The main purpose of this article is to present the theoretical and the practical aspect of the multi-level marketing in creating an effective motivational system in the company. In the theoretical part of the article the motivating system, its functions and the main assumptions of the MLM concept have been explained. First of all attention was paid to the concept of multi-level marketing. It explains what exactly multi-level marketing is and its varieties. Next we can see the history of MLM in Poland and in the rest of the world and its stages of development.The practical part contains the characteristics of the company which is one of the fastest growing companies in the network marketing industry thanks to its unique products and excellent logistics and marketing. In addition, this part of the article presents selected fragments of results and conclusions from the conducted surveys about functioning assessment of the motivating system in the surveyed company.


We estimated the total number of calcitonin-immunoreactive C-cells in rat thyroid gland using the optical fractionator, the unbiased stereological method for estimation of numbers. It was necessary first to use a fixative composed of formalin, acetic acid, and ethanol to distinctly visualize the C-cells. The 40-microm-thick sections had to adhere to chromalum-gelatin-coated Superfrost Plus glass slides, and the immunostaining technique had to stain the C-cells evenly throughout the whole sections. Because the C-cells were irregularly distributed in the thyroid tissues, their counting required screening of about 500 fields per lobe, but the number of C-cells counted need not be high, about 90 per lobe. We estimated that rats have 185,000 +/- 42,000 C-cells (mean +/- SD; n - 7). The C-cell population did not differ significantly between the two lobes of a given rat, but it varied markedly among rats. The biological differences among the animals contributed 83% to the observed variability, whereas the methodological uncertainty contributed 17%. The serum levels of calcitonin and calcium were not closely correlated to the C-cell numbers. Our results indicate that variability in C-cell experiments can be reduced most effectively by increasing the number of animals used. However, the similar C-cell frequency found in the two thyroid lobes of each rat allows the use of one uniformly sampled lobe for quantification and the other lobe for further analysis.


In their natural environment, insects such as the vinegar fly Drosophila melanogaster are bombarded with a huge amount of chemically distinct odorants. To complicate matters even further, the odors detected by the insect nervous system usually are not single compounds but mixtures whose composition and concentration ratios vary. This leads to an almost infinite amount of different olfactory stimuli which have to be evaluated by the nervous system. To understand which aspects of an odor stimulus determine its evaluation by the fly, it is therefore desirable to efficiently examine odor-guided behavior towards many odorants and odor mixtures. To directly correlate behavior to neuronal activity, behavior should be quantified in a comparable time frame and under identical stimulus conditions as in neurophysiological experiments. However, many currently used olfactory bioassays in Drosophila neuroethology are rather specialized either towards efficiency or towards resolution. Flywalk, an automated odor delivery and tracking system, bridges the gap between efficiency and resolution. It allows the determination of exactly when an odor packet stimulated a freely walking fly, and to determine the animal´s dynamic behavioral reaction.


ABSTRACT Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer. Until recently, no durable treatment options were available for patients with advanced disease. As an immunogenic cancer, MCC was hypothesized to be a candidate for PD-L1/PD-1 targeted therapy. On March 23, 2017 the US Food and Drug Administration granted accelerated approval for avelumab, an anti-PD-L1 monoclonal antibody, for the treatment of metastatic MCC on the basis of the JAVELIN Merkel 200 trial. Here we examine the results and implications of this pivotal study, published in Lancet Oncology by Kaufman et al., as well as current developments in the use of immune-checkpoint therapies for treating patients with MCC.


Fungal mycelium extracts were subjected to gel electrophoresis and Western blot analysis with various lectins and polyclonal antisera. These techniques succeeded in identifying bands specific to pathogenic Aphanomyces strains from fish affected by epizootic ulcerative syndrome, redspot disease and mycotic granulomatosis when compared to various other Oomycete fungi. It is concluded that these isolates are conspecific under the name Aphanomyces invadans [previously described by Willoughby et al. 1995 (J Fish Dis 18:273-235) as A. invaderis] and the various protein and carbohydrate bands identified may provide useful species-specific taxonomic markers. Besides the distinctive band profiles for A. invadanson gels subjected to various stains, lectins revealed a specific 45 kDa component, and polyclonal antisera highlighted an imn~unogenic 10 kDa band. Peroxidase and fluorescein conjugated antisera provided an effective diagnostic tool for identifying hyphae in infected fish tissue.


The author presents a detailed study of a wide variety of quantum well infrared photodetectors, which were chosen to have large differences in their optical and transport properties. Intersubband transitions based on photoexcitation from bound-to-bound, bound-to-quasicontinuum and bound-to-continuum quantum well states were investigated. The measurements and theoretical analysis included optical absorption, responsivity, dark current, current noise, optical gain, hot-carrier mean free path, net quantum efficiency, quantum well escape probability, quantum well escape time, as well as detectivity.


Summary Background: We undertook this study to determine the cortical alterations related to the origin of dissociated deviation. Methods: This was a prospective, descriptive and observational study that included 10 children with diagnosis of dissociated horizontal deviation, without previous evidence of neuronal damage. Manual, cerebral and ocular dominance were determined, as well as sensorial state and visual perceptual profile. Cortical response to different stimuli was analyzed: luminous, hyperventilation, slow and saccadic movements of pursuit, gaze and stare through cerebral mapping and neurometric EEG. The biochemical composition to the visual cortex by means of magnetic resonance spectroscopy was also investigated. Results: The following alterations were demonstrated: a) neuroelectric: dysynchronic, paroxysms and/or lentification; b) neurometabolic: elevation of lactate, decrease of N-acetylaspartate and loss of the creatine/choline relationship; c) sensorial: suppression and amblyopia; d) perceptual vision: underyield in visual abilities; e) motor: horizontal and vertical dissociated deviation; f) optometric: hyperopic astigmatism. Conclusions: The study suggests that dissociated deviation has a cortical origin and is related to epileptogenic disease.


Purpose: The purpose of this study was to report long-term visual outcome of acute retinal necrosis. Methods: Medical records of patients with acute retinal necrosis were reviewed. Results: Thirty-two patients were diagnosed with acute retinal necrosis from 1998 to 2007. Twenty patients (25 eyes) had at least 1 follow-up and available medical records. Intravitreal injections of ganciclovir and/or foscarnet were administered in 11 of 25 eyes. Intravenous and oral antiviral medications were used in 14 of 20 and 19 of 20 patients, respectively. Eleven of 25 eyes had <25% of retina affected, 8 of 25 had 25% to 50% of retina affected, and 6 of 25 had >50% of retina affected. Mean visual acuity at all time points was best when retinitis involved <25% and decreased as area increased. All but 1 eye with >50% involvement experienced decreased vision regardless of treatment. Three of 4 eyes with 25% to 50% involvement that received intravitreal antivirals had an improvement in visual acuity of ≥2 Snellen lines. Five of 25 eyes developed retinal detachment. None of the six eyes treated with prophylactic laser detached. Conclusion: Greater extent of retinitis portends a worse visual prognosis. Although intravitreal treatment did not prevent visual acuity loss in patients with severe disease, patients with moderate disease (25-50% retina involved) did well with intravitreal therapy with most having stable or improved visual acuity. Prophylactic laser decreased the rate of detachment.


It has been widely agreed in real estate literature that housing submarkets should be adopted as a working hypothesis. This paper revisits the housing sub-market hypothesis and seeks to spatially delineate residential market segments using Hong Kong geo-coded transaction data. Spatial correlation information inherent in the Hedonic residuals is adopted to define property clusters, with which we define sub-market segments. Chow test is performed across the clusters to examine the segmentation of the market. The results are then compared with the prevailing structure of market segments. Weighted mean square test reveals that the defined sub-market structure can improve the accuracy of price forecast significantly, which is consistent with previous research findings.


ABSTRACT In this paper, we outline a framework to study what we have termed "Predatory Cities", using the artificial offshore island of The Pearl in Qatar as a case study. By focusing on the nexus between urbanisation and resources, we will argue that the master-planning of new cities in the booming global South implies both the access and cheap exploitation of a set of, on the one hand, intangible and, on the other hand, tangible resources that exceed the traditional boundaries. Our point of departure is that the cheap appropriation and exploitation of alien architecture images and resource networks for the making of new, master-planned cities has become a necessary, but highly unsustainable, strategy to survive an increasingly competitive global offering of new destinations.


This digest examines the Fair Work Amendment (Textile, Clothing and Footwear Industry) Bill 2011, currently before the Senate. The Bill: extends the operation of most provisions of the Fair Work Act 2009 (the Act) to contract outworkers in the textile, clothing and footwear (TCF) industry by deeming contract outworkers to be employees provides a mechanism to enable TCF outworkers to recover unpaid amounts including from contractors along the supply chain extends specific right of entry rules that apply to suspected breaches affecting outworkers (which allow entry without 24 hours notice) to the TCF industry, and enables a TCF outwork code to be issued.


Introduction: Calcifying Cystic Odontogenic Tumour (CCOT)/ Calcifying Odontogenic Cyst (COC) display a varying tissue morphology, while exhibiting different biological progression also at the same time. Attempts at classifying COC have largely been unsuccessful due to the present lack of knowledge about the development of these tumours and their underlying molecular changes. Wingless-beta catenin (Wnt–β catenin) signalling pathway has been found to be a cornerstone in the ectodermal development and tumour initiation-progression to malignant tumours, but its specific role in the pathogenesis of odontogenic ghost cell lesions is unknown. Aim: To elucidate the participation and comparison of β-catenin protein expression in pathogenesis of benign odontogenic ghost cell lesions, CCOT and Dentinogenic Ghost Cell Tumour (DGCT). Materials and Methods: A cross-sectional Immunohistochemical (IHC) study was performed in the Department of Oral and Maxillofacial Pathology, AECS Maaruti College of Dental Sciences and Research Centre, Bengaluru, Karnataka, India, from December 2019 to June 2021. Research was conducted on tissue sections of centrally located 16 cases of CCOT categorised as group 1 and four cases of DGCT categorised as group 2 using β-catenin tumour marker. The study samples were retrieved from the archives. IHC stained slides were subjected for histopathological analysis, where labelling index of tumour cells were assessed in three high power fields. Resultant β-catenin expression was compared between Benign Odontogenic Ghost Cell Lesions (BOGCL). Results were subjected to statistical analysis, Statistical Package for Social Sciences for Windows 17.0 (SPSS, Philadelphia, IL) software to analyse the data. Results: β-catenin positivity was assessed in tumour cells of both the groups, 16 CCOT (group 1) and 4 DGCT (group 2). In each case, number of cells in three high power field i.e., under 40X magnification were evaluated. Both the groups expressed membranous, cytoplasmic and nuclear positivity in the basaloid tumour cells. Whereas, ghost cells showed no reactivity to the biomarker, β-catenin. On comparison using Mann Whitney U and Wilcoxon W test, there was no statistically significant difference in β-catenin expression between CCOT and DGCT. Conclusion: β-catenin plays an important role in the tumourigenesis of benign odontogenic ghost cell lesions. Immunohistochemically CCOT and DGCT showed no significant difference in the β-catenin expression. Hence, the results suggest that CCOT and DGCT may show variation in clinical behaviour but share similar histogenesis.


Aims, Objectives and Background Anaphylaxis is seen relatively frequently in the emergency department, and if not managed promptly and appropriately, is associated with significant morbidity and mortality. Often patients are admitted for extended periods of observation due to fears that they may develop a biphasic reaction. NICE has recently updated its guidelines on this but acknowledges the sparsity of research investigating the appropriate length of the observation period. The purpose of this study was to identify the frequency of biphasic reactions and what period of observation would be sufficient for patients following attendance with anaphylaxis. Method and Design This was a retrospective observational study which looked at the presentation, treatment and outcomes of patients presenting to Royal Derby Hospital emergency department with anaphylaxis over the last 10 years. The patients were identified from clinical coding completed at the time of discharge and the information was attained from a combination of electronic and paper notes. We defined a biphasic reaction as a recurrence of anaphylaxis without re-exposure to an allergen following a complete resolution of symptoms and normalisation of observations. Results and Conclusion A total of 377 patients were identified as presenting with anaphylaxis from the discharge coding. After case note review, 346 of these were concluded to have been true anaphylaxis (examples of those excluded were hereditary angioedema and ACE-inhibitor related angioedema). 321 (93%) were given intra-muscular adrenaline at some point and 244 (70%) were admitted to hospital for further treatment or observation. Of the 346 cases included in the study only 5 (1.4%) met the criteria for a biphasic reaction. Interestingly, 1 patient was responsible for 3 of those 5 attendances. The results of our study strongly suggest that the risk of a biphasic reaction is significantly less than previously thought and that admission for prolonged observation may be unnecessary in the majority of cases.


e‐Learning has been frequently heralded as a transforming influence on global education and corporate training. Despite such rhetoric, the adoption, diffusion and exploitation of e‐Learning by educational institutions and organizations have been slower than anticipated. In this paper we attempt to examine the future of e‐learning by adopting a scenario planning approach, which formed the basis of a recent major international conference held in Edinburgh, Scotland in February 2004. We set out the background of the study, the methodology used to investigate the future(s) of e‐learning and reflect on the process and outcomes of the exercise to provide some assistance for practitioners in the field. Our general conclusions are that the scenarios have been a valuable starting point to engage in a more informed discussion of how e‐learning may transform education and training markets and the ways in which people learn over the next decade.


The free-radical copolymerization propagation kinetics of vinyl acetate (VAc) and methyl methacrylate (MMA) at 50 degrees C were investigated through an experimental study combined with a computational analysis based on quantum chemistry. Copolymer composition data, obtained using pulsed laser polymerization followed by size exclusion chromatography (PLP-SEC) and proton nuclear magnetic resonance (NMR), were well represented by the terminal model using monomer reactivity ratios obtained with the computational approach (r(VAc) = 0.001 and r(MMA) = 27.9). Concerning the composition-averaged copolymerization propagation rate coefficient k(p,cop), the differences between the terminal model and the implicit penultimate unit effect (IPUE) model (s(MMA) = 0.544 and s(VAc) = 0.173) are small for VAc/MMA, with the terminal model sufficient to describe the experimental k(p,cop) data measured by PLP-SEC. Monomer and radical charge distributions determined computationally are used to explain the reactivity exhibited by the VAc/MMA system.


We investigated endovascular treatment of cerebral aneurysm by coil and Onyx in vivo experiment in order to promote the advantages of coil embolization,. The aim of this study was to clarify the advantages and problems of coil and Onyx embolization and to evaluate its potentials for application in clinical medicine. We set experimental aneurysms made of external jugular vein to bilateral carotid arteries of 10 Beagle dogs and embolized aneurysm with coils and Onyx. Two months later, the dogs were sacrificed and took out the experimental aneurysms and examined them histologically. We have experienced Onyx migration into the vessel at the beginning of our experiment. Technical problems were as follows; Onyx was not easily visible on DSA monitor particularly in tight coil packing. Catheter tip was often stuck to the Onyx in the aneurysm. Protect balloon could not completely protect the Onyx leakage into the vessel. Microscopic examinations were as follows; The aneurysm was filled with Onyx, coils, and inflammatory reactants. The orifice of the aneurysm was packed with augmented fibrous tissue. This method increased contact between the aneurysm wall and coils. Onyx filled the intra-aneurismal space more tightly. Coils prevented Onyx from flowing out into the vessel. In Onyx, intimal layer was more rapidly formed at the neck of the aneurysm than coils only. The most important problems during Onyx embolization is how to prevent Onyx migration into the vessel. We should like to propose the guideline for Onyx embolization.


Purpose: The Image‐guided Therapy QA Center (ITC) as part of the NCI‐sponsored Advanced Technology QA Consortium (ATC) has nearly 15 years experience in performing data integrity QA review for multi‐institutional advanced technology clinical trials that require digital data submission. This presentation will report on that experience. Method and Materials: Participants in some advanced technology multi‐institutional clinical trials must be able to submit imaging data as well as RT objects (CT, RT Structure Set, RT Dose, and RT Plan) to the ITC for protocol compliance QA review of contoured volumes and dose coverage/heterogeneity. Data are sent via FTP or on media. However, prior to that QA review, experienced personnel at the ITC carefully review each digital data set in regard to completeness of protocol required elements, format of data, and possible data corruption. Results: Thus far over 3000 data sets have been submitted to ITC. Unfortunately, data often need resubmission due to problems discovered by ITC. Errors in submission can be divided into five categories: 1) misuse of UI of treatment planning system (TPS), 2) misunderstanding of protocol requirements, 3) non‐uniformity of DICOM export implementations by TPS vendors, 4) user error with digital data transfer software, and 5) updated TPS software, whose data export feature no longer is ATC compliant. Statistics of number of resubmissions required as well as specific details of these problems will be presented. Conclusion: Digital data submission of complete 3D data set is essential for QA of advanced technology clinical trials. However, collection of these data requires review and troubleshooting by experienced personnel to ensure subsequent protocol compliance QA and later still, quality data analysis. A significant portion of the ITC workload involves digital data integrity QA to ensure quality of submitted digital data. Support: NIH U24 Grant CA81647.


Deep neural networks excel at solving intuitive tasks that are hard to describe formally, such as classification, but are easily deceived by maliciously crafted samples, leading to misclassification. Recently, it has been observed that the attack-specific robustness of models obtained through adversarial training does not generalize well to novel or unseen attacks. While data augmentation through mixup in the input space has been shown to improve the generalization and robustness of models, there has been limited research progress on mixup in the latent space. Furthermore, almost no research on mixup has considered the robustness of models against emerging on-manifold adversarial attacks. In this paper, we first design a latent-space data augmentation strategy called dual-mode manifold interpolation, which allows for interpolating disentangled representations of source samples in two modes: convex mixing and binary mask mixing, to synthesize semantic samples. We then propose a resilient training framework, LatentRepresentationMixup (LarepMixup), that employs mixed examples and softlabel-based cross-entropy loss to refine the boundary. Experimental investigations on diverse datasets (CIFAR-10, SVHN, ImageNet-Mixed10) demonstrate that our approach delivers competitive performance in training models that are robust to off/on-manifold adversarial example attacks compared to leading mixup training techniques.


Abstract The art market, following the example of financial markets, is divided into a primary market, where works are traded directly from artists, and a secondary market that is mainly the auction market. Coronavirus disease 2019 (COVID-19) and galloping inflation have influenced the creation of a bull market in artwork. The high incomes of some buyers and inflation have influenced the emergence of the so-called 'glittery' art market. Works by neglected artists have 'very much taken on a life of their own': fantasy art, works by young poster artists, casting 'nightmares' – have been selling well for more than a year. People terrified of inflation are putting their money 'in works of art'. The auction market dominates the primary market because anonymity makes it easier to enter the art market. The gallery market does not guarantee this anonymity. Very often, the auction market for works of art is used for money laundering. The purpose of this paper is to show that auction mechanisms are a good tool for the efficient allocation of goods and money in an area of galloping inflation and most art auctions are asymmetry.


Particle aggregation with simultaneous surface growth was modeled using a dynamic Monte Carlo method. The Monte Carlo algorithm begins in the particle inception zone and constructs aggregates via ensemble-averaged collisions between spheres and deposition of gaseous species on the sphere surfaces. Simulations were conducted using four scenarios. The first, referred to as scenario 0, is used as a benchmark and simulates aggregation in the absence of surface growth. Scenario 1 forces all balls to grow at a uniform rate while scenario 2 only permits them to grow once they have collided and stuck to each other. The last one is a test scenario constructed to confirm conclusions drawn from scenarios 0-2. The transition between the coalescent and the fully developed fractal aggregation regimes is investigated using shape descriptors to quantify particle geometry. They are used to define the transition between the coalescent and fractal growth regimes. The simulations demonstrate that the morphology of aggregating particles is intimately related to both the surface deposition and particle nucleation rates.


The task of person re-identification (ReID) has attracted growing attention in recent years with improving performance but lack of focus on real-world applications. Most state of the art methods use large pre-trained models, e.g., ResNet50 (~25M parameters), as their backbone, which makes it tedious to explore different architecture modifications. In this study, we focus on small-sized randomly initialized models which enable us to easily introduce network and training modifications suitable for person ReID public datasets and real-world setups. We show the robustness of our network and training improvements by outperforming state of the art results in terms of rank-1 accuracy and mAP on Market1501 (96.2, 89.7) and DukeMTMC (89.8, 80.3) with only 6.4M parameters and without using re-ranking. Finally, we show the applicability of the proposed ReID network for multi-object tracking.


ABSTRACT An oily coal dust that is difficult to remove is easily formed on the surface of coal mining equipment. However, high-power equipment generates a higher surface temperature, which can promote spontaneous combustion of coal, especially in the oxygen-enriched environment of the refuge chamber. This study investigated the effects of lubricating oil on coal spontaneous combustion under different oxygen concentrations using a temperature-programmed experiment, Fourier transform infrared spectroscopy and thermogravimetry-differential scanning calorimetry. The results show that the activation energy is inversely proportional to the lubricating oil content during the low-temperature oxidation stage. With a mass ratio of coal to lubricating oil of 2:1, compared with raw coal, the activation energy was reduced by 6.46 KJ/mol. With a higher lubricating oil content of coal and an increased oxygen concentration, the absorption peak intensities of -CH3, -CH2, -OH were lower and the C-O absorption peak intensity was higher. Therefore, lubricating oil promotes coal spontaneous combustion and the promoting effect is proportional to the lubricating oil content and oxygen concentration. Furthermore, the difference in heat released indicates that the effect of lubricating oil on coal spontaneous combustion is the result of the interaction between coal oxidation and lubricating oil oxidation.


The scope of the European project TIPS (Thin Interconnected Package Stacks) is the fabrication of ultra thin packages for electronic components and the subsequent stacking and interconnection of those packages to form highly compact modules. In the first part of this paper approaches to fabricate ultra thin 10 × 10 mm packages by embedding technologies for chips into printed circuit board environments will be discussed. Technologies for commercial flexible printed circuit board substrates (polyimide sandwiched in Cu layers) and respective fabrication processes are used. After initial patterning of the Cu the chips are die bonded to the flex substrates and subsequently lamination into build up layers. Electrical contact between the chip and a fan out routing on the outer layer of the package are made by micro via formation, electroplating and wet chemical structuring of the metal layers. The thickness of the embedded components is constricted to 50 µm in order to constrain the package thicknesses to a maximum of 100 µm with this approach. Packages are fabricated in batches of 150 × 150 mm sheets of flex substrates. Stacking of individual packages can be performed in an automated package by package placement process using a frame as alignment tool and typical flexible printed circuit boards adhesives. In this way only known-good-packages are stacked in order to minimize yield loss. However, a more straight forward process is stacking of the packages using fabrication batches and established multilayer printed circuit board technologies. The disadvantage is the potential yield loss if one of the packages in a stacked layer is faulty. For either type of stacking process the individual stacks have to be milled out of the stack fabrication batch. After stacking and sound mechanical interconnection the electronic interconnection between layers is made by the sequence mechanical through hole drilling, plating and wet chemical structuring. Test issues, design considerations and results of first fabrication runs will be presented and discussed.


The authors generalize to p-dimensional extended objects and type II superstrings a recently proposed Green-Schwarz type I superstring action in which the tension T emerges as an integration constant of the equations of motion. The action is spacetime scale-invariant but its equations of motion are equivalent to those of the standard super p-brane for T not=0 and the null super p-brane for T=0. They also show that for p=1 the action can be written in 'Born-Infeld' form.


The authors report an unusual presentation of a solitary bone metastasis in the left midtibial shaft with no other skeletal involvement in a patient with breast carcinoma. The incidence of solitary bone metastasis below the knees is rare. Clinically, the lesion was tender when palpated. A bone scan revealed increased blood flow and blood pool activity, with intense midtibial bony uptake in delayed images. These findings are similar to those of acute osteomyelitis. Biopsy revealed bony metastasis from the patient's breast carcinoma.


. In this article I will survey some results about inscribing triangles and quadrilaterals in Jordan curves. I will focus on the recent result of Josh Greene and Andrew Lobb, which says that for any smooth embedded loop C and any aspect ratio λ , there are four points in C which make the vertices of a rectangle of aspect ratio λ .


A fundamental question in developmental biology is how a single fertilized egg cell and its progeny are programmed or instructed to form thousands of different cell types and how these are organized into a complex and functional organism. In this thesis I have explored how a specific subset of cells is formed the vascular endothelial cells lining our blood vessels. As the embryo grows in size, passive diffusion is not sufficient to support the developing tissues with oxygen and nutrients. The cardiovascular system is therefore the first functional organ to be established during embryonic development. Understanding the mechanism driving vascular development could have great implications to our understanding and treatment of multiple pathologies and diseases such as cancer, diabetes and ischemic heart disease. My studies have been focused on the initial de novo generation of endothelial lineage and further specification into arterial and venous endothelial subtypes. These processes have been explored using in vitro differentiation of embryonic stem cells (ESC) to mimic the sequence of events in the developing embryo. In the first paper we addressed the function of vascular endothelial growth factor recptor-2 (VEGFR2) in the generation of endothelial cells and their integration into vascular structures. We showed that ESC lacking VEGFR2 fail to form and incorporate into vascular structures. By reintroducing VEGFR2 using lentiviral transduction we could rescue these defects. Interestingly, neither loss of or over expression of VEGFR2 seemed to influence the de novo generation of, at least immature, endothelial cells. In paper II I present data showing that it is possible to generate endothelial cells with transcriptional and functional arterial and venous characteristics through in vitro differentiation of ESC. VEGF played a critical role where high concentration promoted arterial fate in contrast to intermediate or low VEGF concentration which supported venous differentiation. I could further show that the VEGF signal driving arterial fate was dependent on functional Notch signaling. Having established the model system detailed above, I explored whether the hypoxic state of the embryo prior to functional circulation may influence the arterial venous lineage. Hypoxia did indeed strongly potentiate arterial over venous transcription in a Notch dependent manner. The hypoxia inducible factor (HIF) 1 and more potently 2 activated Adrenomedullin gene transcription. I showed that Adrenomedullin drives Notch signaling through transcriptional induction of the arterially expressed Notch ligand Dll4. In the final paper I aimed to dissect the individual role of two VEGF co-receptors, Neuropillin1 and heparan sulfate (HS) proteoglycans in arterial venous specification. Surprisingly we found NDST1/2 -/ESC which produce HS lacking a critical modification, N-sulfation, to be resistant to in vitro differentiation. These cells maintained transcriptional, morphological and functional characteristics of undifferentiated ESC following four days of embryoid body differentiation in the absence of leukemia inhibiting factor (LIF). We show that N-sulfation is critical specifically for endogenous FGF4 which is responsible for down-regulation of Nanog and thereby initiation of ESC differentiation. Finally, N-sulfation of HS has a functional importance as the efficiency of de novo ESC line derivation from mouse blastocysts greatly increased by the addition of a general sulfation inhibitor. These studies suggest that in vitro differentiation of ESC can be an excellent model system to compliment studies performed in the actual embryo, especially when addressing lineage specifications. LIST OF PUBLICATIONS I. Xiujuan Li, Dan Edholm, Fredrik Lanner, Georg Breier, Filip Farnebo, Anna Dimberg, Lena Claesson-Welsh. Lentiviral rescue of vascular endothelial growth factor receptor-2 expression in Flk1-/embryonic stem cells show early priming of endothelial precursors. Stem Cells (2007) 25, 2987-2995. II. Fredrik Lanner, Marcus Sohl, Filip Farnebo. Functional arterial and venous fate is determined by graded VEGF signaling and Notch status during embryonic stem cell differentiation. Arterioscler Thromb Vasc Biol. (2007) 27, 487-493. III. Fredrik Lanner, Marcus Sohl, Emil Hansson, Peter Carmeliet, Lorenz Poellinger, Urban Lendahl, Filip Farnebo. Hypoxic induction of Adrenomedullin and Notch signaling promotes arterial differentiation of embryonic stem cells. Manuscript (2008). IV. Fredrik Lanner, Marcus Sohl, Katarina Holmborn, Johannes Wilbertz, Filip Farnebo. N-sulfation of heparan sulfate is critical for embryonic stem cell differentiation. Manuscript (2008).


The spectrum of indium was photographed on 10.7 m grazing incidence and 3-m grazing incidence spectrographs in the wavelength region 450-200 Å. The sources used were a triggered spark and a sliding spark. The analysis of the 4d7-4d65p transitions of In VII in 300-230 Å region enabled us to establish 17 of 19 levels of the 4d7 configuration and 131 out of 180 levels of the 4d65p configuration. 419 lines have been classified. The least-squared-fitting parametric calculations support the analysis.


Background and Objectives: Sarcomas are rare malignant tumors of mesenchymal origin. Their low prevalence and histological heterogeneity make their diagnosis a challenging task. To the best of our knowledge, the epidemiology of soft tissue sarcomas (STSs) was not well studied in Jordan. This study thus aimed to determine STS epidemiologic trends at King Abdullah University Hospital (KAUH); a tertiary hospital that provides cancer healthcare for 70% of the population in Irbid Governorate, North Jordan. The findings of this study will provide a good reference point of the burden of STSs in Jordan and the Middle East region. Materials and Methods: All cases with confirmed STS diagnoses who attended KAUH from January 2003 until December 2018 were included in the initial analysis. Bone sarcomas, gastrointestinal stromal tumors and uterine sarcomas were not included in the study. Information collected from the pathology reports and electronic medical records was used to determine STS prevalence, incidence rate, age and gender distributions, histological types and anatomic location. Cases were reviewed by three pathologists with interest in soft tissue tumors. The findings were compared with literature. Results: In total, 157 STS cases were reported (1.9% of cancers diagnosed at KAUH during the 16-year study period). Crude annual incidence rate (IR) per 100,000 person-years ranged from 0.48 in 2015 to 1.83 in 2011 (average = 1.04). Age-standardized IR (ASR)(World WHO 2000–2025) was 1.37. Male:female ratio was 1.3:1. Median age was 39 years. Age ranged from <1 year to 90 years. Overall STS rates increased with age. The most common histological types were liposarcoma (19%), rhabdomyosarcoma (17%) and leiomyosarcoma (10%). The most common anatomic location was the extremity (40.1%), followed by the trunk (14.7%), then head and neck (10.8%). Conclusion: STSs are rare in North Jordan. A slight increase in their incidence was identified during the study period similar to global trends. The collection of relevant data on established risk factors along with a broader scale evaluation of the epidemiology of STS in the Middle East region is recommended to better evaluate disease burden and trends.


In this paper an approach to analyses battery-capability in mobile power applications versus temperature is explored. The harmful effects of the modern material (technology) of power-batteries are to highlights. This paper considers performance of power-batteries; experimental tests-based analyses of these power-batteries are used. The performance of a Lithium-Ion, Nickel-Metal, recent Lead-Acid batteries or Supercapacitors are shown to touch on the most general features of power using in mobile applications. Two aspects of batteries are considered in this paper, battery-capability versus temperature and load-effects of high currents during the charging and discharging process. It is shown that there is an overall reduction in the internal losses due to temperature effects to take a significant reduction in battery-efficiency, so to change battery-capability. The main features of several different types of batteries are shown in this paper including their detailed analysis to show the effect of temperature change. Three possible temperatures are explored: a) -10°C (14 F); b) 10°C (50 F); and c) +25°C (77 F) for low-current and a maximum-current loading to get the performance of batteries behaviors. The results shown that the value of temperature or current-loading has an effect on the capacity, because the internal resistance of batteries is variable.


The application of the high-performance organization (HPO) framework to a European multinational retailer operating in 15 countries showed that the framework is useful in accurately assessing progress in adopting the characteristics of a high-performing organization and in formulating improvement suggestions at various organizational levels. In a similar fashion, managers at other multinational enterprises can apply the framework to evaluate their own organizations' HPO status, facilitate organization-wide communications, and craft an agenda for improving processes and enhancing overall performance. © 2012 Wiley Periodicals, Inc.


The reason behind is that they have their own principles, strategic goals and industrial environment that they have to manage on daily bases. The current labour and talent shortage across Europe forces local companies to supply their demand of manpower from foreign countries – encouraged by the 'four freedoms' of the EU. In consequence of the globalisation, we have to keep in mind that running a talent management system has its challenges. For instance, employees with different cultural background might have unconventional needs. Due to the cultural, demographical and economical differencies, we must know the structure of our labour force to use the most beneficial tools to induct, motivate or retain our human resource. The aim of this research is to analyze Europe's and China's talent management systems to reveal similarities and differencies between them and pick the most notable ones. From the point of comparison, analysing China would be important for European countries to discover further possibilities, as nowadays China has one of the most dynamically developing economy with enormous population behind. The primary result of the research is that deficiency of talent is irrespective of the size of the population and it causes difficulty in both European and Chinese fields, therefore it proves to be a real and general challenge needing attention at organizational level. Furthermore, identifying regional patterns considering peculiarities, the framework of talent management systems can be defined and be found summarised in the article.


In this study I want to investigate and analyze the process of acquisition of L2 Russian on
the example of the acquisition of impersonal sentences:
(1) Mamu pozdravlayut.
Mother (ACC) congratulate (3pl).
'Mother is congratulated.'
(2) Mama pozdravlyayet papu.
Mother(NOM) congratulate(3d sg, PRESENT) father(ACC).
'Mother congratulates father.'
The choice of this type of sentences is defined by its complexity and its closeness in pragmatic
sense to passive constructions. The object is propagated to the subject position but it still keeps
accusative case marking and it is followed by a verb in plural form which pronoun is dropped.
Logical stress in the sentences falls on the verb which means that verb conveys new information, it
is the focus of the sentence; and the 1st NP carries old information. Acquisition of such
constructions and ability to produce target-like sentences requires a lot of grammatical and
pragmatic development of L2 of the learner. The learner should be able to distinguish between
case marking and its role in syntactic marking of the sentence elements, to understand pragmatic
choice of word order in Russian and to realize the process of mapping the arguments to their
function in the sentence.
For my research I have chosen to work within the framework of (Extended) Processability Theory
(PT) developed by M. Pienemann (1998). According to PT any language develops gradually and the
process can be divided into levels which reflects actually the development of inner language
3
processor. PT states that any utterance of the language requires a set of processing
procedures. These procedures define the complexity of the utterance and reflect the level of
the learners' interlanguage development. Processing procedures are language-specific and
they form a hierarchy. A hierarchy of processing procedures is based on LFG grammar. LFG,
as a grammatical formalism, provides a clear view on the internal structure of any utterance.
According to LFG in any language construction we can observe three levels or three parallel
structures: constituent structure, functional structure and argument structure. Constituent
structure is mapped to functional structure via the process of feature unification. And
argument structure is mapped onto functional structure which means that semantic roles are
mapped onto their grammatical functions. All three levels and the mappings from level to
level are very important for the explanation of SLA :they define the level of the interlanguage
development.
In order to process language at high speed, the speaker is required to store grammatical
information about parts of the sentence s/he produces in short term memory. Depending on
the availability of particular processing procedures, the learner can unify this grammatical
information at different levels of constituents. This process of unification is necessary
because the output in language production is linear but mental processes of language
production are not. (Pienemann, 1998:54) The hierarchy of processing procedures is
implicational: ever lower level in the hierarchy is the prerequisite for the higher one.
Extended PT offers an approach that allows to explain a wider range of linguistic
phenomena: passives, causative and topicalisation. The Extended PT has adopted the Lexical
Mapping theory in order to be able to explain the mapping of arguments onto functional
structure. Each argument role can be expressed in different grammatical forms. At lower
levels of L2 development the learners tend to stick to linear mapping of arguments onto
functional structure because it costs less in means of processing procedures. Once the level of
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the learner's L2 development increases the linear mapping can be substituted by non-linear
mappings which allow the learner to produce passives and other complex constructions.
This research aims to answer the following set of questions:
1.How does the PT hierarchy of Russian L2 look like?How many levels does it have
and which procedures correspond to which level?
2. At what level of language IL development the learners of L2 Russian will be able
to produce and to comprehend IMP constructions? What are the prerequisites
for comprehension and production of these constructions?
Methodology.
For building a hierarchy of Russian L2 processing procedures I use LFG formalism. Starting
from single lemmas and words and going to phrases and then sentences I build the repository
of grammar rules and lexical features which reflect the work of inner processor. Then to
each level of language development I assign a set f procedures which are to be acquired.
The hierarchy is tested on the L2 Russian spoken data. The data is collected during the
interviews with the participants of the research. All the interviews are recorder and evaluated.
Participants are offered a set of tests: profiling test and tests on the comprehension and
production of impersonal constructions.
As a result I expect to get for every participants his/her level of interlanguage development
and results for comprehension and production tests. These data will allow me to find the
correspondence between the level of language development and ability to comprehend and
produce impersonal constructions, and to analyze the process of Russian L2 acquisition. This
research contributes to the studies of cross-linguistic aspects of PT and its plausibility for
typologically different languages. PT only once has been applied for the study of
development of Serbian nominal structures by the speakers of Serbian in Australia
(Medojevic, 2009). So this will be the first attempt to account for a wide range of syntactic-
5
pragmatic procedures in L2 Russian as Slavic language. The study of the acquisition of
impersonal constructions contributes to the understanding of L2 Russian syntax and its
acquisition by the learners. It also allows to understand the underlying principles of language
processing by L2 learners and to create an effective methods of teaching Russian as a foreign
language.


Introduction The extent to which measurable factors at birth and/or during early childhood influence lung function in adolescence remains uncertain. Furthermore, it is not entirely clear what factors influence "tracking" of lung function during growth. Aims We sought to quantify if lung function at 14-17 years of age is associated with measurable factors at birth and 8-9 years of age. Methods Data for 2444 Caucasian, term-born, singleton, live births from the Avon Longitudinal Study of Parents and Children (ALSPAC) was used to model raw lung function variables (FEV1, FVC and FEF25-75) at 14-17. We built several regression models to include relevant information including birth-weight, gestation; height and weight at 8-9 years and at 14-17 years of age. Results For FEV1 at 14-17 years, 26% of the model variance was explained by measurements at birth – primarily gender and birth-weight. Adding height, weight and FEV1 values at 8-9 years improved this association with FEV1 at 14-17 years of age to 49%. When measurements available at 14-17 were added, the variance improved to 57%. For FVC at 14-17, the respective figures at birth, 8-9 and 14-17 were 30%, 52% and 59% and for FEF25-75 were 8%, 38% and 42%. Unsurprisingly, lung function values at 8-9 years had the greatest association with lung function at 14-17 years of age. The final model featured lung function and growth measures at 8-9 and 14-17. Birth-weight did not feature as it is correlated with growth at later stages. Conclusions Lung function at 14-17 years of age is marginally associated with birth weight but strongly related to lung and growth parameters at 8 years thus supporting the concept of tracking of lung function.


The aim of this paper is to analyze the autonomic behavior mediated by the baroreceptor response to an orthostatic maneuver (OM) in hypertensive and non-hypertensive subjects. The heart rate (HR) was obtained in 65 subjects (32 hypertensive and 33 non-hypertensive) using a frequency meter polar watch, before and after an OM (sudden standing). The R-R intervals were transformed into a heart rate, temporal series, and interpolation was applied due to a lack of heart rate periodicity. Sampling at 10Hz was performed, and a band-pass filter was applied followed by 1 Hz subsampling. The results showed an increase in sympathetic activity in the hypertensive group that did not occur in the non-hypertensive group after the OM (∆%=59.84%, P<0.01). For the parasympathetic results, decreases were found only in the hypertensive group and not in the non-hypertensive group after the orthostatic intervention (∆%= -43.4%, P<0.001). Increases in both groups were observed for the sympathovagal balance (hypertensive: ∆%= 45.63%, p=0.004; non-hypertensive: ∆%= 67.08%, p=0.013). The results showed increased sympathetic activity in contrast to a decreased parasympathetic response for hypertensive individuals after an OM.


This paper presents the consumptive water use for freshwater pond
aquaculture for semi-intensive carps farming practices. The consumptive use
of water includes evaporation loss, seepage loss and water exchanges requirements.
The water requirement has been estimated to be10.3 m3/Kg of fish production under present
study for semi-intensive culture and with supplemental feeding. Out of which7.6 m3/Kg of fish production is
system associated requirement. On an average the evaporation loss from the pond
is1498.3 mm/year
and seepage loss per year is about1182.60 mm/year. Seepage and water exchange losses
recharge the ground water aquifers and if they are treated and recycled, the
water use in aquaculture can be reduced significantly. A further reduction in
fresh water use in pond aquaculture is possible through development of
intensive and superintensive culture systems and aqua feeds.


Three-dimensional chromatin structures regulate gene expression across genome. The significance of de novo mutations (DNMs) affecting chromatin interactions in autism spectrum disorder (ASD) remains poorly understood. We generated 931 whole-genome sequences for Korean simplex families to detect DNMs and identified target genes dysregulated by noncoding DNMs via long-range chromatin interactions between regulatory elements. Notably, noncoding DNMs that affect chromatin interactions exhibited transcriptional dysregulation implicated in ASD risks. Correspondingly, target genes were significantly involved in histone modification, prenatal brain development, and pregnancy. Both noncoding and coding DNMs collectively contributed to low IQ in ASD. Indeed, noncoding DNMs resulted in alterations, via chromatin interactions, in target gene expression in primitive neural stem cells derived from human induced pluripotent stem cells from an ASD subject. The emerging neurodevelopmental genes, not previously implicated in ASD, include CTNNA2, GRB10, IKZF1, PDE3B, and BACE1. Our results were reproducible in 517 probands from MSSNG cohort. This work demonstrates that noncoding DNMs contribute to ASD via chromatin interactions.


The research team completed a secondary data analysis of primary data from a 2-phase depression treatment engagement behavioural trial to assess African-American adolescents' reported experiences of spiritual and religious coping when dealing with depression. The team utilised data collected from 28 youth who participated in focus groups or individual interviews. Qualitative data were analysed using thematic techniques for transcript-based analysis to identify the key patterns and elements of the study participants' accounts and to extract six primary themes. The main themes are reported in this manuscript and include; "Religion as Treatment Incentive", "Prayer & Agency", "Mixed Emotions", "Doesn't Hurt, Might Help", "Finding Support in the Church", and "Prayer and Church: Barriers to Treatment?" Overall, the data suggested that religion and spirituality play a key role in African-American adolescents' experiences of depression. As well, it is surmised that these factors may be important for improving treatment-seeking behaviours and reducing racial mental health disparities in this population of youth.


One of the central problems in creating information management solutions for precision dairy farming is integration and interpretation of heterogeneous data coming from different equipment and data sources. Establishing a unifying data model is recognized as a cornerstone to such solutions. Here, the challenge lies both in agreeing on a common information context, and in selecting appropriate model representations, model query and update techniques, which guarantee model extensibility. While already existing ISOagriNET Data Dictionaries capture broad variety of the livestock and dairy farming concepts, the existing model representation technics cannot support efficient model extension. In this paper, we present our experience with using the representation and query standards and tools of the Semantic Web, endorsed by the World Wide Web Consortium (W3C), in particular the Resource Description Framework (RDF), the Web Ontology Language (OWL), and the SPARQL query standard, to encode and manipulate the dairy farming domain knowledge in a form of the Dairy Farming Ontology (DFO). Within the research project agriOpenLink the DFO has been created in two phases. The first phase focused on using the Semantic Web tools to facilitate easy encoding and manipulation of the dairy farming domain knowledge and the platform operational data models. The second phase focused on translating ISOagriNET Data Dictionaries into their semantic representations. Resulting DFO is maintained in a semantic repository, and it presents a knowledge graph and as integration backbone for the agriOpenLink decision support platform.


The growth of certain methicillin-resistant Staphylococcus aureus (MRSA) isolates could be inhibited by NaCl higher than 2.5%. The objective of this study was to develop an enrichment method to recover NaCl-susceptible MRSA isolates from meat samples. The growth of 12 MRSA and 10 non-MRSA strains was measured in Mueller-Hinton (MH) broth supplemented with 2.5%, 4%, 6.5%, and 7.5% NaCl. Selective agents, including aztreonam, polymyxin B, NaCl, nalidixic acid, and NaN3, were determined for their inhibitory effect to MRSA and non-MRSA strains in MH broth. Based on these data, a two-step enrichment method was developed to recover both NaCl-susceptible and -resistant MRSA isolates in meat products. Comparing to the enrichment method that only used MH broth supplemented with 6.5% NaCl, five additional NaCl-susceptible MRSA isolates were recovered from 92 retail ground pork samples by this newly developed two-step enrichment method. To the best of our knowledge, this is the first study that considers NaCl-susceptible MRSA recovery from ground pork samples. The application of this new enrichment method might expand the diversity of MRSA isolates recovered from various samples.


T lymphocytes express a T cell antigen receptor (TcR) complex composed of either an TcR alpha/beta or TcR gamma/delta heterodimer in noncovalent association with the CD3 glycoproteins. CD28, a 44-kDa disulfide-linked homodimer, is present on the surface of the majority of TcR alpha/beta-bearing T lymphocytes. Monoclonal antibodies (mAb) directed against CD28 potentiate activation signals delivered through the CD3/TcR alpha/beta complex. Herein, we demonstrate that CD28 is expressed on approximately 40%-60% of TcR gamma/delta-bearing T lymphocytes in most donors. Anti-CD28 mAb substantially augmented proliferative signals delivered through the TcR gamma/delta, demonstrating the presence of functional CD28 molecules on TcR gamma/delta-bearing T lymphocytes. The majority of TcR gamma/delta+ thymocytes also expressed CD28.


A bridge monitoring system is significant to the structural health monitoring of both old/new bridges and flyovers an infrastructure daily used by citizens of their respective countries. The following report is proposed and developed an architecture for bridge monitoring on a more secure level taking into consideration the various parameters that are involved in the structural health of bridges. A 3-level distributed structure is adopted in the monitoring system, which includes a central server, intelligent acquisition node, and local controller. Acquisition nodes are located across the bridge. One local controller manages all the acquisition nodes. Every acquisition node has 8 channels, which can easily and approximately sample the deviation of the line of sight, the vibration of the bridge due to a load of various transports and as well the water level which when cross a threshold lead to a flood. To get high precision data, a 10 bits A/D converter is being used. Compared to the traditional method, the proposed architecture has two features. The acquisition node is a smart device based on a powerful controller. Signals of field sensors are analyzed and real-time compressed in the acquisition node. Only the processing results are sent to the local controller through the IEEE 802.11 wireless network. This operation can relieve the load of a central server. The intelligent monitoring system has run on a large span bridge. Running results show that the proposed system is stable and effective. Keywords— Sensors [A.I.], Input/output and data communications, Microcontroller– Node MCU, M-7053D,


Aechmea aenigmatica Lopez-Ferrari, Espejo, Ceja et A. Mendoza, a new species from Oaxaca, Mexico is described and illustrated. The new taxon is compared with A. lueddemanniana (K. Koch) Mez and A. mexicana Baker, species with similar characteristics, from which it differs by the presence of symmetrical sepals and petals without basal appendages. Identification keys for all species of Aechmea present in Oaxaca, as well as for all species of subgenus Podaechmea are included.


The existence and magnitude of slip velocities between deionized water and a smooth glass surface is studied experimentally. Sub-micron fluorescent particles are suspended in water and imaged using total internal reflection velocimetry (TIRV). For water flowing over a hydrophilic surface, the measurements are in agreement with previous experiments and indicate that slip, if present, is minimal at low shear rates, but increases slightly as the shear rate increases. Surface hydrophobicity is observed to induce a small slip velocity, with the slip length reaching a maximum of 96 nm at a shear rate of 1800$\,{\rm s}^{-1}$. Issues associated with the experimental technique and the interpretation of results are also discussed.


The study was conducted to assess the prevalence of qualitative traits and their influence on morphometric traits. A total of 499 West African Dwarf (WAD) goats were used comprising of 113 and 386 males and females respectively. The qualitative and morphometric traits were identified and their associations were assessed. The distribution and frequencies of qualitative traits were investigated and scored for presence or absence of wattle (Waw or Wa+), beard (Brb or Br+), horn (Ho+ or Hop) were recorded. Four coat colours were observed, the white, white/black, black and mixed colour (white, black and brown). There was a high preponderance of white coat colour (56.51%) followed by white/black (31.06%), the frequencies of black and mixed colour were similar (6.21%). The frequency of wattle was low (0.4%), beard was present in both sexes although a higher frequency was observed in males (56.88%), horn was equally present in both sexes. The presence of wattle had no influence on morphometric traits, whereas goats with beard and horn were significantly (p < 0.05) superior in body length, heart girth and height at wither. Sex significantly (P<0.05) influenced the morphometric traits measured. The significant effect of beard and horn on morphometric traits in this study suggest that beard and horn may be important factors to consider in making selection and culling decisions in WAD goats.


This paper presents the results of an ongoing project whose objective is to develop a model and a simulation that, used as Decision Support System, aid the heads of Hospital Emergency Departments to make the best informed decisions possible. The defined model is a pure Agent-Based Model, formed entirely of the rules governing the behavior of the agents that populate the system. Two distinct types of agents have been identified, active and passive. Active agents represent persons, whereas passive agents represent services and reactive systems. The actions of agents and the communication among them are represented using Moore state machines. The model also includes the environment in which agents move and interact. The simulation has been implemented using NetLogo, and it has been used to evaluate the potential benefits for the ED of the derivation to primary care services of those patients who attend emergency services without requiring an urgent attention.


Programmer resources as measured in available hours are often a limiting or constraining resource in software projects and maintenance. A key element in software project management, therefore, is the forecast of required programming hours. Estimates based on past experience and similar projects are generally unreliable and usually underestimate the level of programming resources required. Function point counting provides a reliable methodology for estimating the level of effort required in software projects. Presents the results of using and modifying function point counting procedures in a maintenance environment where changes are often confined to one or more lines of code. The study indicates that even in this environment, function point counting procedures are useful. Finally, function point counting in the maintenance environment as discussed in this paper helped uncover problems in resource management, training, and personnel evaluation.


The influence of major cultural practices including different nitrogen application rates, population densities, transplanting leaf ages of seedling, and water regimes on rice canopy spectral reflectance was investigated. Results showed that increased nitrogen rates, water regimes and population densities and decreased seedling ages could enhance reflectance at NIR (near infrared) bands and reduce reflectance at visible bands. Using reflectance of green, red and NIR band and ratio index of 810-560 nm could distinguish the different type of rice by fuzzy cluster analysis.


TO THE EDITOR: I read the article by Qureshi and colleagues (1) with concern. Whereas the clinical trial methodology is admirable, the scientific questions are not helpful to understanding the role of data on family history in improving risk assessment. On a superficial level, the idea that risk can only be upgraded is incorrect. If a positive family history is used to upgrade risk, a negative family history should be used to downgrade risk. Otherwise, the calibration of the underlying model is ignored. On a more substantive level, this study provides no evidence on whether data on family history provide value by improving model discrimination or calibration, or whether any reclassification is actually correct. As noted by Qureshi and colleagues, this study also does not address patient behaviors, treatments, or outcomes. The results do not support incorporation of family history assessment into routine clinical practice. We need results documenting improved discrimination, calibration, and correct reclassification. Easy math is not necessarily correct.


Cloud computing is set of resources and services offered through the Internet. Cloud services are delivered from data centres located throughout the world. Cloud computing facilitates its consumers by providing virtual resources via internet. The rapid growth in field of ―cloud computing‖ also increases severe security concerns. Security has remained a constant issue for Open Systems and internet, when we are talking about security, cloud really suffers. Lack of security is the only hurdle in wide adoption of cloud computing. Cloud computing is surrounded by many security issues like securing data and examining the utilization of cloud by the cloud computing vendors. This paper proposes a scheme to securely store and access of data via internet. We have used ECC based PKI for certificate procedure because the use of ECC significantly reduces the computation cost, message size and transmission overhead over RSA based PKI as 160-bit key size in ECC provides comparable security with 1024-bit key in RSA. We have designed Secured Cloud Storage Framework (SCSF) . In this framework, users not only can securely store and access data in cloud but also can share data with multiple users through the unsecure internet in a secured way. This scheme can ensure the security and privacy of the data in the cloud. Keywords— Cloud storage, Cloud computing, ECC, PKI,


A simplified version of differential thermal analysis has been developed resulting in an inexpensive apparatus for determining the latent heat of fusion of phase change materials. The experimental results performed with three samples show that the present method yields results which agree within 5% with the measurements of sophisticated differential scanning calorimetry apparatus.


Wine tourism is one of the best opportunities for rural development, but because it is partially exposed to climatic conditions, it is a climate-vulnerable tourism activity. However, an understanding of the potential impacts of global climate change on this popular activity remains limited. This study proposes a new methodology that combines current daily gridded climate data from the E-OBS project with big spatiotemporal data from the Flickr photo-sharing platform through a generalized additive model This methodology was implemented to study the potential impacts on tourism flows due to climate change and to make predictions about the future using data from the CMIP5 project. We applied the methodology to 5 European wine tourism regions: Alsace (FR), Chianti (IT), La Rioja (SP), Langhe-Monferrato (IT), and Moselle (DE). Results show an increased probability of presence and increased deseasonalization of tourism in all study areas and an anticipation of peak presence from summer to spring in three of the five regions. We believe that these results can be useful for public and private stakeholders to adapt the offer of wine tourism services to changes in demand and to direct the organization of events such as festivals and thematic tours.


Introduction : An allergic phenotype has been reported to be associated with risk of exacerbations in patients with COPD using data from cohort studies conducted in the United States (Jamieson, D.B. et al. Am J Respir Crit Care Med 2013; 188:187-192). Aim : To assess whether the presence of allergic sensitization is associated with worse baseline characteristics and/or clinical course of patients with COPD in a 5-year prospective observational cohort study. Methods : A total of 268 subjects (GOLD 1, 26%; GOLD 2, 45%; GOLD 3, 24%; GOLD 4, 5%) who participated in the Hokkaido COPD cohort study conducted in Japan were included for this analysis. Allergic sensitization was evaluated at enrollment by the presence of serum specific IgE for inhaled antigens measured by MAST assay. Results : 67 COPD subjects (25%) had allergic sensitization to at least one inhaled antigen. The presence of allergic sensitization to at least one antigen was not associated with any of lung function (post-bronchodilator FEV 1 %predicted), airway reversibility, CT emphysema score, and quality of life (SGRQ score) at baseline, and annual decline in FEV 1 and exacerbation frequency during the follow-up period. On the other hand, subjects with allergic sensitization to pollens or fungi had better baseline lung function and lower airway reversibility compared with those without allergic sensitization to them. Conclusion : In this study, the presence of allergic sensitization was not associated either with worse baseline characteristics or with clinical course of patients with COPD.


The COVID-19 outbreak and its associated restrictive measures, such as lockdown, exposed most individuals to an unprecedented stressful situation, increasing worldwide the prevalence of mental health disorders. Here, we aimed at exploring for the first time the effect of COVID-19-lockdown on subjective cognitive functioning as well as mental health, in terms of its prevalence and clinical severity. In addition, potential risk factors characterizing more vulnerable groups were investigated. A nationwide cross-sectional online-survey was conducted during the final phase of lockdown in Italy (after 7-10 weeks of home confinement), leading to a sample of 1215 participants. We found lockdown can have a severe impact on subjective cognitive functioning, along with mental health disorders. Namely, under restrictions, cognitive complaints were mostly perceived in everyday tasks involving attention, temporal orientation and executive functions; while no changes in language abilities were reported. Conversely, a paradoxical effect was observed in memory domain, with people experiencing a reduction of memory failures compared to pre-lockdown times. Further, higher severity and prevalence of depression, anxiety disorders and of other psychological issues (involving sleep, appetite, libido and hypochondria) were observed - with a prevalence of mild-to-severe depression and anxiety rising up to 32.30% and 35.72% respectively, under restrictions. Being female, young (<45 years), repeatedly exposed to COVID-19-media, working from home or being unemployed were identified as relevant risk factors for experiencing cognitive worsening and mental health disorders, related to the COVID-19 lockdown. Being resident in high infection-prevalence areas was related to higher level of depression and health anxiety. As lockdown and quarantine measures could be reimposed, health officials have to carefully consider these more vulnerable groups in their decision-making process, to develop an effective global and long-term response to the mental health challenges of this pandemic as well as to implement psychological interventions and specific guidelines, particularly about COVID-19-media exposure.


This letter describes a two-dimensional (2-D) extension of a recently developed finite-difference time-domain (FDTD) scheme to model wave propagation in bi-isotropic media. To our knowledge this method is the only one successfully generalized to modeling transient microwave signals in general lossy dispersive bi-isotropic media. The new 2-D cell built and computational procedure of the FDTD algorithm developed is described. Condon and Lorentz dispersion models have been included for modeling the frequency dependence of the medium parameters and the auxiliary differential equation (ADE) method is considered to deal with dispersion in order to avoid defining complex back-stored numbers to compute the convolutions recursively. Finally the oblique incidence of a wave on a chiral medium and the propagation in a general lossy bi-isotropic medium have been successfully simulated.


ABSTRACT Impacts of climate change in the Pacific are far reaching and include effects on mental health and wellbeing. Pacific concepts around the interrelation of these global giants are yet to be described. The aim of this study was to seek consensus amongst Pacific mental health and/or climate change experts on key principles underpinning mental health and wellbeing, and climate change, and the intersection of the two, for Pacific peoples. The Delphi method included forming a panel of 70 experts. Two rounds of online questionnaires sought their views on mental health and wellbeing, and climate change and the impact upon Pacific peoples. Of the panel 86% identified with one or more Pacific ethnicities. Six themes emerged, 92% of items reached consensus and 36% reached strong consensus of >95%. Recurring subthemes included culture and spirituality, family and community, connection to ancestors, connection to the environment, resilience, disasters, livelihoods, government, education, workforce, migration and stigma. This is the first time these concepts have been explored and described for, and by Pacific peoples in this format. It is a necessary first step towards development of responses in preparedness of mental health services, in the Pacific region, and Aotearoa New Zealand.


In this paper I propose a novel treatment of genericity. While my diagnosis is that no present theory is satisfactory, I choose Liebesman's simple kind predication t heory (2011) as an initial framework. I reject Liebesman's claim that generics are sentences about kinds and suggest that they are rather sentences about types showing the virtues of such view. While my ultimate goal is to show that the type analysis of generics is both natural and explanatorily superior to its rivals, I also propose both semantic and pragmatic analysis of generic sentences.


This paper presents a general framework for specification and detection of properties in distributed computations. A property of states in distributed computation in progress is defined by predicates (called behavioral patterns) and satisfaction rules (called modal operators). A behavioral pattern is obtained by combining basic predicates that are defined over either local states or consistent global states of the computation. In both cases, we model a distributed computation by a directed acyclic graph in which vertices represent (local or global) states and edges represent causal relation over the states. Specification and verification of behavioral patterns are formulated as instances of the language recognition problem, and basic concepts used in formal language theory are applied. A basic predicate is assimilated to a symbol, and a behavioral pattern is specified as a language (i.e., a set of words) defined over an alphabet of symbols. Based on this model and given a behavioral pattern, we define four modal operators (i.e., four different satisfaction rules). Three of them are equivalent to modal operators previously introduced in related works. Finally, we present algorithms to verify each of the four modal operators over a class of behavioral patterns, called regular patterns.


Europe's proposed Data Protection Regulation is expected to make data protection impact assessment (DPIA) mandatory, a development that could impact hundreds of thousands of organizations (both governmental and private sector) in Europe, as well as non-European entities offering their wares and services there. This article reviews the DPIA provisions outlined in the new regulation. For the nuts and bolts of a privacy impact assessment (PIA) methodology, Europe could select features from the PIA methodologies used in Australia, Canada, Ireland, New Zealand, the United Kingdom, and the United States, the countries with the most experience in PIA. A European Commission (EC)-funded project, called PIAF, reviewed these various methodologies and proposed an "optimized" PIA for Europe (and elsewhere) based on the best practices of the aforementioned countries. Based on these best practices, this article outlines a 16-step PIA process. It argues that while some organizations may regard a PIA as a hassle, in fact, a PIA offers many benefits, as spotlighted in the article.


In Japan, most tax scholars and practitioners have believed that the introduction of "advance-ruling" would dispel the uncertainty about tax consequences and facilitate transactions. However, Givati (2009) shows that in the U.S. advance rulings (Private Letter Ruling and Advance Pricing Agreements) are not frequently used. Givati (2009) argues that some taxpayers avoid applying for advance ruling not because of the "direct cost" of the application, but because of strategic disadvantages. For example, if a taxpayer applies for the advance ruling, the tax authority would audit this taxpayer more carefully. This essay has three purposes. The first is to introduce the U.S. advance ruling systems (Private Letter Ruling and Advance Pricing Agreement) to Japanese readers. The second is to analyze the data and arguments provided by Givati (2009). The Third is to consider how we can improve the advance ruling system in Japan. As a tentative conclusion, I suggest following two points in order to encourage taxpayers to apply for advance ruling and facilitate transactions; (1) the applicant's anonymity needs to be preserved against tax authority in order to avoid increasing the probability of tax audit, and (2) the applicant's privacy and trade secrets need to be protected against their business competitors by introducing some procedures before making the rulings public.


Multiconductor transmission lines have found a wide range of applications, as power lines, as high‐speed interconnects, and as on‐chip interconnects. Electromagnetic interference (EMI) can be described in terms of plane waves that couple to these lines, leading to unwanted disturbance. This paper presents a delayed spectral formulation for the analysis of plane‐wave coupling to multiconductor transmission lines in both the frequency and time domains, called the DeRaG‐EMI model (short for "delay‐rational model based on Green's functions for electromagnetic interference"). The model is based on Green's functions and is described in terms of delayed differential equations in the time domain. The model is suitable for studying the EMI on multiconductor transmission lines in the case of incident fields. The coupling of a plane wave to a line is described in terms of equivalent sources that account for both the delay of the line and the delays of the incoming plane wave. The delay is explicitly extracted and incorporated into the model with hyperbolic functions. The DeRaG‐EMI model does not require any segmentation of the line. Numerical results confirm its accuracy and its improved performance compared with the previous spectral model and with the inverse fast Fourier transform technique.


This paper presents an analysis of the linear dispersion relation for electrostatic waves in a Vlasov plasma of unmagnetized, Maxwellian ions and magnetized, Maxwellian electrons. The electrons undergo E × B and ∇B drifts, and the electron β is small. For propagation in the perpendicular direction, maximum growth rates can be substantially larger than those of the zero magnetic field ion acoustic instability. For propagation outside a few degrees from the perpendicular the dispersion characteristics are essentially those of the ion acoustic instability.


Background New ultrasound techniques (high frequency ultrasound, elastography) have been put in the clinical practice in recent years for the detection of skin involvement in Systemic Sclerosis (SSc). The modified Rodnan skin score (mRSS) is a standard measure used to evaluate severity and extent of skin involvement. The limitations of mRSS include the intraobserver and interobserver variability as well as the necessity of standardization. The pulmonary involvement is very common feature in patient with SSc and the gold standard of its detection was high resolution CT (HRCT). There exist a few studies in the past several years indicating that the Lung ultrasound (LUS) could substitute HRCT in screening of pulmonary interstitial complications. Objectives To determine the correlation between the dermal thickness revealed by high frequency ultrasound and the presence of B-lines at LUS examination in early diffuse SSc. Methods 42 patients with diffuse SSc have been identified in the present stusy by the extent of skin involvement. All subjects have met the ACR diagnostic criteria for SSc. The disease duration have been ≤3 years. The dermal thickness have been measured by means of an 18MHz probe at five different anatomical sites: phalanx, hand, forearm, leg, chest. The obtained values for all sites have resulted in an average skin thickness. LUS have been performed with 2.5-3.5 MHz transducer for anterior, posterior and lateral chest consecutively in determinated areas. LUS examination have been aimed at searching for B-lines, the sonographic marker of interstitial lung disease. Results Patients with diffuse SSc have revealed high dermal thickness during the early edematous phase. This finding correlates with the increased number of B-lines, detected at the LUS examinations. The results of the examinations have been characterized by the following statistical quantities: (i) mean value of dermal thickness x=1.77±0.21, (ii) 73.8±2.4% from the group of patients shows values of B-lines, which are greater than 6, (iv) the correlation is significant at P=0.01 for both methods applied: direct and significant relationship at the following correlation coefficients: Kendal 0.82, Spearman's rxy =0.93, Pearson 0.924. Conclusions A strong correlation has been found in this study between the dermal thickness examined at five anatomical sites and the total amount of B-lines at LUS examination of patients with diffuse SSc. Our opinion is that these new tools could support the diagnostic accuracy in patients with early SSc References Olga Kaloudi, Francesca Bandinelli, Emilio Filippucci, et al. High frequency ultrasound measurement of digital dermal thickness in systemic sclerosis. Ann Rheum Dis 2010 69: 1140-1143. Manal Mohamed Sedky, Samar Mohamed Fawzy, Noha Abd El Baki, et al. Systemic sclerosis: an ultrasonographic study of skin and subcutaneous tissue in relation to clinical findings. Skin Res Technol 2013; 19: e78-e84. R. Hesselstrand, A. Scheja, M.Wildt and A. Akesson. High frequency ultrasound of skin involvement in systemic sclerosis reflects oedema, extension and severity in early disease. Rheumatology 2008;47:84-87. Disclosure of Interest None declared


Abstract Background: More than a decade after the National Institute for Health and Clinical Excellence recommendation of home haemodialysis (home HD) for 10–15% of those needing renal replacement therapy, the uptake across different regions in the UK remains uneven. Methods: This survey is part of the Barriers to Successful Implementation of Care in Home Haemodialysis (BASIC-HHD) study, an observational study of patient and organizational factor barriers and enablers of home HD uptake, in the UK. The study centres had variable prevalence of home HD by design [low: <3% (2), medium: 5–8% (2) and high: >8% (1)]. This survey was administered electronically in 2013, and had 20 questions pertaining to home HD beliefs and practices. A total of 104 members of staff across five study centres were approached to complete the survey. Results: The response rate was 46%, mostly from experienced HD practitioners. Most believed in the benefits of home HD therapy. Across all centres, respondents believed that preconceptions about patients' and carers' ability to cope with home HD (35% to a great or very great extent) and staff knowledge and bias influenced offer of home HD therapy (45%). Also, compared with respondents from high prevalence (HP) centre, those from low prevalence (LP) centres felt that display and presentation of dialysis information lacked clarity and uniformity (44% versus 18%), and that a better set-up for training patients for self-care HD was required (72.8% versus 33.3%). A greater proportion of respondents from the HP centre expressed concerns over caregiver support and respite care for patients on home HD (63.7% versus 33.3%). Conclusions: Survey results indicate that across all centres in the study, there is an appetite for growing home HD. There are some differences in attitudes and practice between LP and HP centres. There are other domains where all centres have expressed concern and addressing these will be influential in navigating change from the current course.


In 1982, the Supreme Court held in Plyer v. Doe that undocumented immigrant students have a right under the Equal Protection Clause to a free public education. In an effort to take stock of the case's impact at the classroom and community levels, this article analyzes the results of surveys and interviews about Plyler with over 150 school personnel in six public schools in Southern Arizona. The authors draw several conclusions about Plyler's complex legacy and future viability from the data collected. First, despite the case's lasting power, its goal of ridding public school classrooms of distinctions based on legal status remains incomplete. Undocumented students remain vulnerable to subtle but pervasive discrimination in school, particularly on the basis of their language abilities. The research also demonstrates how Plyler's equalizing goal is limited at a more fundamental level by the precarious status of undocumented students once they move outside the temporal and geographic bounds of primary and secondary education. The authors suggest policy reforms to address these obstacles to Plyler's successful implementation in schools. At the same time, the research demonstrates the affirmative benefits of Plyler and the likely consequences that would follow from its reversal. Specifically, the data capture significant benefits to teachers, lawfully present students, and immigrant communities that are often left out of discussions of the case's impact. Of particular note, the majority of school personnel who participated in the study strongly support the legal regime established in Plyler. They raised important and often unacknowledged concerns about the impact a reversal of the case would have on their professional morale and the quality of education in their schools. Their insights add an important dimension to discussions about the future of Plyler.


Sensitivity experiments of WRF model using different planetary boundary layer (PBL) and land surface model (LSM) parameterizations are evaluated for prediction of wind fields within the surface layer. The experiments were performed with three PBL schemes (YSU, Pleim, MYJ) in combination with three land surface models (Noah, RUC, Pleim). The WRF model was conducted on a nested grid from 27-km to 1-km horizontal resolution. The simulations validated wind speed and direction at 10 m and 80 m above ground level at a 1-km spatial resolution over the South Korea. Statistical verification results indicate that Pleim and YSU PBL schemes are in good agreement with observations at 10 m above ground level, while the MYJ scheme produced predictions similar to the observed wind speed at 80 m above ground level. LSM comparisons indicate that the RUC model performs best in predicting 10-m and 80-m wind speed. It is found that MYJ (PBL) - RUC (LSM) simulations yielded the best results for wind field in the surface layer. The choice of PBL and LSM parameterization will contribute to more accurate wind predictions for air quality studies and wind power using WRF.


We have combined the Quantum Mechanical/Molecular Mechanical (QM/MM) computational approach with techniques that search for minimum energy reaction paths to investigate retinal deprotonation in the light-driven proton pump protein, bacteriorhodopsin. The calculations indicate that the commonly-used adiabatic mapping method can lead to misleading energy barriers when too simple reaction coordinates are selected. The use of a reaction search method that does not require the a priori definition of a reaction coordinate allows to find multiple low-energy retinal deprotonation pathways whose energy barriers are fully characterized.


Introduction: Nine randomized trials in early breast cancer(EBC) have demonstrated an advantage of aromatase inhibitors(AI's) over tamoxifen in disease-free survival. Joint symptoms are common toxicities and lead to treatment interruption in up to 20% in case of severe aromatase-induced arthralgia(AIA). During menopause levels of markers of inflammation such as IL-1b, TNF-alpha and IL-6 increase. We hypothesized that estrogen deprivation by aromatase inhibition could be associated with similar changes in these markers and that this could play a role in AIA. In an earlier study, similar toxicities were observed in patients(pts) treated with a recombinant form of IL-6. In several cell types it has been shown that ligand activated estrogen receptor blocks nuclear factor kappa beta controlled gene transcription of IL-6. Aim of the study: We initiated a prospective open-label study to examine the role of inflammatory cytokines and other serum markers(CRP and hormones) in the pathogenesis of AIA. Methods: 29 evaluable postmenopausal pts with hormone sensitive, Her 2 negative EBC stage I-III, with baseline G0-1 arthralgia were included. Before chemotherapy, at baseline, at month 3, 6, 9, 12 and 18 after AI initiation, serum samples were taken for CRP and hormones (estradiol, androstenedion) and cytokines were analyzed with a human cytokine 25-plex panel. A detailed rheumatologic questionnaire and Visual Analog Scale(VAS) was performed at each visit. Arthralgia grading was assessed using the CTCAE criteria 4.0. The T-test and the Wilcoxon Signed Rank test were used to look for the difference in terms of IL-6, Il-1b, IL-8, TNF, CRP, estradiol and androstenedion between G0 versus G1-2-3 arthralgia. Results: The mean age was 56 yrs. (34-72yrs). All patients were treated with surgery followed by concomitant chemoradiation and letrozole (31) or anastrazole (1). In 16 pts G1 arthralgia was present before the start of the chemotherapy. Grade 2 and 3 arthralgia appeared at mth 3. The proportion of pts with grade 2 remained more or less the same, while grade 3 pts declined from month 6 onwards and disappeared at month 18. There was a significant correlation between the grade of arthralgia and the VAS score at all-time points (p Conclusion: This study indicates that both menopause and AIA have inflammatory mediators (IL6 and CRP) that correlate with the degree of lowering of estradiol levels. This is consistent with the regulation of IL-6 by the ligand activated ER through NFkB in vitro. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-06.


Objective: Motor vehicle crashes are a leading cause of injury and mortality for children. Mitigation of these injuries requires biofidelic anthropomorphic test devices (ATDs) to design and evaluate automotive safety systems. Effective countermeasures exist for frontal and near-side impacts but are limited for far-side impacts. Consequently, far-side impacts represent increased injury and mortality rates compared to frontal impacts. Thus, the objective of this study was to evaluate the biofidelity of the Hybrid III and Q-series pediatric ATDs in low-speed far-side impacts, with and without shoulder belt pretightening. Methods: Low-speed (2 g) far-side oblique (60°) and lateral (90°) sled tests were conducted using the Hybrid III and Q-series 6- and 10-year-old ATDs. ATDs were restrained by a lap and shoulder belt equipped with a precrash belt pretightener. Photoreflective targets were attached to the head, spine, shoulders, and sternum. ATDs were exposed to 8 low-speed sled tests: 2 oblique nontightened, 2 oblique pretightened, 2 lateral nontightened, 2 lateral pretightened. ATDs were compared with previously collected 9- to 11-year-old (n = 10) volunteer data and newly collected 6- to 8-year-old volunteer data (n = 7) tested with similar methods. Kinematic data were collected from a 3D target tracking system. Metrics of comparison included excursion, seat belt and seat pan reaction loads, belt-to-torso angle, and shoulder belt slip-out. Results: The ATDs exhibited increased lateral excursion of the head top, C4, and T1 as well as increased downward excursion of the head top compared to the volunteers. Volunteers exhibited greater forward excursion than the ATDs in oblique nontightened impacts. These kinematics correspond to increased shoulder belt slip-out for the ATDs in oblique tests (ATDs = 90%; volunteers = 36%). Contrarily, similar shoulder belt slip-out was observed between ATDs and volunteers in lateral impacts (ATDs = 80%; volunteers = 78%). In pretightened impacts, the ATDs exhibited reduced lateral excursion and torso roll-out angle compared to the volunteers. Conclusions: In general, the ATDs overestimated lateral excursion in both impact directions, while underestimating forward excursion of the head and neck in oblique impacts compared to the pediatric volunteers. This was primarily due to pendulum-like lateral bending of the entire ATD torso compared to translation of the thorax relative to the abdomen prior to the lateral bending of the upper torso in the volunteers, likely due to the multisegmented spinal column in the volunteers. Additionally, the effect of belt pretightening on occupant kinematics was greater for the ATDs than the volunteers.


Hypertension (HTN) is a major risk factor for cardiovascular and renal diseases, cerebrovascular accidents (CVA) and a prime underlying cause of worldwide morbidity and mortality. Hypertension is a complex condition and a strong interplay of multiple genetic, epigenetic and environmental factors is involved in its etiology. Previous studies showed an association of overexpression of genes with hypertension. Satisfactory control of Blood Pressure (BP) levels is not achieved in a major portion of hypertensive patients who take antihypertensive drugs. Since existing antihypertensive drugs have many severe or irreversible side effects and give rise to further complications like frequent micturition and headaches, dizziness, dry irritating cough, hypoglycemia, GI hemorrhage, impaired left ventricular function, hyperkalemia, Anemia, angioedema and azotemia. There is a need to identify new antihypertensive agents that can inhibit the expression of these overexpressed genes contributing to hypertension. The study was designed to identify drug-able targets against overexpressed genes involved in hypertension to intervene the disease. The structure of the protein encoded by an overexpressed gene Endothelin-1 was retrieved from Protein Database (PDB). A library of five thousand phytochemicals was docked against Endothelin-1. The top four hits against Endothelin-1 protein were selected based on S score and Root Mean Square Deviation (RMSD). S score is a molecular docking score which is used to determine the preferred orientation, binding mode, site of the ligand and binding affinity. RMSD refines value for drug target identification. Absorption, distribution, metabolism, excretion, and toxicity profiling (ADMET) was done. The study provides novel insights into HTN etiology and improves our understanding of BP pathophysiology. These findings help to understand the impact of gene expression on BP regulation. This study might be helpful to develop an antihypertensive drug with a better therapeutic profile and least side effects.


OBJECTIVE
To investigate the association of CYP3A5 and MDR1 genetic polymorphisms with the concentration/ dose (C/D) ratio of tacrolimus for the feasibility of individualized medication.

METHODS
The concentration of tacrolimus was detected by enzyme-multiplied immunoassay technique, and was adjusted by weight and dosage to C/D ratios. The single nucleotide polymorphisms of CYP3A5 A6986G and MDR1 C3435T, G2677T/ A, T1236C were determined by TaqMan RT-PCR. The differences of C/D ratio were compared among all of the genotype groups.

RESULTS
There were 5 cases with CYP3A5 *1/*1, 22 cases with CYP3A5 *1/*3, and 33 cases with CYP3A5 *3/*3. The C/D ratios of the patients with at least one CYP3A5 *1 allele (130.40 +/- 53.94) was significantly lower than those with CYP3A5 *3/*3 (198.12 +/- 90.80) (P < 0.01). For MDR1, there were 22, 23 and 15 recipients carried C/C, C/T and T/T respectively in C3435T, and 8, 32 and 20 recipients carried T/T, T/ C and C/C respectively in T1236C. The carriers with G/G, G/T, G/A, T/A, T/T were 9, 24, 5, 8 and 14 respectively in G2677T/A. No significant difference was found in the C/D ratios of tacrolimus among different MDR1 genotypes.

CONCLUSIONS
Determination of CYP3A5 genotype could help individualize tacrolimus dose regimen prospectively. The patients with CYP3A5 *3 *3 require less dose of tacrolimus to reach the same concentrations comparing with the patients with at least one CYP3A5 * 1 allele.


This paper describes the types of ground-level shelters, their availability and use by mammals and birds at Parque Estadual Carlos Botelho (PECB), an Atlantic forest area at southeastern Brazil. Eight types of shelters were found: shelters without tunnels under living trees, shelters with tunnels under living trees, shelters under mounds formed by adventitious roots, shelters under fallen trees, burrows not supported by trees or roots, riverbank shelters, stream tunnels and rock shelters. Mammal species that used shelters more frequently were Agouti paca, Philander frenata, Lontra longicaudis, Metachirus nudicaudatus and Trinomys iheringi. Utilization of shelter types and shelter topographic locations by these six species was roughly similar to the proportions in which shelters of different types and locations were monitored, with the exception of otters, which are semi-aquatic mammals and used mainly riverbank shelters. Contrary to expectations, animals did not choose shelters with entrances fitted to their sizes. Shelters were used either by a single species or by different species. I hypothesize that at the PECB other factors such as microclimate inside shelters must be more important in determining shelter use than shelter external characteristics or topographic location. Some species, as coatis Nasua nasua and probably small didelphids and birds, enter shelters to search for invertebrates and small vertebrates.