While the isolation and culture of vascular smooth muscle cells (VSMCs) from large vessels is well established, we sought to isolate and culture VSMCs from the coronary circulation. Hearts with intact aortic arches were removed and perfused via retrograde Langendorff with digestion solution containing 300 Units/ml of collagenase type II, 0.1 mg/ml soybean trypsin inhibitor and 1 M CaCl2. The perfusates were collected at 15 min intervals for 90 min, pelleted by centrifugation, resuspended in plating media, and plated on tissue culture dishes. VSMCs were characterized by presence of SM22α, α-SMA, and vimentin. One of the main advantages of using this technique is the ability to isolate VSMCs from the coronary circulation of mice. Although the small number of cells obtained can limit some of the applications for which the cells can be utilized, isolated coronary VSMCs can be used in a variety of well-established cell culture techniques and assays. Studies investigating VSMCs from genetically modified mice can provide further information about structure-function and signaling processes associated with vascular pathologies.


The parabolic-profile model for the singularity spectrum f(α) of fully-developed turbulence (FDT) is pursued further. This model is shown to provide not only considerable insight into the qualitative aspects of the intermittency problem but also the universal aspects associated with it. The parabolic-profile model also affords, unlike the multi-fractal model, an analytical calculation of probability distribution functions of flow-variable gradients in several FDT cases. Permanent Address: University of Central Florida, Orlando, Florida


Maternal ecdysteroids regulate a variety of cellular processes during early embryonic development of insects, yet little is known about the genes involved in the biosynthesis of these hormones. In this study, we found that ecdysone oxidase (EO) gene, which encodes an enzyme to catalyze ecdysone (or 20-hydroxyecdysone, 20E) to 3-dehydroecdysone (3DE), was highly expressed in the mature ovaries of the domestic silkworm, Bombyx mori. B. mori EO (BmEO) was localized in the cytoplasm around the yolk granules of oocyte. Furthermore, the down-regulated expression of the BmEO gene using RNA interference could not affect normal development of the female silkworm, but lower the 20E titer and hatching rate of its offspring. Rescue experiments by injecting the product (3DE) of BmEO can significantly elevate the 20E level and hatching rate of the BmEO RNAi offspring. Meanwhile, during embryonic stage, the down-regulating expression of 3DE-3β-reductase, which can reduce 3DE into ecdysone, also lowered the 20E titer. Taken together, our results prove that 3DE can be synthesized from ecdysone in maternal ovary yolk granules, and then the maternal 3DE is converted into active ecdysone during the early embryonic development of offspring. Thus, our findings reveal a new pathway to explain the origin of high 20E level before the formation the prothoracic gland in the silkworm.


Abstract An algorithm for the evaluatinion of discontinuity jumps in the DDE initial value problem is presented. That enables the use of the classical numerical methods for DDE initial value problem.


Purpose: To evaluate the diagnostic potential of a slit-lamp (SL)-adapted Fourier-domain (= spectral radar, SR) optical coherence tomography (OCT)—SL-SR-OCT—instrument as an in vivo imaging device for use in examinations of the anterior and posterior segments. Materials and Methods: In a pilot study, 88 eyes from 70 healthy volunteers and patients were examined using a prototype Fourier-domain SL-SR-OCT system. Results were compared to those from the following commercially available systems: the 1310-nm SL-OCT (Heidelberg Engineering, Heidelberg, Germany) for anterior segment and the Stratus OCT (Zeiss Meditec, Jena, Germany) for posterior segment imaging. Our SL-SR-OCT provides 1025 axial scans, 5000 Hz line-scan frequency, scan length of up to 8 mm, axial depth in air of 3.5 mm, and resolution of 9 μm. For posterior visualization, a hand-held 78-diopter ophthalmoscopic lens was used. Results: Our SL-SR-OCT system allowed simultaneous scanning with direct biomicroscopic and SL imaging of anterior and posterior segment structures. Anatomical structures and pathological changes were displayed with high resolution and excellent contrast. Measurements of corneal and retinal thickness were possible. In comparison to images obtained by the SL-OCT, our SL-SR-OCT boasted a higher resolution, thus providing more clinically relevant details of the corneal epithelium, internal structure of filtering blebs, etc. Complete imaging of the chamber angle was limited, however, due to the backscattering properties of the sclera at 830 nm. For posterior segment imaging, excellent delineation of the macula and optic nerve head details, with a distinct portrayal of macular pathology and retinal edema, was possible with SL-SR-OCT. Conclusion: SL-SR-OCT enables detailed imaging of physiological and pathological anterior and posterior segment structures. As a multi-purpose device, it offers a wide spectrum of applications, with high-quality OCT-imaging, in a comfortable setting without the need to move the patient.


The main objective is to develop integrated strategies, guidelines and capacity to increaseintegration of land use and transport planning in select cities in China. Some of the negative impacts and mitigation measures include: This project will focus on the parking facilities of the central urban area, emphatically discuss the parking supply strategies in different areas, improve the management level of existing parking facilities. Through mechanism innovation, it will improve the utilization rate of existing parking facilities and encourage transfer from motor vehicle transport to public transport, so as to mitigate the pressure on the central urban area's parking. The researches include: Analysis the parking status quo and parking demands of central urban area; research on the parking development strategy and management mechanism of central urban are, as well as the development of central urban area's parking industry. It is planned that the capacity for solving technical and project management problems will be improved through learning activities such as workshops, online electronic courses, seminars or field studies.


An infectious disease known as Coronavirus disease 2019 (COVID-19) has caused a worldwide health disaster. This issue also significantly impacted the world economy, including Malaysia. The government encourages business operators to shift to online business services to control the spread of the COVID-19 virus. This has caused most businesses, especially the food industry, to change their strategy by operating their company on online platforms. This research investigated the decision factors in online food delivery service selection, specifically amidst the COVID-19 outbreak in Malaysia. To achieve the study's objective; descriptive analysis, reliability analysis, correlation analysis and multiple linear regression analysis were applied. Safety, time, convenience and price value were the four factors examined. The result discovered that safety, time and price value significantly influence the selection of online food delivery services amidst the COVID-19 pandemic in Malaysia. Among those variables, time was the strongest explanatory factor. The findings of this study may assist the food distribution companies in Malaysia to improve and enhance their service quality to cater to various consumers' preferences.


Identifying deficiencies and monitoring the effectiveness of a pipeline's cathodic protection (CP) system can be difficult, expensive and time consuming — especially when the pipe is located in an area of difficult access. Now that CP may be monitored via in-line inspection tools (smart pigs), the status of CP systems can be confirmed and problems identified regardless of the location, accessibility, or condition of the pipeline right of way. An in-line inspection tool capable of reading and recording the magnitude and polarity of current supplied by cathodic protection has been developed and tested in a variety of pipelines. The results show that CP currents can be quickly, accurately and efficiently measured without access to the outside surface of the pipe. For difficult-to-access areas, the CPCM™ In-Line Cathodic Protection Inspection Tool provides for a reliable, cost-effective, and time-saving way to monitor, validate, or trouble shoot a pipeline's cathodic protection system. This paper will present results from field trials as well as the first commercial deployments of the technology. A discussion of how cathodic protection and pipeline features are identified will be included. This tool is the result of the joint development effort of Shell Pipeline Co. LP, Shell Global Solutions, Baker Hughes PMG and the US DOT.Copyright © 2008 by ASME


Tourism is a highly competitive industry and one of the fastest growing industries in the world. Developing countries have diverse reasons to use tourism as a strategy towards development. Developing countries have been using tourism to generate highly sought after foreign exchange to handle the problems of trade imbalance many of them are facing. Other reasons are to achieve international status, which symbolizes the country's ability to stand on the global stage, using tourism as a mechanism to co-integrate and unify countries that have multi-ethnic population and used as a platform where public money is invested in attempt to enhance the socio-economic wellbeing of deprived local population. The ICTs revolution also has a significant impact to the world tourism industry. However, this Internet revolution is viewed as a double-edged sword for entrepreneurs and small business owners. Through the effective use of e-commerce, small and medium tourisms Enterprises can access new markets and serve new customer. Yet, it will thrust them into a whole new marketplace, where they will experience increased competition from other business and well-established giant that come from well outside of their normal market reach. Therefore, small and medium tourism enterprises (SMTEs) have to adopt innovative and informed e-marketing strategies to be distinct and profitable. In the last three decades, Yogyakarta has grown rapidly as a tourist centre and becoming the third most visited destination by international travellers in Indonesia (after Jakarta and Bali). One potential tourist attraction in Yogyakarta is the region Giriloyo Hamlet, Village Wukirsari, Imogiri, Bantul regency, Yogyakarta (DIY). The potential products of Wukirsari village are the tomb or graves of the kings of Mataram as a tourist destination, batik as a souvenir, learning batik as a study tour project, and also its traditional foods and drink. However, information about Wukirsari village and its attraction is not yet disseminate regularly by Internet, although there are several static website that gives information about Wukirsari and offering no e-commerce facilities. Wukirsari itself already have websites that was established by the help of university student that were doing their field project. However, those websites are not well maintained and not up-to-date. These problems arise because they don't have the skilled human resource for maintaining the website after the student finished their field project. In addition, there are limited telecommunication and internet connection network (infrastructure) in Wukirsari. Policy makers and the SMTEs should work together to increase awareness of e-commerce through training and education for stakeholders, employees and consumers. E-commerce cannot be implemented without


Abstract A theory of conceptual development must provide an account of the innate representational repertoire, must characterize how these initial representations differ from the adult state, and must provide an account of the processes that transform the initial into mature representations. In The Origin of Concepts (Carey 2009), I defend three theses: (1) the initial state includes rich conceptual representations, (2) nonetheless, there are radical discontinuities between early and later developing conceptual systems, (3) Quinean bootstrapping is one learning mechanism that underlies the creation of new representational resources, enabling such discontinuity. Here I argue that the theory of conceptual development developed in The Origin of Concepts constrains our theories of concepts themselves, and addresses two of Fodor's challenges to cognitive science; namely, to show how learning could possibly lead to an increase in expressive power and to defeat Mad Dog Nativism, the thesis that all concepts lexicalized as mono-morphemic words are innate. In response to Fodor, I show that, and how, new primitives in a language of thought can be learned, that there are easy routes and hard ones to doing so, and that characterizing the learning mechanisms in each illuminates how conceptual role partially determines conceptual content.


During the normal menstrual cycle, endometrial tissue undergoes many biochemical and morphological changes which are under the control of steroid hormone levels. DNA methylation plays a key role in gene expression regulation and influences functional changes in endometrial tissue. Eliminating senescent cells from the functional layer of the endometrium is mediated by apoptotic cell death, which helps maintain cellular homeostasis. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and thus apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients with advanced disease. Despite intensive study of the cancer epigenome, there is missing information about disrupted apoptotic gene regulation in DNA methylation levels. Therefore, it is necessary to spread our knowledge in the field of epigenetics to help us differentiate normal and cancer tissues and detect the early stages of cancer disease.


Previous studies have linked life events with depression in chronic schizophrenia, but those studies had methodological limitations. Using a prospective research design and examining events that were clearly independent of the patients' illnesses, the authors sought to determine whether stressful life events could trigger depressive symptoms in the early course of schizophrenia. Schizophrenia patients (n = 99) were followed for 1 year from a point of outpatient stabilization. Life event interviews were conducted every 4 weeks and symptom assessments every 2 weeks. Survival analyses showed a significantly increased risk for an exacerbation of significant depressive symptoms following an independent life event. Of interest is that an analysis of competing risk showed that the odds of psychotic exacerbation following a major independent life event were not significantly greater than the odds of depressive exacerbation. The risk of depression and of psychosis after experiencing a stressful life event is significantly increased for the first month, but the risk period can extend to 3 months.


Coming from India, where two-wheelers form a major portion of the traffic, accidents due to loss of balance are common place. The self balancing two-wheeler project was initially started to decrease these accidents and as the project took shape it also grew into an intuitive trainer, helping the rider hone balanacing skills. This book, takes you through the basics of the principles involved in balancing a two-wheeler - contact polygon and gyroscopic effect. It explores the stability of a two-wheeler and also the previous attempts made to balance it. The combination of the concepts and the integration of the principles along with the proof of concepts are covered. It also guides you through the steps of building a basic system to realise the aforementioned goal. Both the construction and the problems involved are discussed and scope for future work defined. Two-wheeler manufacturers and university students looking for the next innovation and improvement in existing two-wheeler technology should find this work interesting.


In the present study some aspects of Sertoli cells of testicular-biopsy specimens of children from 0 to 8 years old are examined. We can distinguish two main morphological situations. In the first one, Sertoli cells with monomorphic aspect can be seen; in the second can be shown Sertoli cells with various aspects. In this polimorphic situation we can distinguish three Sertoli cell types differing in cellular shape, cytoplasme electron-density and amount of RER and Golgi complex.


The electron spin resonance doublet indicating the width of the two spinon continuum in a spin-1/2 triangular-lattice Heisenberg antiferromagnet Cs2CuCl4 was studied in high magnetic field. The doublet was found to collapse in a magnetic field of a half of the saturation field. The collapse of the doublet occurs via vanishing of the high frequency component in a qualitative agreement with the theoretical prediction for the S=1/2 chain. The field of the collapse is, however, much lower than expected for the S=1/2 chain. This is proposed to be due to the destruction of frustration of interchain exchange bonds in a magnetic field, which restores the 2D character of this spin system. In the saturated phase the mode with the Larmor frequency and a much weaker mode downshifted for 119~GHz are observed. The weak mode is of exchange origin, it demonstrates a positive frequency shift at heating corresponding to the repulsion of magnons in the saturated phase.


Objective: The specific effect of endothelial (eNOS) and neuronal (nNOS) NO-synthase on cardiovascular system was confirmed in young and adult normotensive rats. During the prehypertensive period, information related to a long-term nitric oxide (NO) inhibiton is incomplete (eNOS) or completely missing (nNOS). The aim of this study was to investigate the effect of chronic inhibition of constitutive NO-synthase isoforms on cardiovascular system of 4-weeks-old spontaneously hypertensive rats (SHR). Design and method: 4-weeks-old SHR were treated by 7-nitroindazole (7-NI, specific inhibitor of nNOS, 10 mg/kg/day) or NG-nitro-L-argine methylester (L-NAME; non-specific inhibitor of NOS, 50 mg/kg/day, p.o.) during 6 weeks. Systolic blood pressure (sBP) was measured by the plethysmographic method. The vasoactive responses of thoracic aorta (TA) and mesenteric artery (MA) were measured as changes in isomentric tension. NOS activity was measured in TA using radioactive assay. Results: After treatment with 7-NI the sBP was unchanged, the treatment with L-NAME initiated an increase of sBP in the 4th week of the experiment. The contractile responses were signifcantly increased in both experimental groups. Regarding the L-NAME group the increased contractility was associated with increased sensitivity of adrenergic receptors whereby in 7-NI group an increase of absolute contration was observed. After treatment of L-NAME the contractile responses of MA were decreased as the result of the collapse of the contractile apparatus, the treatment with 7-NI did not affect these responses. The long-term NO inhibition induced no (7-NI) or only a slight (L-NAME) inhibitory effect on endothel-depentent relaxation to acetylcholine (ACh). NOS acitivity was decreased by 50% in both experimental groups. However, an acute administration of L-NAME induced not only an increased adrenergic vasoconstriction but also an inhibition of acetylcholine-evoked vasorelaxation proving a well-preserved production of NO in all followed groups. Conclusions: Results confirmed the specificity of nNOS a eNOS signalization in prehypertensive SHR as well heterogenity in vasoactive responses of elastic (HA) and muscular (MA) types of arteries. HA disposes of compensatory mechanisms in condition of non-specific NO deficiency: adaptive contractile abilities assosiated with activation of NO-derived vasorelaxation which could later compensate effect of sympatic nervous system. Supported by VEGA-2/0074/14; VEGA-2/0067/14; MZ-2012/51-SAV-1.


This study aims to apply Halliday's (Halliday & Hasan, 1976) concept of cohesion using Dooley and Levinsohn's (2001) model of morphosyntactic pattern to Azeri Turkish narratives in an attempt to uncover narrative and morphosyntactic pattern relation. The corpus contains eleven short stories in Azeri Turkish. Findings of the study revealed that echoic utterance as a subtype of the morphosyntactic pattern may be used to mark the narrative peak. Also, there is a violation of morphosyntactic pattern in the corpus. This violation uses the historical present to draw the audience into a climatic situation. The study shows that echoic utterances can be regarded as links in a chain, functioning like cohesive ties in the text. The pragmatic notion, dramatic development, narrative peak, meaning construction, and implicature are also expressed by echoic utterances. Moreover, these discourse-pragmatic structuring constituents have been found to appear at the beginning, in the middle, and at the end of narratives to provide a basis for relating a sentence to its context or mental representation, make the hearer accompany the narrator during the whole story and maintain the unity of the narrative.


Background Recent legalization of therapeutic and recreational cannabis use makes it imperative to have an insight into odds and trends in young-onset stroke-related hospitalizations among cannabis users (18–49 years). Methods The National Inpatient Sample dataset (2007–2014) was utilized to assess national trends, odds of young-onset stroke-related hospitalizations, and outcomes among cannabis users vs. nonusers using provided discharge weights, strata, and cluster design. The rates are described per 100,000 hospitalizations among cannabis users and non-users. Results A total of 3,307,310 hospitalizations were identified among young adults with current or previous cannabis use. Of these, 34,857 (1.1%) were related to young-onset stroke. A relative increase of 13.92% (553 in 2007 to 630 in 2014; ptrend < 0.001) in young-onset stroke admissions was reported among cannabis users. The odds of any stroke (OR 1.16, 95% CI 1.14–1.19, p < 0.001) and acute ischemic stroke (OR 1.41, 95% CI 1.31–1.51, p < 0.001) hospitalizations were considerably higher among cannabis users as compared to nonusers. In-hospital mortality rates were increasing (3.7% to 4.3%) among cannabis users whereas decreasing (7.7% to 5.9%) in nonusers from 2007 to 2014 (ptrend < 0.001). The mean length of stay and the hospitalization charges showed increasing trends in cannabis-related young-onset stroke admissions. There was an increasing trend in young-onset stroke admissions among male cannabis users (578 to 701; ptrend < 0.001) but not among females (516 to 457; ptrend = 0.14). The maximum rise in the young-onset stroke-related admissions was seen in African Americans (743 to 996; ptrend < 0.001). Conclusions We identified rising trends and higher risk (16% higher of overall young-onset stroke, 41% higher of acute ischemic stroke) of stroke-related hospitalizations and worse outcomes among cannabis users aged 18–49 years from 2007 to 2014.


Traditional multiuser receiver algorithms developed for multiple-input-multiple-output (MIMO) wireless systems are based on the assumption that the channel state information (CSI) is precisely known at the receiver. However, in practical situations, the exact CSI may be unavailable because of channel estimation errors and/or outdated training. In this paper, we address the problem of robustness of multiuser MIMO receivers against imperfect CSI and propose a new linear technique that guarantees the robustness against CSI errors with a certain selected probability. The proposed receivers are formulated as probabilistically constrained stochastic optimization problems. Provided that the CSI mismatch is Gaussian, each of these problems is shown to be convex and to have a unique solution. The fact that the CSI mismatch is Gaussian also enables to convert the original stochastic problems to a more tractable deterministic form and to solve them using the second-order cone programming approach. Numerical simulations illustrate an improved robustness of the proposed receivers against CSI errors and validate their better flexibility as compared with the robust multiuser MIMO receivers based on the worst case designs


Large eddy simulations of three-dimensional turbulent compressible flows in curved duct of rectangular crosssection are presented. Strong secondary flows and turbulent structures are the typical features of this type of flow : these are responsible for most of the heat and mass transfer within the duct. Our goal is here to investigate the influence of the duct aspect ratio on the flow development. The results show that this parameter modifies the flow structures in terms of intensity and localisation. Thus it significantly influences the heat transfers when a higher temperature is imposed on the duct convex wall.


Lady's mantle (Alchemilla vulgaris L. syn. Alchemilla xanthochlora Rothm., Rosaceae) has been commonly used in folk medicine to heal inflammations in the mouth, bleeding of the nose, furuncules, gynaecological (menorrhagia and dysmenorrhoea), and gastrointestinal disorders. Although therapeutic indications for lady's mantle are non-specific diarrhoea and gastrointestinal complaints, it has been reported to exert, as well, a variety of biological activities, including wound healing, antimicrobial, neuroprotective, gastroprotective, cytotoxic, and antioxidant. Lady's mantle presents a valuable source of natural bioactive compounds, mostly phenolic compounds – a large amount of tannins, phenolcarboxylic acids, and flavonoids, being responsible for the abovementioned effects. In this work, a literature review of biological properties, investigated in in vitro and in vivo experiments in regard to the determined chemical profile is presented. In addition, the data reported are discussed, and the directions for further investigations are proposed.


The Andean drainage basins of Colombian deltas exhibit a very delicate variety of ecosystems and environments along its prolonged trajectory, which has made it particularly vulnerable to the onslaught of modernity and human activity. While the increasing intensity of natural disasters in tropical areas is often blamed on global warming, the causes might not be as intractable. Soil erosion and deforestation, both caused by unrestrained human activity, can affect deltas more profoundly. Many anthropogenic influences, including deforestation, an agriculture and pasture increase by 75%, poor soil conservation and mining practices, may have accounted for the overall increasing trends of sediment transport from rivers to Colombian deltas. According to our recent study of human activities in terms of deforestation, 32% of the observed variance in sediment transport from the Magdalena River to its delta could be explained by deforestation. Thus, the amount of sediment transported by the Magdalena to its delta plain, approximately 50 Mt annually, is probably due to deforestation. Also, the Patia River in the Pacific coast has witnessed an increase in sediment transport by 45% during the last decade, an increase mainly accounted for by deforestation. Drawing from Colombia's experience with man-made ecological modifications, this paper offers a preliminary discussion on the implications of human pressure on fluvial ecosystems and their deltas, with the hope that this information will better equip citizens and policymakers across the developing world.


Malicious software (malware) pose serious challenges for security of big data. The number and complexity of malware targeting Android devices have been exponentially increasing with the ever growing popularity of Android devices. To address this problem, multi-classifier fusion systems have long been used to increase the accuracy of malware detection for personal computers. However, previously developed systems are quite large and they cannot be transferred to Android platform. To this end, we propose Iterative Classifier Fusion System (ICFS), which is a system of minimum size, since it applies a smallest possible number of classifiers. The system applies classifiers iteratively in fusion with new iterative feature selection (IFS) procedure. We carry out extensive empirical study to determine the best options to be employed in ICFS and to compare the effectiveness of ICFS with several other traditional classifiers. The experiments show that the best outcomes for Android malware detection have been obtained by the ICFS procedure using LibSVM with polynomial kernel, combined with Multilayer Perceptron and NBtree classifier and applying IFS feature selection based on Wrapper Subset Evaluator with Particle Swarm Optimization.


A variable gain amplifier (VGA) topology utilising titanium dioxide (TiO 2 ) memristors is presented. The circuit is analysed based on recently published charge-controlled and voltage-controlled memristor models. The analysis includes a theoretical prediction of total harmonic distortion for the amplifier as a figure of merit. The theoretical results are supported with SPICE circuit simulation including a memristor macromodel.


Fusarium moniliforme is the primary fungus contaminating corn throughout the world. Fumonisin B1 (FB1) is the major metabolite of F. moniliforme. It has been shown that FB1 is the promoter and initiator of liver cancer in rat. The corn of Cixian, in Hebei Province, the high-risk area for esophageal cancer in China, is often contaminated by this fungus. A total of 21 corn samples were collected from households in the Cixian County. High levels of FB1 (88.90+/-13.1 microg/g) were found in 10 moldy samples, and low levels (1.40+/-0.50 microg/g) of FB1 were found in 11 apparently healthy corn samples. The positive detection rates of FB1 in moldy and normal samples were 100 and 90.9%, respectively. The frequency of FB1 contamination in the high-risk area is about twice that in the low-risk areas, and the average content of FB1 in samples from high-risk areas was approximately three times that from low-risk areas. Our data indicate that FB1-contaminated corn may be involved in the carcinogenesis of esophageal cancer in high-risk areas of North China.


Abstract This investigation is carried out to evaluate the repair and strengthening the techniques of elliptical paraboloid reinforced concrete shells with openings. An experimental program of several different techniques in repair and strengthening is executed. The materials, which are considered for strengthening, are; Glass fiber reinforced polymers GFRP at different position of the shell bottom surface, steel strip and external tie. They loaded by four concentrated loads affected on the corners of the opening. The initial and failure loads as well as the crack propagation for the tested shells at different loading stages, deflections and failure load for repaired and shells are recorded. A non-linear computer program based on finite element techniques is used to study the behavior of these types of shells. Geometric and materials nonlinearities are considered in the analysis. The efficiency and accuracy of computer program are verified by comparing the program results with those obtained experimentally for the control shell with opening and strengthened shells.


The extraction of the finite temperature heavy quark potential from lattice QCD relies on a spectral analysis of the real-time Wilson loop. Through its position and shape, the lowest lying spectral peak encodes the real and imaginary part of this complex potential. We benchmark this extraction strategy using leading order hard-thermal loop (HTL) calculations. I.e. we analytically calculate the Wilson loop and determine the corresponding spectrum. By fitting its lowest lying peak we obtain the real- and imaginary part and confirm that the knowledge of the lowest peak alone is sufficient for obtaining the potential. We deploy a novel Bayesian approach to the reconstruction of spectral functions to HTL correlators in Euclidean time and observe how well the known spectral function and values for the real and imaginary part are reproduced. Finally we apply the method to quenched lattice QCD data and perform an improved estimate of both real and imaginary part of the non-perturbative heavy Q ¯ Q potential.


The melanocortin 1 receptor (MC1R) mediates the tanning response through induction of cAMP and downstream pigmentary enzymes. Diminished function alleles of MC1R are associated with decreased tanning and increased melanoma risk, which has been attributed to increased rates of mutation. We have found that MC1R or cAMP signaling also directly decreases proliferation in melanoma cell lines. MC1R overexpression, treatment with the MC1R ligand, or treatment with small-molecule activators of cAMP signaling causes delayed progression from G2 into mitosis. This delay is caused by phosphorylation and inhibition of cdc25B, a cyclin dependent kinase 1-activating phosphatase, and is rescued by expression of a cdc25B mutant that cannot be phosphorylated at the serine 323 residue. These results show that MC1R and cAMP signaling can directly inhibit melanoma growth through regulation of the G2/M checkpoint.


1. The binding of [3H] dihydroalprenolol ((3H]DHA) to beta-adrenoceptors in cerebral cortex membranes (fraction P2) was studied after 13-day oral treatment of male Wistar rats with the Ca2(+)-antagonists nifedipine (20 mg/kg), verapamil (50 mg/kg), flunarizine (10 mg/kg) and with the calmodulin (CaM)-antagonist trifluoperazine (TFP) (3 mg/kg). 2. A significant reduction in the number (Bmax) of binding sites for [3H]DHA was established after the 3 Ca2(+)-antagonists as well as after TFP. 3. No changes in the affinity values (Kd) [3H]DHA binding were found in all treated groups. 4. The fluidity characteristics of the cerebral cortex membranes in nifedipine- and flunarizine-treated rats did not differ from those in controls. 5. Based on these results, we concluded that long-term treatment with Ca2(+)- and calmodulin-antagonists might induce changes in the central adrenergic mechanisms.


Accurate and efficient battery modeling is essential to maximize the performance of isolated energy systems and to extend battery lifetime. This paper proposes a battery model that represents the charging and discharging process of a lead-acid battery bank. This model is validated over real measures taken from a battery bank installed in a research center placed at "El Chocó", Colombia. In order to fit the model, three optimization algorithms (particle swarm optimization, cuckoo search, and particle swarm optimization + perturbation) are implemented and compared, the last one being a new proposal. This research shows that the identified model is able to estimate real battery features, such as state of charge (SOC) and charging/discharging voltage. The comparison between simulations and real measures shows that the model is able to absorb reading problems, signal delays, and scaling errors. The approach we present can be implemented in other types of batteries, especially those used in stand-alone systems.


A string of medical experts have lined up to criticise the decision by the University of Virginia School of Medicine to accept funding for medical research from tobacco company Philip Morris—to the tune of $20m.

The American Medical Association, the American Public Health Association, and the editor of the academic journal Tobacco have all condemned the news.

"A medical school taking funding from the tobacco industry is like a peace studies school taking funding from terrorists," said Tobacco Control 's editor Simon Chapman, professor of public health at the University of Sydney.

Georges Benjamin, executive director of the American Public Health Association, said he too was against the move.

"There is a growing body of evidence that this kind of arrangement results in biased studies in favour of the funder". The real reason he suspects the tobacco industry does this is to help their image and improve the …


Objectives Hodgkin's lymphoma (HL) is the the most common cancer in teenagers and young adults. This nationwide study conducted over a 25-year period in the UK investigates variation in HL incidence by age, sex, region and deprivation to identify trends and high-risk populations for HL development. Design Population-based cohort study. Setting Clinical Practice Research Datalink (CPRD) electronic primary care records linked to Hospital Episode Statistics and Index of Multiple Deprivation data were used. Participants Data on 10 million individuals in the UK from 1992 to 2016 were analysed. Primary and secondary outcome measures Poisson models were used to explore differences in HL incidence by age, sex, region and deprivation. Age-specific HL incidence rates by sex and directly age-standardised incidence rates by region and deprivation group were calculated. Results A total of 2402 new cases of HL were identified over 78 569 436 person-years. There was significant variation in HL incidence by deprivation group. Individuals living in the most affluent areas had HL incidence 60% higher than those living in the most deprived (incidence rate ratios (IRR) 1.60, 95% CI 1.40 to 1.83), with strong evidence of a marked linear trend towards increasing HL incidence with decreasing deprivation (p=<0.001). There was significant regional variation in HL incidence across the UK, which persisted after adjusting for age, sex and deprivation (IRR 0.80–1.42, p=<0.001). Conclusions This study identified high-risk regions for HL development in the UK and observed a trend towards higher incidence of HL in individuals living in less deprived areas. Consistent with findings from other immune-mediated diseases, this study supports the hypothesis that an affluent childhood environment may predispose to development of immune-related neoplasms, potentially through fewer immune challenges interfering with immune maturation in early life. Understanding the mechanisms behind this immune dysfunction could inform prevention, detection and treatment of HL and other immune diseases.


Abstract The development of information and communication technology makes all things we need is more practical and easy. For example, ordering or booking ticket for cinema through an application. It is an example of the application of technology that is used to attract the number of buyers by service providers. The easy access on getting product or item is the desire of every consumer. The entry of technology changes the patterns of consumer behaviour from manual to digital or online. The service provider of online cinema ticket provides some features which can attract and will be the important thing for some buyers. The changing of ticket sales through application will definitely change ticket sales figures. This study aims to determine the factors which influence audience buying interest through the online cinema ticket application. The method used is a qualitative method with a case study approach. Data collection is done through interviews with viewers who use the online ticket booth application in buying tickets in the mall jatinangor town square. The results showed several factors that influence the interest in buying tickets using the application, namely time efficiency, promos and discounts, the latest films available (coming soon), the opportunity to get bigger tickets, can determine the choice of seats, avoid the queue, easy to use in transactions.


The LHC-forward (LHCf) experiment has measured the very forward neutral particle production cross section in proton-proton and proton-lead collisions at the LHC up to √s = 13 TeV and √sNN = 8.16 TeV, respectively. The experiment employs two independent detectors placed on opposite sides along the beam line approximately 140 meters away from the interaction point of the ATLAS experiment (IP1). The detectors are able to measure neutral particles with pseudorapidity greater than 8.4, up to zero-degree. These measurements are extremely useful for the calibration of the hadronic interaction models used to simulate the atmospheric showers of secondary particles induced from an high energy cosmic ray. Decreasing the uncertainty between different models it is possible to improve the precision of the high energy cosmic rays measurements.In this contribution the LHCf physics motivation for the Run III of LHC are discussed. The beam parameters and the expected operation time needed for our minimum physics program are described for both p-p run at 14 TeV and p-O run at 9.9 TeV. Finally, a brief summary of the ongoing upgrade on the Arm2 detector is given.


The aim of this article is to explore the design space of the IoT empowered smart lighting systems from communication theoretic perspective. It is noted that traditional wired solution such as digital addressable lighting interface (DALI) need to be replaced altogether. The solutions proposing to replace just the end connections by wireless transceivers will not fit in the emerging IoT paradigm. Different architectural blocks of smart lighting systems are briefly described. The key enablers for each of these blocks, their evolution trajectories, existing challenges and possible pathways are briefly summarized. It is noted that the functionality of the building block of IoT based smart lighting system can be translated into an abstract reference architecture. A hirerichical networking architecture is proposed and different networking issues are discussed. Finally, a communication theoretic perspective for wireless interface selection is presented.


Termites are small, pale soft bodied insect (order Isopteran) that lives in large colonies with several different castes, typically within a mound of cemented earth. Termites cause widespread damage to a great variety of crops in tropical Africa, are abundant and widely distributed throughout the regions of Ethiopia and pose threat to crops, forestry trees, range land, and domestic houses. So, for the termite situation to be adequately and summarily tackled there is a need to develop participatory involvement of farmers in all stages of technology generation, evaluation, and transfer. For this reason, very simple instrument called termite mound driller was developed and evaluated at Bako Agricultural Research Center on station and it showed effectiveness to minimize termite's damage to crops and natural vegetation's. a scaling up of termite mounds driller technology was conducted for three consecutive years  in  2013/14, 2014/15 and 2015/16 during occurrence seasons in selected Woredas of Kellem and West wollega zones of Oromia regional state, Ethiopia. The objective of the study was to reduce termite colonies through scaling up of termite mound driller device which makes easier chemical application under/on the farmers' field in West and Kellam wollega Zones where termite is a problem on maize , to promote the use of technologies among farmers and improve their income level ,to create awareness of how to develop and transfer these technologies to the resource poor farmers of the area and  also to strengthen linkage between farmers and concerned stakeholders to make this device easily accessible to resource poor farmers. A 360 mounds were poisoned in 253 farmers field in full span of the project span. Among the mounds poisoned only six mounds were regenerated a year later after its application. To poison the specified amount of termite mounds (360), 45 liters of chemicals were used in the three years duration of the project; a rate of 70 milliliter of chemical  and 20 liter of water in combined form was applied to poison a single termite mound. Hence, Farmers are very satisfied with technology and the achievements provided. They evaluate the technology in relation to its effectiveness, time and energy saver, urgent interventions and participatory. Keywords: Termite Mound Driller, and Diazinon (Ethiozinon)


The nonlinear development of the interfacial-surfactant instability is studied for the semi-infinite plane Couette film flow. Disturbances whose spatial period is close to the marginal wavelength of the long-wave instability are considered first. Appropriate weakly nonlinear partial differential equations (PDEs) which couple the disturbances of the film thickness and the surfactant concentration are obtained from the strongly nonlinear lubrication-approximation PDEs. In a rescaled form each of the two systems of PDEs is controlled by a single parameter C, the 'shear-Marangoni number'. From the weakly nonlinear PDEs, a single Stuart–Landau ordinary differential equation (ODE) for an amplitude describing the unstable fundamental mode is derived. By comparing the solutions of the Stuart–Landau equation with numerical simulations of the underlying weakly and strongly nonlinear PDEs, it is verified that the Stuart–Landau equation closely approximates the small-amplitude saturation to travelling waves, and that the error of the approximation converges to zero at the marginal stability curve. In contrast to all previous stability work on flows that combine interfacial shear and surfactant, some analytical nonlinear results are obtained. The Hopf bifurcation to travelling waves is supercritical for C < Cs and subcritical for C > Cs, where Cs is approximately 0.29. This is confirmed with a numerical continuation and bifurcation technique for ODEs. For the subcritical cases, there are two values of equilibrium amplitude for a range of C near Cs, but the travelling wave with the smaller amplitude is unstable as a periodic orbit of the associated dynamical system (whose independent variable is the spatial coordinate). By using the Bloch ('Floquet') disturbance modes in the linearized PDEs, it transpires that all the small-amplitude travelling-wave equilibria are unstable to sufficiently long-wave disturbances. This theoretical result is confirmed by numerical simulations which invariably show the large-amplitude saturation of the disturbances. In view of this secondary instability, the existence of small-amplitude periodic solutions (on the real line) bifurcating from the uniform flow at the marginal values of the shear-Marangoni number does not contradict the earlier conclusions that the interfacial-surfactant instability has a strongly nonlinear character, in the sense that there are no small-amplitude attractors such that the entire evolution towards them is captured by weakly-nonlinear equations. This suggests that, in general, for flowing-film instabilities that have zero wavenumber at criticality, the saturated disturbance amplitudes do not always have to decrease to zero as the control parameter approaches its value at criticality.


Objectives Attention-deficit hyperactivity disorder (ADHD) is a highly heritable, common developmental disorder. Although a few confirmed associations have emerged from candidate gene studies, these have shown the same limitations that have become evident in the study of other complex diseases, often with inconsistent and nonreplicated results across different studies. Methods In this report, 27 ADHD candidate genes were explored in greater depth using high-density tag single nucleotide polymorphism (SNP) genotyping. Association with 557 SNPs was tested using the transmission disequilibrium test in 270 nuclear pedigrees selected from an ongoing ADHD genetic study that includes all disease subtypes. Results SNPs in seven genes including SLC1A3, SLC6A3, HTR4, ADRA1A, HTR2A, SNAP25, and COMT showed a nominal level of association with ADHD (P values <0.05), but none remained significant after a stringent correction for the total number of tests performed. Conclusion The strongest signal emerged from SNPs in the promoter region (rs3808585) and in an intron (rs17426222, rs4732682, rs573514) of ADRA1A, all located within the same haplotype block. Some of the SNPs in HTR2A and COMT have already been reported by others, whereas other SNPs will need confirmation in independent samples.


Human beta2-glycoprotein I (beta2GPI), also known as apolipoprotein H, has been implicated in haemostasis and the production of anti-phospholipid antibodies. There is a wide range of interindividual variation in beta2GPI plasma levels that is thought to be under genetic control, but its molecular basis remains unknown. To understand the genetic basis of beta2GPI variation, we analyzed the 5' flanking region of the beta2GPI gene for mutation detection by DHPLC and identified a point mutation at the transcriptional initiation site (-1C-->A) with a carrier frequency of 12.1%. The mutation was associated with significantly lower beta2GPI plasma levels (P < 0.0001) and low occurrence of anti-phospholipid antibodies in lupus patients (4.8% antibody-positive group vs. 16.6% in the antibody-negative group; P = 0.019). Northern blot analysis confirmed that the -1C-->A mutation was associated with lower mRNA levels and it reduced the reporter (luciferase) gene expression by twofold. Electrophoretic gel mobility shift assay (EMSA) revealed that the -1C-->A mutation disrupts the binding for crude hepatic nuclear extracts and purified TFIID. These results suggest that the substitution of C with A at the beta2GPI transcriptional initiation site is a causative mutation that affects its gene expression at the transcriptional level and ultimately beta2GPI plasma levels and the occurrence of anti-phospholipid antibodies.


Human consciousness is the most interesting and mysterious phenomenon in the world, In this paper, the results of the computational studying and simulation of the conscious behaviour, such as the learning of language and image patterns, traditional conditioning, association, imagination and dream, have been presented. Based on these results, an experimental conscious system — CONSCITRON, has been developed. Further discussion on development of adaptive conscious systems is also provided.


Electron-spin resonance of ${E}^{\ensuremath{'}}$ centers in vitreous silica was studied using force-detection techniques at temperatures down to 5 K. Cyclic adiabatic inversion of electron spins was performed by frequency modulation of the applied microwave magnetic field. This produced an oscillatory magnetic force between the electron spins and a nearby permanent magnet, resulting in the vibration of a cantilever on which the sample was mounted. By pulsing the microwave field prior to the force-detection sequence, nutation of the spins could be observed. Spin echoes were observed mechanically using a modified echo-pulse sequence. The decay of magnetization during cyclic adiabatic inversion was also studied and is discussed in terms of utility for future single-spin detection experiments.


To the Editor. —Dr Iezzoni 1 makes an eloquent plea for greater physician understanding and knowledge of the many issues concerning ambulation and wheelchairs. Her problem was not only her own physician's lack of familiarity with walking difficulties, wheelchairs, and wheelchair technology, but also the physician's unfamiliarity with a specialty that is very familiar with these issues. Dr Iezzoni would have benefited from a referral to a physiatrist: a physician specializing in physical medicine and rehabilitation who is skilled in treating persons with disabilities. The physiatrist would have been able to perform a functional evaluation and assist her to maximize her independent mobility. This would include the possibility of ambulation with an assistive device, possibly with bracing or other rehabilitative interventions, as well as helping with the prescription and acquisition of the most effective, comfortable, and safe wheelchair. Many individuals who can ambulate shorter distances will also benefit from the use of a


This report presents the findings of research into how and when differences in work behaviour between men and women develop, focusing on the evolution of the gender gaps immediately after childbirth and during the initial years of family development. The analysis presented focuses on two crucial periods in family development: when a new baby arrives and when a child starts school. The study uses two data sources: the first thirteen waves from the British Household Panel Survey covering the years 1991 to 2003 and the first five waves from the Families and Children Study covering the years 1999 to 2003.


We developed a vascularly isolated in situ preparation of the left hemidiaphragm in which arterial blood was only provided through the left phrenic artery and the venous blood only drained through the phrenic vein. The costal margins were secured and connected to three force transducers. Muscle shortening was measured by sonomicrometry. The presence of arterial collaterals between the left hemidiaphragm and the systemic circulation was excluded by the systemic injection of a vital dye (Lissamine Green), a neuromuscular blocking agent (succinylcholine), and by the injection of epinephrine. Left phrenic nerve stimulation produced homogeneous shortening and tension. The degree of shortening in the isolated and intact left diaphragm at the same resting length was similar. The preparation was stable for 2 h with less than 10% decline in maximum tension. Two advantages of this preparation are particularly important. 1) Diaphragmatic energetics can be studied independently of systemic factors, and 2) the role of phrenic nerve afferents in the control of breathing and systemic circulation can easily be assessed without activating nonphrenic nerve afferents.


The amount of strain that cardiac surgery exerts on blood bank services is an example that emphasizes the need for multimodel blood conservation stratergy. The most common factor which is being attributable to increased bleeding after cardiac surgery is hyperfibrinolysis. Thererfore the use of antifibrinolytics during high risk cardiac surgery becomes inevitable. Commonly used antifibrinolytic include Tranexamic Acid (TA) and EpsilonAmino-Caproic Acid (EACA) .The aim of our study was to compare the effectiveness of both TA and EACA in reducing post-surgical bleeding in on-pump CABG surgeries and to assess the post-operative complications associated with its use. Material and Methods After obtaining informed written consent, approval of ethics and research committee patients who were scheduled for on-pump CABG were included in the study. Patients were divided into two groups randomly by using a computer generated randomized block design namely group TA (n=40) and group EACA (n=40). TA group received tranaxamic acid at a dose of 10 mg/kg IV over 20 min at the time of induction then 1-2 mg/kg in CPB prime followed by 1 mg/kg/hour infusion during surgery. Group EACA received EACA in a dose of 100 mg/kg/IV over 20 min at the time of induction then 5-10 mg/kg in CPB prime followed by 10 mg/kg/hour infusion during surgery. Patients were assessed for blood loss and were monitored for fibrinogen level and D-dimer levels, Re-exploration and post-operative complications. Result Primary outcomes like bleeding at 4 hours, there was no significant difference between the groups but when total bleeding at 24 hours was compared there was a significantly lesser bleed in group TA group compared to group EACA (p=0.0022).The requirement of PRBC in group TA was for 3 patients, whereas in EACA group 4 patients required PRBC (p>0.05).There was no significant difference in the rate of post-operative complications between the groups (p>0.05). Conclusion from our study we concluded that both TA and EACA effectively inhibits fibrinolysis during on pump CABG surgery and thus results in decreased post-operative bleeding. When compared between the two, TA was slightly better with respect to post-operative bleeding at 24 hours. Our study also re-emphasized the fact that neither of the drug led to any additional risk of post-operative thrombotic complications.


An active control system is described for the automatic alignment of the mirrors in a two-beam
interferometer. From an initial unaligned position the active control system determines the degree of
misalignment and adjusts the relative mirror positions accordingly. An embodiment of the system is
described for a Michelson interferometer in which one of the mirrors is mounted upon three
piezoelectric transducers PZT arranged so that they can both tilt and retard the mirror. Laser
sources and corresponding photodetectors are also incorporated such that a control system can use
the PZT actuators to produce a series of mirror movements relative to the fixed mirror and give a
set of two-dimensional diffraction patterns one for each of the laser photodetectors. Amplitude and
phase information is extracted from these patterns which enables the control system to align the
mirrors such that the diffraction pattern maxima is at the center of the instrument central
photodetector. In a further stage of the control algorithm, the alignment accuracy is refined using
information from the laser photodetectors during retardation of the mirror. In this manner, the initial
mirror alignment, maintaining that alignment during retardation and diagnosis of possible
misalignment, become part of a single active control technology for instrument alignment.


Improvement of the instrumental and technological design process of granule formation in the production of fertilizer grade «Superagro N: P 10:40» is proposed in the thesis. The results of pilot-scale tests are given.


Abstract As the body of scientific evidence about effective policies and practices grows, so does the need to effectively communicate that evidence to policy-makers and practitioners. Clearinghouses have emerged to facilitate the evidence-based decision-making process for education practitioners. While the results and methods for developing and analyzing the data in clearinghouses are based upon rigorous and scientific study, there has been little rigor or empirical effort to determine effective ways of presenting that evidence to practitioners. In this paper, we present a new visualization for clearinghouse data, called a Meta-Analytic Rain Cloud (MARC) Plot, designed based on evidence from the data visualization and statistical cognition literatures. We evaluate the efficacy of this visualization in a statistical cognition experiment and find that compared to three other visualizations used in practice, the MARC Plot is more effective in helping participants correctly interpret evidence (0.76, 0.43, and 0.43 standard deviation improvements respectively; each p < 0.05, corrected for multiple comparisons). To our knowledge, this is one of the first studies providing evidence regarding how to best present the type of information found in clearinghouses.


The colonic microbiome contributes to the initiation of colorectal cancer through poorly characterized mechanisms. We have shown that commensal-polarized macrophages induce gene mutation, chromosomal instability, and endogenous transformation through microbiome-induced bystander effects (MIBE). In this study we show that MIBE activates Wnt/β-catenin signaling and pluripotent transcription factors associated with dedifferentiation, reprogramming, and the development of colorectal cancer stem cells (CSCs). Exposure of murine primary colon epithelial cells (YAMC) to Enterococcus faecalis-infected macrophages increased Wnt3α expression while suppressing Wnt inhibitor factor 1 (Wif1). Wnt/β-catenin activation was confirmed by increased active β-catenin and Tcf4. in vivo, active β-catenin was evident in colon biopsies from E. faecalis-colonized Il10 knockout mice compared to sham-colonized mice. This effect was mediated, in part, by 4-hydroxy-2-nonenal and tumor necrosis factor α. MIBE also activated pluripotent transcription factors c-Myc, Klf4, Oct4, and Sox2 in YAMC cells and colons from E. faecalis-colonized Il10 knockout mice. These transcription factors are associated with cellular reprogramming, dedifferentiation, and induction of colorectal CSC progenitors. In support of this was an increase in the expression of Dclk1 and CD44, two colorectal CSC markers, in YAMC cells that were exposed to MIBE. Finally, compared to normal colon biopsies and hyperplastic polyps, DCLK1 expression increased in human tubular adenomas and invasive colorectal cancers. Blocking β-catenin/TCF4 signaling using FH535 and CTNNB1-specific small interfering RNA decreased DCLK1 expression in HCT116 human colon cancer cells. These findings provide mechanism for microbiome-induced colorectal cancer and identify new potential targets for colorectal cancer prevention.


In agriculture, a timely and accurate estimate of ripeness in the orchard improves the post-harvest process. Choosing fruits based on their maturity stages can reduce storage costs and increase market results. In addition, the estimation of the ripeness of the fruit based on the detection of input and output indicators has brought about practical effects in the harvesting process, as well as determining the amount of water needed for irrigation. pepper, the amount of fertilizer for the end of the season appropriate. In this paper, propose a technical solution for a model to detect persimmon green grapefruit fruit at agricultural farms, Vietnam. Aggregation model and transfer learning method are used. The proposed model contains two object detection sub models and the decision model is the pre-processed model, the transfer model and the corresponding aggregation model. Improving the YOLO algorithm is trained with more than one hundred object types, the total proposed processing is 500,000 images, from the COCO image data set used as a preprocessing model. Aggregation model and transfer learning method are also used as an initial step to train the model transferred by the transfer learning technique. Only images are used for transfer model training. Finally, the aggregation model with the techniques used to make decisions selects the best results from the pre-trained model and the transfer model. Using our proposed model, it has improved and reduced the time when analyzing the maximum number of training data sets and training time. The accuracy of model union is 98.20%. The test results of the classifier are proposed through a data set of 10000 images of each layer for sensitivity of 98.2%, specificity 97.2% with accuracy of 96.5% and 0, 98 in training for all grades.


The discontinuous permafrost zone of north-western Canada is characterised by a heterogeneous landscape of tree-covered permafrost plateaus that rise 0.5 m to 2.0 m above the surrounding fens and bogs. The depth to permafrost or "frost table" is influenced to some extent by vegetation canopy cover, which drives complex feedbacks related to permafrost thaw. Spectral remote sensing offers the possibility of large area mapping of canopy and ground surface characteristics that may be used as a proxy for permafrost thaw within remote northern areas. However, this depends on whether or not spectral bands can be used to identify slight variations in vegetation characteristics. The following study compares vegetation and topographic characteristics obtained using airborne Light Detection And Ranging (LiDAR) with high spatial resolution WorldView-2 spectral bands and in situ transect measurements of the depth to frost table. The results of this study indicate that the depth to the frost table is related to above ground vegetation cover and tree height, yet relationships are complicated by canopy and understory characteristics, topographic derivatives, and the position of the measured frost-table transect within the fragmented plateau. Comparisons between vegetation structural characteristics and WorldView-2 spectral bands are also examined so that confidence can be applied to depth of frost table estimates from WorldView-2 based on canopy characteristics. Discrete WorldView-2 pixels are related to depth to frost table (bands red, near infrared 1,2) and canopy metrics/topography obtained from airborne LiDAR. Variability is due, in part to absorption of near infrared by shadow fractions observed within WorldView-2 pixels, and spectral reflectance of ground vegetation visible within mixed pixels. High resolution spectral imagery, therefore, provides a link to processes controlling spatial variability of the depth to frost table.


This in vivo study used a 3-D photogrammetric technique to measure distortion of 3 unit implant frame-works and bone surrounding osseointegrated implants after securing misfitting superstructures to the implants. Four adult loop-eared rabbits were provided with 3 implants each in the proximal part of 1 tibia each. After a healing period of 8 weeks, a titanium frame-work was connected with a misfit to the central implant. Three-dimensional photographs were taken before and after securing the central screw, which induced a calculated mean preload of 246 N. Measurements and comparisons of the topography of the frame-works and surrounding bone before and after tightening the central screw indicated a complex and inconsistent deformation pattern. Generally, it could be observed that the top edge of the central cylinder showed vertical movement towards the bone of about 150 microns, always in combination with a rotation of the entire super-structure. The head of the central implant seemed to show a corresponding displacement towards the frame-work of about 50 to 200 microns. Bone deformation was found to be basically localized between the implants, where compressions of about half a millimetre were observed. This concentration of bone deformation as a result of misfit may be one contributing factor to initial marginal bone loss, occasionally observed after insertion of implant supported prostheses.


Objective: To explore tissue expression of cyclin-dependent kinase inhibitor p27Kip1 and β-catenin in multiple endocrine neoplasia type1 (MEN1)-related parathyroid tumors (MHPT). Methods: Immunohistochemistry was performed to analyze the expression of p27Kip1 and β-catenin in parathyroid glands from 31 subjects with MHPT collected at Peking Union Medical College Hospital from 2002 to 2013. Five normal parathyroid glands were used as control. Results: In MHPT subjects, nuclear expression of p27Kip1 was absent in 4 (12.9%), weak in 10 (32.3%) and moderated staining in 17 parathyroid specimens (54.8%), respectively. While, in normal subjects, the nuclear expression of p27Kip1 was observed in all subjects and was stronger than that from MHPT subjects (P=0.001). As to the expression of β-catenin, normal parathyroid showed a distinct to moderate membrane staining, a moderate to weak cytoplasmic staining and negative nuclear staining. Similarly, MHPT exhibited a marked to moderate membrane (P=0.087), a moderated to weak cytoplasmic (P=0.357), and negative nuclear β-catenin staining. Conclusions: The expression of p27Kip1 is reduced or absent in MHPT tissue, and no nuclear expression of β-catenin is observed in the tumors, which suggesting p27Kip1, but not β-catenin nuclear accumulation, play a role in the development of the tumors.


Continuous blood pressure (BP) monitoring is important for the prevention and early diagnosis of cardiovascular diseases. Cuffless BP estimation using pulse arrival time (PAT) via a mathematical model which enables continuous BP measurement has recently become a popular research topic. In this study, simultaneous biomedical signals from ten healthy subjects were acquired by electrocardiogram (ECG) and photoplethysmogram (PPG) sensors and the continuous reference BP data were collected by a cuff-based Finometer PRO BP monitor. A hierarchical model was applied to estimate the parameters of a nonlinear model which in turn is used to estimate systolic blood pressure (SBP) using PAT with few calibration measurements. The mean absolute difference (MAD) between the estimated SBP and reference SBP is 4.35±1.43 mmHg using the proposed hierarchical model with three calibration measurements and is 4.36±1.17 mmHg with a single calibration measurement.


Lemons (Citrus limon L.) are one of the most economically important and consumed fruit worldwide. The species is vulnerable to several postharvest decay pathogens, of which Penicillium italicum associated with blue mold disease is the most damaging. This study investigates the use of integrated management for blue mold of lemon using lipopeptides (LPs) extracted from endophytic Bacillus strains and resistance inducers. Two resistance inducers; salicylic acid (SA) and benzoic acid (BA) were tested at 2, 3, 4, and 5 mM concentrations against the development of blue mold on lemon fruit. The 5 mM SA treatment produced the lowest disease incidence (60%) and lesion diameter (1.4 cm) of blue mold on lemon fruit relative to the control. In an in vitro antagonism assay eighteen Bacillus strains were evaluated for their direct antifungal effect against P. italicum; CHGP13 and CHGP17 had the greatest inhibition zones of 2.30 and 2.14 cm. Lipopeptides (LPs) extracted from CHGP13 and CHGP17 also inhibited the colony growth of P. italicum. LPs extracted from CHGP13 and 5 mM SA were tested as single and combined treatments against disease incidence and lesion diameter of blue mold on lemon fruit. SA + CHGP13 + PI had the lowest disease incidence (30%) and lesion diameter (0.4 cm) of P. italicum on lemon fruit relative to the other treatments. Furthermore, the lemon fruit treated with SA + CHGP13 + PI had the highest PPO, POD, and PAL activities. The postharvest quality analysis of the lemon fruit including fruit firmness, total soluble solids, weight loss, titratable acidity, and ascorbic acid content revealed that the treatment SA + CHGP13 + PI had little effect on fruit quality compared to the healthy control. These findings indicate that Bacillus strains and resistance inducers can be used as components of integrated disease management for the blue mold of lemon.


Cancer patient's initial appraisal of the disease (i.e., as a threat, harm, or challenge), as well as their level of hope, has been linked to patients' coping strategies (i.e. approach or avoidance coping). However, it is unclear whether the well-established relationship between primary appraisals and coping in moderated by cancer patients' levels of hope. To determine if hope moderated this realationship, colorectal cancer patients (N=122) completed measures of appraisals and hope following their diagnosis and a measure of coping six-months later. Results indicated that patients appraised cancer as more of a challenge than a threat reported high levels of baseline hope. both challenge appraisals and baseline higher hope predicted approach coming six months later, however, hope did not moderate the relationship between appraisals and coping. This study highlights may of the conceptual, design, and psychometric problems present when measuring appraisals, hope, and coping among cancer patients.


Topically-administered ophthalmic medication may reach clinically significant serum concentrations, as evidenced by the variety of systemic side effects reported. These drugs may interact with other drugs administered orally and intravenously, increasing the frequency and severity of their side-effects. We report 4 patients examined in the emergency room because of various systemic manifestations, in whom the symptoms could be attributed either to antiglaucomatous eye drops, or to interaction between these eye drops and systemic medication. Considering the high incidence of glaucoma (0.5-2%), physicians should be aware of the systemic side-effects of antiglaucomatous eye drops and of possible interaction between such treatment and systemic medications.


Protecting the personal data contained in current software systems is a complex issue that requires legal regulations and constraints that can be used to manage personal data, along with methodological support with which to develop software systems that will safeguard their respective users' data privacy. The Privacy by Design (PbD) approach has, therefore, been proposed in order to address this issue and has been applied to systems development in a variety of application domains. The aim of this work is to determine the presence of PbD and the extent to which it exists in software development efforts. A systematic mapping study was conducted in order to identify relevant literature that collects PbD goals in software development, in addition to methods and/or practices that support privacy aware software development. Of the 49 papers selected, 30 address PbD from a theoretical perspective. The majority of the contributions (34) were categorized as being software requirements and software design. The main privacy goal discussed in the primary papers is data minimization. The findings suggest that PbD in software engineering is still an immature field and that there is a need for privacy-aware approaches for software engineering and their validation in industrial settings.


The manuscript provides a review of the representation of reservoir operations in a range of hydrology models, then presents a reservoir operations model which explicitly represents storage zones. The optimization scheme AMALGAM is then used to optimize the releases and reservoir zones parameters toward reproducing observed operations. Authors evaluate the models over 37 reservoirs globally and with respect to other previously established reservoir operations schemes. Authors conclude that this explicit representation of storage zones increases the accuracy of representation of reservoir operations. Caveats include the need for data to support the optimization of the operations and the reliance on good calibration of hydrology models to reduce biases in inflow.


In this book Edward Kamens analyzes a wide selection of poems to show how utamakura came to wield special powers within Japanese poetry. He reveals how poets in generation after generation returned, either in person or in imagination, to these places and to poems about them to encounter again the forms, styles, and techniques of their forbears, and to discover ways to create new poems of their own. Kamens focuses especially on one figure, "the buried tree, " which refers to fossilized wood associated in particular with an utamakura site, the Natori River, and is mentioned in poems that first appear in anthologies in the early tenth century. The figure surfaces again at many points in the history of traditional Japanese poetry, as do the buried trees themselves in the shallow waters that otherwise conceal them. After explaining and discussing the literary history of the concept of utamakura, Kamens traces the allusive and intertextual development of the figure of the buried tree and the use of the place-name Natorigawa in waka poetry through the late nineteenth-century. He investigates the relationship between utamakura and the collecting of fetishes and curios associated with utamakura sites by waka connoisseurs. And he analyzes in detail the use of utamakura and their pictorial representations in a political and religious program in an architectural setting the Saishoshitennoin program of 1207.


Methods The study included 60 patients according to sample size calculation, recruited from patients seeking tooth extraction at oral and maxillofacial surgery clinic at Umm Al-Qura University, Faculty of Dentistry. Patients were divided into three groups. Group Ӏ included 20 patients managed by advanced platelet-rich fibrin after extraction. Group ӀӀ included 20 patients managed by leukocyte-platelet-rich fibrin after tooth extraction. Group ӀII included 20 patients left without any addition. Each group was further subdivided into surgical and nonsurgical extraction. Afterwards, patients in each group were assessed for postextraction pain by VAS, number of analgesics, and early soft tissue healing by LWHI. Results The study outcomes demonstrate that the use of A-PRF significantly reduces postoperative pain in the 1st and 2nd day. VAS pain scores on the first day were significantly higher in the control surgical extraction group and L-PRF nonsurgical extraction group. In early soft tissue healing. The Landry Wound Healing Index (LWHI) was used after 1 and 2 weeks of extraction to evaluate the extraction site. In first week, the A-PRF group and L-PRF group (nonsurgical extraction) had a better healing index when compared to control group, and A-PRF group (surgical extraction) had a best healing index when compared to L-PRF and control groups. In the second week, individuals in the A-PRF group (surgical and nonsurgical extraction) had a better healing index when compared to L-PRF and control groups.


Discipline maturity and, more often, discipline development are recurrent themes in technical and professional communication scholarship. This paper reviews 25 years of the IEEE TRANSACTIONS ON PROFESSIONAL COMMUNICATION in terms of how and who creates knowledge. Specifically, we identify methods used by whom in an attempt to explore how the journal has developed complexity. We posit that the journal has evolved from describing practice to positing theory and finally to employing empirical research methods to evaluate theoretical application.


An important issue facing vision-based intelligent systems today is the lack of accessibility-aware development. A main reason for this issue is the absence of any large-scale, standardized vision benchmarks that incorporate relevant tasks and scenarios related to people with disabilities. This lack of representation hinders even preliminary analysis with respect to underlying pose, appearance, and occlusion characteristics of diverse pedestrians. What is the impact of significant occlusion from a wheelchair on instance segmentation quality? How can interaction with mobility aids, e.g., a long and narrow walking cane, be recognized robustly? To begin addressing such questions, we introduce X-World, an accessibility-centered development environment for vision-based autonomous systems. We tackle inherent data scarcity by leveraging a simulation environment to spawn dynamic agents with various mobility aids. The simulation supports generation of ample amounts of finely annotated, multi-modal data in a safe, cheap, and privacy-preserving manner. Our analysis highlights novel challenges introduced by our benchmark and tasks, as well as numerous opportunities for future developments. We further broaden our analysis using a complementary real-world evaluation benchmark of in-situ navigation by pedestrians with disabilities. Our contributions provide an initial step towards widespread deployment of vision-based agents that can perceive and model the interaction needs of diverse people with disabilities.


The properties of the radiation field in a two-dimensional photonic crystal with and without a microcavity introduced are investigated through the concept of the position-dependent photon density of states. The position-dependent rate of spontaneous radiative decay for a two-level atom with random orientation is deduced from the photon density of states using the Fermi Golden Rule.


From the Publisher:
Since 1977, Douglas R. Hofstadter and his graduate students at Indiana University and the University of Michigan have been developing computer models of discovery, creation, and analogical thought. What has emerged is a sophisticated and unorthodox vision of the mind in which perception, at an abstract level, is the key: perception of situations, of patterns, of patterns among patterns, even perception of one's perceptions. Fluid Concepts and Creative Analogies conveys this bold vision to a broad public as well as to cognitive scientists. Two ideas pervade the research. One is that the key question to answer is "What is a concept?" This means understanding how concepts overlap and trigger one another, how their fluid boundaries come about, how they give rise to generalizations and analogies, and so on. The second idea is that mental activity is fundamentally parallel, with many tiny agents independently carrying out small "subcognitive" acts and collectively building up coherent mental structures. Such agents lie far above the neural level, yet far below the conscious level; the hypothetical level of the brain at which they reside thus constitutes a largely uncharted substrate for thought. With these intuitions as guides, Hofstadter and the members of the Fluid Analogies Research Group have developed computer models that operate in small but extraordinarily challenging domains: playful anagram and number puzzles, analogy puzzles involving letter strings or tabletop objects, and fanciful alphabetic styles. These subtle ideas are spelled out with verve, charm, and clarity by Hofstadter and his co-workers in a series of chapters alternating with prefaces; the latter tie the projects together and give insight into their evolution. Readers of earlier works by Hofstadter will find this book a natural extension of his style and his ideas about creativity and analogy; in addition, psychologists, philosophers, and artificial-intelligence researchers will find in this el


We present results testing the hypothesis that there is a different reaction pathway for the electrochemical reduction of PC versus EC-based electrolytes at graphite electrodes with LiPF6 as the salt in common. We examined the reduction products formed using ex-situ Fourier Transform Infrared (FTIR) spectroscopy in attenuated total reflection (ATR) geometry. The results show the pathway for reduction of PC leads nearly entirely to lithium carbonate as the solid product (and presumably ethylene gas as the co-product) while EC follows a path producing a mixture of organic and inorganic compounds. Possible explanations for the difference in reaction pathway are discussed.


In this investigation, Rayleigh–Ritz method is used to calculate the natural frequencies of rectangular isotropic and laminated symmetric and anti-symmetric cross and angle ply composite plate with general elastic supports along its edges. Each of the admissible functions here is composed of a trigonometric function and an arbitrary continuous function that is introduced to ensure the sufficient smoothness of the so-called residual displacement function at the edges. Perhaps more importantly, this study has developed a general approach for deriving a complete set of admissible functions that can be applied to various boundary conditions. Several numerical examples are studied to demonstrate the accuracy and convergence of the current solution with considering some design parameters such as boundary conditions, aspect ratio, lamination angle, thickness ratio, orthotropy ratio, also these results are compared with other researchers and give a good agreement .


Large-scale underground structures excavated during construction of the Thames Tideway Tunnel have facilitated observations of the in-situ geology and revealed sedimentary characteristics that were not fully evident in disturbed samples from ground investigation boreholes or laboratory tests. These have led to significant improvements in understanding the groundmass behaviour of several strata within the London Basin geological sequence that are not easily studied by intrusive ground investigations, especially those involving sand channels and the 'Pebble Bed' within the Lambeth Group deposits. Further validation of the ground model and geology projected over the scheme during preconstruction design has been gained from logging the geology within deep shafts, open face connection tunnels and the main 8.8 m outer diameter tunnel from behind the tunnel boring machine cutterhead. It is recommended that an archive of field logs, as obtained during construction, be established to augment archives of borehole logs.


Vector (911 light-trap catches from 269 sites) and serological surveillance data were obtained during recent bluetongue (BT) outbreaks in Sicily. The distributions of Culicoides vectors are compared with that of bluetongue virus (BTV) to determine the relative role of different vectors in BTV transmission in Sicily. The 'best' climatic predictors of distribution for each vector species were selected from 40 remotely-sensed variables and altitude at a 1 km spatial resolution using discriminant analysis. These models were used to predict species presence in unsampled pixels across Italy. Although Culicoides imicola, the main European vector, was found in only 12% of sites, there was close correspondence between its spatial distribution and that of the 2000 and 2001 outbreaks. All three candidate vectors C. pulicaris, C. newsteadi and C. obsoletus group were widespread across 2002 outbreak sites but C. newsteadi was significantly less prevalent in outbreak versus non-outbreak sites in Messina and BTV has been isolated from wild-caught adults of both C. pulicaris and C. obsoletus in Italy. The yearly distribution and intensity of outbreaks is attributable to the distribution and abundance of the vectors operating in each year. Outbreaks were few and coastal in 2000 and 2001 due to the low abundance and prevalence of the vector, C. imicola. They were numerous and widespread in 2002, following hand-over of the virus to more prevalent and abundant novel vector species, C. pulicaris and C. obsoletus. Climatic determinants of distribution were species-specific, with those of C. obsoletus group and C. newsteadi predicted by temperature variables, and those of C. pulicaris and C. imicola determined mainly by normalised difference vegetation index (NDVI), a variable correlated with soil moisture, vegetation biomass and productivity. The predicted continuous presence of C. pulicaris along the Appenine mountains, from north to south Italy, suggests BTV transmission may be possible in a large proportion of this region and that seasonal transhumance between C. imicola-free areas should not generally be considered safe. Future distribution models for C. imicola in Sicily should include non-climatic environmental variables that may influence breeding site suitability such as soil type.


The rapidly increasing complexity of systems is driving the movement towards autonomic systems that are capable of managing themselves without the need for human intervention. Without autonomic technologies, many conventional systems suffer reliability degradation due to the accumulation of errors. The autonomic management techniques break the traditional reliability degradation trend. This paper comprehensively describes the roles and functions of various autonomic components, and systematically reviews past and current technologies that have been developed to address the specific areas of the autonomic computing environment. A new mechanism of model-driven autonomic management is further presented, which is more intelligent and efficient.


The relatively recent entry of multinational corporations (MNCs) into low-income markets, particularly in developing countries, affords the opportunity for the more inclusive capitalism envisioned by globalists. Alternatively, an expansion of MNC marketing in less developed economies might foreshadow the greater exploitation of disadvantaged consumers predicted by many critics of expanded free trade. To diffuse the charge of "exploitative" marketing, it is imperative that corporate marketing efforts seeking to engage impoverished segments be grounded in a strong ethical framework. This article unveils one such framework—the "integrative justice model" (IJM). The IJM is an aspirational model that outlines how to market ethically to disadvantaged consumers in both developed and developing countries. The authors derive the elements of this model from frameworks of moral philosophy and management theory. Although the IJM is normative in nature, the authors connect it to real-world examples, which provides MNCs that market to the poor practical benchmarks for conducting their business operations with fairness and equity. The article concludes with a discussion of the implications of the IJM for public policy.


Since interactions and conflicts between polar bears (Ursus maritimus) and people are reportedly increasing across the Arctic, there is a pressing need to better understand how such conflicts can be prevented or their outcomes ameliorated. A great deal of knowledge about what strategies work for both preventing and mitigating human-polar bear conflicts lies with local experts, yet this knowledge has often remained relatively inaccessible to contemporary wildlife managers. This study had three main aims: to document and synthesize local knowledge of polar bear behaviour in Churchill, Manitoba, to characterize perceptions and interpretations of polar bears, and to examine the linkage between local experts' knowledge, perceptions, and actions. We identified a suite of bear behaviours that local experts consistently observe and interpret as cues to the bears' intent. These behaviours are not unique to this locale. Nevertheless, differences in perspectives on the predictability of polar bear behaviour and in interpretations of the nature of bears significantly influence study participants' strategies for responding to bears. Our findings demonstrate that human-related factors are more complex than current models of human-bear interactions account for, so there is a need to develop richer models for understanding what motivates and influences human behaviours and responses towards bears.


Non-negative matrix factorization, which decomposes the input non-negative matrix into product of two non-negative matrices, has been widely used in the neuroimaging field due to its flexible interpretability with non-negativity property. Nowadays, especially in the neuroimaging field, it is common to have at least thousands of voxels while the sample size is only hundreds. The non-negative matrix factorization encounters both computational and theoretical challenge with such high-dimensional data, i.e., there is no guarantee for a sparse and part-based representation of data. To this end, we introduce a co-sparse non-negative matrix factorization method to high-dimensional data by simultaneously imposing sparsity in both two decomposed matrices. Instead of adding some sparsity induced penalty such as l1 norm, the proposed method directly controls the number of non-zero elements, which can avoid the bias issues and thus yield more accurate results. We developed an alternative primal-dual active set algorithm to derive the co-sparse estimator in a computationally efficient way. The simulation studies showed that our method achieved better performance than the state-of-art methods in detecting the basis matrix and recovering signals, especially under the high-dimensional scenario. In empirical experiments with two neuroimaging data, the proposed method successfully detected difference between Alzheimer's patients and normal person in several brain regions, which suggests that our method may be a valuable toolbox for neuroimaging studies.


It is stated that the new version of the IP protocol, IPv6, is the answer to the majority of the problems that were raised during the enormous expansion of the Internet and its transformation to a global communication platform with commercial scope. At the same time it is also stated that IPv6 dominance will not be easy and there will be a period when the two versions of the protocol will co‐exist. In this paper we describe some of the main transition mechanisms that can be deployed in order to facilitate the transition process to the new version of the IP protocol. Furthermore, the presented mechanisms are discussed regarding their usability, usefulness and manageability. Describes the way some of these mechanisms were applied to the Greek Research & Technology Network (GRNET).


Acromegaly is a severe disease often diagnosed late. Morbidity and mortality are high, particularly due to cardiovascular and respiratory complications. Clinical diagnosis is often difficult to confirm, particularly in ectopic forms. In addition, recent reassessment of cure criteria have reduced the number of patients considered to be successfully cured. The therapeutic strategy for acromegaly is thus changing with the advent of somatostatin agonists. Medical treatment is proposed increasingly as the first intention treatment, particularly antitumoral therapy for macroadenomas with surgery or radiotherapy being used as second line treatment. The recent development of GH analogs offers new perspectives for the treatment of acromegaly.


Using an eGFP-RBD3 probe, which specifically binds Ras-GTP, we recently showed that the fluorescent probe was localized to the plasma membrane and to the nucleus in wild type cells growing exponentially on glucose medium, indicating the presence of active Ras in these cellular compartments. To investigate the nuclear function of Ras-GTP, we generated a strain where Ras2 is fused to the nuclear export signal (NES) from the HIV virus, in order to exclude this protein from the nucleus. Our results show that nuclear active Ras2 is required for invasive growth development in haploid yeast, while the expression of the NES-Ras2 protein does not cause growth defects either on fermentable or non-fermentable carbon sources and does not influence protein kinase A (PKA) activity related phenotypes analysed. Moreover, we show that the cAMP/PKA pathway controls invasive growth influencing the localization of active Ras. In particular, we show that PKA activity plays a role in the localization of active Ras and influences the ability of the cells to invade the agar: high PKA activity leads to a predominant nuclear accumulation of active Ras and induces invasive growth, while low PKA activity leads to plasma membrane localization of active Ras and to a defective invasive growth phenotype.


We investigate consumers' preferences towards local and organic food via a framed field experiment involving revealed multiple discrete–continuous choices. Participants were endowed with a cash amount as a budget to purchase any desired quantity of different products. We modelled choices via the multiple discrete–continuous nested extreme value model. Central to our investigation is the test of the hypothesis of the constant effect of attitudes across consumption doses, which is normally an assumption invoked a priori and without testing in discrete choice analyses. Our results support the hypothesis and reveal a strong preference towards organic and local products, associated with both the highest baseline utility and the lowest satiation effect.


Computer-assisted synthetic planning has seen major advancements that stem from the availability of large reaction databases and artificial intelligence methodologies. SynRoute is a new retrosynthetic planning software tool that uses a relatively small number of general reaction templates, currently 263, along with a literature-based reaction database to find short, practical synthetic routes for target compounds. For each reaction template, a machine learning classifier is trained using data from the Pistachio reaction database to predict whether new computer-generated reactions based on the template are likely to work experimentally in the laboratory. This reaction generation methodology is used together with a vectorized Dijkstra-like search of top-scoring routes organized by synthetic strategies for easy browsing by a synthetic chemist. SynRoute was able to find routes for an average of 83% of compounds based on selection of random subsets of drug-like compounds from the ChEMBL database. Laboratory evaluation of 12 routes produced by SynRoute, to synthesize compounds not from the previous random subsets, demonstrated the ability to produce feasible overall synthetic strategies for all compounds evaluated.


The Witcher 3: Wild Hunt (CD Projekt Red, 2019) is an award-winning role-playing video game (RPG); the third instalment of The Witcher game series inspired by Polish author Andrzej Sapkowski's fantasy novels. Centring upon the protagonist Geralt of Rivia, The Witcher 3 has been praised for developing a complex, authentic, and immersive game environment that combines magic and fantasy elements within a broadly medieval setting. A central aspect of the game's success is its soundtrack – the fusion of music, sound, and voice – which further contributes to building the game's overall narrative and the complex construction of its central characters. This paper explores how The Witcher 3's soundtrack constructs identity, focusing in particular on its use of neo-medievalist signifiers and its contrasting representations of masculinity and femininity. Neo-medievalist sounds are a central concept in building the game's identity; these sounds draw on folkloristic elements surrounding the choice of instrumentation and the recurrence of folk music throughout the game's narrative, thus increasing the player's immersion within The Witcher 3's world. Regarding gender, female vocalisations are used within the soundtrack to add depth and emotion to male characters – particularly Geralt of Rivia, who due to his mutations lacks in conventional emotional capabilities. Despite the inclusion and emphasis of female voices on the soundtrack, the placement of women in influential roles is limited through other musical scoring techniques, which effectively reduces the agency of these characters, thus suggesting an imbalanced treatment towards gender. Through exploring these aspects, I argue that the soundtrack is a crucial part of how gender and identity are constructed throughout The Witcher 3, further exploring how these elements affect the player's overall in-game immersion.