set of phones is more or less the same, varying mostly in the phonotactics across languages. There has also been borrowing of sounds and words across languages over time due to intermixing of cultures. Since syllables are fundamental units of speech production and Indian languages are characterised by syllable-timed rhythm, acoustic analysis of syllables has been carried out. In this paper, instances of common and most frequent syllables in continuous speech have been studied across six Indian languages, from both Indo-Aryan and Dravidian language groups. The distributions of acoustic features have been compared across these languages. This kind of analysis is useful for developing speech technologies in a multilingual scenario. Owing to similarities in the languages, text-to-speech (TTS) synthesisers have been developed by segmenting speech data at the phone level using hidden Markov models (HMM) from other languages as initial models. Degradation mean opinion scores and word error rates indicate that the quality of synthesised speech is comparable to that of TTSes developed by segmenting the data using language-specific HMMs.


Erectile dysfunction (ED) is an important kind of postoperative complication of pelvic surgery that affects patients' quality of life. Transplantation of mesenchymal stem cells (MSC) has been found to alleviate ED caused by cavernous nerve injury (CNI) in rats. However, little is known about whether induced pluripotent stem cell-derived mesenchymal stem cells (iMSC) have a therapeutic effect on CNI ED. We established an ED model on rats and evaluated the effect of iMSC on it. Methods: Eight-week-old male Sprague-Dawley rats were assigned to four groups and received following operation: sham operation (sham group); bilateral CNI and phosphate-buffered saline (PBS) injections (PBS group); bilateral CNI and adipose-derived mesenchymal stem cells transplantation (adMSC group); or bilateral CNI and iMSC injection (iMSC group). After therapy, the cavernous nerve was stimulated by electricity and the intracavernous pressure (IAP)/mean arterial blood pressure (MAP) was measured. The endothelial and smooth muscle tissue in the penis was assessed histologically with Masson's trichrome stain. Immunofluorescence/immunohistochemical stains were applied for the detection of nNOS, vWF, eNOS, SMA, Desmin, S100β, and caspase-3. Nude rats CNI ED model was established for the evaluation of iMSC longevity and differentiation capacity. The paracrine factors were assessed by real-time PCR. Results: Transplantation of iMSC significantly restored the IAP/MAP in this CNI ED model and showed long-term effects. It could rescue the expression of vWF, eNOS, SMA, and Desmin, which indicated the alleviation of endothelial and smooth muscle tissues of the penis. iMSC therapy also could increase the expression of nNOS in the cavernosum and S100β in the major pelvic ganglia (MPG) which contributed to the erectile function. Moreover, the level of BAX and caspase-3 were reduced and Bcl-2 was increased, which indicated the anti-apoptosis effects of iMSC. The iMSC showed little transdifferentiation and exerted their function by activating the secretome of the host. Conclusion: Transplantation of iMSC significantly improved ED induced by CNI. The iMSC may exert their effects via paracrine factors and may be a promising therapeutic candidate for treating CNI ED in the future.


Information provision is a relatively recent but steadily growing environmental policy tool. Its emergency and topicality are due to the current escalation of ecological threats. Meanwhile, its high complexity and flexibility require a comprehensive approach to its design, which has to be tailored for specific characteristics of production process, market structure, and regulatory goals. This work proposes such an approach and builds a framework based on a three-level mathematical program extending well-known two-level Stackelberg game by introducing one more economic agent and one extra level of this sequential game. This study provides simple and very intuitive algorithms to compute optimal multi-tier information provision policies, both mandatory and voluntary. The paper urges for the wide implementation of such efficient environmental policy design tools.


The air temperature and relative humidity and the intensity of photosynthetically active radiation are the basic ecological factors determining geographical distribution of a species. Wood plant adaptation depends on the intensity of physiological and biochemical processes of plants as a response to changing environmental factors. Investigations to reveal (detect) the variability of modification and genetic components of the photosynthetic parameters in needles of the Siberian cedar (Pinus sibirica Du Tour) mountain ecotypes, distributed in central part of the Altai Mountains, were carried out. Also, the survey was extended to some experiments with these ecotypes introduced to mild climate and flat regions from south-western of Siberia. The length and thickness of needles, the size of chloroplasts, content of the photosynthetic pigments, and the functional activity of chloroplasts at the level of photo system II were the evaluated traits. Growing under mountainous conditions (at about 2000m elevation), the two-year-old needles were shorter and thicker and contained very large in size chloroplasts while the content of chlorophylls and carotinoids was twice lower than that in the local ecotype growing in the lowlands. On the other hand, more green and yellow pigments were found in needles of mountain ecotypes planted in the lowlands compared to the local lowland ectype trees. A decrease in pool of the photosynthetic pigments in the highlands ecotypes is probably due to decreased biosynthesis and increased photo-destruction caused by severe light and temperature conditions. These parameters are likely to be associated with modifications due to intense insolation, low temperature, ozone concentration, UV radiation, and other negative factors that are more pronounced at high elevation. Despite the large pool of accumulated photosynthetic pigments, the functional activity of chloroplasts in the mountain ecotype at the level of photosystem II was lower than that in the local ecotype. Thus, the increased photosynthetic intensity under favorable conditions follows the path of formation of both a larger number of reaction centers and light-harvesting pigments.


BACKGROUND
Microvascular decompression (MVD) and vagoglossopharyngeal rhizotomy (VGR) are effective treatment for glossopharyngeal neuralgia (GN). However, surgical choice is controversial due to the need to maximize pain relief and reduce complications.

OBJECTIVE
To retrospectively compare safety, efficacy, long-term quality of life (QOL), and global impression of change following MVD and VGR for treatment of GN.

METHODS
Patient database reviews and telephone surveys were conducted to assess baseline characteristics and long-term outcomes. The effects of pain and complications on QOL were assessed using Brief Pain Inventory-Facial (BPI-Facial) questionnaire. Complication tolerance and surgery satisfaction were sorted using the global impression of change survey.

RESULTS
Of 87 patients with GN, 63 underwent MVD alone, 20 underwent VGR alone, and 4 underwent VGR following a failed MVD. The long-term rate of pain relief was slightly, but not significantly, lower following MVD than VGR (83.6% vs 91.7%, P = .528). However, long-term complications occurred much more frequently following VGR (3.0% vs 50.0%, P < .001). The BPI-Facial, which evaluates pain and complications, showed that MVD had better postoperative QOL than VGR (P < .001). However, 91.7% of patients who underwent VGR experienced no or mild complications. There was no significant difference in the overall satisfaction rates between the groups (83.3% vs 83.6%, P > .99).

CONCLUSION
Although VGR resulted in lower postoperative QOL due to a high complication rate, most of these complications were mild. The overall satisfaction rates for the 2 surgeries were similar.


A priori global identifiability deals with the uniqueness of the solution for the unknown parameters of a model and is, thus, a prerequisite for parameter estimation of biological dynamic models. Global identifiability is however difficult to test, since it requires solving a system of algebraic nonlinear equations which increases both in nonlinearity degree and number of terms and unknowns with increasing model carrier. In this paper, a computer algebra tool, GLOBI (GLOBal Identifiability) is presented, which combines the topological transfer function method with the Buchberger algorithm, to test global identifiability of linear compartmental models. GLOBI allows far the automatic testing of a priori global identifiability of general structure compartmental models from general multi input-multi output experiments. Examples of usage of GLOBI to analyze a priori global identifiability of some complex biological compartmental models are provided.


Protostelids and myxomycetes have been isolated from dead plant parts in many different habitats, including tropical rain forests and deserts. However underwater habitats largely have been overlooked. The purpose of this study was to determine whether protostelids do occur in aquatic habitats and to survey the myxomycetes associated with these habitats. Protostelids and myxomycetes were isolated from substrates collected from just above and just below the surface of the water. Several species of both groups were present, and their distributions above and below the water were different. It is not surprising that the trophic cells of slime molds occur in ponds because they are known to grow in films of water. However these findings are significant because this is the first study to demonstrate clearly the occurrence of protostelids in underwater environments and one of the few surveys of myxomycetes from aquatic systems.


Restudy of the type specimen and preliminary study of additional material of alcovensis [from Natrona County, Wyoming] led to the conclusion that Corosaurus is the most advanced nothosaur known to date. Its shoulder and pelvic girdles show specializations resembling those of Liassic plesiosaurs. The structure of the limbs also shows advanced aquatic specialization, but not in the direction of plesiosaurian paddles. This conclusion agrees with stratigraphic evidence to suggest that the Alcova limestone is of late Triassic age.


Photonic circuits require elements that can control optical signals with other optical signals. Ultra-low-light-level operation of all-optical switches opens the possibility of photonic devices that operate in the single-quantum regime, a prerequisite for quantum-photonic devices. We describe a new type of all-optical switch that exploits the extreme sensitivity to small perturbations displayed by instability-generated dissipative optical patterns. Such patterns, when controlled by applied perturbations, enable control of microwatt-power-level output beams by an input beam that is over 600 times weaker. In comparison, essentially all experimental realizations of light-by-light switching have been limited to controlling weak beams with beams of either comparable or higher power, thus limiting their implementation in cascaded switching networks or computation machines. Furthermore, current research suggests that the energy density required to actuate an all-optical switch is of the order of one photon per optical cross section. Our measured switching energy density of ~4.4 × 10-2 photons per cross section suggests that our device can operate at the single-photon level with modest system improvement.


Excessive use of nitrogen fertilizer in crop production in China leads to environmental problems, and farmers' lack of knowledge is the primary constraint. The public extension system, however, lacks the accountability and capability to deliver ecoagricultural extension services to farmers. Previous studies show that extension staff had little incentive to deliver extension services because they were overwhelmed by assigned non-extension activities. By applying a combined incentive scheme of cash rewards and political motivation on extension agents from 2009 to 2010, we found that knowledge training effectively reduced nitrogen use by 7% with no impact on yields in wheat production in two locations in Shandong Province, a major grain production region in north China. As such, improving nitrogen management has a great potential for a low-carbon agriculture in China and should be included into the extension program. However, the effectiveness of the training depends largely on the institutional capacity of the local extension system, which varies by region. In counties where extension employees were overwhelmed by assisting township administrations, a pure economic incentive without a long-term commitment was not effective. In the future, China faces challenges with delivering low carbon technologies through the existing agricultural extension system.


Over the years many Intelligent Tutoring Systems (ITSs) have been used successfully as teaching and training tools with proven results through evaluation studies. Even though ITSs are effective in providing individualized tutoring to many students at the same time, very few attempts have been made to embed them with existing systems. This area of research has a lot of potential in providing life-long learning and work place training anytime and anywhere. We present the evaluation of DM-Tutor, an ITS that provides training on plantation decision making. DM-Tutor has been embedded with a Management Information System (MIS) to provide scenario-based training using real life operational data and actual plantation conditions. The pilot study conducted in February 2011 shows that DM-Tutor is an effective teaching tool; the performance of the participants on the post-test was significantly higher than their performance on the pre-test. The questionnaire responses show that the participants found the system easy to use and useful.


Get your children out of their seats and talking about stories. * Explore literature through art, drama, puppets and other innovative techniques. * Brings projects to life with colour photographs and samples of work. * Helps you link reading and writing. * Self-contained: comes with all the full-length texts you need. * Shows you how to develop talk for writing.


The potential of spaceborne lidar to monitor aerosol layering and mixing with high vertical resolution is reviewed. An overview is presented on aerosol lidar techniques of past, present, and future NASA and ESA lidar missions. The potential of a standard backscatter lidar (LITE, 1994), a backscatter/polarization lidar (CALIPSO, since 2006), a polarization High Spectral Resolution Lidar (HSRL, ATLID, EARTHCARE), and of a multiwavelength polarization HSRL are discussed regarding their ability to derive height profiles of optical and microphysical properties of aerosols and to resolve aerosol types and mixtures as a function of height. The important role of ground-truth activities is emphasized. Measurement examples taken with ground-based lidars illustrate that these systems provide a detailed characterization of complex aerosol scenarios in contrast to the snapshot-like observations with spaceborne lidars.


Aiming at amplifying the energy productive motion of wave energy converters (WECs) in response to irregular sea waves, the strategies of discrete control presented here feature some major advantages over continuous control, which is known to require, for optimal operation, a bidirectional power take-off able to re-inject energy into the WEC system during parts of the oscillation cycles. Three different discrete control strategies are described: latching control, declutching control and the combination of both, which we term latched–operating–declutched control. It is shown that any of these methods can be applied with great benefit, not only to mono-resonant WEC oscillators, but also to bi-resonant and multi-resonant systems. For some of these applications, it is shown how these three discrete control strategies can be optimally defined, either by analytical solution for regular waves, or numerically, by applying the optimal command theory in irregular waves. Applied to a model of a seven degree-of-freedom system (the SEAREV WEC) to estimate its annual production on several production sites, the most efficient of these discrete control strategies was shown to double the energy production, regardless of the resource level of the site, which may be considered as a real breakthrough, rather than a marginal improvement.


The goal of this study carried out on street children and care providers was to determine the opinions of the staff of these institutions--foster homes--and their degree of satisfaction. Out of twenty homes of the zone or healthcare district of Kasavubu in the city of Kinshasa in the Democratic Republic of the Congo (DRC), ten were chosen at random (50%). In them, we selected one hundred street children--the beneficiaries--, ten care providers and ten protocol programs--of guardianship. The players--beneficiaries and providers--answered questions on their perceptions and expectations regarding to following: the range of activities provided, its organization, its quality and their degree of satisfaction of the site and on the development of skills. The results obtained demonstrated the predominance on useful activities ("welfarism") and on charity. The respondents declared they sometimes commit antisocial actions (theft) to access education, which is similar to a form of obtaining independence. The protocols for guardianship are often the conceived by experts. However, in a general way for young respondents, it is relatively difficult for experts alone (assistants and social educators or others) to provide precise and exhaustive data on the needs felt by street children. In view of these results, it is thus ethically acceptable to resort to the ability-based approach in the conception, the setting up and the evaluation of guardianship protocols for street children. What the youth think, the range of activities provided, the conception and the quality of the guardianship protocols is an important stake in the development of the skills. It is highly probable that the emergence of such protocols cannot be undertaken except if street children have a degree of independence in relation to experts and can assert a specific point of view.


Dr Duncan Bate (ARK Geophysics) presents a recent oil company sponsored case study in
France pointing to the value of 4D microgravity modelling as a cost-effective and unintrusive
way of enhancing reservoir information.

Measuring the Earth's gravitational field as a means to mapping subsurface density distributions has been an exploration technique for decades. Gravitational anomalies may be related to subsurface geological structures and thus indicate features including faults, intrusives, and salt structures. High spatial resolution gravity data (as acquired with 3D seismic surveys) may be used in combination with 3D modelling to help define end member salt volumes in seismic imaging processes such as pre-stack depth migration
(PSDM). The measurement of the time varying (4D) gravity field as a method of observing subsurface fluid flow in a hydrocarbon reservoir is a more recent application of gravity data. ARK Geophysics (ARK) conducted a time-lapse microgravity field trial over the Izaute gas storage reservoir in the Gascoigne district of South-Western France approximately 60 km north of Pau, between January 2003 and June 2004. The reservoir is operated by Total Infrastructure Gaz France (TIGF). The project was coordinated by ITF and funded by Statoil, Shell, and Total.
The reservoir is a domestic gas storage buffer – filled throughout the summer months and depleted during the winter. The objective of this trial was to investigate whether time changes in the observed gravity field could practically be measured
and if so, whether the observations correlated to known changes in gas stock levels. Twelve repeat gravity surveys were performed (each comprising over 200 stations) and two continuous gravity meters were employed.
Overall the measured time-lapse gravity data correlate well with the predicted gravity changes from the reservoir model. Any observed differences between the predicted gravitational response of the reservoir model and the measured time varying gravity field requires further investigation. Sources of such observed discrepancies include system noise but also geological information that may not have been captured in the reservoir model such as reservoir compartmentalization, porosity, and permeability differentials as well as unmapped thief zones. The continuous data recorded over the reservoir show a good correlation with the reservoir gas pressure data.
The aim of this study was to assess whether the time varying gravity field generated by a propagating density interface (e.g. oil-water or gas-water contact) can be measured by currently available cost-effective instrumentation. A two-fold approach was employed, utilizing time-lapse (or dynamic) and continuous gravity acquisition techniques. A dynamic gravity project comprises repeat static gravity surveys and is sometimes referred to as time-lapse or 4D. Workers in this field have successfully applied this technique to hydrothermal energy exploration (Hallinan et al., 1989; Allis et al., 1986) and hazard monitoring (Rymer & Brown, 1986; Yokoyama, 1989). A continuous gravity survey involves recording the variations in gravity continuously over a period of time. This technique has previously been used for long term studies of earth tides and volcano monitoring.
There are several designs of gravity meter that can measure to the required accuracy for this project. The LaCoste and Romberg G and D meters with Aliod electrostatic feedback nulling system were used. This system has a range of approximately
100 mgal ( /-50) with a resolution of 0.01, or 0.001 mgal depending on which version is fitted.
The Izaute, and its neighbouring Lussagnet, gas storage facilities have been created from porous submolassic sand reservoirs in the upper section of a vast multi-layer reservoir that contains the 'inframolassic aquifer' stretching from the Pyrenees to north of Bordeaux. The Izaute reservoir is formed by a gently plunging anticline, with an overburden of approximately 500 m. The reservoir thickness ranges from 50 to 80 m, has a porosity of between 25% and 35% and a permeability of between 6 and 20 Darcys. Gas is injected in the summer months (May to October) and recovered in the winter months (November to April). The total seasonal variation in the depth to the gas-water contact is 24 m.


We study the effects of actors ' audience-specific reputations on their levels of success with different audiences in the same field. Extending recent work that has emphasized the presence of multiple audiences with different concerns, we demonstrate that considering audience specificity leads to an improved understanding of reputation effects. Using data on emerging artists in the field of contemporary art from 2001 to 2010, we investigate the manner in which artists ' audience-specific reputations affect their sub-sequent success with two distinct audiences: museums and galleries. Our findings suggest that audience-specific reputations have systematically different effects with respect to success with museums and galleries. Our findings also illuminate the extent to which audience-specific reputations are relevant for emerging research on the contingent effects of reputation. In particular, our findings support our predictions that audiences differ from one another in terms of the extent to which other signals (specifically, status and interaction with other audiences) enhance or reduce the value of audience-specific reputations. Our study thus advances theory by providing empirical evidence for the value of incorporating audience-specific reputations into the general study of reputation.


Voice training and voice knowledge have all but disappeared from Norwegian teacher education, in a general decline of the standing of practical-aesthetical subjects in compulsory school. Yet the voice is a teacher's primary tool for establishing authority, commanding attention, and for guiding, motivating and building a trusting relationship with students. Voice trouble is a major cause of health problems and professional dysfunction in teachers. In this article, "the audible body" denotes both voice physiology and the relational meanings that color production and perception of a human voice, within a matrix of social and cultural connotations of beauty, quality, normalcy and health. The study consists of interviews with six music student teachers having received voice lessons during their three-year bachelor program, concerning voice awareness and voice care during studies and as student teachers in practice periods. The students were able to identify the relational authority and attention-producing qualities inherent in a well-functioning voice, and had learned to prevent and remedy common voice problems. Findings from the interviews are contrasted with previous survey data from a student group exposed to a minimal amount of voice education. The article discusses the importance of teachers' awareness of physiological, relational and emotional influences on voice function, and of strategies for dealing with the challenges of being the audible center of pupils' attention, where pupils become the teacher's "magic mirror". The disappearance of voice training from teacher education conveys ignorance of the bodily and relational foundations of human functioning, and may negatively affect teachers' professional functioning.


Background The discharge of Palliative Care patients is deemed complex solely by their nature of being Palliative. Observational studies of discharged patients within a palliative care unit revealed them to be fragmented and tardy. A time and motion study was undertaken with the aim of highlighting the complexities of discharge and its planning, the length of time taken, and evaluation of the time wasted. Method Data were collected from 12 patients over a six week period using a purposefully designed pro-forma comprising 13 elements of discharge. Staff self-assessed discharge activities prospectively using a tick box system. Each pro-forma was nurse anonymous and space allocated for start and completion time of activities and for staff to write notes concerning the element they were involved in. Missing data was calculated using the average duration of activities previously recorded for the same data field. Findings An average of 4 nursing staff were involved in each discharge, taking 1 hour and 39 minutes per patient. 116 activities were recorded in total, averaging 10 per patient. Calls to community staff were the most time consuming activity, averaging 5 calls per patient at 20 minute duration. Waiting for return calls impeded discharge. Data reporting and findings are under reported due to time constraints on staffing. Conclusion A discharge coordinator role should be considered to create a more integrated patient pathway and redress some of the problems currently highlighted. Enabling the development of a discharge policy encompassing a rapid discharge pathway for patients who's preferred place of care is home, a more coherent and in-depth holistic assessment, and the commencement of national and local incentives such as Coordinate my Care. A discharge coordinator would provide patients with a timely and succinct discharge pathway, and enhance communication with community teams. Nursing time saved would be better utilized giving hands-on care.


Increasing the fault and test coverage is an important goal in the DFT strategies of semiconductor companies. In particular, the growing distribution in the automotive market leads to strict test requirements and high fault coverage demands. A wide-spread method to increase the fault coverage is to insert controllability and observability test points in order to ease fault excitation and detection. Since test points cause hardware overhead, it is important to restrict their number to a minimum to prevent high costs. The paper targets the identification of effective test points in order to make untestable faults testable. Optimization-SAT-based ATPG techniques are used to calculate a minimum set of effective test points, which is able to make all previously undetectable faults of a fault set $F$ detectable. Additionally, untestable fault ordering heuristics are introduced to reduce the number of needed test points. Experimental results on benchmark circuits show that the proposed method is able to generate a small set of test points, which is able to provide 100% fault coverage for stuck-at faults.


Unpaid care is an important part of long-term care systems. It is increasingly recognised that carers have their own health and well-being needs. Carer-specific interventions, as well as support for the care-recipient, may enable carers to maintain their own health and well-being alongside
 caring. This study seeks to establish whether and how community-based care services affect carers' quality of life. The Adult Social Care Outcomes Toolkit for Carers was used to capture carers' social care-related quality of life through qualitative interviews and a survey of carers
 in England in order to provide insights into the impact of community-based care services on carers' quality of life outcomes.


Content-addressable memory (CAM) is a hardware storage commonly used in the fast lookup applications. However, the parallel comparison feature costs the CAM memory large power consumption. In this paper, we propose a new CAM word architecture, called master–slave match line (MSML) design, which aims to combine the master–slave architecture and charge refill minimization technique to reduce the CAM power dissipated in the match lines (MLs). Unlike the conventional design, where only one single ML is used, our design uses one master-ML (MML) and several slave-MLs (SMLs) to perform the search operation. By sharing the MML charge with only the mismatched SML, our design can minimize the MML charge refill swing, such that the ML power consumption can be reduced effectively. Theoretically, the ML power saving is at least 50%, which is independent of the search pattern and match case. Compared with the conventional NOR-type CAM design, the simulation results show that the MSML design with the best configuration can reduce the ML energy consumption by range 7%–57%, which increases with the word size. In addition, we further propose a modified CAM cell to facilitate the MSML match performance, MSMLhp design, which can even result in 28% and 69% energy-delay product improvement compared with the original MSML and traditional CAM designs in the 128-bit word size case.


(UL1TR000427 to K.C.K.). This funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: ß 2014 The PLOS ONE Staff. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The production of Clostridium sordelli veterinary vaccine is prepared by culturing the microorganism in large industrial bioreactors and purifying the toxin from culture supernatants. Currently, the harvesting time is established as function of bacterial growth, but not always this moment is associated to the maximum concentration of toxin present in the supernatant. Thus, it is easy to find different total amounts of toxin produced batch to batch. Besides, at present the toxin concentration is measured by in vivo LD50 methods, and results can be obtained only after 72h, when the bioreactor was already stopped.Moreover, the method is labour intensive and requires the use of a significant number of experimental animals We describe the development of a latex agglutination reagent for semiquantification of Clostridium sordelli lethal toxin (TcsL) and its use in industrial bioreactors. The reagent was developed and characterized in our laboratory achieving a considerable low detection limit (8ng of toxin per ml of culture supernatant) and then it was validated in actual industrial conditions. The use of such a rapid (i.e, in minutes) and easy to use reagent will allowto followthe culture in real time and thus standardizing the optimal end-point for harvesting in terms of toxin quantity.As an immediate consequence, the efficiency of TcsL industrial production may be optimized.


Measuring theoretical concepts, so-called constructs, is a central challenge of Player Experience research. Building on recent work in HCI and psychology, we conducted a systematic literature review to study the transparency of measurement reporting. We accessed the ACM Digital Library to analyze all 48 full papers published at CHI PLAY 2020, of those, 24 papers used self-report measurements and were included in the full review. We assessed specifically, whether researchers reported What, How and Why they measured. We found that researchers matched their measures to the construct under study and that administrative details, such as number of points on a Likert-type scale, were frequently reported. However, definitions of the constructs to be measured and justifications for selecting a particular scale were sparse. Lack of transparency in these areas threaten the validity of singular studies, but further compromise the building of theories and accumulation of research knowledge in meta-analytic work. This work is limited to only assessing the current transparency of measurement reporting at CHI PLAY 2020, however we argue this constitutes a fair foundation to asses potential pitfalls. To address these pitfalls, we propose a prescriptive model of a measurement selection process, which aids researchers to systematically define their constructs, specify operationalizations, and justify why these measures were chosen. Future research employing this model should contribute to more transparency in measurement reporting. The research was funded through internal resources. All materials are available on https://osf.io/4xz2v/.


High-quality motion planning can be quite expensive to perform, yet is critical for many video games. As a result, many approximations are employed to reduce costs. Common approximations include pathfinding on a grid or on a navigation mesh instead of in a real-valued world. As a result, the paths that are found are not immediately appropriate for use, and often require post-processing, such as smoothing. An alternate approach is to incorporate pathfinding constraints directly into A* search. This approach is expensive and so it hasn't been widely applied in games. In this paper we analyze the complexity of planning with complex motion constraints and suggest optimizations which make such planning feasible for use in modern games. We propose the use of two ideas, abstract perimeter heuristics and intermediate search truncation, which can reduce the cost of search by an order of magnitude or more.


This article considers the relationship between postfeminism and gender subjectivity through a critique of the retro-aesthetic encoded into Virgin Atlantic's Still Red Hot advertising campaign. Launched in 2009, and prompting a series of complaints to the Advertising Standards Authority, this high-profile 25th-anniversary campaign featured crowds of people staring in awe at a group of 1980s-styled female cabin crew, and a male pilot, walking through an airport arrivals lounge. As they pass they elicit a number of not only admiring glances but also clearly sexualized responses, albeit portrayed in an exaggerated and, therefore, comedic manner, all set to the sound of Frankie Goes to Hollywood's 'Relax'. Focusing on the relationship between performativity, materiality and signification, or what Judith Butler (1990) calls 'the scenography of production', the analysis presented here reflects on the cooptation process played out in this particular advertisement, arguing that while ostensibly parodying the sexual iconography associated with the airline industry, it can also be read as an example of the organizational appropriation of postfeminist ideas regarding gender, sexuality and subjectivity. The discussion emphasizes how this retro-styled campaign is dependent upon the commodification of a knowing, ironic and playful subjectivity preoccupied with the self as a performative project, one that characterizes postfeminist writing but that is at odds with a critique of the discrimination and disadvantage perpetuated within and by the industry.


Flower essential oils can't be taken by distillation, which is the oils' component will damage because of hydrolysis and polymerization process. High-boiling components can't be transported by water vapor so its yield and quality of the oil product is low. The alternative method for producing flower essential oils is an enfleurage process. Enfleurage is essential oil extraction process using cold fat, where the scent of flowers is absorbed by fat. The aim of the research is to obtain information about the optimum conditions based on essential oils of flowers through enfleurage method. Enfleurage process was begun with prepared the adsorbent which was made from mixing of vegetable fat and animal fat in ratio of 1:1. Fat was heated up to 60 0C further stirring for 15 minutes. As long as stirring, the fat mixture was mixed with benzoate and stirred for 2 hours. After the adsorbent was ready, a chassis was smeared with a layer of fat and flowers were palced in surface of fat for 1, 3, 5, 7, 9 and 11 days. The process was repeated with change the flowers every 24 hour with fresh flowers. When contact time had finished, fat was extracted using alcohol and it was separated by vacum distillation. The maximum yield was obtained for 5 days 0.89 % for jasmine, 0.88 % for rose and 0.84 % for frangipani. The enfleurage process is an effective method to produce flowers essential oils. The success of it depends on type of adsorbent, the level of florescence, as well as enfleurage's period.


We propose a semiconductor-insulator-semiconductor (SIS) heterojunction diode consisting of monolayer (1-L) MoS2, hexagonal boron nitride (h-BN), and epitaxial p-GaN that can be applied to high-performance nanoscale optoelectronics. The layered materials of 1-L MoS2 and h-BN, grown by chemical vapor deposition, were vertically stacked by a wet-transfer method on a p-GaN layer. The final structure was verified by confocal photoluminescence and Raman spectroscopy. Current-voltage (I-V) measurements were conducted to compare the device performance with that of a more classical p-n structure. In both structures (the p-n and SIS heterojunction diode), clear current-rectifying characteristics were observed. In particular, a current and threshold voltage were obtained for the SIS structure that was higher compared to that of the p-n structure. This indicated that tunneling is the predominant carrier transport mechanism. In addition, the photoresponse of the SIS structure induced by the illumination of visible light was observed by photocurrent measurements.


Background Multiple sequence alignments (MSAs) are a prerequisite for a wide variety of evolutionary analyses. Published assessments and benchmark datasets for protein and, to a lesser extent, global nucleotide MSAs are available, but less effort has been made to establish benchmarks in the more general problem of whole genome alignment (WGA). Results Using the same model as the successful Assemblathon competitions, we organized a competitive evaluation in which teams submitted their alignments, and assessments were performed collectively after all the submissions were received. Three datasets were used: two of simulated primate and mammalian phylogenies, and one of 20 real fly genomes. In total 35 submissions were assessed, submitted by ten teams using 12 different alignment pipelines. Conclusions We found agreement between independent simulation-based and statistical assessments, indicating that there are substantial accuracy differences between contemporary alignment tools. We saw considerable difference in the alignment quality of differently annotated regions, and found few tools aligned the duplications analysed. We found many tools worked well at shorter evolutionary distances, but fewer performed competitively at longer distances. We provide all datasets, submissions and assessment programs for further study, and provide, as a resource for future benchmarking, a convenient repository of code and data for reproducing the simulation assessments.


Copolymerization between alkyl diazoacetates and α,β-unsaturated aldehydes, which is a one-pot, one-step and catalyst-free reaction, is presented. The product is a ternary copolymer composed of an alkyl diazoacetate, an α,β-unsaturated aldehyde and an α-carbalkoxy carbene, which is derived from the alkyl diazoacetate by the release of N2. Thus, the reaction is named as the C1N2/C2/C1 copolymerization. Various diazoacetates and α,β-unsaturated aldehydes were utilized to establish the methodology. The products are down-/up-conversion fluorescence molecules that can significantly enhance cell imaging through the synchronized excitation of near-ultraviolet and near-infrared light and may be widely used in other optical fields. The up-conversion fluorescence is the result of a two-photon excitation process.


The present paper synthesizes the results of the Ruhr-Katowice Comparison Project. This research was conducted at the International Institute for Applied Systems Analysis (IIASA) between 1994 and 1996 as part of an Industrial Metabolism project which focused on the impacts from production, use and disposal of materials containing heavy metals on soils in the Upper Basins of the Elbe and Oder rivers. Using tools of massbalance analysis and soil science this project traced the sources, flows, and accumulations of heavy metals. The Ruhr-Katowice Comparison Project aimed at a better understanding of policy options for reducing heavy metal contamination and managing heavy metal contaminated soils. The Ruhr area in Germany and Katowice Voivodship in Poland are the two "hot spots" in Europe of heavy metal pollution. They have many economic features in common due to the historical orientation of their economies on coal mining and heavy industries. They differ with respect to environmental policies, however. Pollution has been largely mitigated in the Ruhr area by measures that started in the 1960s while hardly any emphasis was given to environmental protection in Poland before the 1990s. The Ruhr-Katowice Comparison Project analyzed the role of environmental policies from the perspective of soil protection and identified the key elements that led to the historical reduction of atmospheric heavy metal emissions in the Ruhr area. A complementary analysis was performed on current efforts directed towards environmental clean-up in the Katowice Voivodship. This study takes an economic point of view. Economic analysis of environmental policy compares the cost and benefits of different policy options. As a comprehensive empirical cost-benefit analysis is not feasible, an assessment is made based on the concept of environment economy integration. This notion describes attempts to design policies with proper regard to the interrelationships that exist between the environment and the economy in order to exploit synergies or to minimize conflicts between environmental and economic objectives. Six dimensions of integration are distinguished which represent different, though not independent, strategies to coordinate environmental and economic objectives. Requirements are derived which policies have to correspond to in order to promote environment-economy integration. These requirements are used as criteria for an assessment of historical policies in the Ruhr area and current approaches in the Katowice Voivodship. Based on the identification of the successes as well as the failures of efforts in the Ruhr area and the strengths and deficits of current approaches in Katowice guidelines are proposed for improving environment economy integration for land maintenance. The results presented in the present paper are summarized from a series of studies commissioned for the Ruhr-Katowice Comparison Project; they are referenced throughout the text and marked in the list of references. The results of the commissioned studies were discussed at two workshops held at IIASA. The Ruhr-Katowice Comparison Project yielded four main results: first, it contributes to the methodology of assessing policy options by developing and applying the concept of environment economy integration. Second, it yields a historical review of the beginning of systematic environmental policies in the Ruhr area. Third, gives an overview of current approaches to managing heavy metal pollution in the Katowice Voivodship. Last but not least it proposes a set of guidelines for the integration of environmental and economic objectives in land management.


In object-oriented software engineering roles are considered both classifications and instances. To reduce the gap between the conceptual modeling of roles and a corresponding implementation, we propose a new role modeling concept based on warped inheritance hierarchies. We integrated this new modeling concept in our prototype-based object-oriented round-trip engineering environment SelfSync. In this way it is possible to model roles in an Extended Entity-Relationship diagram while the corresponding implementation objects are automatically created and synchronized with the conceptual model. We apply constraint enforcement during the lifetime of role objects, based on dependency and role combinations.


The Upper Cretaceous shale which has been called Carlile in the Laramie Basin, Wyoming, overlies the Frontier formation and is, in turn, overlain by the chalky beds of the Niobrara. The fauna of the upper part of the Frontier is of the same age as that of the upper type Carlile of Colorado, whereas the fauna of the "Carlile" of the Laramie Basin is of Niobrara age. It is believed, therefore, that the use of the name, Carlile, should be discontinued in the Laramie Basin and the name, Niobrara, extended downward to embrace the beds erroneously called Carlile. This basal Niobrara shale is correlated with the Sage Breaks shale member of the Niobrara of the Black Hills, and the name, Sage Breaks, is here substituted for the abandoned name, Carlile.


This paper explores the relationship between church and state in Serbia and Montenegro by examining the development of 'twin toleration'. In particular, it aims to explain why there is still no 'twin toleration' in these states, and why it is important to impose such institutional arrangement in church–state relations. The 'Twin toleration' concept suggests that institutional arrangements between the state and religious communities in a democratic society should be based on mutual autonomy, in which the state should not interfere in the matters of religious communities, and vice versa. However, since the fall of communism and resurgence of religion, both the Serbian and Montenegrin states have tended to have close relations with the dominant religious communities in order to achieve their narrow political interests. On the other side, religious communities often interfere in political issues. Such a situation does not contribute to the further development of democracy in these countries. In this paper I employ content analysis in order to investigate constitutions and specific laws on religious communities, if any, in the states mentioned above. Besides its theoretical perspective, aim of this paper is to offer practical suggestions on how to rearrange church–state relations in Serbia and Montenegro in order to make these countries more democratic.


We provide a full theoretical understanding of the recent observations of excitation of Raman two-peak states in solid-core photonic crystal fibers. Based on a "gravity-like" potential approach we derive simple equations for the "magic" peak power ratio and the temporal separation between pulses forming these two-peak states. We develop a model to calculate the magic input power of the input pulse around which the phenomenon can be observed. We also predict the existence of exotic multipeak states that strongly violate the perturbative pulse splitting law, and we study their stability and excitation conditions.


"Finding Sonnets about Sand: Using Local Voices in Literature Classrooms" focuses on the importance of presenting beginning literature students with texts that have some relevance to their lives. With eight years experience of teaching in the Middle East, the author argues that in lower-level literature classes, students should have a chance to see their lifeways and values represented in addition to foreign cultures. The article concludes with a short bibliography of texts which are useful in teaching Introduction to Literature classes.


Hand-based interaction is one of the most widely-used interaction modes in the applications based on optical see-through head-mounted displays (OST-HMDs). In this paper, such interaction modes as gesture-based interaction (GBI) and physics-based interaction (PBI) are developed to construct a mixed reality system to evaluate the advantages and disadvantages of different interaction modes for near-field mixed reality. The experimental results show that PBI leads to a better performance of users regarding their work efficiency in the proposed tasks. The statistical analysis of T-test has been adopted to prove that the difference of efficiency between different interaction modes is significant.


Summary Declining oil production and increasing water cut in mature fields indicate the need for improved conformance control. In this paper we report on the numerical modeling performed to evaluate the in-depth water diversion pilot performed for the Snorre field, offshore Norway. For this pilot 240 000 m3 of a sodium silicate solution was injected in the period July to October 2013. The goal of the pilot was to form an in-depth flow restriction for improving the sweep. The setup, execution and measured data from response monitoring for the pilot have been presented in previous papers. As discussed therein, the operation clearly resulted in a strong in-depth flow restriction resulting in delayed tracer responses and decrease in the water cut. However, the monitoring was only limited to well observations, so to understand the spatial and temporal forming of the flow restrictions we had to rely on numerical simulation and modeling. In short, we calibrated simulation models to the observed well responses by introducing flow restrictions; i.e. using history matching techniques. Through the reservoir modeling work we reproduce the pilot response well by introducing sound flow restrictions. This gives us clear indications on the location, timing, strength and corresponding uncertainties of the introduced flow restriction. Moreover, the modeling work supports interpretations from the response monitoring program. Finally, in addition to help evaluating the performed pilot, the learnings from the modeling work will hopefully give more accurate evaluation of potential future water diversion candidates.


Although conclusive evidence is lacking for its establishment, the thesis that complexity adds stability to communities is probably accepted by the majority of ecologists. I believe this attitude found its origins in the indisputable fact that there are latitudinal and altitudinal changes in community complexity. As one progresses northward or southward from the equator, or higher in altitude in most parts of the world, one cannot help but notice that communities tend to become simpler, that is, there are fewer species per community. At the same time, these communities appear to become less stable. But perhaps this change in stability is in appearance only; they appear to be less stable because of the relatively greater number of individuals comprising each species population in temperate areas. Each population, because of its greater numbers, is therefore conspicuous, and changes in these numbers are noticed. We are particularly aware of such changes because populations in these areas of the world have been comparatively well studied. Many of the most studied populations include species of economic importance where changes in population numbers are vital to agricultural or forestry practices. Equatorial populations, on the other hand, contain smaller numbers of individuals of each species because of the greater number of species present. Number changes are simply not as noticeable because the population itself is not as obvious among the other populations. It may be that when (if ever) we have as much data on equatorial populations as we have on those of temperate climates, we will find fluctuations of equal relative magnitude (but not of equal numbers, of course). If, on the other hand, we really do find a correlation between complexity and stability, the suggestion by May (12) that stability permits complexity may be well worth investigating. Because of its organization and physical setting, the Rhopalomyia community I have studied might be expected to have considerable stability. In fact, however, it does not. Each of the populations in the community fluctuates greatly and irregularly in both percentages and numbers, and these populations apparently become locally extinct occasionally, because they sometimes cannot be found even in extensive collections. After studying several of the more important parasitoid species, it is evident to me that there is little or nothing about their interactions that might induce greater community stability. Each species seems to have evolved into the community with no higher purpose than simply to usurp what it can from some other member, and it does this by concentrating its energies on better competitive mechanisms rather than higher reproductive capacities. There are never empty niches to be filled by organisms having the "correct specifications" because new niches are created out of parts of older, broader niches which were occupied by other, more r-selected organisms. Thus, perhaps we have read too much into community organization. Perhaps the "ifiling of niches" is essentially nothing more than the haphazard result of competitive jostling among species; and that as communities develop, they are not necessarily programmed for such things as greater stability or better energy utilizationthe species merely become more closely packed.


: Examination of 36 infants of the first year of life, who had been operated on under extracorporeal circulation, revealed the activation of the monocytic cellular pool. This reaction was accompanied by an increase in the content of activated HLA-DR-positive cells. Limitation of the monocytic test via apoptotic mechanisms was inadequate. The control children undergoing cardiac surgery without extracorporeal circulation showed the same trend in the number of monocytic cells, which counts in favor of the fact that surgical injury is just a trigger of their activation. Extracorporeal circulation prolongs these changes to 3-4 postoperative days.


Technology scaling accompanied with higher operating frequencies and the ability to integrate more functionality in the same chip has been the driving force behind delivering higher performance computing systems at lower costs. Embedded computing systems, which have been riding the same wave of success, have evolved into complex architectures encompassing a high number of cores interconnected by an on-chip network (usually identified as Multiprocessor Systemon-Chip). However these trends are hindered by issues that arise as technology scaling continues towards deep submicron scales. Firstly, growing complexity of these systems and the variability introduced by process technologies make it ever harder to perform a thorough optimization of the system at design time. Secondly, designers are faced with a reliability wall that emerges as age-related degradation reduces the lifetime of transistors, and as the probability of defects escaping post-manufacturing testing is increased. In this thesis, we take on these challenges within the context of streaming applications running in network-on-chip based parallel (not necessarily homogeneous) systems-on-chip that adopt the no-remote memory access model. In particular, this thesis tackles two main problems: (1) fault-aware online task remapping, (2) application-level self-adaptation for quality management. For the former, by viewing fault tolerance as a self-adaptation aspect, we adopt a cross-layer approach that aims at graceful performance degradation by addressing permanent faults in processing elements mostly at system-level, in particular by exploiting redundancy available in multi-core platforms. We propose an optimal solution based on an integer linear programming formulation (suitable for design time adoption) as well as heuristic-based solutions to be used at run-time. We assess the impact of our approach on the lifetime reliability. We propose two recovery schemes based on a checkpoint-and-rollback and a rollforward technique. For the latter, we propose two variants of a monitor-controller-adapter loop that adapts application-level parameters to meet performance goals. We demonstrate not only that fault tolerance and self-adaptivity can be achieved in embedded platforms, but also that it can be done without incurring large overheads. In addressing these problems, we present techniques which have been realized (depending on their characteristics) in the form of a design tool, a runtime library or a hardware core to be added to the basic architecture.


This chapter explores the general aspects of herbicide selectivity on plants, describing the various aspects of the topic, especially the action of herbicides on root crops and present‐ ing a case study with the suggestion of a methodology to evaluate herbicide action on roots in perennial culture and thus determine their selectivity. This study was carried out under field conditions, over a period of four years, where the effect of indaziflam and glyphosate herbicides on roots of Coffee and Citrus plants was evaluated. The results demonstrate that the methodology used to assess the effect of herbicides on the roots was important to validate and qualify safe herbicide selectivity towards crops. Thus, this anal‐ ysis should be indicated as a routine method for studies to assess the selectivity of herbi‐ cides to crops.


Abstract "All perceiving is also thinking, all reasoning is also intuition, all observation is also invention" Rudolph Arnheim Among the places found inside contemporary cities, a certain kind of space exists, the importance of which is often overlooked, even by those who are charged with creating them. This could be explained by the fact that, singularly, these spaces do not have a specific location, since they are in essence symbolic or conceptual in character. I am referring to our way of graphically representing our environment: maps. As will soon be explained, the map in itself is a place that substitutes the reality that it represents. It is a surrogate space that operates fundamentally through analogy and abstraction. The production and use of this type of space carries important implications in the configuration of our physical environment at any scale, be it that of a project, a city or the land. The transformative capacity of cartographic activity will be comparable here to project design, refuting the usual conception about both as having essentially different natures; project design is usually seen as being dynamic in character and tinged with specific actions leading to a transformation of the environment over time, while maps are reduced to being a static projection of an existing physical reality onto a smaller surface. The fundamental idea behind putting maps and projects on the same level rests on the fact that any form of spatial representation entails an exercise of acting upon the represented object.


Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by the aberrant expression of several growth-regulating, oncogenic effectors. Exportin 1 (XPO1) mediates the nucleocytoplasmic transport of numerous molecules including oncogenic growth-regulating factors, RNAs, and ribosomal subunits. In MCL cells, the small molecule KPT-185 blocks XPO1 function and exerts anti-proliferative effects. In this study, we investigated the molecular mechanisms of this putative anti-tumor effect on MCL cells using cell growth/viability assays, immunoblotting, gene expression analysis, and absolute quantification proteomics. KPT-185 exhibited a p53-independent anti-lymphoma effect on MCL cells, by suppression of oncogenic mediators (e.g., XPO1, cyclin D1, c-Myc, PIM1, and Bcl-2 family members), repression of ribosomal biogenesis, and downregulation of translation/chaperone proteins (e.g., PIM2, EEF1A1, EEF2, and HSP70) that are part of the translational/transcriptional network regulated by heat shock factor 1. These results elucidate a novel mechanism in which ribosomal biogenesis appears to be a key component through which XPO1 contributes to tumor cell survival. Thus, we propose that the blockade of XPO1 could be a promising, novel strategy for the treatment of MCL and other malignancies overexpressing XPO1.


This article presents a theoretical study on an optical module (OM) that can be inserted between an object under investigation and a Fourier-domain optical coherence tomography system, transforming the latter into a polarisation-sensitive optical coherence tomography optical coherence tomography (OCT) system. The module consists of two electro-optic modulators, a Faraday rotator, a linear polariser and a quarter-wave plate. A detailed description on how the module can be used to extract both the net retardance and the fast axis orientation of a linear birefringent sample is presented. This is achieved by taking two sequential measurements for different values of retardance produced by the electro-optic modulator. The module keeps measurements free from undesired polarimetric effects due to birefringence in the single-mode optical fibre and diattenuation in fibre-based couplers within OCT systems. Simulations have been carried out in order to evaluate the effects of chromatic behaviour of the components within the OM.


In this paper we present a fundamental lexical semantics of Sinhala language and a Hidden Markov Model (HMM) based Part of Speech (POS) Tagger for Sinhala language. In any Natural Language processing task, Part of Speech is a very vital topic, which involves analysing of the construction, behaviour and the dynamics of the language, which the knowledge could utilized in computational linguistics analysis and automation applications. Though Sinhala is a morphologically rich and agglutinative language, in which words are inflected with various grammatical features, tagging is very essential for further analysis of the language. Our research is based on statistical based approach, in which the tagging process is done by computing the tag sequence probability and the word-likelihood probability from the given corpus, where the linguistic knowledge is automatically extracted from the annotated corpus. The current tagger could reach more than 90% of accuracy for known words.


TURBULENT CIRCULAR CULVERT FLOW: IMPLICATIONS TO FISH PASSAGE DESIGN Amin Mohebbi, Ph.D. University of Nebraska, 2014 Advisor: Junke Guo Culverts are popular conveyance structures in America and Canada to be used as a fish passage or in sewage collection and disposal systems. Fish passage design criteria is based on biological capabilities of fish whereas it should satisfy hydraulic and hydrological constraints as well. Failing to provide enough low velocity regions for aquatic organisms may result in their mass extinctions. Currently, proper road crossing design depends on either model studies or numerical simulations via Computational Fluid Dynamic (CFD) packages, both of which are expensive and time consuming. Further, although the design procedures released by FHWA recently ensures safe fish migration from downstream toward upstream, it results in an unnecessarily large cross-sections increasing the overall project cost. In addition, the extensively used Manning model is not capable of providing local velocities or modeling the maximum velocity position (dip phenomenon). This study describes an attempt to solve Reynolds-Averaged Navier-Stokes Equations (RANS) for a steady state and uniform circular open channel flow at mild slopes, resulting in an analytical solution for a partially-filled pipe velocity distribution. Moreover, an empirical model based on the modified log-wake (MLW) law from previous knowledge of rectangular open channel flow was developed to further shed light on the topic. Both models were verified with experimental data collected with Stereoscopic Particle Image Velocimetry (S-PIV) through the work of the writer in the Turner-Fairbank Highway Research Center of the Federal Highway Administration and various other benchmark data from the literature. These models can be used as a novel and powerful design tool resulting in an optimum cross-section along with an enough low velocity region to facilitate safe fish passage.


There is an increased market demand of "smart" sensor systems, both from system and product developers as well as end users. The first generation intelligent sensor systems are sensors with some limited processing capacity that may be used for processing or compressing data, or sending data, calculating average etc. Our proposed definition of the second generation intelligent sensors are that they are capable of behaviour, that a human would classify as intelligent if seen in s sensor. This functionality may be integrated into the hardware, or in the sensors control program. Example of such functionality may be to identify if the sensor is fully functional and self-calibrating properties. The sensor may also send confidence estimation on how confident it is in the current sensor readings. The sensor may also learn to recognise different internal and external disturbances, e.g. learn how the signal of a close mobile phone influences the sensor readings and correct the readings. Some sensors may also have delegated responsibilities, e.g. turn some sensitive equipment of if they detect some serious conditions needing immediate action, and where a human or centralized response would not be able to arrive in time. This could be to lower the clock speed to avoid overheating. If sensors are equipped with communication capabilities then an intelligent sensor could be classified as an agent. Wooldridge and Jennings (1995) defines agents to be computer systems (hardware and software, able to observe its environment and influence its environment) that have properties such as: • autonomy • social abilities • reactivity and pro-activeness This does not necessarily mean that they have to be designed and implemented with different methods than today. Methods and techniques from artificial intelligent (AI), such as agents or learning systems are today implemented with main steam methods and techniques. The difference is what the requirements are and it is a different way of thinking, often opening a door to new solutions, not always thought of when taking an incremental approach to improvement and extended functionality. Suggested important properties in an agent based approach to sensors are: 1. flexibility and decentralised decision making. 2. localized learning and experience reuse. 3. learning and experience sharing between agents with similar tasks. 4. ability to collaborate with other agents or even humans This functionality could be implemented both in hardware or software. An interesting question is how a sensor handles feedback, both positive and negative. Other interesting opportunities arise when sensors communicate, e.g. sensors may have limited knowledge on their functionality and relation. This enables an intelligent sensor to verify its own functionality by comparing its own readings with other sensor readings. Also learning optimal intervals for cleaning or recalibrations may be such an option. If these sensors are part of a complex centrally controlled process, the process may preserve some basic behaviour if the central control process is experiencing some dysfunctions. Methods and techniques from artificial intelligence area already widely used in many areas but also offer interesting and potential valuable benefits also to areas not traditionally thought of when speaking of AI, e.g. microsystems.


Iraq has a variety of geomorphological landscapes, because of the varied and beautiful desert landforms and these forms may tell us the tectonic history on a long term and also the climate of this part of the Arabian plate. Tar Al-Sayed and Tar Al-Najaf area have geomorphological landscapes that are variable and reflect different exogenic processes and these features been observed in the field are: Barchans and sand sheet which are mobile features, and they are widespread, but the smallest Geomorphological Landscapes are wind ripples, other features are Mesas and escarpments as a result of the erosion of sequences of sedimentary rocks. Also, butte these are flattened top hills, Zeugen obvious feature in the study area found in soft strata been eroded by the wind. In the areas where the wind erosion predominates over water erosion in moulding some of these features. Yardangs are wind- roded, aerodynamic hills. Tafoni Caves are arch-shaped entrances sized several centimeters to several meters in diameter and depth. When weathering together with mass collapse found, then Natural Arches formed. They most commonly occur in sandstone and claystone. Slope Instability which it is extensively landslide phenomena. The Drainage Systems in the study area have dendritic pattern and it is the most predominant. Some of the features composed of fluvial sediments as in Alluvial Fans.


The paper presents a numerical analysis of the unstable behaviour of a pump-turbine operating in turbine mode near the no-load condition. The entire machine, including the adduction and draft tube, was modelled and leakage flow rates were also considered in the numerical simulations. To validate the numerical model, transient simulations were carried out by means of AnsysCFX 14 on the pump-turbine model in stable operating conditions and the resulting performance was compared with the experimental ones. Then, to study in-depth the unsteady phenomena which lead to the S-shape of the turbine characteristic, an unsteady numerical analysis, running through the flow-speed characteristic up to the pump-turbine brake zone during load rejection, was carried out. The flow rate was decreased at each time step, defined according to an impeller rotation of one degree, and about 20 impeller revolutions were necessary to completely define the unstable operating area.


The effect of tool traverse speed on microstructure and mechanical properties of friction stir welded 7020-T6 aluminum alloy was investigated. For this purpose, 5 mm thick 7020-T6 aluminum alloy plates were friction stir welded at traverse speeds of 50, 100, 150, and 200 mm/min and constant rotational speed of 900 r/min. Also, the peak temperatures of the joints during friction stir welding were recorded by accurate thermocouples. Moreover, the microstructure, hardness, tensile properties, and fracture surfaces of the joints were examined. The results showed that increasing the tool traverse speeds from 50 to 200 mm/min decreased the peak temperature from 331 ℃ to 211 ℃, and hence caused to lower heat input during friction stir welding. Furthermore, the higher hardness and ultimate tensile strength of the joints welded at higher traverse speeds was related to the grain boundary, precipitation, and substructure strengthening mechanisms. In addition, the fracture surfaces of the joints welded at higher heat input conditions showed more ductile mode in comparison with those welded at lower heat input condition, which confirmed the lower tensile elongation of the joints welded at higher traverse speeds.


Grid synchronization is an important part in the control of grid-connected power electronic converters. The fundamental phase-angle at the point of common coupling should be tracked on-line in order to control energy transfers. Digital implementation allows to implement high performance algorithms, which are robust in the presence of power quality phenomena. However, different kinds of distortion cause a reduction of the effective bandwidth, and hence, affects to the transient response of the equipment. This paper reviews some of the highest performance algorithms for grid synchronization: phase locked loops (PLL), schemes based on synchronous reference frames (SRF) and digital filtering and finally, stochastic filtering based methods. The pros and cons of each one are assessed and some interesting techniques to enhance the dynamics are provided. The assessment in the presence of frequency deviations is analyzed in detail. The most significant techniques to provide a better frequency adaptation are enumerated and analyzed in the last section of this paper.


As a widely consumed spice and traditional Chinese medicine, Zingiber officinale Roscoe (ginger) has been used in the treatment of nausea, coughs, and colds. In this article, 18 new glycosides (1-18) and six known analogues (19-24) were isolated from the peel of ginger. The planar structures of these compounds were determined by using HR-ESI-MS and extensive spectroscopic techniques (UV, IR, 1D-NMR, and 2D-NMR). Their relative and absolute configurations of the stereogenic centers in the new natural products were determined by analysis of NMR data, using a quantum mechanical NMR approach and time-dependent density functional theory based electronic circular dichroism calculations. The renal fibrosis activities of the isolated natural products together with those of 6-gingerol (6-Gi), 8-gingerol (8-Gi), and 10-gingerol (10-Gi) were evaluated in TGF-β1 induced NRK-52E cells. Compounds 9, 10, 15, 22-24, 6-Gi, 8-Gi, and 10-Gi were found to be active toward extracellular matrix, indicating that they have potential renal fibrosis activities.


Aims
This research project aims to explore a variety of qualified early years' practitioner's from a selection of state and privately run early years' establishments. It will critically investigate early years' practitioner's experiences and expectations when caring for and supporting children experiencing the adoption process. The practitioner's role is
specified in early years' settings, and critically analyses whether practitioners receive substantial training in supporting children experiencing insecure attachments (Nutbrown, 2012). The research focuses on the experiences of adopted/looked-after children and identifies various psychological and behavioural outcomes that became
evident through the literature review. The theoretical foundations for this research sit in the attachment theory (Bowlby, 1977), which is used as a basis for understanding children who have experienced broken relationships and are expressing concerning behaviour attributes. Attachment theory is used here to show an awareness through
the review of literature; of the connection between broken relationships, the adoption process and the child's behaviour and development (Smith et al, 2000).One of the predominant aims of this research was to investigate the training that
practitioners have partaken, concentrating on whether the participants became educated in the attachment theory before they became child care practitioners or whether an additional on-site attachment theory training was endured. It explores
whether state or privately run early years' establishments held the higher level of support for children experiencing insecure attachments. The aim of this part of the research is to display an absence of knowledge and understanding of the attachment theory in early years' settings (Nutrown, 2012).
Methodology
This qualitative research was carried out using the semi-structured interviewing method. This method was specifically chosen to gain more understanding of the experiences the participants share during the interview. By observing body
languages (Thomas, 2013), sensing emotion and possessing eye contact allowed a rapport to build between the researcher and participant. Choosing this method has allowed reflexivity to materialise throughout the research project (Thomas, 2013), this gives a meaning and assists a 'story telling' style to present the motivation towards why this research is being carried out (Webb-Mitchell, 1995). Discussionssurrounding ethical issues and problems that could influence the reliability of the research become evident. It is ensured objectivity is maintained throughout this project as the topic is a personal matter.
Conclusions
It is hoped that the findings of this research project will inform early years' practitioners in the importance of the attachment theory in connection with the adoption process. This research has drawn attention and focus to a gap in child care qualifications level two and three (Nutbrown, 2012). The research project concludes that an unexpected and 'unprofessional' level of stigmatism is evident in early years' settings. Perhaps further uses for the findings in this research may show awareness and inform future collaborative personnel for future improvements when taking the care and support for children experiencing the adoption process into consideration.


The abundance of an aggressive Australian honeyeater, the Noisy Miner Manorina melanocephala, was reduced at four small (<8 ha) Grey Box Eucalyptus microcarpa woodland remnants by experimental removal. The diversity and abundance of small insectivorous and nectarivorous birds increased at three of the four sites (relative to matching control sites) over the twelve months following the removal of the Noisy Miners. The one exception occurred at a pair of sites where eucalypts began flowering at one site and finished at the other during the Noisy Miner removal period. These results, taken together with those from three earlier experiments where the abundance of Noisy Miners was reduced in Mugga Ironbark E. Sideroxylon woodland remnants, demonstrate that Noisy Miners affect avian diversity and abundance by aggressive exclusion of other species. In five out of seven experiments, Noisy Miners did not reinvade the small woodland remnants during the ensuing twelve months. When Noisy Miner abundance was reduced, increased populations of small insectivorous and nectarivorous birds used small degraded woodland remnants. Colonizing populations of small birds have the potential to reduce insect infestations and may assist in the recovery of dieback-affected woodland remnants. Research is continuing to test this hypothesis. Reducing the abundance of Noisy Miners in remnant eucalypt woodlands may also be a useful, short-term measure, which could assist in the recovery of threatened or endangered bird species.


In the automatic imitation task (AIT) participants make a cued response during simultaneous exposure to a congruent or incongruent action made by another agent. Participants are slower to make the cued response on incongruent trials, which is thought to reflect conflict between the motor representation activated by the cue and the motor representation activated by the observed action. On incongruent trials, good performance requires the capacity to suppress the imitative action, in favor of producing the cued response. Here, we introduce a new experimental paradigm that complements the AIT, and is therefore a useful task for studying the control of self and other activated representations. In what we term the "Controlled Imitation Task (CIT)", participants are cued to make an action, but on 50% of trials, within 100 ms of this cue, an on-screen hand makes a congruent or incongruent action. If the onscreen hand moves, the participant must suppress the cued response, and instead imitate the observed action as quickly and accurately as possible. In direct contrast to the AIT, the CIT requires suppression of a self-activated motor representation, and prioritization of an imitative response. In experiment 1, we report a robust pattern of interference effects in the CIT, such that participants are slower to make the imitative response on incongruent compared to congruent trials. In experiment 2, we replicate this effect while including a non-imitative spatial-cue control condition to show that the effect is particularly robust for imitative response tendencies per se. Owing to the essentially opposite control requirements of the CIT versus the AIT (i.e., suppression of self-activated motor representations instead of suppression of other-activated motor representations), we propose that this new task is a potentially informative complementary paradigm to the AIT that can be used in studies of self-other control processes.


In this paper, we evaluate the performance of multiple machine-learning methods in the emulation of agent-based models (ABMs). ABMs are a popular methodology for modelling complex systems composed of multiple interacting processes. The analysis of ABM outputs is often not straightforward, as the relationships between input parameters can be non-linear or even chaotic, and each individual model run can require significant CPU time. Statistical emulation, in which a statistical model of the ABM is constructed to allow for more in-depth model analysis, has proven valuable for some applications. Here we compare multiple machine-learning methods for ABM emulation in order to determine the approaches best-suited to replicating the complex and non-linear behaviour of ABMs. Our results suggest that, in most scenarios, artificial neural networks (ANNs) and support vector machines outperform Gaussian process emulators, currently the most commonly used method for the emulation of complex computational models. ANNs produced the most accurate model replications in scenarios with high numbers of model runs, although training times for these emulators were considerably longer than for any other method. We propose that users of complex ABMs would benefit from using machine-learning methods for emulation, as this can facilitate more robust sensitivity analyses for their models as well as reducing CPU time consumption when calibrating and analysing the simulation.


1. About one-third of the CO(2) fixed during photosynthesis by washed suspensions of Chlorobium thiosulfatophilum strain 8346 gave rise to alpha-oxoglutarate and branched-chain oxo acids, mainly beta-methyl-alpha-oxovalerate. Another one-third to one-half gave rise to a polyglucose. 2. The fixation of CO(2) was inhibited by fluoroacetate, increasing concentrations up to 1mm stimulating the accumulation of alpha-oxoglutarate and causing a decrease in the formation of the branched-chain oxo acids and polyglucose. 3. Acetate was converted into the same products as was CO(2). 4. Fluoroacetate (1mm) had a negligible effect on the formation of polyglucose from acetate and caused a slight inhibition of the formation of the branched-chain oxo acids and increased accumulation of alpha-oxoglutarate. 5. Iodoacetate (1mm) strongly inhibited polyglucose formation from acetate and caused accumulation of pyruvate. The formation of the branched-chain oxo acids from acetate was only slightly affected by this inhibitor. 6. Pyruvate can be metabolized by this organism in the presence of a suitable electron donor whether CO(2) is present or not. In the absence of CO(2) pyruvate is converted into polyglucose. 7. The accumulation of oxo acids during CO(2) fixation is completely inhibited by NH(4) (+) ions. The formation of the branched-chain oxo acids is considerably decreased by the presence of isoleucine, leucine or valine, or a mixture of these. 8. CO(2) fixation in two other strains of Chlorobium appears to exhibit a similar pattern to that in C. thiosulfatophilum strain 8346. 9. It is concluded that in washed suspensions, CO(2) is fixed mainly by a mechanism involving the reductive carboxylic acid cycle. Acetate, the product of the cycle, is converted into polyglucose via pyruvate synthase and a reversal of glycolysis or into branched-chain oxo acids by an unknown mechanism.


Both the news media and citizens have been blamed for citizens' lack of political sophistication. Citizens' information source choices can certainly contribute to suboptimal results of opinion formation when citizens' media menus feature few, redundant, or poor-quality outlets. How strongly news consumers' choices affect the quality of information they receive has rarely been investigated, however. The study uses a novel method investigating how content-as-sent translates into content-as-received that is applicable to high-choice information environments. It explores quality-as-sent and quality-as-received in a content analysis that is combined with survey data on news use. This study focuses on 'selection quality' measured in terms of scope and balance of subtopic units, information units, and protagonist statements sent/received. Regarding quality-as-sent , the scope of news proves to be lowest in TV news and substantially greater for online news and newspapers; imbalance of coverage varies only moderately between outlets. As for quality-as-received, the scope citizens received was only a small fraction of what the news outlets provided in combination or what the highest-quality news outlet provided, but was close to what one average news outlet provided. There was substantial stratification in the extent to which news coverage quality materializes at the recipient level. Scope-as-received grew mainly with using more news, relatively independent of which specific news outlets were used. Imbalance-as-received, however, was a function of the use of specific outlet types and specific outlets rather than the general extent of news use. Using additional news media improved the quality-as-received, invalidating the notion that different news outlets merely provide "more of the same."


The problem of isosurface extraction in uncertain data is an important research problem and may be approached in two ways. One can extract statistics (e.g., mean) from uncertain data points and visualize the extracted field. Alternatively, data uncertainty, characterized by probability distributions, can be propagated through the isosurface extraction process. We analyze the impact of data uncertainty on topology and geometry extraction algorithms. A novel, edge-crossing probability based approach is proposed to predict underlying isosurface topology for uncertain data. We derive a probabilistic version of the midpoint decider that resolves ambiguities that arise in identifying topological configurations. Moreover, the probability density function characterizing positional uncertainty in isosurfaces is derived analytically for a broad class of nonparametric distributions. This analytic characterization can be used for efficient closed-form computation of the expected value and variation in geometry. Our experiments show the computational advantages of our analytic approach over Monte-Carlo sampling for characterizing positional uncertainty. We also show the advantage of modeling underlying error densities in a nonparametric statistical framework as opposed to a parametric statistical framework through our experiments on ensemble datasets and uncertain scalar fields.


Soil-transmitted helminths are among the neglected tropical diseases (NTDs) of poverty. They are a common type of parasitic infections in the world, caused by three main species commonly known as roundworms, whipworms, and hookworms. The diseases have major health and socio-economic repercussions and significantly contribute to public health problems in developing countries.

 This study investigated the prevalence, intensity, and factors associated with soil-transmitted helminths among children in Chililabombwe district of Zambia.

 A cross-sectional design was used, consisting of 411 guardian – child pairs aged between 17-77 years and 1-15 years, respectively. This was conducted between October and December 2017. Systematic sampling and simple random sampling were used to select the household and 411 participants, respectively. The study used a structured pre-tested questionnaire and stool tests to obtain information on socio-demographic, environmental, behavioral, and service-related factors associated with helminth infection. Stool samples were collected and examined for the presence of parasites using formol-ether concentration and Kato-Katz techniques. Geometric mean was used to report the intensity of infection. An investigator-led stepwise regression was used to identify factors associated with developing Soil-Transmitted Helminth infection and the level of significance was set at 0.05.

 Prevalence of soil-transmitted helminth infection was 59/411 (14.4%) and the most dominant parasite was roundworms 58/411 (14.1%). The overall intensity of infection was light (<5000epg) with a few heavy infections (>50000epg). Factors independently associated with soil-transmitted helminth infection after adjusting for other variables were residence (AOR=0.26; 95% CI [0.09-0.73]), household income (AOR=2.49; 95% CI [1.01-6.12]), and overcrowding (AOR =1.33; 95% CI [1.09-1.62]).

 Our findings indicate that STH infections are still prevalent. Low household income, residence, and overcrowding are the factors associated with infection. This indicates that reinfection is common even after deworming.


A scaffolding role for YAP in cytokinesis and a role for the cell cycle kinase BUB1 at the TGF-β receptor are revealed. An emerging theme in regulatory biology is the identification of "noncanonical" mechanisms of activation of downstream effectors and "noncanonical" roles of signaling proteins. This week's issue of Science Signaling includes a paper that describes one of these "moonlighting" functions for the protein YAP, which is best known as a transcriptional regulator involved in the regulation of cell size and proliferation downstream of the Hippo kinase cascade. Bui et al. discovered a role for YAP in mitotic cells. The cell cycle kinase CDK1 phosphorylated YAP, which directed YAP to the site of cytokinesis. Cells that could not direct YAP to the cytokinesis midbody failed to recruit proteins associated with regulation of the contraction needed to divide the cells into the two separate daughters. Thus, in interphase YAP functions as a transcriptional regulator, whereas in mitotic cells YAP helps organize the cytokinesis machinery. In a similar study, Nyati et al. found an unexpected association of the cell cycle kinase BUB1 with the receptor complex for transforming growth factor–β (TGF-β). In mitotic cells, BUB1 promotes chromosome alignment at the spindle and is necessary to ensure that each daughter cell gets the correct complement of chromosomes. BUB1 now has a role in interphase cells, where it interacts with TGF-β receptors, stabilizes the ligand-bound receptor complex, and promotes downstream signaling. Maybe we should be less surprised that proteins have different regulatory functions in dividing cells and nondividing cells; because the subcellular organization is so different in these contexts, proteins will have opportunities to interact with different partners. Science Signaling is interested in studies that investigate these moonlighting functions and anticipates that the terms "canonical" and "noncanonical" will have less and less meaning as more researchers explore different readouts of regulatory proteins and networks. D. A. Bui, W. Lee, A. E. White, J. W. Harper, R. C. J. Schackmann, M. Overholtzer, L. M. Selfors, J. S. Brugge, Cytokinesis involves a nontranscriptional function of the Hippo pathway effector YAP. Sci. Signal. 9, ra23 (2016). [Full Text] S. Nyati, K. Schinske-Sebolt, S. Pitchiaya, K. Chekhovskiy, A. Chator, N. Chaudhry, J. Dosch, M. E. Van Dort, S. Varambally, C. Kumar-Sinha, M. K. Nyati, D. Ray, N. G. Walter, H. Yu, B. D. Ross, A. Rehemtulla, The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-β signaling. Sci. Signal. 8, ra1 (2015). [Full Text]