In a recent contribution to Geology, Espurt et al. (2007) advanced a new model to explain the presence of a major structural high, the Fitzcarrald Arch, in the Amazonian foreland basin. This model implies much greater coupling between subducting and overriding plates than previously suspected, and has implications for the tectonics of active margins far from the trench. In Espurt et al.'s interpretation, the presence of the Fitzcarrald Arch can be related to subduction of the buoyant Nazca Ridge in the presence of fl at-slab subduction. However, evidence from the Andes and other active margins worldwide indicates that their model is unlikely to be correct. The Fitzcarrald Arch is 650 m high and extends ~750 km from the trench. This degree of relative uplift is at odds with the general observation that in ridge-trench collision zones temporary uplift is high in the outer forearc but decreases rapidly landward. The vertical tectonic response to Nazca Ridge collision is well known from studies of multichannel seismic profi les and Ocean Drilling Program (ODP) drill sites from the Lima Basin, Peru. These data suggested up to 3 km of uplift close to the trench during the initial collision ~11 Ma, but this value decreased rapidly onshore (Clift et al., 2003). ODP Site 679 showed that the shelf was uplifted by <400 m, and possibly as little as 200 m, during ridge subduction. This value was attained ~130 km from the trench axis, much closer than proposed for the Fitzcarrald Arch. Constraints are also available from the onshore sedimentary sequences of the Pisco Basin, which presently overlies the crest of the subducting ridge. A backstripped analysis of the stratigraphy and terracing of the coastal zone, aimed at isolating the tectonic component of uplift in the collision area, indicates only ~120 m of post–2 Ma uplift ~160 km from the trench (Clift and Hartley, 2007). Furthermore, the fact that similar Pleistocene uplift is seen along much of the northern Andean margin suggests that much of that value is not linked to ridge subduction. Comparison with other arc-ridge collisions supports the idea that the temporary uplift does not extend far landward from the trench. In Costa Rica, subduction of Cocos Ridge deforms the forearc, but onshore uplift is minimal ( Vannucchi et al., 2006). On the Andean margin, collision with the Juan Fernandez and Iquique ridges results in dramatic uplift of the outer forearc regions, but little verti cal motion onshore or even in the coastal zones (Laursen et al., 2002; von Huene and Ranero, 2003). As in the Nazca Ridge subduction, these regions are also affected by fl at-slab subduction. Espurt et al. used an orogen-parallel seismic line to argue that the Fitzcarrald Arch was not formed by thrust faulting and is tectonically inactive. However, an across-strike seismic profi le would be needed to exclude thrust faulting as a mechanism, and this is suggested by both shallow (<70 km) earthquakes (Engdahl et al., 1998) and a tilted fault block topography. Espurt et al. noted that the southern arch is characterized by radial drainage networks. However, the Subandean zones and Eastern Cordillera also exhibit congruent geomorphological patterns with NW-SE–oriented promontories. Indeed any topographic profi le in the eastern Andes between 12°S and 13.5°S would yield a similar pattern to the Fitzcarrald Arch, suggesting a common mechanism for the uplift of the whole region. Marques and Cobbold (2006) modeled the effects of tectonic indenters as causing transfer zones to develop along indenter sides. The eastern Andes can be considered as an intender into the Amazon foreland (Carlotto, 1998), with its core located in the Eastern Cordillera. The area of the Fitzcarrald Arch marks a change in orogenic strike from NNW-SSE to NW-SE going south, and is a largescale transfer zone, which could have generated arch uplift. Additional mechanisms also contributing to uplift include differential erosion, shear stress along the subduction zone, and inherited heterogeneities from a Permo-Triassic rift. Espurt et al. reported that the Neogene is partially eroded between the Mashansha and Panguana drill sites. We note that this eroded region closely overlies a Paleozoic structure with similar orientation. Reactivation of these structures is the most likely cause of uplift and active tectonism in the arch. Although it is not yet clear what processes control Andean morphology south of the Fitzcarrald Arch, it seems unlikely to be subduction of the Nazca Ridge.


In this paper, a framework for localization of multiple co-channel transmitters using phase difference measurements between two antennas mounted on sensors of a sensor network is proposed. To pursue localization, we equip each sensor with two antennas and we use temporal cross-correlations between the received signals of the two antennas to extract the phase differences between each antenna pairs, named as phase interferometry measurements (PIMs), provoked by each transmitters using tensor decomposition. We calculate Cramer-Rao lower bound of error of localization using PIMs. Our simulation results show that highly accurate estimations can be achieved using PIMs. We also compare the accuracy of our proposed technique with a sensor network that exploits highly directional linear array antennas and show that our proposed technique can perform similar to a network that employs very large antenna arrays.


In the 2015-2016 academic school year, 3.3 million high school seniors are expected to graduate, and six percent of them are gifted and talented individuals who may be entering an AP Calculus course. Research shows that many students entering AP Calculus end up terminating their mathematical careers before even starting college. This thesis provides an alternative approach to AP Calculus; a nonAP Calculus exemplar unit that provides deeper conceptual knowledge of the slope, connected to the derivative, which may better prepare students for their college mathematics career. High school is a place to encourage students to accomplish their goals and better preparation at the high school level for college calculus may better equip students for future success. Is AP Calculus the best option? 3 Table of


Article history: Received July 21, 2015 Received in revised form August 29, 2015 Accepted 8 October 2015 Available online 8 October 2015 With the focus on calculating the equilibrium constant (Ka) of arsonic acids (RAsO(OH)2) in aqueous media, the behavior of both neutral and negatively charged species of some arsonic acids have been considered through the isodesmic reaction scheme with polarized continuum model of solvation. The relative pKa values of a number of arsonic acids were calculated using density functional theory (DFT), with methylarsonic acid (CH3AsO(OH)2) used as a reference molecule. Various basis sets such as (6-31G(d), 6-31+G(d), 6-311++G(d,p) and 6311++G(2d,2p)) in conjunction with B3LYP computational method were examined. Finally the latter one was found to give better results. The results of applied B3LYP 6-311++G(2d,2p) method for pKa values of 25 arsonic acids in aqueous media showed good agreement with corresponding experimental pKa values. In this level of theory the average error was less than 0.3 pKa units. The type of substituent affected the acid strength, with electron withdrawing substituents lowering the pKa and electron releasing groups increasing it. © 2016 Growing Science Ltd. All rights reserved.


The T4 nucleic acid (NA) ligases repair breaks in nucleic acids, which can be double-stranded DNA, RNA or a combination of both. The bacteriophage T4 has 3 NA ligases, one is a DNA ligase (T4Dnl) and two are RNA ligases: T4 RNA ligase 1 (T4Rnl1) and T4 RNA ligase 2 (T4Rnl2). These T4 DNA and RNA ligases are widely used as tools in a number of molecular biology techniques. A structural bias has been reported when the T4 RNA ligases are used in next generation sequencing (NGS) adapter ligation and there are issues with nucleic acid manipulation; these biochemical activities could be improved. Synthetic biology techniques were used to engineer a number of novel enzymes by combining the ligases with other proteins which have specific biochemical activities; and by mutating amino acid residues. A total of 22 novel enzymes have been constructed and tested to check changes in ligation activity and additional functions of the ligase fusions. This includes 8 ligases with specific amino acid changes to motif I, 4 ligases with nucleotide binding domain swaps, 3 adenylate kinase (AK)-T4 NA ligase fusions, 3 polynucleotide kinase (Pnk)-T4 NA ligase fusions and 3 fusions with truncated Mycobacterium smegmatis LigD (MSLigD) and the T4 NA ligases.
Ligation analysis revealed that a number of the fusion ligases were functional, and exhibited novel biochemical activities. This included utilising a new co-factor for the AK-ligase fusions, where ADP was used instead of ATP for ligation. Lower quantities of AKRnl1 were required to achieve the same ligation as T4Rnl1, an interesting feature for industrial retail. The Pnk-ligase fusions correctly ligated substrates that could not be ligated by the original T4 NA ligases, where the DNA/RNA substrate break had 3' phosphate instead of 5' phosphate. The amino acid mutations indicated the published sequences for the conserved polypeptide motifs are often lacking important surrounding amino acids. Fusions of T4Dnl with truncated MSLigD offered a way to use higher concentrations of ATP for ligation, in high ATP concentrations MsLigD dissociates from the DNA and is unable to complete the ligation reaction. Optimisation studies need to be completed for the new functional ligase fusions and the modified T4 NA ligases, considering temperature, buffer constituents and reaction time. The ligases detailed in this body of work offer exciting examples of creating fusion multi-function enzymes with novel activities. These new ligases may become alternative tools for molecular techniques, especially in NGS adapter ligation. This PhD work is part of a BBSRC iCASE studentship with Inspiralis (Norwich Research Park Innovation Centre, Colney Lane, Norwich NR4 7GJ) who retail T4 nucleic acid ligases.


ABSTRACT An outbreak of human botulism was due to consumption of ham containing botulinum neurotoxins B and E. A Clostridium botulinum type E strain isolated from ham was assigned to a new subtype (E12) based on bont/E gene sequencing and belongs to a new multilocus sequence subtype, as analyzed by whole-genome sequencing.


Over the last thirty years, the notion that the criminal justice system can help provide closure for victims and their families has gained remarkable traction, both in popular discourse and in the legal arena. Closure is offered—often successfully—as an argument for imposing death sentences, trimming procedural protections, permitting victim impact statements, truncating appeals, denying clemency petitions, speeding up executions, televising executions, and granting the bereaved access to the execution chamber. More broadly, it has transformed the debate about the legitimacy of the capital system—recasting the imposition of the death penalty from a retributive act to an act of compassion for bereaved families. Closure is a puzzle. Its parameters are fuzzy, its dynamics are murky, and its origins seem to have more to do with law and politics than with psychology. There is an argument to be made that closure isn't an emotion at all, but rather a set of legal aspirations for the conduct of criminal proceedings. Yet closure has increasingly come to be viewed as an emotional state—and one that the criminal justice system is capable of helping victims and survivors attain. It has become a prime example of the power of the criminal justice system to shape emotional expectations. This chapter discusses the evolution of closure as a legal concept, the definitional ambiguities surrounding the term, and the institutional consequences of these ambiguities for the criminal justice system. It examines the symbiotic relationship between closure and the criminal justice system, arguing that the criminal justice system has played a powerful role in reshaping the emotional expectations of victims and their families. The chapter then reviews the empirical literature on closure and criminal justice. Finally, it identifies directions for further study.


The structural effect of what is known in the International Relations (IR) literature as the 'polarity' of any given moment has been a central theme in mainstream theories and across the discipline more widely. Yet there are at present competing perceptions of polarity across popular and scholarly discourse. Is the United States still a unipolar power? Are we currently in or about to enter a multipolar era? Or will the US-Sino relationship dominate world politics in the coming decades creating a new bipolarity?

This thesis proposes a redefinition of the concept of polarity in order to be able to theoretically account for such competing visions of global order. It argues for the continued utility of the concept, particularly given its widespread use by practitioners and analysts alike, but that polarity analysis needs to be re-configured along more analytically eclectic lines than is the case in the existing literature. Using the English school of IR, the thesis builds a theoretical framework for redefining polarity, not as the distribution of material capabilities in the international system, but instead as the number of states that hold a particular status in international society. This framework is then applied to the period of 1815-2012 in order to understand the difference this makes to a macro-historical analysis of changes in the inter-state order. The historical analysis is used to demonstrate both the need for a new definition of polarity but also to draw a number of conclusions regarding the sources of perceptions of polarity.


In this thesis, the modelling and scheduling of remanufacturing systems is considered. An eXtended two-level Coloured Petri Net (XCPN) model is proposed for the objective of modelling remanufacturing shops. The extended model integrates the formalism of an existing two-level Coloured Petri net model and the object-oriented modelling approach, which includes the concept of modules. This modular concept is different from existing ones in that the model development is easy and the developed models are flexible and highly reusable. In order to provide the modeller with a systematic procedure for model development, a modelling methodology based on XCPN is proposed. The proposed methodology ensures clear separation of resource modelling from the modelling of process plans and parts. A software prototype is developed for building XCPN models and for their quantitative analysis by simulation. Remanufacturing is considered as a production with high level of uncertainties (uncertainties in the quantity and quality of used products and uncertainties in process plans and processing times). Modelling approaches for highly uncertain environments are analysed and a completely reactive approach based on Priority Dispatching Rules (PDR) is selected. Three new PDRs are proposed with the goal to minimise tardiness related performance measures. Extensive simulation experiments are conducted in order to evaluate the performance of the new and existing rules in several environments, which are typical of remanufacturing shops. In many cases, the new rules outperform existing rules or are not significantly worse than the best of them with respect to the tardiness related performance measures. At the same time, existing PDRs are shown to be applicable in the remanufacturing environment especially with respect to the flow-time related performance measures. In order to show the effectiveness of the new rules they are tested in two case studies of real-life remanufacturing systems using the proposed modelling methodology and software.


Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on a region harboring a locus for AMD on 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms for association with AMD in two independent case-control populations. Significant association (P = 4.95 × 10-10) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 → histidine-402 protein polymorphism in the gene encoding complement factor H. Possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD.


We present a new scalable and decentralized design for a server cluster that provides a single service with a certain QoS objective: maximum response time guarantee. Our design is based upon providing autonomy for each node in the cluster by having the node maintain only partial information about the system and having a mechanism for each node to process jobs or redirect it to a neighbor node. Also, each node decides whether it should remain an active node in the system or got to a standby mode, based upon information about its neighbor node and its own utilization. The metrics for the system performance are the rate of rejected requests in the system, the average experienced response time for service requests, the system size, and the ability of the system to react rapidly to changes in external load or node failures. Our system performed well in all metrics compared to a similar system that provides the same goals


Religion, it has been noted, speaks the language of violence as often as of peace. This article explores the pronounced role of military language and a martial outlook in one particularly intriguing and unlikely branch of Judaism, the Satmar Hasidic movement. Widely known for its posture of theological quietism, Satmar Hasidism, under the leadership of founding rabbi Joel Teitelbaum (1887 –1979), has frequently engaged in combative struggle against its foes, especially Zionism. This article highlights this martial impulse by examining three episodes in which the Teitelbaum family and Satmar Hasidim were engaged in conflict, exemplified by the publication of a series of books under the title "Commanded War. " Ranging over a century, these episodes reveal the way in which the pervasive language of war emerged out of a sense of the grave perils posed by modernity. They also illustrate how the martial language of Satmar turns over time from a focus on external enemies to a focus on internal rivals. HASIDISM WAS a Jewish pietist movement that took rise in Eastern Europe in the late eighteenth century. It sought to restore a sense of the vibrancy of spiritual experience that had been neglected,


Abstract The paper focuses on the ethical teachings of Classical Antiquity philosophers in the poetry of Saint Gregory of Nazianzus, especially on the parallels between the author's work and the Cynics and the Stoics. The syncretic nature of Gregory's work, reflected in the assimilation of the teachings of ancient philosophical schools and the then expanding Christianity creates conditions for the explanation and highlighting of basic human virtues. Gregory of Nazianzus' legacy also draws on the teachings of such philosophers as Plato and Aristotle, but he always approaches them from the perspective of a strictly Christian worldview. He understands philosophy as a moral underlying basis from which one can draw inspiration for a virtuous and happy life. Gregory thinks that philosophy cannot harm Christians in the pursuit of a virtuous life. Nevertheless, Christian teachings and God are the highest authority. They stand above all philosophical schools or ideas advanced by specific philosophers. Gregory's moral poetry thus directs his readers, if they are to deserve eternal life, to follow the commandments, which is possible only if one lives a practical and virtuous life.


Elevated numbers of blood and tissue eosinophils were induced in mice and rats by parasitic and non-parasitic means. Mice infected with the nematode Trichinella spiralis developed a peripheral blood eosinophilia which peaked approximately 21 days post infection. Histological examination of various tissues showed that the blood does not always reflect total body changes in eosinophil distribution. The numbers of eosinophils in skeletal muscle continued to increase at a time when the numbers of eosinophils in the blood were decreasing. The involvement of T. spiralis antigens in eliciting this eosinophilia was investigated using an artificial method to localize parasitic material in tissue. A homogenate of T. spiralis larvae was shown to be antigenic by precipitation with serum from a T. spiralis- infected rabbit. This antigenic preparation, designated TSAG, was also capable of eliciting a humoral response when injected into a rabbit. Although not a pure antigenic preparation, the TSAG did contain antigenic components which could bind to inert latex particles. This was demonstrated in vitro by agglutination and fluorescent techniques. When these TSAG-coated particles were injected into mice in such a manner as to result in their embolization in the pulmonary vasculature, they elicited a greater peripheral blood eosinophilic response than mcoated particles. However, similar studies on mice injected with latex particles coated with a non-parasite antigen (BGG) induced a comparable eosinophilia to that induced by parasite antigen- coated particles. The eosinophilia could not, therefore, be directly related to TSAG. Histological measurements of pulmonary cellular accumulations around the embolized particles also showed that TSAG was not more effective than BGG at inducing pulmonary cell accumulations, and furthermore, that uncoated particles also induced cell accumulations. The response to uncoated particles suggested a non-specific mechanism for the induction of eosinophilic responses. This latex model was used to investigate the ability of athymic (Rnu/Rnu) nude rats to develop an eosinophilia following pulmonary embolization of BGG-coated or uncoated latex particles. The number of circulating eosinophils increased in both cases, with the greater response occurring in rats injected with latex-BGG. A similar response was observed in euthymic (Rnu/+) littermates. Pretreatment of both Rnu/Rnu and Rnu/+ rats with antithymocyte serum altered the magnitude of the response but did not totally abrogate it. Studies on interleukin-1 activity in lung lavages recovered from these rats showed that injection of latex particles did not enhance alveolar macrophage activity 48 hours after their pulmonary embolization. The level of activity was similar in both Rnu/Rnu and Rnu/+ rats suggesting that macrophages were not involved in the response in Rnu/Rnu rats which are T cell deficient. The results show that the possibility of a residual T cell population in these rats cannot be excluded. In addition to these responses to physical manipulations, evidence is provided for inherent fluctuations in the number of circulating eosinophils, emphasizing the importance of careful experimental design when investigating haematological phenomena.


When an earthquake occurs, magnetic minerals are formed in the gouge under the combined action of frictional heating and fluid. Generally, the gouge is altered, and a detailed analysis of neoformed minerals is difficult. The Taiwan Chelungpu fault Drilling Project provided continuous records of the active Chelungpu fault gouges. By analyzing the magnetic parameters along the 16 cm thick gouge which houses the principal slip zone of the 1999 Chi‐Chi earthquake (Mw 7.6), we observed a 4 cm shift between the maximum of magnetic susceptibility and the maximum of remanence. The maximum magnetic susceptibility is localized along the principal slip zone. The main identified magnetic minerals are magnetite and goethite, which have very different magnetic parameters. We propose that the maximum of the concentration of magnetite and goethite corresponds to the maximum of magnetic susceptibility and remanence, respectively. By modeling the concentration of these two magnetic minerals, we explain satisfactorily the profiles of magnetic susceptibility and remanence. This quantitative modeling indicates that ~200 ppmv of magnetite formed in the principal slip zone and its main contact area. Similarly, ~1% of goethite is formed in the center of the gouge, where the fluids are more enriched in iron. We propose that the magnetite and goethite are formed and altered during seismic cycles.


The French Riviera has been a fabled resort for more than a century. As an enclave for the rich and famous, as well as a scenic tourist spot, it represents all that is beautiful and amusing. But for many of the twentieth century's finest painters, sculptors, photographers, and architects it has been much more: a place of potent myth and extraordinary creativity. Picasso, Matisse, Beckmann, Brancusi, Lartigue, Le Corbusier, and Eileen Gray, among many others, were inspired to create some of their greatest work on the Cote d'Azur. This study examines the impact of modernity and the artistic imagination on an idyllic landscape. Touching on the issues of pleasure and escape, work and leisure, and desire and ecstasy, Making Paradise offers a fresh look at the Cote d'Azur and its historical significance as a site for modernist innovation from 1890 to the present. Beginning with the neoimpressionists, moving to the Fauves, and ending with such contemporary artists as David Hockney and Faith Ringgold, the book examines the splendid light and terrain of the southeastern coast of France and the region's influence on the artists who worked and played there. Like the book, the exhibition it accompanies features unexpected juxtapostitions: masterworks by Bonnard and Picasso with the photographs of Lartigue and Model; the villas of Le Corbusier, Gray, and Mallet-Stevens with designs for the Ballets Russes de Monte Carlo; and ceramics of Picasso with the found-object constructions of the Ecole de Nice of the early 1960s. Copublished with the AXA Gallery, New York. Exhibition informationAXA GalleryNew York, New YorkApril 26-July 14, 2001


Productive design of scientific workflows often depends on the effectiveness of the communication between the discipline domain experts and computer scientists, including their ability to share their specific needs in the design of the workflow. Discipline domain experts and computer scientists, however, tend to have distinct needs for designing workflows including terminology, level of abstraction, workflow aspects that should be included in the design. This paper discusses the use of a ModelBased Workflow (MBW) approach as an abstract way to specify workflows that conciliate the needs of domain and computer scientists. Within the context of GEON, an NSF cyberinfrastructure for Earth Sciences, the paper discusses the benefits of using a Gravity Map MBW generated from an ontology about gravity. The Gravity Map MBW is based on terms derived from the gravity ontology that was developed by geophysicists; it does not include some of the workflow properties that tend to make workflow specifications look too complex for discipline domain experts to understand; and it provides a framework for developing strategies to derive executable Gravity Map workflow encodings with only limited interaction from computer scientists.


BACKGROUND AND PURPOSE
We describe four cases of aneurysmal rupture during embolization with Guglielmi electrodetachable coils (GDCs) in an attempt to identify those aneurysms whose rupture during embolization represents a life-threatening risk; our emphasis is on emergency management, in particular, ventriculostomy.

METHODS
Medical records were reviewed retrospectively for 91 aneurysms treated with GDCs 0 to 21 days after subarachnoid hemorrhage. Rupture was ascertained by the presence of extravascular effusion of contrast medium.

RESULTS
Of the perforated aneurysms, two involved the anterior communicating artery, one the posterior inferior communicating artery, and one the basilar artery. Only two patients, whose aneurysms were located in the posterior fossa, had major complications (arterial hyperpressure, mydriasis, angiographically documented circulatory arrest or slowing). One of these patients died and the other improved after emergency ventriculostomy.

CONCLUSION
Aneurysmal perforation during embolization may be accompanied by severe intracranial hypertension, which causes either a decrease or arrest of cerebral perfusion, the duration of which determines clinical outcome. Emergency ventriculostomy (which should be performed in the angiographic suite) is an effective means to reduce intracranial pressure. Recognition of aneurysms associated with a high risk of mortality by rupture in the course of embolization (recently ruptured small aneurysms, posterior fossa aneurysms, associated ventricular dilatation, massive cisternal hemorrhage) and use of proper logistics should ensure the effective management of this devastating complication.


The association term of the nonrandom hydrogen bonding theory, which is an equation of state model, is extended to describe the dimerization of carboxylic acids in binary mixtures with inert solvents and in systems of two different acids. Subsequently, the model is applied to describe the excess enthalpies and the vapor-liquid equilibrium of relevant binary mixtures containing low molecular weight organic acids. The model sheds light on the interplay of intermolecular interactions through the calculation of the various contributions to the mixing enthalpies, namely from hydrogen bonding and non-hydrogen bonding (dipolar, induced polar or dispersive) interactions. According to model predictions, the acid molecules are so strongly associated that the addition of inert solvents to carboxylic acids with small carbon numbers at ambient temperature does not dramatically alter their degree of association. Consequently, the observed endothermic dissolution process is mainly attributed to the hindering of polar interactions. Furthermore, upon mixing of two carboxylic acids, the rearrangement of hydrogen bonds due to the formation of cross associating species results in an insignificant contribution to the heats of mixing due to the rather constant dimerization enthalpy that is revealed by the available experimental data for low molecular weight compounds.


The number of applications that use virtualized cloud-based systems is growing, and one would like to use this kind of systems also for real-time applications with hard deadlines. There is scheduling on two levels in real-time applications executing in a virtualized environment: traditional real-time scheduling of the tasks in the real-time application, and scheduling of different Virtual Machines (VMs) on the hypervisor level. Traditional real-time scheduling is well understood, and most of the existing results calculate schedules based on periods, deadlines and worst-case execution times of the real-time tasks. In order to apply the existing theory also to cloud-based virtualized environments we must obtain periods and worst-case execution times for the VMs containing real-time applications. In this paper, we describe a technique for calculating a period and a worst-case execution time for a VM containing a real-time application with hard deadlines. This new result makes it possible to apply existing real-time scheduling theory when scheduling VMs on the hypervisor level, thus making it possible to guarantee that the real-time tasks in a VM meet their deadlines.


Objective: The aim of the present study was to investigate associations between abdominal obesity/dynapenia/dynapenic abdominal obesity and a single fall/recurrent falls as well as determine the effect size of such associations using two cutoff points for dynapenia. Methods: A cross-sectional study was conducted with 1.063 older adults pertaining to the third wave of the Saúde, Bem Estar e Envelhecimento (SABE – Health, Wellbeing and Ageing) study. Abdominal obesity was defined as a waist circumference of >102 cm for men and > 88 cm for women. The following were the cutoff points for dynapenia: grip strength < 30 kg for men and < 20 kg for women or < 26 kg for men and < 16 kg for women. Dynapenic abdominal obesity was defined by the combination of abdominal obesity and dynapenia. Regarding the outcome, the individuals were classified as non-fallers, single fallers or recurrent fallers. Socioeconomic, neuropsychiatric and environmental factors as well as living habits, polypharmacy, health status and functionality were the control variables in the multinomial regression models. Results: Adopting a cutoff point of 30/20, only one association was found: dynapenic abdominal obesity and a single fall (RRR = 2.37; 95% CI: 1.48-3.80). However, adopting a cutoff point of 26/16, dynapenic abdominal obesity (RRR = 1.93; 95% CI: 1.09-3.44), abdominal obesity (RRR = 1.65; 95% CI: 1.08-2.52) and dynapenia (RRR = 1.77; 95% CI: 1.01-3.13) were associated with a single fall, with a larger effect size of the association with dynapenic abdominal obesity than the other two conditions. Moreover, dynapenia defined using the 26/16 cutoff point was associated with recurrent falls (RRR = 2.39; 95% CI: 1.19-4.82). Conclusions: The cutoff point used to define dynapenia affects associations between abdominal obesity/dynapenia/dynapenic abdominal obesity and a single fall/recurring falls. A cutoff point of 26/16 is better for identifying such associations.


Adrenal incidentaloma, a tumor discovered unexpectedly during imaging performed for non-adrenal related causes, has become a frequent clinical concern. Although in most cases they are benign and hormonally nonfunctioning, it is important to appropriately identify those few cases of malignant or hyperfunctioning lesions of surgical resolution. Although several proposals for an optimal diagnostic strategy have been designed, controversy over a series of questions still persists. In the present retrospective study we analyzed 34 patients with adrenal incidentaloma. Of these, 32% of the patients displayed hyperfunctioning pathologies that included subclinical Cushing's syndrome in four patients, probable primary hyperaldosteronism in two, late onset congenital adrenal hyperplasia in one, adrerocortical carcinoma in one and pheochromocytoma in three. CT and/or MRI permitted the identification of adenomas and were crucial to decide on surgery in two patients with nonfunctioning pheochromocytomas and in a patient carrying a primitive adrenocortical carcinoma, a diagnosis also suggested by a mixed pattern of hypersecretion of androgens and cortisol. In a diabetic and hypertensive patient with subclinical Cushing's syndrome both comorbidities were solved by surgery. Nonfunctioning tumors were mainly adenomas (87%) with individual cases of histoplasmosis, pseudocyst, idiopathic adrenal hyperplasia and mielolipoma. Six of the eight operated patients presented malignant and/or hyperfunctioning tumors. The pathology associated with incidentalomas represents a broad spectrum of risk for patients and reaffirms the necessity for a meticulous clinical, biochemical, and imaging evaluation in order to make appropriate decisions.


This paper presents a dynamic modeling and control strategy for a sustainable microgrid primarily powered by wind and solar energy. A current-source-interface multiple-input dc-dc converter is used to integrate the renewable energy sources to the main dc bus. Potential suitable applications range from a communication site or a residential area. A direct-driven permanent magnet synchronous wind generator is used with a variable speed control method whose strategy is to capture the maximum wind energy below the rated wind speed. This study considers both wind energy and solar irradiance changes in combination with load power variations. As a case study a 30-kW wind/solar hybrid power system dynamic model is explored. The examined dynamics shows that the proposed power system is a feasible option for a sustainable microgrid application.


Background: It is increasingly recognized that transgender young people require affirming medical care, however the provision of such care may be mitigated by the availability of services and the views of parents. Aims: This study aimed to explore the views of Australian transgender young people (aged 11-17) and their parents with regards to medical treatment. Methods: Ten qualitative interviews were conducted with parent-child dyads in two Australian states. Thematic analysis was undertaken on responses to interview questions related to family relationships, views about medical treatment (specifically hormone blockers and hormones), and the relationship between medical treatment and sense of self. Results: Themes developed focused on the importance of strong supportive parent-child relationships, the meaning of and access to hormone blockers, and the meaning of and access to hormones. Discussion: The paper concludes by discussing the implications of the findings for clinical services, particularly in relation to supporting parents to be affirming of a transgender child, the need to prepare transgender young people and their parents for the passage of time in regards to medical treatment, and the need to focus on expectations in regards to sense of self in relation to medical treatment.


ABSTRACT Pseudomonas aeruginosa strains are opportunistic pathogens associated with infections in immunocompromised hosts and patients with cystic fibrosis. Like many other mucosal pathogens,P. aeruginosa cells express flagella which provide motility and chemotaxis toward preferred substrates but also provide a ligand for clearance by phagocytic cells. We tested the role of flagella in the initial stages of respiratory tract infection by comparing the virulence of fliC mutants in a neonatal mouse model of pneumonia. In the absence of fliC, there was no mortality, compared with 30% mortality attributed to the parental strain PAK or 15% mortality associated with infection due to a pilAmutant PAK/NP (P < 0.0001). The fliCmutants caused pneumonia in only 25% of the mice inoculated, regardless of whether there was expression of the pilus, whereas the parental strain was associated with an 80% rate of pneumonia. Histopathological studies demonstrated that the fliCmutants caused very focal inflammation and that the organisms did not spread through the lungs as seen in infection due to either PAK or PAK/NP. Purified flagellin elicited an intense inflammatory response in the mouse lung. 125I-labeled flagellin bound to the glycolipids GM1 and GD1a and to asialoGM1 in an in vitro binding assay. However, flagellin-mediated binding to epithelial gangliosides was a relatively unusual event, as quantified by binding assays of wild-type or fliC mutant organisms to CHO Lec-2 cells with membrane-incorporated GM1. Fla+ organisms but not fliC mutants were efficiently taken up by murine macrophages. P. aeruginosa flagella are important in the establishment of respiratory tract infection and may act as a tether in initial interactions with epithelial membranes. This function is offset by the contribution of flagella to host clearance mechanisms facilitating phagocytic clearance and the role of flagellar genes in mucin binding and clearance.


Chronic myeloid leukemia (CML) is a clonal multistep myeloproliferative disease originating from and ultimately sustained by a rare population of BCR-ABL(+) cells with multilineage stem cell properties. Imatinib, the most successful of molecular targeted therapies, has revolutionized treatment of patients with CML. Despite this achievement, CML is often not curable, largely due to the innate insensitivity of CML stem cells, particularly when in a quiescent state. This failure of not only imatinib but also the second-generation tyrosine kinase inhibitors (TKIs) frequently leads to relapse upon drug discontinuation. Thus, any curative therapy must eliminate CML stem cells. A comprehensive understanding of the biological properties of CML stem cells and an elucidation of the molecular mechanisms and signaling pathways enabling these CML stem cells to self-renew, combined with insight into the regulation of apoptosis signaling and the mechanisms governing the interaction of CML stem cells with their bone marrow microenvironment, will facilitate the development of therapies for targeting these cells. Here, we discuss the biological properties of CML stem cells and potential strategies to eliminate them.


The rotation of octahedra (octahedral tilting) is common in $AB{\mathrm{O}}_{3}$ perovskites and relevant to many physical phenomena, ranging from electronic and magnetic properties, metal-insulator transitions to improper ferroelectricity. Hydrostatic pressure is an efficient way to tune and control octahedral tiltings. However, the pressure behavior of such tiltings can dramatically differ from one material to another, with the origins of such differences remaining controversial. In this paper, we discover several new mechanisms and formulate a set of simple rules that allow us to understand how pressure affects oxygen octahedral tiltings via the use and analysis of first-principles results for a variety of compounds. Besides the known $A\text{\ensuremath{-}}\mathrm{O}$ interactions, we reveal that the interactions between specific $B$ ions and oxygen ions contribute to the tilting instability. We explain the previously reported trend that the derivative of the oxygen octahedral tilting with respect to pressure ($\mathit{dR}/\mathit{dP}$) usually decreases with both the tolerance factor and the ionization state of the $A$ ion by illustrating the key role of $A\text{\ensuremath{-}}\mathrm{O}$ interactions and their change under pressure. Furthermore, three new mechanisms/rules are discovered, namely that (i) the octahedral rotations in $AB{\mathrm{O}}_{3}$ perovskites with empty low-lying $d$ states on the $B$ site are greatly enhanced by pressure, in order to lower the electronic kinetic energy; (ii) $\mathit{dR}/\mathit{dP}$ is enhanced when the system possesses weak tilt instabilities, and (iii) for the most common phase exhibited by perovskites---the orthorhombic Pbnm state---the in-phase and antiphase octahedral rotations are not automatically both suppressed or both enhanced by the application of pressure because of a trilinear coupling between these two rotation types and an antipolar mode involving the $A$ ions. We further predict that the polarization associated with the so-called hybrid improper ferroelectricity could be manipulated by hydrostatic pressure by indirectly controlling the amplitude of octahedral rotations.


The incidence of obesity and type 2 diabetes (T2D) are increasing in the UK and there is evidencethat these disorders influence the ageing process. The mechanisms by which obesity/diabetesmight regulate ageing are poorly understood. This study aimed to investigate the links betweenbody composition, metabolic disease and ageing, as well as the role of cellular senescence onnutrient homeostasis. Study participants had biochemical and anthropometric measurements taken. DNA analysis was used to measure telomere length (TL) using real-time PCR and plasmawas used to quantify circulating factors using ELISA. Human dermal fibroblasts were madesenescent and conditioned media was collected and used to treat AML-12, C2C12 and 3T3-L1cell lines. Following treatment glucose content of cell media was measured. TL exhibited a significant negative association amongst individuals retaining excess visceral fat(p <0.001) and plasma irisin levels positively correlate and predict TL (p = 0.01) in the controlcohort. There was no significant association between irisin and TL in the T2D cohort (p = 0.333),and a 3-fold higher concentration of irisin was observed in individuals with T2D in comparisonto controls (p < 0.0001). Irisin was a statistically significant predictor of soluble E-selectin (p =0.003) in type 2 diabetics. 40% Conditioned media from senescent HDF reduced the ability ofC2C12 to utilise glucose after 24 and 48 hours and AML-12 hepatocytes after 48 hours (p<0.0001, p <0.01) quantification of circulating glycerol in 3T3-L1 adipocytes following treatmentwith 20% and 40% conditioned media suggests lipotoxic tendencies (p <0.05 and p <0.001). In conclusion this study highlights the importance of maintaining adequate body fat in preservingTL, provides novel data regarding the role of irisin in healthy and obese/type 2 diabeticindividuals and insights into the relation between ageing and insulin resistance.


Nanobacteria (NB) contribute to pathological calcification in the human and animal body. It has been isolated from salivary stones and suggested that it may act as a nucleus for the initiation of these stones. In the present study, we examined its role in the recurrent salivary gland stones using immunodetection with NB-specific monoclonal antibodies and scanning electron microscopy (SEM) hoping to provide a method for preventing the recurrence of these stones in the patient that has suffered from salivary stones. Our study comprised 30 patients with recurrent salivary gland stones (group I) and 30 patients with salivary gland stones for the first time (group II), in addition to 30 normal controls (group III). We could detect 100–500 nm nanoparticles in 24/30 (80%) cases in group I with significant difference <0.05 and <0.01 when compared with group II and group III in which they were detected in 19/30 (63.3%) and 6/30 (20%) respectively. Also there was a significant difference <0.05 between group II and group III. We proposed that salivary stone formation is a nanobacterial disease initiated by bacterial infection. This bacteria may play an important role in the recurrence of salivary stone. So the use of calcium chelator, ethylene diamine tetra acetic acid (EDTA), before or in combination with the suitable antibiotic that is given in an amount effective to inhibit or prevent the growth and development of nanobacteria may eradicate these stones and prevent their recurrence.


Several factors affect the viability of biosensor design. This thesis presents the development of a computer-based model that will enable the sources and effects of noise and variations in concentrations within an evanescent field immunosensor to be analysed. The model was developed as a series of modules, each representing one aspect of the sensor, which when linked provide a simulation of the whole sensor. A complete solution of the complex biochemical reactions involved in the immunoassay module was achieved using a Markov chain approach. More traditional methods of solving sets of equations, such as optimisation, genetic algorithms and simulated annealing, all failed to produce satisfactory results. Two alternative assays, a sandwich and a competitive assay, are presented. The light module details the modelling of the coupling into a planar monomode waveguide and calculation of fluorescence excited by the resulting evanescent field using standard electromagnetic formulae. However, both beam divergence and scattering from the immobilised antibody layer were incorporated into the model. Two alternative coupling techniques were modelled, prism coupling and coupling through a "resonant mirror" multilayer. The detection system modelled the amplification of the fluorescence by a photomultiplier tube. The resulting model represents the most rigorous modelling undertaken in this area and the potential applications and benefits of such a model were detailed. Analysis of noise within the sensor allowed the impact of variation in the physical parameters defining the sensor to be determined and compared. The model was used to compare different protocols and confirmed that the sandwich assay produced the more sensitive device. A study of the kinetic response of the assay determined that measurements could be performed at half the time taken to reach equilibrium without significant loss of sensitivity. An analysis of the effect of scattering at the waveguide surface showed this to be significant noise factor. An initial study of the impact of the humectant layer illustrated that this is an issue that merits further consideration.


A model is developed for the optimal operation of the releases from a reservoir which are used to irrigate an area in an arid environment. The operation is based on a forecast technique. The forecast consists of expected values based on the application of Dynamic Programming Technique as well as on the use of generated inflows. The generation model for rivers in arid areas consists of three components. The first determines if the following year will be dry or wet. The second generates a sequence of days in which a flow may occur, and the third calculates the magnitude of such a flow. The third component depends directly on the first. The optimization problem has two state variables and one decision variable, and is solved by Dynamic Programming. The state variables are the reservoir content and the soil moisture of the irrigation area. The decision variable is that quantity of water which should be applied to irrigation. Because of the rapidly changing inflow process the model has to provide "adequate" representation of the evaporation losses which are calculated on a daily basis. The optimal scheduling process is non-stationary because of the continuing reservoir sedimentation which gradually decreases the reservoir volume.


Background: In randomized controlled trials, due to the randomization process the covariates are equally distributed between the groups. For these reason at the end of the study the researcher can assume that the outcomes happens only because of interventions. This strict control of bias leads the randomized controlled trials to become the gold standard in clinical research. However in some cases, like in surgical studies, it is very difficult to run a randomized controlled trial. Observational studies have some strengths and can play an important role in studies of surgical specialties. Discussion: Observational studies are very commonly used nowadays, once that they are easy to conduct, needs less time and budget than randomized controlled trials. It is also a great design to test new hypothesis that could be developed in future studies. Observational design could be an excellent option to surgical research when randomized controlled trials have an ethical or feasibility issue. Besides the ethical and feasibility issues the research could have a rare outcome that is difficult to assess and measure. To all this issues observational study offers a solution.


In our increasingly digital societies, many companies have business models that perceive users' (or customers') personal data as a siloed resource, owned and controlled by the data controller rather than the data subjects. Collecting and processing such a massive amount of personal data could have many negative technical, social and economic consequences, including invading people's privacy and autonomy. As a result, regulations such as the European General Data Protection Regulation (GDPR) have tried to take steps towards a better implementation of the right to digital privacy. This paper proposes that such legal acts should be accompanied by the development of complementary technical solutions such as Cognitive Personal Assistant Systems to support people to effectively manage their personal data processing on the Internet. Considering the importance and sensitivity of personal data processing, such assistant systems should not only consider their owner's needs and values, but also be transparent, accountable and controllable. Pluralist approaches in computational cognitive modelling of human needs and values which are not bound to traditional paradigmatic borders such as cognitivism, connectionism, or enactivism, we argue, can create a balance between practicality and usefulness, on the one hand, and transparency, accountability, and controllability, on the other, while supporting and empowering humans in the digital world. Considering the threat to digital privacy as significant to contemporary democracies, the future implementation of such pluralist models could contribute to power-balance, fairness and inclusion in our societies.


Interviews and focus groups have long been employed to research the ways in which literary and televisual texts are understood by their contemporary consumers, and the historical study of reading and of reception has often taken the same approach to written descriptions of reading experiences. The appeal of this kind of information is obvious: where better to learn about readers than straight from the horse's mouth?

Nonetheless, there are problems with treating such data, whether researcher-elicited or spontaneous, as transparent. Acknowledgement of this has led to an emerging 'crisis of representation' within the fields of cultural and reception studies, whereby researchers have begun to question their ability to represent social reality with any objectivity. Whether we are interested in acts of reading past or acts of reading and viewing present, this apparently leaves us with a choice between closing our eyes to obvious difficulties and restraining ourselves only to such topics of investigation as can be approached by the powerful but impersonal methods of quantitative sociology, book history and economics. In this chapter, we propose an alternative approach whose roots lie in ethnomethodology.


We propose a novel image-based rendering algorithm for handling complex scenes that may include reflective surfaces. Our key contribution lies in treating the problem in the gradient domain. We use a standard technique to estimate scene depth, but assign depths to image gradients rather than pixels. A novel view is obtained by rendering the horizontal and vertical gradients, from which the final result is reconstructed through Poisson integration using an approximate solution as a data term. Our algorithm is able to handle general scenes including reflections and similar effects without explicitly separating the scene into reflective and transmissive parts, as required by previous work. Our prototype renderer is fully implemented on the GPU and runs in real time on commodity hardware.


Building systems with the robustness of human reasoning capabilities requires inspirations from cognitive science. The primary objective of this study is to investigate the possibility of representing some basic principles of cognitive semantics' Mental Spaces Theory such as domain construction, reality status of domains and their elements, and mental attitudes in a knowledge representation framework for the purpose of developing cognitively plausible knowledge representation systems. The model used as the basis of representation is the extended version of conventional semantic networks, namely Multi-Layered Extended Semantic Networks (MultiNet). The data used in this study have been selected from English expressions and have been represented in MWR, MultiNet's knowledge representation software. Results obtained from analysis of represented data and their comparison to principles of mental spaces theory shows that theoretical constructs of mental spaces theory such as domain construction, reality status of domains and their elements, and mental attitudes can be formally represented in the MultiNet framework.


Globalization brings the threat of a weakened SME sector, since its role in exporting is less than proportional to its size; this reflects the economies of scale characterizing big markets. But globalization can also increase the importance of a strong SME sector, either where direct SME exports are feasible or where SME subcontractors help keep the country's large exporters competitive.
The domestic industry by using knowledge, innovation development and upgrading the capacity of the small and medium enterprises can take the necessary changes for its output and increase export performance. All of this can contribute to sustainability of the economic growth and economic integration especially of small and open economies.
Many transition and developing countries, in particular face a need to promote and strengthen the long term development of the SME sector, which requires access to market opportunities, as well as to new technology and management know-how, often in a situation of considerable resource scarcity.
This paper aims to focus on contribution for developing financial strategies that could help to strengthen the SME sector in a way to record benefits from labor markets. Implementation of good strategies should increase the attractiveness of the labor markets in transition and developing countries for foreign investors which will improve the capacity of the SME sector.


Content-based image retrieval has been an active area of research for more than ten years. Gabor schemes and support vector machine (SVM) method have been proven effective in image representation and classification. In this paper, we propose a retrieval scheme based on Gabor filters and SVMs for hepatic computed tomography (CT) images query. In our experiments, a batch of hepatic CT images containing several types of CT findings are used for the retrieval test. Precision comparison between our scheme and existing methods is presented.


A two-dimensional fluid simulation of polysilicon etching with chlorine in an inductively-coupled high density plasma source is presented. A modular approach was used to couple in a self-consistent manner the disparate time scales of plasma and neutral species transport. This way, complex plasma chemical reactions (involving electrons, ions and neutrals) as well as surface chemistry can be included in the simulation, The power deposited into the plasma was calculated by an electromagnetics module which solves Maxwell's equations. The power deposition was used in the electron energy module to find the electron temperature and the rate coefficients of electron-impact reactions. These were in turn used as source terms in separate neutral and charged species transport modules. By iterating among the modules, a self-consistent solution was obtained. Quantities of interest, such as power deposition, species density and flux, and etch rate and uniformity were thus calculated, As power deposition was increased, the electron density increased linearly, the plasma became less electronegative, the degree of gas dissociation increased, and the plasma potential remained constant. The radial uniformity of the Cl atom flux was better than that of the ion flux. The reactivity of the wafer as compared to that of the surrounding electrode surface significantly affected the etch uniformity, despite the low pressure of 10 mtorr. >


Various heuristic and pattern recognition techniques have been applied to a data base of 125 underivatised nucleoside mass spectra to determine certain aspects of structure from an unknown spectrum. A heuristic program has been written encoding nucleoside mass spectral fragmentations in order to determine molecular weight, formula weight of the purine or pyrimidine base part, and, unsuccessfully, base type. The pattern recognition methods of statistical linear discriminant function analysis, learning machine approach, distance from the mean, and k-nearest neighbour classification have been applied to the same data base divided into training and prediction sets. Analyses were conducted to determine numbers of carbon, oxygen, and nitrogen atoms present in the base alone and in the nucleoside as a whole, substitution patterns, and base type. Prediction success for all approaches was typically in the range 76-86%, or in terms of the figure of merit 0.20 0.27. 1.1 Overview Chapter 1


The opioid, morphine, is very effective in the treatment of moderate to severe cancer pain and pain experienced by patients with non-malignant conditions. Indeed, in the World Health Organization analgesic ladder, morphine is cited as the main example of a strong opioid that should be used when non-opioids (such as paracetamol) and weak opioids (such as codeine) fail to control pain. Morphine can also relieve the sensation of breathlessness. However, many myths surround the use of morphine. These include addiction, tolerance, sedation, respiratory depression and a shortened life. These myths result in patients being reluctant to take their prescribed doses and those who prescribe morphine setting inappropriate dose limits. There is no evidence to support the theory that opioids, used in a carefully titrated way for the control of breathlessness in palliative care, increase the risk of respiratory depression. This article aims to dispel the myths and misconceptions surrounding morphine. It will answer the common questions associated with morphine use. Conflicts of interest: none


Our goal, in this paper, is to infer the topology of a network when (i) we can send probes between sources and receivers at the edge of the network and (ii) intermediate nodes can perform simple network coding operations, i.e., additions. Our key intuition is that network coding introduces topology-dependent correlation in the observations at the receivers, which can be exploited to infer the topology. For undirected tree topologies, we design hierarchical clustering algorithms, building on our prior work in [24]. For directed acyclic graphs (DAGs), first we decompose the topology into a number of two source, two receiver (2-by-2) subnetwork components and then we merge these components to reconstruct the topology. Our approach for DAGs builds on prior work on tomography [36], and improves upon it by employing network coding to accurately distinguish among all different 2-by-2 components. We evaluate our algorithms through simulation of a number of realistic topologies and compare them to active tomographic techniques without network coding. We also make connections between our approach and other alternatives, including passive inference, traceroute, and packet marking.


The introduction of an internal market into New Zealand's publicly financed health system based on a purchaser-provider separation was highly controversial. From four Regional Health Authorities, the purchasing side of the internal market was subsequently reconfigured into a single national purchasing agency, the Health Funding Authority, in 1997. This Working Paper reviews the original rationale for the separation of purchase from provision, discusses the recent experience of the separation in New Zealand and reviews options for the possible evolution of the purchasing function. The options reviewed include vertical integration (ie, the abolition of the purchaser-provider split). It is argued that there are benefits associated with the separation of purchaser and provider, and that, on balance, it was a good thing, although its application to all services was probably inadvisable. However, no one model of purchaser organisation can fulfil all the requirements described by proponents of system change. Health services' purchasers are inescapably in a weak position vis-a-vis their providers. Whichever model of purchasing/planning services is implemented, purchasers will need to develop a new set of relationships with primary care providers, especially general practitioners, since primary care services are important for the functioning of the remainder of the health system. There are currently few incentives on primary care providers to consider the wider implications of their decisions for the rest of the sector and the delivery of primary care is imperfectly coordinated with other services. This paper is a background paper and does not provide policy advice, nor does it propose any particular course of action. The Treasury has chosen to publish it (or make it available) in order to encourage peer comment with a view to ensuring that it is of good quality. The views expressed in the paper is/are those of the author(s) and do not necessarily reflect the views of the New Zealand Treasury. The Treasury takes no responsibility for any errors or omissions in, or for the correctness of, the information contained in this paper.


Abstract. The last couple of decades have seen the outburst of a number of satellite-based precipitation products with Tropical Rainfall Measuring Mission (TRMM) as the most widely used for hydrologic applications. Transition of TRMM into the Global Precipitation Measurement (GPM) promises enhanced spatio-temporal resolution along with upgrades to sensors and rainfall estimation techniques. The dependence of systematic error components in rainfall estimates of the Integrated Multi-satellitE Retrievals for GPM (IMERG), and their variation with climatology and topography, was evaluated over 86 basins in India for year 2014 and compared with the corresponding (2014) and retrospective (1998–2013) TRMM estimates. IMERG outperformed TRMM for all rainfall intensities across a majority of Indian basins, with significant improvement in low rainfall estimates showing smaller negative biases in 75 out of 86 basins. Low rainfall estimates in TRMM showed a systematic dependence on basin climatology, with significant overprediction in semi-arid basins, which gradually improved in the higher rainfall basins. Medium and high rainfall estimates of TRMM exhibited a strong dependence on basin topography, with declining skill in higher elevation basins. The systematic dependence of error components on basin climatology and topography was reduced in IMERG, especially in terms of topography. Rainfall-runoff modeling using the Variable Infiltration Capacity (VIC) model over two flood-prone basins (Mahanadi and Wainganga) revealed that improvement in rainfall estimates in IMERG did not translate into improvement in runoff simulations. More studies are required over basins in different hydroclimatic zones to evaluate the hydrologic significance of IMERG.


This thesis addresses the fundamental problem of determining the radial and lateral structure of the earth's interior using body wave observations. My approach is a cautious one, involving detailed analysis of a substantial data set in which I attempt to isolate the contributions from radial and lateral structure in both the upper and lower mantles. This is an elusive task, as I am concerned with the 2 or 3% fluctuations about standard earth models, which produce rather subtle effects on teleseismic signals. However, this is the level of precision to which the three dimensional structure of the earth must be determined if we are to map the dynamical and compositional configuration of the earth. Studies similar to those described here cannot be conducted on a detailed global basis, given the intrinsic limitations due to station and earthquake distribution, so I have repeatedly emphasized the qualitative implications of my results, as they probably provide a representative sampling of the subtle, but significant heterogeneity of the earth. The topics addressed in the following work appear unrelated at first glance, ranging from determination of the detailed shear velocity structure at the base the mantle to variations in attenuation and velocity structure of the upper mantle. However, the data set used throughout is largely the same, and this in itself indicates the need to consider all of the complexity discussed herein for future progress to be made in mapping the three dimensional structure of the earth with a high level of confidence. The first chapter of the thesis presents results of a waveform analysis of transversely polarized SH signals that propagate through the lowermost mantle. The waveforms of these phases show clear interference patterns due to interaction with a discontinuous shear velocity increase about 280 km above the core-mantle boundary. This discontinuity, which has not been detected previously, is manifested in signals sampling three widely separated portions of the lower mantle, and hence is a good candidate for a global radial earth structure. Very detailed inspection of the signals reveals evidence for lateral variations in the depth of the discontinuity, which provides a procedure by which to map the structure of the D" region in detail. Analysis of the relative amplitudes of SH and ScSH signals reveals that the velocity gradient above the core boundary is consistent with the smoothly varying gradients in most gross earth models, but evidence for local high velocity gradients at the base of the mantle is detected in ScSV signals. Chapter II presents a travel time analysis of the same data set used in Chapter I, which was motivated by the observation of large amplitude and travel time anomalies in the S and ScS data. An emphasis is placed on isolating the portions of the S and ScS paths which are anomalous. A strong empirical case is made for the existance of localized regions with scale lengths of 1000 to 2000 km and 2% velocity anomalies within the lower mantle at depths from 1000 to 2700 km. The long period signals traversing these regions show as much as a factor of 2 amplitude enhancement or diminution. This result demonstrates that both amplitude and travel time anomalies are induced by lateral structure in the portion of the mantle assumed to be homogeneous in most seismological studies. The third chapter is an analysis of the influence of upper mantle variations in attenuation, velocity structure and receiver structure on the S and ScS signals analyzed in the lower mantle studies. These variations contaminate and complicate the interpretation of any data set used to study deeper earth structure. Along with evidence for very strong and abrupt variations in upper mantle properties, results are presented which indicate the inadequacy of assumptions that are frequently made about the nature of long period body-wave receiver functions.


Transparency has been an important element in the construction of hard and soft law and norm regimes in the international sphere. This chapter considers transparency and business in international environmental law. It is divided into five sections. Section A considers conventional sources of international environmental law for its transparency effects, looking at both hard law and soft law frameworks. Section B examines other potentially applicable transparency rules, principally the recent efforts at transnational regulation of economic actors. It concentrates on two examples — the OECD framework and the recently endorsed Guiding Principles of Business and Human Rights. Section C examines transparency at the intersection of domestic and international law. It concentrates on the environmental transparency effects of extraterritoriality, of the incorporation of international norms within domestic legal orders, and the internationalization of domestic rule frameworks. Section D then considers transparency and governance beyond the state. For that purpose three distinct regimes are identified and examined. The first are hybrid governance efforts — the ISO and Global Compact systems. The second are private non-corporate governance regimes, principally the GRI and product certification programs. Third, private corporate governance transparency regimes are examined. The potential and tensions in transparency are examined more closely in the context of environmental disclosure by BP during the time of the Deepwater Horizon explosion and oil spill of 2010, which also suggests both the possibilities and limits of domestic and international law, in its transparency aspects. The chapter ends with Section F's consideration of miscommunication and coherence in moving toward the future of environmental transparency at the international sphere.


This article presents the results of empirical studies of critical incidents in airline services in Sweden and the United States. The main aim is to describe and analyze service break downs from the customer's point of view and thus create a basis for crisis management. The aim is also to compare Sweden, a monopoly market, with the United States, a market with keen competition in airline services. The discussion is based on personal interviews with 320 customers and 80 airline employees in Sweden and 241 customers and 100 employees in the United States. The study focuses on negative critical incidents in the relations between the service provider and business passengers.


Purpose – The goal of this study is to use the institution-based view as the background for an investigation of how formal institutions influence the internationalization processes of firms from an emerging economy. Design/methodology/approach – Our case study is based on semistructured interviews with twenty-one representatives of formal institutions and firms in the Brazilian wine industry. Findings – It was noted that formal institutions have positive influences on the internationalization of Brazilian wineries by providing learning, relationship networks, intelligence about foreign markets, costs reduction, internationalization of business processes, and by promoting the home country's image as a wine producer in foreign markets, and as a recognized supplier to the domestic market. They also have negative influences, as excessive bureaucracy, strikes, erection of legal barriers to trade with other countries, insufficient technical knowledge, high taxes, and favoritism benefiting the largest wine producers in the industry. Originality/value – The paper closes with suggestions for future research on how phenomena such as the relationship strategies established by the wineries impact upon internationalization and how decisions of a political nature made by formal institutions influence the wine industry, providing a new outlook on the internationalization of these firms.


Today we can state that in spite of a considerable number of cervical osteochondrosis studies, there is a lack of research devoted to analysis of its course. There is no correlation between initial expert evaluations of cervical osteo-chondrosis cases and further course of pathological process. Goal of the research is to develop system of course prognosis of cervical osteochondrosis taking into account environmental infuence, heredity, living conditions, psychological profle of patient's personality. Materials and methods. Dynamics of degenerative-dystrophic changes progressing of cervical vertebrae in 236 patients was analyzed. Results. Received data demonstrated that probability of stage I changing to stage II, III and IV depended on patients' sex, age and type of labour activity, frequent supercooling and stress. Probability of fast progression of cervical osteochondrosis (5-year cycle of stage I changing to stage III and IV) was to a great extent associated with heredity, urban living, presence of endocrine system diseases, syndrome of nonspecifc dysplasia of connective tissue and low indices of quality of life. Conclusion. Proposed system allows making prognosis of morphologic changes in spinal cord, and is based on radiation methods of verifcation without taking into consideration dynamics of neurological symptomatology.


Laboratory courses can be difficult to fit into an engineering program at a liberal arts-focused university, which requires students to be exposed to appropriate breadth, as well as sufficient depth in their engineering education. One possible solution to this issue is to integrate laboratory exercises with lecture in a 'studio' format, in which students apply lecture concepts directly to in-class assignments. Another possible solution is to give students 'take-home' laboratory assignments. Both of these methods have shortcomings: the studio format takes away valuable lecture time, and the take-home format provides limited access to the instructor. As such, this work presents a mixed learning method that includes lectures and laboratory work in both the studio and take-home formats, implemented in a junior level signal processing course. Students learn skills during lecture in studio laboratory exercises, and apply these skills to two in-depth take-home projects. Students refine their applied skills during projects, thereby informing a better studio lab experience. In order to assess the student's developed skills, project results are delivered as research papers formatted to comply with IEEE standards, which are submitted for blind review to several faculty members, as well as their peers. Reviewers employ a prescriptive rubric to rate papers as accept/revise/reject and provide associated comments. To assess the success of this mixed learning method, the overall ratings for the research papers from the first project will be compared to the second project, accounting for project complexity. The chief contribution of this work is the presentation of a method for providing laboratory instruction in a mid-year DSP course, demonstrating that this method may be adapted for other courses at similar institutions.


In experiments to assess the changes in testis protein and enzyme activities induced by exposure to sodium fluoride (NaF) and sulfur dioxide (SO2), ninety-six adult male Wistar rats were divided randomly into four groups of twentyfour rats each. One group was left untreated as controls, and the other three groups were administered, respectively, for eight consecutive weeks, (1) 100 mg NaF/L (45 mg F–/L) in their drinking water, (2) SO2 in ambient air (15 ppm SO2, 4 hr/day), or (3) were exposed to both NaF and SO2 together. In comparison with the control group, the combination of NaF and SO2 resulted in lower protein levels and higher lactate dehydrogenase (LDH) activities in the testis of male rats than in the groups treated by NaF or SO2 alone. The activity of gamma-glutamyl transpeptidase (g-GT) decreased significantly in the NaF+SO2 group and in the SO2 group at week 4, and then increased markedly at weeks 6 and 8 in the same group. However, an increase in the activity of Na+K+and Ca2+-ATPases in the SO2 group and the NaF+SO2 group occurred at week 2 and then decreased at weeks 4 and 6, respectively. Mg2+-ATPase activity at week 4 in the testis of male rats was significantly lower in all three treatment groups. These changes in protein and spermatogenesis-dependent enzymes undoubtedly affect the physiological functions of the testis, which may thereby cause low sperm motility.


This collective monograph was prepared by scientists of social psychology laboratory of the Institute of Psychology named by G.S. Kostiuk of NAPS of Ukraine. There are considered social-psychological patterns of youth' economic culture becoming in the national educational space. The authors reveal the features and dynamics of formation of pupils' and students' economic culture.
Special attention is paid to the relationship between "economy" and "morality" in the system of interconnected and interacting of economic and psychological factors like individual awareness of in social-economic sphere; value-emotional attitude to the social-economic area; instruction with active forms of economic activity of the individual.
The features of economic culture types depending on the age of students are studied. Types of monetary culture of senior pupils, depending on the attitude to money are shown. Then it was constructed structural-functional model of youth' economic culture becoming. It could be used in the practice of the economic education of young people.
The monograph is addressed to psychologists: scientists and practitioners, academics and all other professionals working in the field of youth' economic education.


Objective
Interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) is currently one of the preferred treatment options for advanced ovarian, fallopian tube or peritoneal cancer. This study was conducted to evaluate the clinical efficacy and safety of dose-dense paclitaxel plus carboplatin therapy (ddTC therapy) as NAC for these cancers.

Patients and methods
A retrospective study was conducted in 25 patients with Stage III/IV ovarian, fallopian tube or peritoneal cancer who received ddTC therapy as NAC. For ddTC therapy, paclitaxel (80 mg/m2) was administered intravenously on Days 1, 8 and 15 and carboplatin (AUC 6.0 mg/ml × min) was administered intravenously on Day 1 every 3 weeks. IDS was performed after three cycles of ddTC therapy, and ddTC therapy was also continued after surgery.

Results
With ddTC therapy as NAC, the response rate was 92% and disease progression did not occur in any patient. Grade 4 hematologic toxicity and ≥Grade 3 non-hematologic toxicity both occurred in 8% of the patients, but no patient discontinued NAC because of adverse events. When IDS was performed, the complete surgery rate was 64% and the optimal surgery rate was 96%. ≥Grade 3 perioperative complications occurred in 16% of the patients, but there were no perioperative deaths. Median overall survival was 35.7 months and median progression-free survival was 17.7 months.

Conclusion
This study showed that ddTC therapy was considerably effective and tolerable as NAC. The complete surgery rate was high with IDS, and perioperative complications were acceptable.


Paget's disease of the bone is a common metabolic bone disease in most European countries, Australia, New Zealand, and North America. Conversely, this disease is rare in Scandinavia, Asia, and Africa. In Japan, it is extremely rare, with a prevalence of 0.15/100000. Paget's disease is a localized disorder of bone remodeling. Excessive bone resorption and abnormal bone formation result in biomechanically weakened bone and predispose patients to fracture. Delayed union and non-union of fractures have been reported in patients with Paget's disease. Therefore, open reduction and internal fixation of fractures has been recommended to prevent such complications. Here we report an unusual case of a 63-year-old Asian woman with delayed union of a femur fracture secondary to Paget's disease, which was treated successfully by functional bracing. Introduction Paget's disease of the bone was first described by Sir James Paget in 1877. It is a well documented metabolic bone disorder in European countries and the United States, with a reported incidence of 3-4% in the adult population [1-3]. Interestingly, it is extremely rare in Africa and Asia, and rarely occurs in Japanese individuals [3-6]. Although the etiology of Paget's disease remains unclear, it is characterized by increased bone resorption, bone formation, and remodeling. The axial skeleton is frequently involved and the bones most commonly affected include the pelvis (70%), femur (55%), lumbar spine (53%), skull (42%) and tibia (32%) [7]. Increased bone turnover and remodeling leads to altered bone quality, thickening, enlargement, and deformity. Paget's disease is associated with significant disability, impaired quality of life and a variety of complications, such as osteoarthritis, pathological fracture, and nerve compression syndromes. Here we present an unusual case of delayed union of a femur fracture secondary to Paget's disease in an Asian patient, which was treated successfully by functional bracing. Case presentation The patient, a 63-year-old Japanese woman, presented at our hospital with severe thigh pain after suffering a fall. Plain radiography showed a displaced transverse fracture of the left femur (Figure 1). Osteosclerosis, osteolysis, enlargement, and bowing deformity were also noted in the femur. Laboratory tests revealed an elevated serum alkaline phosphatase level (455 IU/L; normal range: 115359) with otherwise normal liver enzyme levels. Radionuclide bone scan showed dense uptake in the left femur (Figure 2). We diagnosed the patient as having pathological fracture secondary to monostotic Paget's disease. As she suffered from multiple concomitant illnesses, she was judged to be a poor risk for surgery. We therefore performed a closed reduction and stabilization with an external fixator. Later, however, we had to remove the external fixator because of infection at the pin site, and after 6 months of treatment there were no signs of bone healing (Figure 3). We diagnosed delayed union of the femur fracture, but surgical treatment for this situation could not be performed because of the patient's generally poor condition. We therefore applied a functional brace with the hope that the patient would be able to walk with crutches. X-ray revealed fracture healing after 6 months of treatment by functional bracing (Figure 4). At the latest follow-up 5 years after injury, there was complete healing * Correspondence: email@example.com 1 Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, Japan Full list of author information is available at the end of the article BioMed Central © 2010 Takigami et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Takigami et al. Journal of Orthopaedic Surgery and Research 2010, 5:33 http://www.josr-online.com/content/5/1/33 Page 2 of 4 of the fracture (Figure 5), the patient is able to walk unaided with a single T-cane. Discussion Although Paget's disease of the bone is a relatively common disease in Australia, New Zealand, North America and most European countries, but it has a low incidence in Scandinavia, and is extremely rare in the Japanese population, with a prevalence of 0.15/100000; in patients aged 55 years of more, the proportion reaches 0.41/ 100000 [1-4,6]. The characteristic feature of Paget's disease is excessive bone resorption coupled with increased and disorganized bone formation. The affected bone is enlarged, disorganized in structure, and weakened. Pathological fractures are the most common complication of Paget's disease, and the treatment of such fractures is challenging. An increased rate of complications including delayed union, non-union, and malunion in pagetic bone fracture has been reported [8-10]. Open reduction and internal fixation of fractures has been recommended to prevent such complications[10]. However, plate and screw fixation requires extensive exposure, and in the present patient this was not possible because of her poor medical condition. Recently, there have been some reports of good fracture healing with the use of intramedullary nailing [11,12]. However, the latter is available only for mild bowing deformities. In the present patient, we decided to use an external fixator to fix this pathological fracture because of the above situation. However, after 6 months of treatment, the external fixator had to be removed due to pin site infection, even though fracture union had not been obtained. We then had no alternative but to apply a functional brace for delayed union of the femur fracture with the aim of allowing the patient to walk on crutches, although, to the best of our knowledge, no familial cases were found in the reported cases. Fortunately, in this case, fracture union was obtained 6 months after application of the functional brace. This treatment period is comparable to that reported by others using functional brace in the treatment of delayed union of the tibia [13-15]. We speculate that this treatment was advantageous because the external fixator and functional bracing did not violate the fracture site, allowing vascular regeneration and eliminating further damage to the peripheral and intramedullary blood supply which occurs during plate and screw fixation and intramedullary nailing. The success of this treatment suggests that functional Figure 1 Transverse fracture at the junction of proximal and middle thirds, and Paget's disease involving the entire femur. Figure 2 Radionuclide bone scan showing markedly increased uptake affecting the left femur. Takigami et al. Journal of Orthopaedic Surgery and Research 2010, 5:33 http://www.josr-online.com/content/5/1/33 Page 3 of 4 bracing, a biological fracture treatment, may be a viable alternative for the treatment of fracture, delayed union, and non-union resulting from Paget's disease of the bone. This would be especially useful in the elderly and those considered at high risk from major corrective surgery. In recent years, the concept of biological osteosynthesis has gained a reputation in fracture treatment. Minimally invasive plate osteosynthesis (MIPO) techniques minimize the extent of soft tissue trauma to the injury zone, theoretically maintaining a better blood supply around the fracture area. Treatment of fractures secondary to Paget's disease using MIPO techniques might avoid the significant complications associated with more commonly used techniques of internal fixation. This unusual case of delayed union of the femur fracture associated with Paget's disease of the bone for which functional bracing was ultimately successful illustrates the usefulness of biological fracture treatment in patients with this potentially refractory condition. Consent Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal


This dissertation studies the impact of judicial efficiency on leverage and debt-maturity structure of 370 firms that are listed on the Karachi Stock Exchange, over the period 2001-2006.In a set of regressions where dependent variable is leverage ratio, baseline results show that leverage ratio increases with size of firm, ratio of fixed-assets-to-totalassets, and decreases with profitability, volatility of net income, dividends payments and growth opportunities. The largest economic effect on leverage ratio is that of the size of firm. These results demonstrate that the trade-off theory and the information asymmetry theory best explains observed capital structure. The results also indicate that leverage ratio decreases when judicial efficiency decreases; however, this relationship is not statistically significant. This is due to the composition effect. Allowing judicial efficiency to interact with the included explanatory variables, the results show that worsening judicial efficiency increases leverage ratios of large firms and decreases leverage ratios of small firms which is an indication of the fact that creditors shift credit away from small firms to large firms in the presence of inefficient judicial system. Results also indicate that the effect of inefficient courts is greater on leverage ratios of firms that have fewer tangible assets as percentage of total assets than on leverage ratios of firms that have more tangible assets. And finally there is some evidence that firms with more volatile net incomes are affected more than firms with less volatile net incomes when judicial efficiency decreases. In debt-maturity regressions, the baseline results indicate that debt-maturity increases with size, tangible assets, and decreases with the firm's growth opportunities and inefficiency of judiciary; however, volatility of net income and firm's quality do not show any statistically significant relationship with debt-maturity ratio. Allowing for the possibility that judicial inefficiency does not impact all firms alike, the measure of judicial efficiency is interacted with dummy variables that are based on the quartiles of the included explanatory variables. Results of these regressions show that worsening judicial efficiency has far greater negative impact on the debt-maturity ratio of small firms than on the debt-maturity ratio of large firms. Similarly, results show that the effect of inefficient courts is greater on firms that have fewer tangible assets as percentage of total assets than on firms that have more tangible assets. Other firm-specific features like growth opportunities, volatility of net income, and firm's quality do not change the impact of judicial inefficiency on the firms' debt-maturity ratios.


This paper studies the determination of informal long-term care (family aid) to dependent elderly in a worst case scenario concerning the "harmony" of family relations. Children are purely selfish, and neither side can make credible commitments (which rules out efficient bargaining). The model is based on Becker's "rotten kid" specification except that it explicitly accounts for the sequence of decisions. In Becker's world, with a single good, this setting yields efficiency. We show that when family aid (and long-term care services in general) are introduced the outcome is likely to be inefficient. Still, the rotten kid mechanism is at work and ensures that a positive level of aid is provided as long as the bequest motive is operative. We identify the inefficiencies by comparing the laissez-faire (subgame perfect) equilibrium to the first-best allocation. We initially assume that families are identical ex ante. However, the case where dynasties differ in wealth is also considered. We study how the provision of long-term care (LTC) can be improved by public policies under various informational assumptions. Interestingly, crowding out of private aid by public LTC is not a problem in this setting. With an operative bequest motive, public LTC will have no impact on private aid. More amazingly still, when the bequest motive is (initially) not operative, public insurance may even enhance the provision of informal aid.


We report on the characterization of photodarkening (PD) kinetics of Yb-doped fiber samples in a wide temperature range from 77 to 773 K and with respect to different Yb2O3 concentrations from 0.09 up to 0.68 mol%. The thermal dependency of important PD parameters is presented for a uniform Yb inversion of about 0.46. We have found out that PD kinetics is affected remarkably by temperature during pumping and that PD saturation is an equilibrium of optical and thermal processes, achieved after passing a loss maximum. The saturated loss for time tending to infinity obviously depends on the fiber temperature.


Although several genes are implicated in the pathogenesis of schizophrenia, in animal models for such a severe mental illness only some aspects of the pathology can be represented (endophenotypes). Genetically modified mice are currently being used to obtain or characterize such endophenotypes. Since its cloning and characterization CB1 receptor has increasingly become of significant physiological, pharmacological and clinical interest. Recently, its involvement in schizophrenia has been reported. Among the different approaches employed, gene targeting permits to study the multiple roles of the endocannabinoid system using knockout (-/-) mice represent a powerful model but with some limitations due to compensation. To overcome such a limitation, we have generated an inducible and reversible tet-off dependent tissue-specific CB1-/- mice where the CB1R is re-expressed exclusively in the forebrain at a hypomorphic level due to a mutation (IRh-CB1-/-) only in absence of doxycycline (Dox). In such mice, under Dox+ or vehicle, as well as in wild-type (WT) and CB1-/-, two endophenotypes motor activity (increased in animal models of schizophrenia) and pre-pulse inhibition (PPI) of startle reflex (disrupted in schizophrenia) were analyzed. Both CB1-/- and IRh-CB1-/- showed increased motor activity when compared to WT animals. The PPI response, unaltered in WT and CB1-/- animals, was on the contrary highly and significantly disrupted only in Dox+ IRh-CB1-/- mice. Such a response was easily reverted after either withdrawal from Dox or haloperidol treatment. This is the first Inducible and Reversible CB1-/- mice model to be described in the literature. It is noteworthy that the PPI disruption is not present either in classical full CB1-/- mice or following acute administration of rimonabant. Such a hypomorphic model may provide a new tool for additional in vivo and in vitro studies of the physiological and pathological roles of cannabinoid system in schizophrenia and in other psychiatric disorders.


Distributed embedded systems usually have strict quality requirements which need to be verified, and the allocation of software to hardware needs to be considered throughout the whole development process. In this paper, we present usage of simulation in analyzing development process of embedded systems using CARMA principle which combines two paradigms - Component-Based Software Engineering and Model Driven Development. In development process two types of parallel modeling of hardware are distinguished: modeling of a virtual hardware structure and of the physical structure. Two kinds of verification activities are introduced: milestone verification, which integrates the product requirements into the process through frequent analyses and measurements of the development artifacts, and exploratory analysis, which is informal and carried out by individual developers, similar to debugging. Based on the process model, we have constructed a queuing network model, used for simulations to further explore the characteristics of the development model. Initial simulations give by hand that by increasing the amount of analysis and verification in a project, more errors are found with the same amount of effort and time. There are also dependencies on project risks and the strength of the analysis tool support.