A model of the feature-oriented requirements of a software system usually contains a large number of non-trivial features; each feature may have unintended interactions with other features. It may be difficult to comprehend or verify such a model. Model slicing is a useful approach to overcome such a challenge by enabling views of models of individual features that preserve feature interactions. Model slicing evolves from traditional program slicing; it is a technique to extract a sub-model from the original model with respect to a slicing criterion. In this thesis we focus on one type of model: state-based models (SBMs). Because of the difference in granularity between programs and SBMs, as well as the difficulty of maintaining well-formedness of a sliced SBM, SBM slicing is much more challenging than program slicing. Among a diverse range of slicing approaches, dependence-based slicing is the most popular; it relies on the computation of dependence relations among states and transitions in order to determine which model elements of the original model must be in the slice and which can be omitted. We present a workflow and tool for automatically constructing a feature-based slice from a feature-oriented state-machine model of the requirements of a software system. Each feature in the model is modeled as a complete state-transition machine called a featureoriented state machine (FOSM). The workflow consists of two tasks—a preprocessing task and a slicing task. The preprocessing task mainly computes three types of dependences: hierarchy dependence (HD), which represents the state hierarchy relation among states in the original model; data dependence (DD), which captures the define-use relationship among transitions with respect to a variable; and control dependence (CD), which captures the notion of whether one state can affect the execution of another state or transition. The slicing task forks off multiple slicing processes; each process considers one of the FOSMs as the feature of interest (FOI)—which is the slicing criterion—and the rest of FOSMs as the rest of the system (ROS)—which is to be sliced. Each slicing process constructs a sliced model to preserve the portion of the ROS that interacts with the FOI. The construction process is multi-staged; it firstly identifies an initial set of transitions in the ROS that directly affect the FOI; it then finds more states and transitions in the transitive closure of dependences; and it eventually restructures the model to further reduce the model size and maintain its well-formedness property. We provide a correctness proof that shows that the resulting sliced models simulate the original model, by proving that an execution step of a given execution trace in the original model can always be projected to an execution step of at least one execution trace in the sliced model.


Predator-prey relationship indicates the status of wildlife conservation. Identifying preys and their contribution to the diets of tigers are important for making conservation meaningful. The main objective of this research was to investigate the distribution pattern of tigers and availability of their preys in the Shuklaphanta Wildlife Reserve (SWR), Far west Nepal. This research mainly focused on distribution and identification of scats, determination of prey species and factors affecting their selection. This study was conducted in SWR of 305 km2 area in Kanchanpur district, lowland, Far west Nepal. It was gazatted as Royal Shuklaphanta Wildlife Reserve in 1973. Data were collected through direct field observations and Participatory Rural Appraisal (PRA) method. Relationship between tigers and preys was determined through scats analysis. Data were analyzed with the help of Scatman and vegan through R Software. Prey and habitat selection analysis showed that chital (Axis axis) preferred sal (Shorea robusta) forests while barking (Muntiacus muntjak) and swamp (Rucervus duvauceli) deer were abundant in river sides and fireline/mixed forests respectively. Then, identified eight prey species from 65 scats of which six percent had double preys and 94% single preys. Chital constituted 30% and swamp deer 17% of the total tiger's diet. The population density of chital was the highest (54.10 animals/km2) followed by common langur (25.27 animals/km2), swamp deer (21.50 animals/km2) and hog deer (16.30 animals/km2). Chital, hog deer and langur were preyed significantly (P ≤ 0) higher by tigers indicating positive selection of these species. Swamp deer was preyed significantly low (P > 0) indicating negative selection probably due to its large size. Tigers prefer medium to slightly large prey species like chital of about 55 kg body weight compared to large sized swamp deer and sambar weighing more than 150 and 210 kg respectively in SWR. Since, both tigers and preys are endangered due to poaching and habitat loss, regular monitoring of them is essential to develop the tiger conservation plan.


Competitiveness of city regions has gained a more and more central position in regional development and regional planning within the last decades. A reason for this is that globalisation has caused pressure on industrial structures forcing firms to increase their competitiveness by more actively promoting innovation and knowledge creation. Access to knowledge has therefore become vital for most types of productions in the Western economies. As creation of and access to knowledge have become increasingly important in order to stay competitive, a growing focus has been put on the geography of highly skilled labour. A growing string of this literature argues that large cities shall be understood as locomotives of regional development and growth because they have an attractive effect on highly skilled labour. This line of thinking is called the urban turn in economic geography. This study examines the urban turn by studying the dynamics of location of economic activities in Nordic countries. The thesis consists of 5 papers and a research report and offers both quantitative and qualitative analyses of the dynamics of location of economic activities in the knowledge economy. It approaches regional development both from an interregional perspective and an intraregional perspective. It provides a critical and thorough examination of the technology, talent and tolerance approach to regional development put forward by Richard Florida in his book The Rise of the Creative Class by examining the adequateness of the approach in a Swedish and Nordic context, and next it retheorises the approach based on empirical findings. Further, by studying intraregional dynamics in the greater metropolitan area of Copenhagen, the thesis addresses the geographical heterogeneity of the city region on the one side and the importance of social relations for location of economic activities on the other. Thereby the presented research calls for an intraregional perspective in mainstream regional development. (Less)


The objective of this paper is to provide information on how value-based management is perceived, implemented, and utilized in leading industrial corporations in the US, and to examine factors that influence the decision to utilize it. We gather data through a survey of the chief financial officers (CFOs) of a large sample of US industrial corporations, in order to ascertain their opinions of and experiences with value-based management systems and metrics. The results suggest that there is room for improvement in the design and implementation of value-based management systems. If value-based management is to have an impact on corporate strategy and value and reduce intra-firm agency costs, then its scope within the firm may need to be expanded.


Populations of the lizard Anolis limifrons were censused for 19 yr at the Lutz site on Barro Colorado Island (BCI) and for 4 yr at 20 additional sites in central Panama. Census data provided estimates of population density at the end of the wet season (December) and indices of per-capita food intake and annual recruitment. Year-to-year changes in density of as much as 5- to 8-fold were observed at Lutz over 19 yr and of 2- to 3-fold were observed over 4 yr at other sites. Changes in population density at 11 BCI sites were synchronous over 1983-1986, while population density fluctuated independently at non-BCI sites. Populations of A. limifrons exhibited significantly greater generation-to- generation variability than populations of West Indian Anolis and of lizards in temperate- zone habitats (mostly arid lands in North America). An index of per-capita food intake was negatively related to density both for temporal comparisons at Lutz and for spatial comparisons among sites. The relative number of young individuals at the end of the wet season was negatively related to population density and positively related to an estimate of food intake. Partial correlations indicated that the positive association between the relative number of young individuals in the population and food intake was independent of the negative association between food intake and population density. Recruitment was thus depressed when density was high and enhanced when food was relatively abundant. Despite the potential for density-dependent regulation, Anolis limifrons populations are highly unstable, presumably because of random perturbations of the environment. Rainfall is implicated causally although population density was only weakly associated with rain- fall-density at BCI was positively associated with rainfall during the dry season and negatively associated with rainfall during the wet season and with total annual rainfall. Population attributes that contribute to instability are rapid population turnover and a middle-level trophic position in a complex food web.


Inoculants containing Bradyrhizobium japonicum are available for soybean [Glycine max (L.) Merr.] production but may not be necessary in fields where soybean previously has been produced. The objective of this study was to determine yield response and probability of an economic return from inoculants in fields with a recent history of soybean production. Fifty-one inoculant products were evaluated in experiments (n = 73) conducted in Indiana, Iowa, Minnesota, Nebraska, and Wisconsin between 2000 and 2008. Inoculant products were similar and did not produce a yield response relative to an untreated control different from zero (P > 0.05) at 63 environments. Probability for a break-even economic return at a soybean sale price of $0.33 kg -1 was 59% for Nebraska, 36% for Wisconsin, 25% for Minnesota, 25% for Indiana, and 4% for Iowa. Attaining a return on investment of 67 kg ha -1 (a 2:1 return) reduced success to 11, 2, 1, 7, and 0.2%, for the five states, respectively. Data from this range of environments and products indicate that application of an inoculant offers limited success for either a yield increase or improved economic return on soils where soybean has previously been grown in the upper Midwest.


The UK Airports Commission has short-listed three options for expanding airport capacity in the UK. One option concerns expansion of Gatwick with an additional runway. The other options concern expansion of runway capacity at Heathrow. The impacts of expansion on passenger and air freight user welfare do not only depend on the macro-economic and aviation industry future, as defined by the aviation scenarios already developed by the Airports Commission, but also on the airline responses that can be expected as capacity comes on stream. This report summarises a quantitative analysis of the likely responses from airlines in all segments of the market building on a companion report that identifies the main drivers of airline behaviour and considers the possible influence of changes to existing business models and the introduction of new types of aircraft, such as the Boeing Dreamliner and Airbus A350. Four sets of airline responses are modelled, two following expansion of Gatwick and two following expansion of Heathrow, to test outcomes under a range of scenarios for the overall development of the global aviation market. The analysis quantifies impacts on connectivity and potential benefits to the consumer through airline competition and relieving congestion at airports and reducing the associated economic rents.


It has been speculated that marine microplastics may cause negative effects on benthic marine organisms and increase bioaccumulation of persistent organic pollutants (POPs). Here, we provide the first controlled study of plastic effects on benthic organisms including transfer of POPs. The effects of polystyrene (PS) microplastic on survival, activity, and bodyweight, as well as the transfer of 19 polychlorinated biphenyls (PCBs), were assessed in bioassays with Arenicola marina (L.). PS was pre-equilibrated in natively contaminated sediment. A positive relation was observed between microplastic concentration in the sediment and both uptake of plastic particles and weight loss by A. marina. Furthermore, a reduction in feeding activity was observed at a PS dose of 7.4% dry weight. A low PS dose of 0.074% increased bioaccumulation of PCBs by a factor of 1.1-3.6, an effect that was significant for ΣPCBs and several individual congeners. At higher doses, bioaccumulation decreased compared to the low dose, which however, was only significant for PCB105. PS had statistically significant effects on the organisms' fitness and bioaccumulation, but the magnitude of the effects was not high. This may be different for sites with different plastic concentrations, or plastics with a higher affinity for POPs.


Before equipment is installed at AT&T Bell Laboratories, Allentown, a hazard and operability (HAZOP) analysis is done. Through a systematic process, a team leader guides a group of knowledgeable individuals through the equipment design to discover the hazards and the operating range of the equipment. During this M O P analysis, the equipment engineer responsible for the CVD process becomes aware of all aspects of the equipment from the electrical and chemical hookup of the process chamber to the treatment of the effluent. At our facility, HAZOP analysis has proven to be an effective tool. We present a sample HAZOP analysis for an MOCVD installation along with the short, easy-to-use questionnaire that the responsible engineer completes before the HAZOP analysis begins.


In car racing simulation games, finishing first is the main goal. To reach that goal, it is required to go around a racing track, competing against other cars aiming for the same goal. Implementing a bot for doing so may have its difficulties, although using a technique called multi-agent systems combined with artificial potential field, let- ting the agents take care of subtasks like keeping the car on the track, minimize how much the car turns in a curvature and basics in navigation around the track, has showed that artificial potential fields very well fit the problem of driving a car in simulated car racing in a competitive way.


Structural health monitoring of civil infrastructure systems is an important procedure in terms of both safety and serviceability. Traditionally, large structures have been monitored using surveying techniques, while fine-scale monitoring of structural components has been done with instrumentation for civil engineering purposes. As a remote sensing technique, photogrammetry does not need any contact with the object being monitored, and this can be a great advantage when it comes to the deformation monitoring of inaccessible structures. The paper shows a low-cost setup of multiple off-the-shelf digital cameras and projectors used for three-dimensional photogrammetric reconstruction for the purpose of deformation monitoring of structural elements. This photogrammetric system setup was used in an experiment, where a concrete beam was being deformed by a hydraulic actuator. Both static and dynamic loading conditions were tested. The system did not require any physical targets other than to establish the relative orientation between the involved cameras. The experiment proved that it was possible to detect sub-millimetre level deflections given the used equipment and the geometry of the setup.


The histone-like protein HU is the most-abundant DNA-binding protein in bacteria. The HU protein non-specifically binds and bends DNA as a hetero- or homodimer, and can participate in DNA supercoiling and DNA condensation. It also takes part in DNA functions such as replication, recombination, and repair. HU does not recognize any specific sequences but shows a certain degree of specificity to cruciform DNA and repair intermediates such as nick, gap, bulge, etc. To understand the features of HU binding to DNA and repair intermediates, a fast and easy HU protein purification method is required. Here we report a two-step purification procedure of HU from Halobacillus karajensis (the gram positive and moderately halophilic bacteria isolated from Karaj surface soil). The method of HU purification allows obtaining a pure non-tagged protein. Salting out and ion exchange chromatography were applied for purification, and the purified protein was identified by immunoblotting. Results showed that the molecular weight of the purified protein was approximately 11 kDa which is immunologically similar to the Bacillus subtilis HU protein (HBsu).


One of the biggest challenges in urban areas is the redevelopment of brownfields. Most brownfield site are currently not fully in use or even totally vacant, derelict or contaminated. They are not available for intended use without a drastic intervention. During the decision making process the developer has to deal with a complex of environmental, economic, legal, social, and land use issues. Brownfield problems are not easily to resolve and the real estate features of these sites deserve special attention. This papers deals with the complex decision making process during redevelopment and with the selection of critical REFs by the developer. Typical real estate development assumes the existence of especially two characteristics: a) the institutional factors enabling investment and rewards for undertaking a project; b) the urban infrastructure to which the project is expected to connect the technologies and construction used in development, together regarded as Real Estate Features (REFs). There are more than a thousand factors which should be checked before the land acquisition and more than a hundred risk types involved during the process of development. They are all correlated. Nowadays classification derived in heuristic way and does not incorporate more rational approach. This paper introduces both a qualitative technique and a quantitative method. Quality Function Deployment is a market oriented qualitative technique for upgrading a product value. It is used as stepping point to realize basic requirements of developers and major characteristics of urban development area giving insights about their correlation. Further on, Risk Analysis is compared as appropriate methodology for indentifying the key real estate features. The findings - data collections, are based on interviews with professionals addressing their decision making process. We strongly support idea that using the mathematical oriented (scientific) tools will demystify traditionally fogy real estate business.


The goal of this thesis is to present the virtual environments research community with a thorough investigation of collaborative awareness in Tele-immersion and related immersive virtual environments. Tele-immersion was originally defined in 1996 by Tom Defanti of the Electronic Visualization Laboratory (EVL), is "the union of networked VR and video in the context of significant computing and data mining" [Leigh, et. al., 1997]. Since then, research on Tele-immersion has outgrown most of its system and performance-related issues and now focuses supporting collaborative interaction and usability. Tele-immersion now deals with the "[creation of persistent virtual environments] enabling multiple, globally situated participants to collaborate over high-speed and high-bandwidth networks connected to heterogeneous supercomputing resources and large data stores" [Leigh, et. al., 1997, p. 1 of 9]. In the early stages of Tele-immersion there were two main factors driving the research: the significant processing load of real-time and simulated computational steering, and the sheer bulk of the data sets being generated for scientific visual analysis [Leigh, et. al., 1997]. Now the growing number of immersive VR sites is motivating a need to support human-to-human interaction and work over wide networks of immersive virtual environments. This research focuses heavily on issues of collaborative awareness in these networked, immersive virtual environments. Collaborative awareness, in this context, is a concept that encompasses the caveats of one's knowledge about the CVE and its occupants. As a result of this study, software has been designed to provide support not only for collaborative awareness, but also for several other dimensions of collaboration.


Dysexecutive symptoms such as apathy, impulsivity and distractibility have been reported on clinical ground in HD. However previous studies have assessed dysexecutive behavioural disorders using clinical interview or nonspecific questionnaires incorporating other features resulting in highly variable evaluation with poorly defined performance indices. This study aimed to assess dysexecutive behavioural abnormalities in HD, using a validated instrument, the Behavioural Dysexecutive Syndrome Inventory (BDSI). 14 patients (mean age: 55.5 years; SD 12.4; range: 34–73; mean duration: 8.7 years; SD=7; range: 2–30; mean MMSE score: 25; SD=3.4) with clinically diagnosed and genetically confirmed HD, were included. The assessment of depressive symptoms (Montgomery Asberg Depression Scale) showed a mild depression in 7 patients. The BDSI is a highly structured caregiver based interview which rates frequency and severity of 12 dysexecutive disturbances (global hypoactivity with apathy, hyperactivity, irritability-impulsivity, euphoria, perseverative behaviour; environmental dependency, social behaviour disorders). The analysis of individual performance was performed using cutoff scores at the 5% level using normative data obtained in 96 controls1. The prevalence of behavioural dysexecutive syndrome was high (50%; 95% CI: 24–76). The behavioural profile was characterised by the prominence of irritability (50%), hyperactivity (43%), apathy (29%), disinterest (22%) and difficulties for anticipation (14%). This study based on the BDSI revealed in HD that behavioural dysexecutive disorders are: 1 frequent with a prevalence of 50%, 2 characterised by a specific profile with the prominence of irritability and hyperactivity-distractibility, 13 whereas the hypoactivity-apathy disorders were less frequent contrary to most other degenerative disorders. 1 Godefroy et al. Ann Neurol. 2010


Background: Triple-negative breast cancer (TNBC) carries a poor prognosis and therapeutic options are limited to date. The aim of this study was to investigate to what extent the epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR2), hypoxia inducible factor-1 alpha (HIF-1α) and insulin-like growth factor-1 receptor (IGF-1R) are expressed in TNBC and to determine if these expressions have a predictive role.Methods: Of 923 breast cancer patients who were treated and followed in Academic Center for Education, Culture and Research (ACECR) from 2006-2010, 104 of them had TNBC. Immunohistochemistry analyses were performed on tissue microarray blocks with antibodies for EGFR, VEGFR2, HIF-1α and IGF-1R.Results: We analyzed tumor samples from 104 patients with classic primary invasive ductal carcinoma (IDC). Fifteen patients (14%) were in stage I, 46.6% in stage II, 30.1% in stage III and 5.8% in a metastatic stage (stage IV). The median overall survival (OS) was 48 months. EGFR was expressed in 15 (14%), VEGFR2 in 63 (61%), IGF-1R in 81 (78%) and HIF-1α in 57 (55%) samples. EGFR expression was significantly associated with poor outcome in terms of OS (P = 0.021, OR = 3.9).Conclusions: Among the four investigated tumor markers, only EGFR was significantly associated with survival of patients with TNBC.


Massive open online courses (MOOCs) are growing exponentially in higher education. They have attracted the attention of higher education institutions, course designers, and policy makers. They challenge the mainstream of higher education and provide global learning opportunities to a huge number of students so they can learn anytime and anywhere. The value and applicability of the MOOC model in the current era of higher education and the nature of learning in such an open online format need to be investigated. This study focused on participants' experiences and perceived value of participation in connectivist MOOCs (cMOOCs) in terms of dealing with an abundance of resources and tools, learning activities, and network engagement. The results suggest a high extent of technology deployment for learning and interactions by the participants in cMOOCs. Creating networks and developing professional connections through networking technologies are advantages of participating in cMOOCs. The study's findings contribute to a better understanding of the nature of learning and participation in MOOCs from the perspective of students, who are the main stakeholders of such new learning experiences.


This study, the role of small and medium sized enterprises for economic growth, was undertaken to find out how SME sub-sector in Nigeria has performed and its impact on the economic growth of the country. Small and Medium Scale Enterprises (SMEs) is accepted globally as a tool for empowering the citizenry and economic growth. It has been associated with the rapid economic growth of countries in Asia and North America. In Nigeria efforts have been made by successive governments to reduce poverty and accelerate economic growth by increasing foreign direct investment, diversifying the economy, enacting policy frameworks which favour small business ownership and sometimes initiating employment and entrepreneurship programmes. Specifically this study tends to figure out: how profitable SME business is; whether infrastructural development could be attributed to the presence of SMEs; if significant number of people are employed within the SME sector; whether the SME market has attracted banks and financial institutions with increase in loans and incentives; whether there is increase in information Technology related businesses due to presence of SMEs and if there is need for the government to encourage and develop more opportunities for SMEs. A total of 200 SMEs were randomly selected from Matori, a city in Lagos state Nigeria. A questionnaire was constructed and distributed to the selected SMEs. The responses were collated and analyzed using Statistical Package for Social Sciences (SPSS) analytical tool. The study reveals that while SME businesses are profitable problems of policy inconsistency and poor infrastructural development continuously undermine the potentials of the market. Though the presence of SMEs has attracted infrastructural development, such developments in most cases are community effort or privately driven which limits the amount of developments achieved. For example their efforts could be limited to patching and maintaining existing bad road networks but not expanding or creating new road networks. The study also revealed that financial institutions like banks are attracted to areas where SMEs are established but getting funds through these institutions via loans has not been easy due to high interest rates and harsh conditions like types of collateral to present. It was also established that SMEs are good employers of labor but not without required support and facilities. SMEs will not engage more people to work for them when their businesses do not thrive. For their businesses to thrive they need government to encourage them and develop more opportunities such opportunities could be in terms of providing infrastructures like stable power supply and good transport networks (rails and roads), easy access to finance (low interest rates), stable government policies, reducing multiple taxations, ensuring availability and access to modern technology and raw materials locally etc. The result of the study confirms existing theories in the field which support the belief that SMEs remains a tool for economic growth in Nigeria. There are enormous potentials and opportunities for SMEs in Nigeria to mature and play the crucial role of economy growth, poverty reduction, employment and wealth creation. This will entail having the government provide required supports and addressing identified problems. While the SMEs also need to change their attitudes relating to entrepreneurship development, government needs to involve the SMEs in policy formulation and execution for maximum effect. There is also need to introduce entrepreneurial studies in our Universities in Nigeria in addition to emphasizing practical and technological studies at all levels of our educational system.


Since the publication of the first edition in 1985, Missouri Government and Politics has been widely acclaimed as an outstanding text. This revised and enlarged edition updates all of the chapters to reflect the changes that have occurred in the state's government during the last decade. Five new chapters have been added on topics previously unaddressed: economic development, energy, and the environment; state policy making in higher education; funding for education in the 1990s; the statewide elected executive officials; and the types of law in Missouri. The twenty-six chapters are grouped into four main categories: "The Context of Missouri Politics," "State Governmental Framework," "Policies and Policy Making in Missouri," and "Local Government and Politics in Missouri." Helpful additions to the basic text include more than fifty tables and figures, a glossary giving clear definitions of many governmental terms, and a bibliography on Missouri politics and government. The authors have become experts about Missouri by serving as teachers and researchers in Missouri colleges and universities, as candidates and workers in Missouri political campaigns, and as officeholders and public administrators in Missouri state government. Their collective experience in Missouri politics ensures that this new edition provides the most thorough and comprehensive overview of the structure and inner workings of Missouri's political system.


We apply X-ray interferometry to study the profile structure of Langmuir−Blodgett (LB) monolayers containing maquette peptides, de novo di-α-helical synthetic peptides designed as model systems for studying biological electron transfer. The results demonstrate that it is possible to create monolayers with the peptide vectorially oriented with its helical axis (the direction of electron transfer within the holopeptide) approximately normal to the surface of the solid support. This orientation can even be achieved when the orientation of the peptide in the precursor Langmuir film at the air/water interface is parallel to the surface, indicating that reorganization of the monolayer can occur during or after LB deposition. Though issues regarding the low density of the film and variability between samples remain to be addressed, the work represents an important step toward future correlated functional/structural studies of these peptides.


Single-cell transcriptomics allows the identification of cellular types, subtypes and states through cell clustering. In this process, similar cells are grouped before determining co-expressed marker genes for phenotype inference. The performance of computational tools is directly associated to their marker identification accuracy, but the lack of an optimal solution challenges a systematic method comparison. Moreover, phenotypes from different studies are challenging to integrate, due to varying resolution, methodology and experimental design. In this work we introduce matchSCore (https://github.com/elimereu/matchSCore), an approach to match cell populations fast across tools, experiments and technologies. We compared 14 computational methods and evaluated their accuracy in clustering and gene marker identification in simulated data sets. We further used matchSCore to project cell type identities across mouse and human cell atlas projects. Despite originating from different technologies, cell populations could be matched across data sets, allowing the assignment of clusters to reference maps and their annotation.


Modern silicon technology offers unprecedented spatial and temporal control of electrons with high levels of integrated complexity. Integrating nanophotonic functionality onto silicon should then allow us to extend this level of control to photons. Resulting nano-optoelectronic systems will inevitably create new functionality, which not only enables next-generation technologies like optical interconnects, but also gives rise to yet unforeseen applications.Directly growing III-V nanomaterials on silicon provides an advantageous pathway towards optoelectronic integration. Conventional wisdom often breaks at the nanoscale, and traditional integration challenges like lattice mismatch are circumvented. In particular, III-V nanoneedles and nanopillars with attractive optical properties grow on silicon under conditions that are compatible with the process constraints of CMOS technology.This dissertation will present a variety of nano-optoelectronic devices developed using the nanoneedle and nanopillar platform. Nanolasers are demonstrated under optical pumping, and progress towards electrical injection is shown. Under reverse bias, nanopillars enable avalanche photodiodes featuring gain-bandwidth products in excess of 100 GHz. Nanopillar devices also exhibit clear photovoltaic effects and even support nonlinear optical generation. The breadth of functionality shown suggests that a powerful marriage between photons and electrons on silicon is well within reach.


The use of enzymes (lipases) to convert triglycerides to acylesters (biodiesel) holds potential as an alternative to the conventional base catalyzed processes. Advantages include the ability to utilize impure feedstocks, less downstream processing, and potentially overcoming the requirement to dedicate expensive agricultural land for raw oil production. Lipid sources such as oleaginous microorganisms along with processing wastes may provide renewable substrates requiring minimal pre-processing. Transesterification of vegetable oils and restaurant grease has been studied using immobilized enzymes as catalysts with an optimal temperature of around 35°C. This study investigates ester formation from unrefined tallow at 50°C employing similar enzymes used for vegetable oils. Novozyme 435 (a commercially available immobilized enzyme) proved best at a loading of 2 % w/w based on tallow reaching 98 % conversion after 96 h using methanol as the chosen alcohol, with immobilized lipase from Pseudomonas cepacia (PS-30) (69 % conversion) proving superior to free PS-30 (11 % conversion), and the other lipases barely registering any activity. Immobilized PS-30 was chosen to investigate the effect of lipase level, alcohol reactant, water content of the tallow, grade of tallow, and influence of solvent or a solvent-free system. Results showed that water content of up to 0.6 % and the tallow grade had no effect on ester formation, while enzyme loadings of at least 4 % were needed to achieve a good conversion that plateaued at around 6–8 % water content. The primary alcohols ethanol, propanol, and butanol reacted equally efficiently with immobilized PS-30, reaching 96–99 % conversion, while methanol performed less well along with 2-propanol and 2-butanol where conversion was only in the range of 10–40 %. Transesterification reactions worked best in a non-polar environment with hexane as solvent (95 % conversion), with a higher polarity solvent, acetonitrile, also proving an efficient medium (80 % conversion), while solvents intermediate to these had little comparative activity, suggesting that solubility of reactants and products is a key driver in the conversion. Interestingly, petro-diesel proved to be a better solvent than using either a solvent-free system or a diethylether environment.


Framing American Politics. Karen Callaghan and Frauke Schnell, eds. Pittsburgh, PA: University of Pittsburgh Press, 2005. 248 pp. $27.95. New Media Campaigns and the Managed Citizen. Philip N. Howard. New York: Cambridge University Press, 2006. 265 pp. $65.00 hbk. $23.99 pbk. These two books provide insightful perspectives about different areas of political communication research, all at varying levels of conceptual development. Considering them in comparison offers valuable insight into how key political communication research approaches develop and mature and helps explain why particular methodological designs are favored over others. Callaghan and Schnell's edited work demonstrates how scholars have come to a more refined understanding of framing over time, in this case viewing it as a specific research paradigm rather than an overarching theory. Howard's shrewd examination of political uses of new technology could have important implications for future theorizing about electronic campaigning. In Framing American Politics, Callaghan and Schnell gather an impressive group of scholars from the framing debate to examine the utility of this concept in macro-level studies of how frames are set by "political elites" and micro-level studies of how these frames affect individual consumers of political content. Framing is understood here as a "top down" process whereby "political elites, such as the news media, politicians, interest groups, and other political players, define the political space and erect the boundaries within which a public policy issue will be considered." Callaghan and Schnell clearly stake their turf in this typically muddied field of research. They provide a solid framework for this volume with a concise yet cogent introduction and a solidly argued conclusion. Framing is treated as a "coherent research paradigm," and the book focuses on the aspects of this concept considered most relevant to political communication. This is not another discussion of "What is framing?" as much as it is an exploration of the question, "Why is this concept relevant to our discipline?" Considering the overall strength of the contributors to this book and the coherence of the arguments presented, Framing American Politics is a work best considered in its entirety. While most of the chapters could stand on their own merit, the collective volume offers a compelling and balanced argument for why framing should continue to inform political communication studies. The book also brings to light the central issues that scholars, even with their more refined understanding of framing, must grapple with in order to truly advance this particular line of inquiry. Key among these issues is finding a more effective way to learn from studies of framing effects. Callaghan discusses the "file-drawer" problem, where members of the academic community hesitate to publish the results of quantitative work that fail to support the hypothesized relationships. This challenges the assumption that only studies that locate statistical significance can advance the framing debate. The book's discussion of framing effects illustrates how these types of studies can be both promising and problematic. Schnell and Callaghan's own effects research in chapter 5, "Terrorism, Media Frames, and Framing Effects," does well to support the book's overall focus on a framing paradigm within which political communication scholars can incorporate both micro- and macro-level considerations. They use content analysis and experimental research to explore the effect of changing news coverage of the gun control debate following the September 11 attacks. They explore how focusing events contribute to changes in news frames, thereby merging two important political communication concepts. There seems to be a natural link between this study and the frame-changing model that was proposed in 2004 by Chyi and McCombs, although this study is not referenced in the chapter. …


As daily deal promotions have exploded in popularity, there is considerable debate regarding their benefits and pitfalls. However, empirical evidence regarding the change in revenues and profits resulting from a daily deal promotion for a business, the potential exposure value it provides, and patterns of redemption rates over the course of the promotion is scarce in the public domain. Such knowledge is important to understand the real potential associated with daily deal promotions. To examine these issues, we conduct an in-depth descriptive analysis of the experience of Gourmet Prep Meals (GPM), a Houston-based startup, with running a Groupon promotion. Our results provide evidence of significant exposure value, defined as the increase in sales because of exposure received by the business to the Groupon customer base. For GPM, the Groupon promotion's exposure value is approximately 140% of its baseline sales over the six month period. We also find that although the promotion itself had no material impact on the firm's profits, when the earnings from unredeemed Groupons are taken into account, GPM enjoyed a substantial 30% lift in profits compared to baseline levels. The firm lost a small amount of money on the average Groupon user, but more than made up for it from the increased rate of purchase - which was more than three times higher - by full price-paying customers from the increased exposure. The Groupon promotion also helped GPM identify its target customers and fine-tune its product and service offerings. We conclude that the Groupon promotion was beneficial to GPM in multiple ways, and that daily deal promotions can be effective marketing tools for retail startup businesses in local markets to achieve exposure and stimulate sales.


The International 0-group fish survey in the Barents Sea (1965-2002) aimed to give initial indication of the re- cruiting year class strengths. Since 2003 the 0-group survey has been a part of a Joint Norwegian-Russian ecosystem sur- vey of the Barents Sea, conducted by IMR (Norway) and PINRO (Russian Federation). The electronic 0-group databases were missing some data and contained errors, therefore the databases have been quality checked and corrected for the pe- riod 1980-2006. Two separate sets of 0- group indices were re-estimated, both with and without correction for capture ef- ficiency, using a stratified sample mean approach, and 0-group indices were correlated with other appropriate abundance indices. The exclusion of errors from the database has improved our confidence in the indices and analysis. In general, the 0-group indices seem to be reliable predictors of year class strengths and are adequate to use as input in stock assessment- models and recruitment studies.


Reel 2
July 1907-March 1909
From Mukden on 9 August 1907 Straight wrote a note of commendation to John Foord of the American Asiatic Association, and on 3 December he wrote at length to Edwin Denby, who was planning to publish a monthly on Asiatic affairs. In mid-November Straight prepared a memorandum on Manchuria that he later handed to William Howard Taft when they conferred in Vladivostok. Copies of some State Department trade reports incorporating Straight's dispatches are filmed at the end of 1907. Some letters in late 1907 and early 1908 concern a news service George Marvin was conducting for the Chinese government. A Marvin letter of 13 January urged that American college men establish friendly relations with Chinese students, as Straight had done with Alfred Sze at Cornell. There are letters from a number of consuls in other commercial centers in Korea and Manchuria. An attack on the gateman of the American consulate in Mukden by a Japanese postman, and the fracas that ensued, led Straight to complain to the Japanese consul. The injudicious release to the press of Straight's colorful account of the incident, referred to as the "Mukden affair" in the Japanese papers, led to the termination of Marvin's news venture.
Some other correspondents in the Mukden period are Henry Prather Fletcher, Frederick McCormick, William Phillips, Henry Schoellkopf, and Francis Mairs Huntington Wilson. On 24 May 1908 Straight and an associate began a three-month journey into Northern Manchuria, studying the transportation, agriculture, and trade in outlying areas, and observing and recording the extent of Russian and Japanese control and colonization. In September Straight returned to the United States to help Special Ambassador T'ang Shao-yi place his Manchurian Bank proposal before American financiers. Straight exchanged a number of notes with Harriman and Jacob Henry Schiff. A letter from Elihu Root on 11 December 1908 defines the State Department's attitude toward the undertaking. T'ang's recall in January left Straight in Washington, where he prepared a number of reports for the Division of Far Eastern Affairs.


Azimuthal anisotropies of muons from charm and bottom hadron decays are measured in Pb+Pb collisions at $\sqrt{s_{NN}}=$ 5.02 TeV. The data were collected with the ATLAS detector at the Large Hadron Collider in 2015 and 2018 with integrated luminosities of 0.5 ${nb}^{-1}$ and 1.4 ${nb^{-1}}$, respectively. The kinematic selection for heavy-flavor muons requires transverse momentum 4 $<p_{T}<$ 30 GeV and pseudorapidity $|\eta|<$ 2.0. The dominant sources of muons in this $p_{T}$ range are semi-leptonic decays of charm and bottom hadrons. These heavy-flavor muons are separated from light-hadron decay muons and punch-through hadrons using the momentum imbalance between the tracking and muon spectrometers. Azimuthal anisotropies, quantified by flow coefficients, are measured via the event-plane method for inclusive heavy-flavor muons as a function of the muon $p_{T}$ and in intervals of Pb+Pb collision centrality. Heavy-flavor muons are separated into contributions from charm and bottom hadron decays using the muon transverse impact parameter with respect to the event primary vertex. Non-zero elliptic ($v_{2}$) and triangular ($v_{3}$) flow coefficients are extracted for charm and bottom muons, with the charm muon coefficients larger than those for bottom muons for all Pb+Pb collision centralities. The results indicate substantial modification to the charm and bottom quark angular distributions through interactions in the quark-gluon plasma produced in these Pb+Pb collisions, with smaller modifications for the bottom quarks as expected theoretically due to their larger mass.


Japan is reemerging as the most important source of foreign direct investment (FDI) in the United States. In 2013 Japanese firms were the largest source of new inflows of FDI into the United States for the first time since 1992, injecting almost $45 billion of fresh investment into the US economy in that year alone. Moran and Oldenski show how Japanese investment in the United States differs from that of other countries along several dimensions. These differences not only make FDI by Japanese firms especially valuable but point to some important policy goals for attracting it. Although the automotive sector is the single largest industry for Japanese investment in the United States, the focus should not be on competing to attract the auto industry in particular nor should any active industrial policy of "picking winners" be pursued. Japanese investment is unique because of its research and development intensity, manifested across a number of industries in which Japanese multinationals invest other than automobiles. US policy should focus on reinforcing and expanding the factors that attract high-performing firms and high-value production stages to the United States, regardless of industry.


Abstract. Here we present the first observations of simultaneous ozone deposition fluxes and ultrafine particle emission fluxes over an extensive infra-littoral zone. Fluxes were measured by the eddy covariance technique at the Station Biologique de Roscoff, on the coast of Brittany, north-west France. This site overlooks a very wide (3 km) littoral zone controlled by very deep tides (9.6 m) exposing extensive macroalgae beds available for significant iodine mediated photochemical production of ultrafine particles. The aspect at the Station Biologique de Roscoff provides an extensive and relatively flat, uniform fetch within which micrometeorological techniques may be utilized to study links between ozone deposition to macroalgae (and sea water) and ultrafine particle production. Ozone deposition to seawater at high tide was significantly slower (vd[O3]=0.302±0.095 mm s−1) than low tidal deposition. A statistically significant difference in the deposition velocities to macroalgae at low tide was observed between night time (vd[O3]=1.00±0.10 mm s−1) and daytime (vd[O3]=2.05±0.16 mm s−1) when ultrafine particle formation results in apparent particle emission. Very high emission fluxes of ultrafine particles were observed during daytime periods at low tides ranging from 50 000 particles cm−2 s−1 to greater than 200 000 particles cm−2 s−1 during some of the lowest tides. These emission fluxes exhibited a significant relationship with particle number concentrations comparable with previous observations at another location. Apparent particle growth rates were estimated to be in the range 17–150 nm h−1 for particles in the size range 3–10 nm. Under certain conditions, particle growth may be inferred to continue to greater than 120 nm over tens of hours; sizes at which they may readily behave as cloud condensation nuclei (CCN) under reasonable supersaturations that may be expected to pertain at the top of the marine boundary layer. These results link direct depositional loss and photochemical destruction of ozone to the formation of particles and hence CCN from macroalgal emissions at a coastal location.


We present a novel way to efficiently compute Riemannian geodesic distance over a two- or three-dimensional domain. It is based on a previously presented method for computation of geodesic distances on surface meshes. Our method is adapted for rectangular grids, equipped with a variable anisotropic metric tensor. Processing and visualization of such tensor fields is common in certain applications, for instance structure tensor fields in image analysis and diffusion tensor fields in medical imaging. The included benchmark study shows that our method provides significantly better results in anisotropic regions in 2-D and 3-D and is faster than current stat-of-the-art solvers in 2-D grids. Additionally, our method is straightforward to code; the test implementation is less than 150 lines of C++ code. The paper is an extension of a previously presented conference paper and includes new sections on 3-D grids in particular.


Introduction: Nursing is the largest healthcare profession in Malawi with more than 11,000 registered nurses (RNs), nurse technicians and midwives (NTM) practicing in hospitals and other settings like nursing colleges nationwide. Student preparation is mostly done by nursing tutors in all the nursing colleges using numerous types of teaching aids. Methods: Descriptive exploratory design which utilized both qualitative and sequential quantitative methods was applied to Iterated Purposive Probability Sampling (IPPS) of 10 nursing colleges in Malawi. This was done to 129 students and 82 nurse tutors in two structured questionnaires, 40 nurse tutors in-depth interviews and 10 students focus groups. There were 32 variables for the teaching aids under five ranked Likert scale and the Cronbach's Alpha was found to be 0.932 without standardisation and it was 0.952 after standard-disation. Results: Although nurse tutors show that they use manikins to teach (0.011 < p = 0.05), students seem not to agree on the utilization of the manikins during teaching both in class and at the clinical area (0.05; p = 0.05). There is also increased discrepancy between students and nurse tutors on internet utilization as the teaching aid as the Beta Coefficient value was (B = 0.202) for the nurse tutors and (B = 1.061) for the students basing on their experience. Use of patient as a teaching aid is very common in Malawi and both the nurse tutors and students agree that it is the realistic and best way in teaching and has a strong binary logistic regression with a model outcome of (OR = 1.431; 95%CI (0.890 ± 2.304); p = 0.139). Conclusion: There is a need to develop the teaching strategies that would be conducive with the current scarcity of the teaching aids. Use of patients if ethically followed remains the most effective and efficient teaching aid in developing countries.


Abstract Britain's vote to leave the EU has raised more questions than answers, which is ironic given that David Cameron's aim for the referendum was to settle the European question in British politics. The outcome, which reflected a range of causes, leaves significant uncertainties overhanging UK politics, UK-EU relations and wider European politics. It is likely that the confused outcome of the referendum and the technicalities of Brexit mean that for both the UK and the EU future relations will resemble fifty shades of grey rather than some black and white division of in or out.


The resettlement action plan (RAP) for the Madagascar Integrated Growth Poles Project includes the country ' s regulatory and legal frameworks, and the Bank ' s safeguard policies, and principles for resettlement, stipulating the criteria for ensuring compensation to project affected people (PAP) as required, due to subprojects implementation. The RAP addresses the following mitigating measures: cultural heritage sites are to be protected and respected in compliance with the country ' s legislation, and the Bank safeguards policy; mitigation measures for project affected people (PAP) will ensure that PAPs will gain benefit from the project and improve their standard of living; measures necessary to mitigate adverse impacts will be determined with participation of the displaced persons during design and implementation of the project; addressing the needs of displaced PAPs will be a priority during periods of transition and adaptation to new or temporary settlements; compensation to PAPs for the cost of losses from involuntary relocation, as required; and the previous level of community services and access to resources will be maintained or improved after resettlement.


We review several different languages for collective decision making problems, in which agents express their judgments, opinions, or beliefs over elements of a logically structured domain. Several such languages have been proposed in the literature to compactly represent the questions on which the agents are asked to give their views. In particular, the framework of judgment aggregation allows agents to vote directly on complex, logically related formulas, whereas the setting of binary aggregation asks agents to vote on propositional variables, over which dependencies are expressed by means of an integrity constraint. We compare these two languages and some of their variants according to their relative succinctness and according to the computational complexity of aggregating several individual views expressed in such languages into a collective judgment. Our main finding is that the formula-based language of judgment aggregation is more succinct than the constraint-based language of binary aggregation. In many (but not all) practically relevant situations, this increase in succinctness does not entail an increase in complexity of the corresponding problem of computing the outcome of an aggregation rule.


Sea cucumbers (Echinodermata: Holothuroidea) are large and abundant members of marine benthic communities. Overexploitation worldwide has raised concern because they have important functions within ecosystems. The ecological roles of commercially exploited sea cucumbers (Aspidochirotida and Dendrochirotida) are reviewed here, focusing on recent literature. Of the more than 70 species commercially exploited, at least 12 regularly bury into sand and mud, playing major roles in bioturbation. Most aspidochirotids are deposit-feeders, reducing the organic load and redistributing surface sediments, making them bioremediators for coastal mariculture. Sea cucumbers excrete inorganic nitrogen and phosphorus, enhancing the productivity of benthic biota. This form of nutrient recycling is crucial in ecosystems in oligotrophic waters such as coral reefs. Feeding and excretion by sea cucumbers also act to increase seawater alkalinity which contributes to local buffering of ocean acidification. Sea cucumbers host more than 200 species of parasitic and commensal symbionts from seven phyla, thereby enhancing ecosystem biodiversity. They are preyed on by many taxa, thereby transferring animal tissue and nutrients (derived from detritus and microalgae) to higher trophic levels. Overexploitation of sea cucumbers is likely to decrease sediment health, reduce nutrient recycling and potential benefits of deposit-feeding to seawater chemistry, diminish biodiversity of associated symbionts, and reduce the transfer of organic matter from detritus to higher trophic levels. Ecosystem-based fisheries management needs to consider the importance of sea cucumbers in marine ecosystems and implement regulatory measures to safeguard their ecological roles.


As the curation of data for machine learning becomes increasingly automated, dataset tampering is a mounting threat. Backdoor attackers tamper with training data to embed a vulnerability in models that are trained on that data. This vulnerability is then activated at inference time by placing a"trigger"into the model's input. Typical backdoor attacks insert the trigger directly into the training data, although the presence of such an attack may be visible upon inspection. In contrast, the Hidden Trigger Backdoor Attack achieves poisoning without placing a trigger into the training data at all. However, this hidden trigger attack is ineffective at poisoning neural networks trained from scratch. We develop a new hidden trigger attack, Sleeper Agent, which employs gradient matching, data selection, and target model re-training during the crafting process. Sleeper Agent is the first hidden trigger backdoor attack to be effective against neural networks trained from scratch. We demonstrate its effectiveness on ImageNet and in black-box settings. Our implementation code can be found at https://github.com/hsouri/Sleeper-Agent.


The term Dutch Disease is not new but it always remains an updated notion due to the expansion of capital flows coming from the export of natural resources that can produce reverse effects on the economy of rich countries in these resources. ¶Indeed, this situation can lead, in the case of a developing country, to a contraction of sectors producing tradable goods apart from the booming sector, and the development of sectors producing non-tradable goods. ¶However, several authors highlight the existence of a similarity between the increase in incomes coming from the exploitation of natural resources, the transfers of the foreign residents, the foreign assistance and tourist receipts. ¶In this paper, we will study the theory of the "Dutch Disease" to analyze the phenomenon of the deindustrialization which characterizes the Moroccan economy within the last decades, considering the importance of the shares that have these resources in the Moroccan GDP, in order to give recommendations to neutralize its effects. ¶After a brief talk on the contents and the theoretical statue of the ¦Dutch ¦¦Disease models¦, we will proceed, on the basis of empirical checking, to a critical analysis of the theory using a Vector Error Correction Model VECM, aiming to identify the transmission channels of the Dutch Disease in the Moroccan economy and explain the challenges with which industrialization is confronted.¶


This paper examines the relationship between adult mortality and religious affiliation in the contemporary U.S. using data from the Health and Retirement Study. Jews and Mainline Protestants have longer life expectancies, even when controlling for background characteristics such as gender and race. I test whether these mortality differences can be attributed to differences in education, health behaviors, or psychosocial support. The first two reduce but do not eliminate mortality differences. The effect of psychosocial support, measured separately by attendance and importance, varies dramatically by religion. These results show that studies examining the effect of "religiosity" on health and mortality need to consider differences by religious affiliation.


This paper seeks to shed light on the impacts of drug war policies and marijuana suppression efforts on African American men, and to explore recent changes within the law that may affect this segment of the population. Although discourse regarding the war on drugs is becoming more prevalent, it is important for policy makers, law enforcement, and scholars to recognize the unique circumstances that African American men face in light of the historical discrimination and oppression they have experienced, and to craft narrowly tailored solutions to address the myriad issues they encounter. Unless deliberate action is taken to address these concerns, these men will continue to be systematically excluded from mainstream society, and are at grave risk of cycling in-and-out of the revolving doors of the criminal justice system.


This paper documents the procedures in constructing China's employment and compensation metrics and measuring labor input in the Chinese economy. We begin with discussions of major conceptual, coverage, and classification problems in the official labor statistics and then propose strategies to solve the problems using a labor indexing methodology. This methodology allows the human capital attributes of any employed person weighted by their specific costs and the sum of the costs is controlled by the national income accounts. It guides our basic data work to adjust breaks, fill gaps, and restore consistencies in annual statistics and in benchmark marginal matrices. We use the iterative proportional filling (IPF) approach to obtain full-dimensioned employment and compensation matrices for benchmarks and, based on which, we then construct the matrices in time series. We show that China's total (cost-weighted) labor input grew by 4.1% per annum in 1980-2010, of which changes in quality and in hours worked made almost equal contributions. We also find that nearly half of the 2% quality improvement was attributable to changes in the industrial structure, followed by changes in education attainment and age structure.


In the last ten years, we have been witnessing the vast growth in wireless communications due to the popularity of many wireless devices, mobiles, smart phones etc. As a result, the demand for high data rates, bandwidth, and spectrum utilization has increased. From a survey, it has been shown that limited spectrum is a crucial factor to the continued growth in wireless services. To fulfill this demand, the designers are having many difficulties with radio spectrum, multipath fading, interference etc. To meet the problem, they introduce multiple-input multiple-output (MIMO), where multiple antennas are used in transceivers to increase the diversity and multiplexing gains over single antenna systems. But, it seems impractical to implement in wireless devices. Thus, to overcome this drawback, cooperative communications has been proposed for single antennas to gain same benefits from MIMO, which helps to maintain the spatial diversity gain. The concept of cooperative communication is to enhance the wireless network by adding a relay as a third terminal to assist the direct communication. The use of relay as an intermediate terminal helps to increase the probability of detection. In this report, we analyze the detection probability in cognitive radio networks (CRNs) over correlated Nakagami-m fading channel assisted by amplify-and-forward (AF) cooperative networks using orthogonal space-time block codes (OSTBCs). We evaluate the impact of correlation in channel on the spectrum sensing performance in CRNs. We calculate the closed-form expressions of the detection probability, false alarm probability and probability of miss detection in correlated non-identical Nakagami-m fading channels. Moreover, we present a set of complementary receiver operating characteristics (ROC) curves for different scenarios to describe the effect of antenna correlation on the spectrum sensing performance of CRNs.


INTRODUCTION
The Gyrification Index (GI) represents the degree of cortical folding and is of special interest in schizophrenia, since alterations in cortical folding indirectly reflect white matter development and axonal connectivity underneath. To the best of our knowledge, very few studies have investigated the effect of sex on GI in schizophrenia. Differences in the GI between patients with schizophrenia and healthy controls and the relation between sex, age symptoms and duration of illness with GI were investigated.

METHODS
T1-images were acquired from schizophrenia patients (24 males [SZ-M] and 24 females [SZ-F]) and healthy volunteers (24 males [NC-M] and 24 females [NC-F]) matched for age, sex and handedness. GI analyses were performed using the fully automated CIVET pipeline.

RESULTS
Significantly lower GI was found in patients relative to controls bilaterally in frontal, temporal, and parietal cortex. Sex differences were found: negative correlation was found between the duration of illness and the right parietal GI and right occipital GI in SZ-M, while SZ-F was found in the left frontal and bilateral temporal GI. Patients, regardless of sex, showed positive correlations between negative symptoms and GI in the right occipital. NC-F had greater GI values than SZ-F and both male groups.

CONCLUSIONS
Since GI reflects, in part, alterations in cerebral development and connectivity, the decrease in GI observed in patients is in agreement with the neurodevelopmental model of disconnectivity in schizophrenia; in addition, we emphasize the importance of sex differences in schizophrenia.


Background : Surgery is the most important treatment in gastric cancer (GC) patients and also chemotherapy and radiotherapy are used as adjuvant and/or neo-adjuvant therapies for reducing locally relapse and metastasis. This study aimed to compare patients' survival and affected factors in this two treatment groups.
Materials and Methods: This historical cohort study was conducted on 181 patients underwent chemotherapy (group 1) and 201 patients underwent surgery (group 2). The effect of demographic, clinical and pathological risk factors on patients' survival was assessed by log-rank test and Cox Proportional Hazard (CPH) model. Data were analyzed using SPSS16.
Results: Fifty and six patients (30.6%) in surgery group and 69 patients (34.3%) in chemotherapy group passed atoay death by the end of the study. The median survival time in two groups was 19 and 28 months, respectively. Age at diagnosis and tumor grade in surgery group, and gender and pathologic stage in chemotherapy group were significant (p<0.05).
Conclusion: Demographic and pathological characteristics of patients are the significant determinant of treatment success and increasing survival, however, assessing the causal effect of treatments on survival will be well achieved via controlled clinical trials through which the effects of confounders can be controlled.
Keywords: Gastric cancer, Survival analysis, Chemotherapy, Surgery, Cox model.


This PhD thesis discusses the question to what extent the Soil Protection Act (SPA) offers space for an integrated approach for deeper groundwater in addition alongside aspects of the soil quality other aspects can be referenced to the use, development or the management of soil in the decision-making. To assess this question, demands are made on the flexibility of the law and the possibility to make integral considerations. Due to this, a freedom of choice is available but this is not without limitations. The space that exists must remain inside the lines that are imposed in this regard in a democratic constitutional state. The legal tenability of the integrated approach is based on European law and legal principles. The SPA contains conditions that especially are useful to produce a case-to-case based area approach of the contamination of the deeper groundwater. These are: a phased remediation (article 38 clause 3 SPA), partial remediation (article 40 SPA), and a cluster approach (article 42 SPA). The use of these instruments is limited because the law prescribes in which specific cases they can be used. Moreover, the case-to-case approach in the SPA is not flexible enough for a broad application concerning the contamination of the deeper groundwater on an area scale. The biggest obstacle for an integrated approach is the absence of the possibility of a wide consideration of interests. In addition to the specific general interest of the protection of the soil, other relevant aspects for an integrated area oriented approach of the contamination of the deeper groundwater and private interests that do not correspond, can not be involved. After implementation of the regulation concerning an area oriented approach in paragraph 3b of chapter IV of the SPA, the possibilities for the approach of the contamination of the deeper groundwater on area scale are increased considerably. The case criterion (gevalscriterium) is partly abandoned, but not all obstacles are hereby solved. The limited consideration of interests remains problematic with the exception of the indication of an area. Therefore, the assessment of the control plan (beheerplan) does not allow room for a wide administrative consideration of interests. In an area oriented approach that is based on the SPA, problems with European regulation (Water Framework Directive, Groundwater Directive) can be negated. This might change if the extent of the polluted area increases significantly in comparison with what can be achieved through a stable end-point remediation (stabiele, milieuhygienische, aanvaardbare eindsituatie). Moreover, the relation with environmental law principles is a point of particular interest. Because uncertain risks play an important role in an integrated area oriented approach of the deeper groundwater, there is a correlation with the precautionary principle (voorzorgsbeginsel). Additionally the polluter pays principle is a weak element .


Soft ferromagnetic cubic NaZn13-type La0.7Pr0.3Fe11.4Si1.6 has turned out to be a standout amongst the most fascinating compounds for investigating substantial magnetocaloric effect (MCE) on the grounds that the attractive properties of this compound shows large enough spontaneous magnetization for applications, strongly doping dependent, and as well as delicate soft ferromagnetism. These impacts can be attributed to the itinerant electron metamagnetic (IEM) transition especially around the first-order magnetic transition region. However, this compound is difficult to frame by the basic cementing process because of the inherent deficiency of the peritectic response, Υ-Fe + La → La(Fe,Si)13(τ1a), which frequently brings about a blended microstructure of α-Fe + La(Fe,Si)13(τ1a) + LaFeSi(τ4). Additionally, dependability of La(FexSi1−x)13 is no middle-of-the-road stage and common solvency amongst Fe and La in the Fe-La framework as a reality is represented by response dispersion as indicated by magnetic and electronic states' contribution. From this point of view, the structure, attractive properties and MCE of this compound have been talked about in detail as indicated by various temperatures and times of the annealing treatment. In addition, efficiently contemplating on the doping impact from various concentrations of transition metal elements such as Copper (Cu) and Chromium (Cr) on Iron (Fe) in the La0.7Pr0.3Fe11.4Si1.6 compound is likewise discussed.


This essay, written ten years after the first human death from avian influenza, reviews scientific, social, and policy aspects of pandemic influenza, and asks whether the near-crisis level of concern is justified. That there will be another influenza pandemic is certain, and a number of factors suggest it will occur sooner rather than later. It is impossible, however, to predict two of the pandemic's crucial characteristics-its pathogenicity and the age-attack curve. The scientific arsenal has never been stronger, yet gaps in the availability of antiviral drugs and vaccines are inevitable, and the world is poorly prepared to cope with the politics of drug shortage. Some studies suggest emergent pandemics can be "ring-fenced," but these studies are not broadly accepted. Assuming that they cannot, rapid and global deployment of a range of responses, including social distancing, travel limitations, and prophylactic/curative application of antiviral drugs such as Tamiflu, can limit impacts. However, the impacts are bound to be significant if not severe. Overall health-sector strengthening, rural development (particularly in the area of veterinary health), and addressing the local, national, and international governance issues that cut across all aspects of infectious disease are more likely to bear fruit, especially in the developing world, than the pandemic preparedness planning now in vogue. Copyright 2007 The Population Council, Inc..


Association rule mining approaches traditionally generate rules based only on database contents, and focus on exact matches between items in transactions. In many applications, however, the utilization of some background knowledge, such as ontologies, can enhance the discovery process and generate semantically richer rules. Besides, fuzzy logic concepts can be applied on ontologies to quantify semantic similarity relations among data. In this context, we extended SSDM (Semantically Similar Data Miner) algorithm in order to obtain from a fuzzy ontology the semantic relations between items. As a consequence, the generated rules can be more understandable, improving the utility of the knowledge supplied by them.


Nowadays the management of water resources has become a top priority issue for Spanish public administration. This management of water resources is especially delicate in South eastern Spain where water is particularly scarce, principally as a result of the irregular distribution of rainfall and secondly, just as important, as a result of its overwhelming use in overly dense population areas where water has to meet great demands in many activities that range from agricultural, industrial, urban to sports facilities such as for golf courses among others. To counteract the effects derived from water scarcity, changes are being proposed to improve the management of the limited resources within a sustainable framework. In this way, an appealing alternative both from a technical and from an economic and environmental perspective would suggest the need to re-use urban wastewater to satisfy the demands that require nondrinkable water. Needless to say, in order to re-use urban wastewater, we need to depend on existing infrastructures for drainage and water treatment. Such infrastructures and those for regeneration and re-usage of urban wastewater feature the physical layout of an integral drainage system. In this paper we present the planning of an integral drainage system for a coastal area in Southeastern Spain. The proposal was developed as a result of an agreement reached between the Benissa city council in Alicante and the Institute of Water and Environmental Sciences of the University of Alicante.


Various human pathologies, such as cancers or, notably, exudative age-related macular degeneration (AMD), are characterized by an abnormal vascular proliferation (angiogenesis), which in the case of this type of AMD, can rapidly lead to blindness if no countermeasures are taken. In the past few years, it has become possible to stop - or at least to notably slow down - the evolution of AMD, by applying treatments based on photodynamic therapy (PDT), whereby, through the action of a molecule acting as photosensitizer (PS) which is targeted preferentially to the choroidal neovessels (CNV), the effects of this abnormal angiogenesis are stopped by provoking the closure of the neovessels. In particular, the PDT group at EPF-Lausanne has, in the past, already tested on the model of the chick embryo chorioallantoic membrane (known as the CAM model) several PSs of potential interest as substitute to the product currently considered as standard (Visudyne® , itself co-developed in this group) for the treatment of the CNV associated with AMD. The aim of this thesis was to study new molecules and/or formulations, potentially suitable as substitutes to the current photodynamic treatment of AMD, while diminishing its negative side-effects: general phototoxicity due to diffusion of the product out of the vasculature and further lack of selectivity leading to (undesirable) partial occlusion of the normal vasculature. In order to enable extrapolation and comparison of the results obtained, we have focused our attention on vascular effects only and administered the tested PSs under essentially similar conditions (formulation in DMSO; same delivery system through biodegradable nanoparticles built with the same polymer). In addition, the same animal model (the CAM model) was used throughout the entire study, the formulations being administered by intravenous injection. This model, importantly, allows for an easy and real-time semi-quantitative visualisation and recording of the vascular effects of a PS induced during a PDT session. In the first part of this work, we demonstrate that the tetra-phenylporphyrin molecule, when formulated in nanoparticles based on poly(D, L - lactic acid, of well defined size (ca. 200 nm or less) is a very interesting PS-candidate potentially suitable as a replacement of the currently used one. We show that inclusion of this PS in nanoparticles notably reduces the PDT's general phototoxicity. We believe therefore that this PS would deserve more thorough pre-clinical studies, on an animal model closer to the human case (for example, Ryan's model). The second part of this thesis aimed at elaborating a strategy allowing, in due time, for an improved selectivity of occlusion of the neovasculature, said strategy aiming at an active targeting of neovessels. Recently, a number of possible biochemical targets have been identified, including the so-called ανβ3 receptors, which are highly expressed at the level of the neovessels' endothelial cells. Our approach consisted in coupling a fluorescent molecule (fluorescein, easily visualized by epi-microscopy) to a protein (a kistrin) which contains the RGD peptide sequence, known for its affinity for the ανβ3 receptors. We have thus been able to demonstrate that the kistrin was effectively linked to these receptors and, therefore, that active targeting of the neovessels had indeed taken place. A complete proof of this concept by realizing the coupling of this kistrin with a PS molecule will be the next step in this research.


Good intentions often have unintended consequences. This applies to recent changes in the injunction law in patent cases. Although these changes were intended to alleviate some of the problems caused by patent owners that do not practice their invention, the changes have also unintentionally made it more difficult for patent owners in certain industries to obtain injunctions.
An injunction in patent litigation is generally an order prohibiting the manufacture, use, sale, or importation of any device that embodies the patented technology. As authorized by the Patent Act, courts "may grant injunctions in accordance with the principles of equity." Outside patent law, the "principles of equity" traditionally means that an injunction can be granted only if the plaintiff can show that the following four factors, in the aggregate, favored an injunction: (1) irreparable injury, (2) an inadequate remedy at law, (3) a balance of hardships between the parties, and (4) the public interest. However, different standards developed for injunctions in patent cases. In 1982, Congress created the US Court of Appeals for the Federal Circuit (the Federal Circuit), giving it jurisdiction over all patent law appeals. From its inception, this court has instead interpreted the phrase "principles of equity" to mean that injunctions should routinely be granted after a patent was found to be valid and infringed. A denial was appropriate only in "exceptional circumstances." Indeed, one study found that, prior to 2006, injunctions were granted in over 95 percent of cases. The rationale for this nearly automatic grant of injunctions was that the right to exclude is "the essence" of a patent, and, without an injunction, the value of that right would be significantly diminished. However, because of the increasing number of patent plaintiffs that do not, themselves, practice their invention, many began to question the soundness of this general rule.
These nonpracticing entity (NPE) plaintiffs can come in many forms — an individual inventor who does not have the resources to offer a product or service, a university or research institute that does not have an interest in doing so, or a company whose business model is to earn revenue through licensing, rather than by practicing its invention. Members of the last group are sometimes derisively referred to as "patent trolls" because they are not seen by critics as contributing to the technological development of an industry. Instead, they act like the mythical troll under a bridge, exacting a toll through litigation and licensing on those who do contribute. The advantage of being an NPE is that, because it does not offer a product or service, such a plaintiff cannot be threatened with counterclaims for infringement. This significantly reduces the risks of litigation for these plaintiffs and decreases the chance of a low-cost settlement for a defendant.
This advantage, combined with the once-customary practice of granting injunctions as a matter of course, contributed to the problem of patent holdup. The threat of an injunction, particularly when a defendant had already significantly invested in the potentially infringing product, provided a plaintiff with considerable leverage in negotiations. Because an injunction was likely to be issued after successful litigation of the validity and infringement issues, a defendant that could not negotiate a license was faced with the possibility of having to remove its product from the market until it could design around the patent. The result was often a royalty overcharge; the plaintiff obtained licensing royalties that were significantly more than the true market value of the patented technology. This royalty overcharge was, essentially, a tax on innovation in an industry.
One particularly high-profile example occurred when an NPE brought an infringement action against Research in Motion, the maker of the once-ubiquitous BlackBerry device. This case gained widespread attention because it almost led to the shutdown of all BlackBerry devices. In that case, the jury found the patent was valid and had been infringed and awarded a 5.7 percent royalty, resulting in approximately $53.7 million in damages. The court also granted an injunction. While the injunction was stayed pending appeal, the parties settled the case for $612.5 million, eleven times the damages award. This outsize settlement award was attributed to the pending injunction. In response to this and similar cases, the Supreme Court addressed the injunction issue in eBay v. MercExchange. In that case, the Court unanimously rejected the "general rule" employed by the Federal Circuit, holding that the four-factor test does apply in patent cases. Commentators consider the eBay case a response by the Court to the NTP settlement. This decision was intended, at least in part, to make it more difficult for NPEs to obtain injunctions.
This article empirically evaluates the aftermath of the eBay decision, looking at ten years of post-eBay injunction decisions. Numerous early studies were conducted to evaluate the effect of the eBay decision on NPEs. Although this study confirms the findings in the earlier literature that NPE plaintiffs are significantly disadvantaged, more interestingly, our results reveal that firms in certain industries are likewise granted injunctions at significantly lower rates than other industries that can reduce the innovation incentive in these industries. In the case of NPEs, the innovation incentive is not a problem because these patent owners merely license their technology for others to exploit, and the primary concern is whether an injunction provides excessive leverage in settlement negotiations. However, for patent owners that do practice their inventions, the reduced likelihood of an injunction can have an impact on the potential value of a patent and thus can materially affect the incentive value of patents.
The article is organized as follows. Part II provides a detailed history of Ebay, following the case from the district court to the ultimate Supreme Court resolution and reviewing the early empirical research on this issue. Part III describes the research methodology and the study's results. Finally, Part IV offers some preliminary conclusions regarding this research.


CRISPR/Cas9 is a transformative tool for making targeted genetic alterations. In plants, high mutation efficiencies have been reported in primary transformants. However, many of the mutations analyzed were somatic and therefore not heritable. To provide more insights into the efficiency of creating stable homozygous mutants using CRISPR/Cas9, we targeted LsNCED4 (9-cis-EPOXYCAROTENOID DIOXYGENASE4), a gene conditioning thermoinhibition of seed germination in lettuce. Three constructs, each capable of expressing Cas9 and a single gRNA targeting different sites in LsNCED4, were stably transformed into lettuce (Lactuca sativa) cvs. Salinas and Cobham Green. Analysis of 47 primary transformants (T1) and 368 T2 plants by deep amplicon sequencing revealed that 57% of T1 plants contained events at the target site: 28% of plants had germline mutations in one allele indicative of an early editing event (mono-allelic), 8% of plants had germline mutations in both alleles indicative of two early editing events (bi-allelic), and the remaining 21% of plants had multiple low frequency mutations indicative of late events (chimeric plants). Editing efficiency was similar in both genotypes, while the different gRNAs varied in efficiency. Amplicon sequencing of 20 T1 and more than 100 T2 plants for each of the three gRNAs showed that repair outcomes were not random, but reproducible and characteristic for each gRNA. Knockouts of NCED4 resulted in large increases in the maximum temperature for seed germination, with seeds of both cultivars capable of germinating >70% at 37°. Knockouts of NCED4 provide a whole-plant selectable phenotype that has minimal pleiotropic consequences. Targeting NCED4 in a co-editing strategy could therefore be used to enrich for germline-edited events simply by germinating seeds at high temperature.


The bile salt export pump (BSEP) is located on the canalicular plasma membrane of hepatocytes and plays an important role in the biliary clearance of bile acids (BAs). Therefore, any drug or new chemical entity that inhibits BSEP has the potential to cause cholestasis and possibly liver injury. In reality, however, one must consider the complexity of the BA pool, BA enterohepatic recirculation (EHR), extrahepatic (renal) BA clearance, and the interplay of multiple participant transporters and enzymes (e.g., sulfotransferase 2A1, multidrug resistance–associated protein 2, 3, and 4). Moreover, BAs undergo extensive enzyme-catalyzed amidation and are subjected to metabolism by enterobacteria during EHR. Expression of the various enzymes and transporters described above is governed by nuclear hormone receptors (NHRs) that mount an adaptive response when intracellular levels of BAs are increased. The intracellular trafficking of transporters, and their ability to mediate the vectorial transport of BAs, is governed by specific kinases also. Finally, bile flow, micelle formation, canalicular membrane integrity, and BA clearance can be influenced by the inhibition of multidrug resistant protein 3or ATPase-aminophospholipid transporter–mediated phospholipid flux. Consequently, when screening compounds in a discovery setting or conducting mechanistic studies to address clinical findings, one has to consider the direct (inhibitory) effect of the parent drug and metabolites on multiple BA transporters, as well as inhibition of BA sulfation and amidation and NHR function. Vectorial BA transport, in addition to BA EHR and homoeostasis, could also be impacted by drug-dependent modulation of kinases and enterobacteria.


A B ST R ACT. Self-help doctrines pervade the law. They regulate a legal subject's attempts to cure or prevent a perceived wrong by her own action, rather than through a mediated process. In their most acute form, these doctrines allow subjects to take what international lawyers call countermeasures -measures that would be forbidden if not pursued for redressive ends. Countermeasures are inescapable and invaluable. They are also deeply concerning, prone to error and abuse and to escalating cycles of vengeance. Disciplining countermeasures becomes a central challenge for any legal regime that recognizes them. How does American constitutional law meet this challenge? This Article contends that a robust set of unwritten, quasi-legal norms shapes and constrains retaliation as well as cooperation across the U.S. government, and it explores how these conventions of self-help correspond to regulatory principles that have emerged in public international law. Re-envisioning intragovernmental conflict through the lens of self-help gives us new descriptive and critical purchase on the separation of powers. By attending to the theory and practice of constitutional countermeasures, the Article tries to show, we can advance familiar debates over legislative obstruction and presidential adventurism, and we can develop richer models of constitutional contestation within and beyond the branches.


The democratic surge in the past twenty years has led many Americans to assume that all societies are, or should be, making progress toward becoming practicing democracies. Many in the United States approach countries such as China, Iran, and Vietnam with impatience and bewilderment. These seemingly intransigent holdouts are the subject of intense policy debates, not in the least because they also play important roles in U.S. security and economic policy. This book takes a fresh look at the prospects for political change in these countries and argues that immediate opportunities exist to advance political liberalization, with the possibility that democratization will follow in the mid to long term. But to encourage these trends, the United States must de-emphasize short-term human rights and democracy strategies to focus on more subtle attitudinal and institutional changes in both state and society, and develop new policy measures to enlarge political space.


This book re-evaluates and extends understandings about how work was conceived and what it could entail for women in the premodern period in Europe from c. 1100–1800. It does this by building on the impressive growth in literature on women's working experiences, and by adopting new interpretive approaches that expand received assumptions about what constituted '"work'" for women. While attention to the diversity of women's contributions to the economy has done much to make the breadth of women's experiences of labour visible, this volume takes a more expansive conceptual approach to the notion of work and considers the social and cultural dimensions in which activities were construed and valued as work. This interdisciplinary collection thus advances concepts of work that encompass cultural activities in addition to more traditional economic understandings of work as employment or labour for production. The chapters reconceptualise and explore work for women by asking how the working lives of historical women were enacted and represented, and analyse the relationships that shaped women's experiences of work across the European premodern period.


Childlessness was about 12–13 per cent for cohorts born in 1927 to 1941, but increased in younger cohorts, with the childlessness of men born in 1957–1961 reaching 20 per cent. Using data from the 2006 Canadian General Social Survey on families, we show that the intention to be childfree among young men has largely remained low, at 8 to 10 per cent. As men grow older, the intention to be childfree increases such that at age 45–49, 16 per cent intend not to become fathers. Rather than a deliberate choice, the increase in childlessness could be the result of a waiting game. Longer stays in school, later entry into the work force, and starting marital relations at older ages contribute to delays in becoming fathers. While for many men the delay does not necessarily end in childlessness, for others the period of waiting changes their intention to become fathers. The adjustment of intentions and the eventual childlessness are made easier because of the reduced normative pressure to have children.


We designed and tested new concept imaging devices, based on a thin scintillating crystal, aimed at the online monitoring of the range of protons in tissue during proton radiotherapy. The proposed crystal can guarantee better spatial resolution and lower sensitivity with respect to a thicker one, at the cost of a coarser energy resolution. Two different samples of thin crystals were coupled to a position sensitive photo multiplier tube read out by 64 independent channels electronics. The detector was equipped with a knife-edge Lead collimator that defined a reasonable field of view of about 10 cm in the target. Geant4 Monte Carlo simulations were used to optimize the design of the experimental setup and assess the accuracy of the results. Experimental measurements were carried out at the Skandion Clinic, the recently opened proton beam facility in Uppsala, Sweden. PMMA and water phantoms studies were performed with a first prototype based on a round 6.0 mm thick Cry019 crystal and with a second detector based on a thinner 5 × 5 cm2, 2.0 mm thick LFS crystal. Phantoms were irradiated with mono-energetic proton beams whose energy was in the range between 110 and 160 MeV. According with the simulations and the experimental data, the detector based on LFS crystal seems able to identify the peak of prompt-gamma radiation and its results are in fair agreement with the expected shift of the proton range as a function of energy. The count rate remains one of the most critical limitations of our system, which was able to cope with only about 20% of the clinical dose rate. Nevertheless, we are confident that our study might provide the basis for developing a new full-functional system.


Summary The lymphatic vasculature is essential for the maintenance of normal fluid balance and for the immune responses, but it is also involved in a variety of diseases. Hypoplasia or dysfuction of the lymphatic vessels can lead to lymphedema, whereas hyperplasia or abnormal growth of these vessels are associated with lymphangiomas and lymphangiosarcomas. Lymphatic vessels are also involved in lymph node and systemic metastasis of cancer cells. Recent novel findings on the molecular mechanisms involved in lymphatic vessel development and regulation allow the modulation of the lymphangiogenic process and specific targeting of the lymphatic endothelium. Recent results show that the homeodomain transcription factor Prox-1 is an important lymphatic endothelial cell (LEC) fate-determining factor which can induce LEC-specific gene transcription even in blood vascular endothelial cells (BECs). This suggests that the distinct phenotypes of cells in the adult vascular endothelium are plastic and sensitive to transcriptional reprogramming, which might be useful for future therapeutic applications involving endothelial cells Vascular endothelial growth factor-C (VEGF-C) and VEGF-D are peptide growth factors capable of inducing the growth of new lymphatic vessels in vivo in a process called lymphangiogenesis. They belong to the larger family which also includes VEGF, placenta growth factor (PlGF) and VEGF-B. VEGF-C and VEGF-D are ligands for the endothelial cell specific tyrosine kinase receptors VEGFR-2 and VEGFR-3. In adult human as well as mouse tissues VEGFR-3 is expressed predominantly in lymphatic endothelial cells which line the inner surface of lymphatic vessels. While VEGFR-2 is thought to be the main mediator of angiogenesis, VEGFR-3 signaling is crucial for the development of the lymphatic vessels. Heterozygous inactivation of the VEGFR-3 tyrosine kinase leads to primary lymphedema due to defective lymphatic drainage in the limbs. Other factors that seem to be involved in lymphangiogenesis include the Tie/angiopoietin system, neuropilin-2 and integrin α9. VEGF-C induces lymphatic vessel growth, but high levels of VEGF-C also resulted in blood vessel leakiness and growth. The VEGFR-3-specific mutant form of VEGF-C called VEGF-C156S lacks blood vascular side effects but is sufficient for therapeutic lymphangiogenesis in a mouse model of lymphedema. As VEGF-C156S is a specific lymphatic endothelial growth factor in the skin, it provides an attractive molecule for pro-lymphangiogenic therapy. This publication was partially financed by Serono. Part of this paper was originally presented at the 2nd International Workshop on New Therapeutic Targets in Vascular Biology, which took place in Geneva, Switzerland from February 6-9, 2003.