909 resultados para metaphor, research and development, homeostatic property cluster phenomena
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The service sector has acquired a growing importance in every country economy, which has stimulated research in the field of service innovation, a new field in management studies. This text aimed to state a research agenda upon service innovation, based on an articulated discussion of the results of several articles that compose the state of the art of this concept. 73 empirical articles were analyzed, 33% of them exploring the innovation strategies and technology; 18% of the articles describe research on economic performance and enterprise productivity; 16% are related to antecedents and determinants of innovation; another 16% about network capacity development, alliances and collaboration among organizations; 9% of the articles explore service quality, innovation taxonomy, flexible systems and regional systems of innovation; and another 8% are related to themes such as intensive knowledge, research and development. The researches were concentrated in the Engineering & Technology and Hospitality Industries, which accounted for 31% and 24% of the texts, respectively. The remaining 45% of the articles referred to sectors such as Telecommunications, Health, Retail, Financial & Insurance and Public Services. The main gaps identified in these texts refer to the difficulties on measuring service innovation, besides the small number of researches on the public sector. At the end, a research agenda in the subject is presented, including the development of a scale for orientating the innovation and identifying the determining factors of the innovation in the public environment.
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Abstract Background Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but reliable diagnostic and prognostic markers have not been discovered so far. Some studies have evaluated the potential use of microRNA as biomarkers with clinical application in HNSCC. Methods MicroRNA expression profile of oral squamous cell carcinoma samples was determined by means of DNA microarrays. We also performed gain-of-function assays for two differentially expressed microRNA using two squamous cell carcinoma cell lines and normal oral keratinocytes. The effect of the over-expression of these molecules was evaluated by means of global gene expression profiling and cell proliferation assessment. Results Altered microRNA expression was detected for a total of 72 microRNAs. Among these we found well studied molecules, such as the miR-17-92 cluster, comprising potent oncogenic microRNA, and miR-34, recently found to interact with p53. HOX-cluster embedded miR-196a/b and miR-10b were up- and down-regulated, respectively, in tumor samples. Since validated HOX gene targets for these microRNAs are not consistently deregulated in HNSCC, we performed gain-of-function experiments, in an attempt to outline their possible role. Our results suggest that both molecules interfere in cell proliferation through distinct processes, possibly targeting a small set of genes involved in cell cycle progression. Conclusions Functional data on miRNAs in HNSCC is still scarce. Our data corroborate current literature and brings new insights into the role of microRNAs in HNSCC. We also show that miR-196a and miR-10b, not previously associated with HNSCC, may play an oncogenic role in this disease through the deregulation of cell proliferation. The study of microRNA alterations in HNSCC is an essential step to the mechanistic understanding of tumor formation and could lead to the discovery of clinically relevant biomarkers.
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The subject of this thesis is multicolour bioluminescence analysis and how it can provide new tools for drug discovery and development.The mechanism of color tuning in bioluminescent reactions is not fully understood yet but it is object of intense research and several hypothesis have been generated. In the past decade key residues of the active site of the enzyme or in the surface surrounding the active site have been identified as responsible of different color emission. Anyway since bioluminescence reaction is strictly dependent from the interaction between the enzyme and its substrate D-luciferin, modification of the substrate can lead to a different emission spectrum too. In the recent years firefly luciferase and other luciferases underwent mutagenesis in order to obtain mutants with different emission characteristics. Thanks to these new discoveries in the bioluminescence field multicolour luciferases can be nowadays employed in bioanalysis for assay developments and imaging purposes. The use of multicolor bioluminescent enzymes expanded the potential of a range of application in vitro and in vivo. Multiple analysis and more information can be obtained from the same analytical session saving cost and time. This thesis focuses on several application of multicolour bioluminescence for high-throughput screening and in vivo imaging. Multicolor luciferases can be employed as new tools for drug discovery and developments and some examples are provided in the different chapters. New red codon optimized luciferase have been demonstrated to be improved tools for bioluminescence imaging in small animal and the possibility to combine red and green luciferases for BLI has been achieved even if some aspects of the methodology remain challenging and need further improvement. In vivo Bioluminescence imaging has known a rapid progress since its first application no more than 15 years ago. It is becoming an indispensable tool in pharmacological research. At the same time the development of more sensitive and implemented microscopes and low-light imager for a better visualization and quantification of multicolor signals would boost the research and the discoveries in life sciences in general and in drug discovery and development in particular.
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The goal of many plant scientists’ research is to explain natural phenotypic variation in term of simple changes in DNA sequence. DNA-based molecular markers are extensively used for the construction of genome-wide molecular maps and to perform genetic analysis for simple and complex traits. The PhD thesis was divided into two main research lines according to the different approaches adopted. The first research line is to analyze the genetic diversity in an Italian apple germplasm collection for the identification of markers tightly linked to targeted genes by an association genetic method. This made it possible to identify synomym and homonym accessions and triploids. The fruit red skin color trait has been used to test the reliability of the genetic approaches in this species. The second line is related to the development of molecular markers closely linked to the Rvi13 and Rvi5 scab resistance genes, previously mapped on apple’s chromosome 10 and 17 respectively by using the traditional linkage mapping method. Both region have been fine-mapped with various type of markers that could be used for marker-assisted selection in future breeding programs and to isolate the two resistance genes.
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Software is available, which simulates all basic electrophoretic systems, including moving boundary electrophoresis, zone electrophoresis, ITP, IEF and EKC, and their combinations under almost exactly the same conditions used in the laboratory. These dynamic models are based upon equations derived from the transport concepts such as electromigration, diffusion, electroosmosis and imposed hydrodynamic buffer flow that are applied to user-specified initial distributions of analytes and electrolytes. They are able to predict the evolution of electrolyte systems together with associated properties such as pH and conductivity profiles and are as such the most versatile tool to explore the fundamentals of electrokinetic separations and analyses. In addition to revealing the detailed mechanisms of fundamental phenomena that occur in electrophoretic separations, dynamic simulations are useful for educational purposes. This review includes a list of current high-resolution simulators, information on how a simulation is performed, simulation examples for zone electrophoresis, ITP, IEF and EKC and a comprehensive discussion of the applications and achievements.
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Stem cells reside within tissue, ensuring its natural ability to repair an injury. They are involved in the natural repair of damaged tissue, which encompasses a complex process requiring the modulation of cell survival, extracellular matrix turnover, angiogenesis, and reverse remodeling. To date, the real reparative potential of each tissue is underestimated and noncommittal. The assessment of the biophysical properties of the extracellular environment is an innovative approach to better understand mechanisms underlying stem cell function, and consequently to develop safe and effective therapeutic strategies replacing the loss of tissue. Recent studies have focused on the role played by biomechanical signals that drive stem cell death, differentiation, and paracrinicity in a genetic and/or an epigenetic manner. Mechanical stimuli acting on the shape can influence the biochemistry and gene expression of resident stem cells and, therefore, the magnitude of biological responses that promote the healing of injured tissue. Nanotechnologies have proven to be a revolutionary tool capable of dissecting the cellular mechanosensing apparatus, allowing the intercellular cross-talk to be decoded and enabling the reparative potential of tissue to be enhanced without manipulation of stem cells. This review highlights the most relevant findings of stem cell mechanobiology and presents a fascinating perspective in regenerative medicine.
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Over the last decade, translational science has come into the focus of academic medicine, and significant intellectual and financial efforts have been made to initiate a multitude of bench-to-bedside projects. The quest for suitable biomarkers that will significantly change clinical practice has become one of the biggest challenges in translational medicine. Quantitative measurement of proteins is a critical step in biomarker discovery. Assessing a large number of potential protein biomarkers in a statistically significant number of samples and controls still constitutes a major technical hurdle. Multiplexed analysis offers significant advantages regarding time, reagent cost, sample requirements and the amount of data that can be generated. The two contemporary approaches in multiplexed and quantitative biomarker validation, antibody-based immunoassays and MS-based multiple (or selected) reaction monitoring, are based on different assay principles and instrument requirements. Both approaches have their own advantages and disadvantages and therefore have complementary roles in the multi-staged biomarker verification and validation process. In this review, we discuss quantitative immunoassay and multiple reaction monitoring/selected reaction monitoring assay principles and development. We also discuss choosing an appropriate platform, judging the performance of assays, obtaining reliable, quantitative results for translational research and clinical applications in the biomarker field.
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Book review of: Kendall, Ann Rodríguez, Abelardo. Desarrollo y Perspectivas de los Sistemas de Andenerías en los Andes Centrales del Perú (Development and Perspectives of Irrigated Terrace Systems in the Peruvian Central Andes). Cuzco, Peru. ISBN: 978-9972-691-93-5.
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Mountain regions provide a multitude of goods and services for much of humanity (Price and Butt 2000; Becker and Bugmann 2001), especially in the realms of water supply, biodiversity, and other ecosystem services (Schimel et al 2002; Körner et al 2005; Viviroli et al 2007; Viviroli et al 2011). However, the future ability of mountain regions to provide goods and services to both highland and lowland residents is seriously threatened by climatic changes, environmental pollution, unsustainable management of natural resources, and serious gaps in understanding of mountain systems (Huber et al 2005). Disciplinary, interdisciplinary, and transdisciplinary research is required to maintain these goods and services in the face of these forces. The global mountain research community, however, has historically operated at a suboptimal level because of insufficient communication across geographic and linguistic barriers, less than desirable coordination of research frameworks, and a lack of funding.
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Theoretical studies of the problems of the securities markets in the Russian Federation incline to one or other of the two traditional approaches. The first consists of comparing the definition of "valuable paper" set forth in the current legislation of the Russian Federation, with the theoretical model of "Wertpapiere" elaborated by German scholars more than 90 years ago. The problem with this approach is, in Mr. Pentsov's opinion, that any new features of the definition of "security" that do not coincide with the theoretical model of "Wertpapiere" (such as valuable papers existing in non-material, electronic form) are claimed to be incorrect and removed from the current legislation of the Russian Federation. The second approach works on the basis of the differentiation between the Common Law concept of "security" and the Civil Law concept of "valuable paper". Mr. Pentsov's research, presented in an article written in English, uses both methodological tools and involves, firstly, a historical study of the origin and development of certain legal phenomena (securities) as they evolved in different countries, and secondly, a comparative, synchronic study of equivalent legal phenomena as they exist in different countries today. Employing the first method, Mr. Pentsov divided the historical development of the conception of "valuable paper" in Russia into five major stages. He found that, despite the existence of a relatively wide circulation of valuable papers, especially in the second half of the 19th century, Russian legislation before 1917 (the first stage) did not have a unified definition of valuable paper. The term was used, in both theoretical studies and legislation, but it covered a broad range of financial instruments such as stocks, bonds, government bonds, promissory notes, bills of exchange, etc. During the second stage, also, the legislation of the USSR did not have a unified definition of "valuable paper". After the end of the "new economic policy" (1922 - 1930) the stock exchanges and the securities markets in the USSR, with a very few exceptions, were abolished. And thus during the third stage (up to 1985), the use of valuable papers in practice was reduced to foreign economic relations (bills of exchange, stocks in enterprises outside the USSR) and to state bonds. Not surprisingly, there was still no unified definition of "valuable paper". After the beginning of Gorbachev's perestroika, a securities market began to re-appear in the USSR. However, the successful development of securities markets in the USSR was retarded by the absence of an appropriate regulatory framework. The first effort to improve the situation was the adoption of the Regulations on Valuable Papers, approved by resolution No. 590 of the Council of Ministers of the USSR, dated June 19, 1990. Section 1 of the Regulation contained the first statutory definition of "valuable paper" in the history of Russia. At the very beginning of the period of transition to a market economy, a number of acts contained different definitions of "valuable paper". This diversity clearly undermined the stability of the Russian securities market and did not achieve the goal of protecting the investor. The lack of unified criteria for the consideration of such non-standard financial instruments as "valuable papers" significantly contributed to the appearance of numerous fraudulent "pyramid" schemes that were outside of the regulatory scheme of Russia legislation. The situation was substantially improved by the adoption of the new Civil Code of the Russian Federation. According to Section 1 of Article 142 of the Civil Code, a valuable paper is a document that confirms, in compliance with an established form and mandatory requisites, certain material rights whose realisation or transfer are possible only in the process of its presentation. Finally, the recent Federal law No. 39 - FZ "On the Valuable Papers Market", dated April 22 1996, has also introduced the term "emission valuable papers". According to Article 2 of this Law, an "emission valuable paper" is any valuable paper, including non-documentary, that simultaneously has the following features: it fixes the composition of material and non-material rights that are subject to confirmation, cession and unconditional realisation in compliance with the form and procedure established by this federal law; it is placed by issues; and it has equal amount and time of realisation of rights within the same issue regardless of when the valuable paper was purchased. Thus the introduction of the conception of "emission valuable paper" became the starting point in the Russian federation's legislation for the differentiation between the legal regimes of "commercial papers" and "investment papers" similar to the Common Law approach. Moving now to the synchronic, comparative method of research, Mr. Pentsov notes that there are currently three major conceptions of "security" and, correspondingly, three approaches to its legal definition: the Common Law concept, the continental law concept, and the concept employed by Japanese Law. Mr. Pentsov proceeds to analyse the differences and similarities of all three, concluding that though the concept of "security" in the Common Law system substantially differs from that of "valuable paper" in the Continental Law system, nevertheless the two concepts are developing in similar directions. He predicts that in the foreseeable future the existing differences between these two concepts will become less and less significant. On the basis of his research, Mr. Pentsov arrived at the conclusion that the concept of "security" (and its equivalents) is not a static one. On the contrary, it is in the process of permanent evolution that reflects the introduction of new financial instruments onto the capital markets. He believes that the scope of the statutory definition of "security" plays an extremely important role in the protection of investors. While passing the Securities Act of 1933, the United States Congress determined that the best way to achieve the goal of protecting investors was to define the term "security" in sufficiently broad and general terms so as to include within the definition the many types of instruments that in the commercial world fall within the ordinary concept of "security' and to cover the countless and various devices used by those who seek to use the money of others on the promise of profits. On the other hand, the very limited scope of the current definition of "emission valuable paper" in the Federal Law of the Russian Federation entitled "On the Valuable Papers Market" does not allow the anti-fraud provisions of this law to be implemented in an efficient way. Consequently, there is no basis for the protection of investors. Mr. Pentsov proposes amendments which he believes would enable the Russian markets to become more efficient and attractive for both foreign and domestic investors.
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The Centre for Development and Environment (CDE) is the University of Bern's center for sustainable development research. Founded in 1988 as a part of the Institute of Geography, CDE became an interdisciplinary university center in 2009. Its current overall aim is to foster sustainable development-oriented research across various institutes and departments of the University of Bern. In view of this new mandate, CDE devised a new strategy focusing on 6 strategic themes. These are explored and advanced by groups of researchers organized in thematic clusters. Three of the 6 clusters address sustainable development from a comprehensive perspective: global change impacts, innovations for sustainable development, and education for sustainable development. These clusters are complemented by 3 clusters that investigate sustainable development with a specialized perspective: natural resources and ecosystem services, multidimensional disparities, and governance of land and natural resources.
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Heavy metal-rich copper mine tailings, called stamp sands, were dumped by mining companies directly into streams and along the Lake Superior shoreline, degrading Keweenaw Peninsula waterways. One of the largest disposal sites is near Gay, Michigan, where tailings have been moved along the shoreline by currents since mining ceased. As a result, the smallest sand particles have been washed into deeper water and are filling the interstitial spaces of Buffalo Reef, a critical lake trout spawning site. This research is the first to investigate if stamp sand is detrimental to survival and early development of eggs and larvae of lake sturgeon, lake trout, and Northern leopard frogs, and also examines if the presence of stamp sands influences substrate selection of earthworms. This study found that stamp sand had significantly larger mean particle sizes and irregular shapes compared to natural sand, and earthworms show a strong preference for natural substrate over any combination that included stamp sand. Additionally, copper analysis (Cu2+) of surface water over stamp sand and natural sand showed concentrations were significantly higher in stamp sand surface water (100 μg/L) compared to natural sand surface water (10 μg/L). Frog embryos had similar hatch success over both types of sand, but tadpoles reared over natural sand grew faster and had higher survival rates. Eggs of lake sturgeon showed similar hatch success and development over natural vs. stamp sand over 17 days, while lake trout eggs hatched earlier and developed faster when incubated over stamp sand, yet showed similar development over a 163 day period. Copper from stamp sand appears to impact amphibians more than fish species in this study. These results will help determine what impact stamp sand has on organisms found throughout the Keweenaw Peninsula which encounter the material at some point in their life history.
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Acer saccharum Marsh., is one of the most valuable trees in the northern hardwood forests. Severe dieback was recently reported by area foresters in the western Upper Great Lakes Region. Sugar Maple has had a history of dieback over the last 100 years throughout its range and different variables have been identified as being the predisposing and inciting factors in different regions at different times. Some of the most common factors attributed to previous maple dieback episodes were insect defoliation outbreaks, inadequate precipitation, poor soils, atmospheric deposition, fungal pathogens, poor management, or a combination of these. The current sugar maple dieback was evaluated to determine the etiology, severity, and change in dieback on both industry and public lands. A network of 120 sugar maple health evaluation plots was established in the Upper Peninsula, Michigan, northern Wisconsin, and eastern Minnesota and evaluated annually from 2009-2012. Mean sugar maple crown dieback between 2009-2012 was 12.4% (ranging from 0.8-75.5%) across the region. Overall, during the sampling period, mean dieback decreased by 5% but individual plots and trees continued to decline. Relationships were examined between sugar maple dieback and growth, habitat conditions, ownership, climate, soil, foliage nutrients, and the maple pathogen sapstreak. The only statistically significant factor was found to be a high level of forest floor impacts due to exotic earthworm activity. Sugar maple on soils with lower pH had less earthworm impacts, less dieback, and higher growth rates than those on soils more favorable to earthworms. Nutritional status of foliage and soil was correlated with dieback and growth suggesting perturbation of nutrient cycling may be predisposing or contributing to dieback. The previous winter's snowfall totals, length of stay on the ground, and number of days with freezing temperatures had a significant positive relationship to sugar maple growth rates. Sapstreak disease, Ceratocystis virescens, may be contributing to dieback in some stands but was not related to the amount of dieback in the region. The ultimate goal of this research is to help forest managers in the Great Lakes Region prevent, anticipate, reduce, and/or salvage stands with dieback and loss in the future. An improved understanding of the complex etiology associated with sugar maple dieback in the Upper Great Lakes Region is necessary to make appropriate silvicultural decisions. Forest Health education helps increase awareness and proactive forest management in the face of changing forest ecosystems. Lessons are included to assist educators in incorporating forest health into standard biological disciplines at the secondary school curricula.
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Swiss National Research Programs (NRPs) are usually geared to addressing issues of major societal concern. In so doing these programs produce different kinds of knowledge: analytical knowledge necessary for revealing the driving forces, conflicting interests and institutional settings that govern the processes under scrutiny; target knowledge oriented towards revealing the directions in which the processes should be guided; and action knowledge that informs about the means by which this can best be achieved. Analytical knowledge answers the questions “what is the problem?” and “what causes it?” while target knowledge helps to define “what is our vision for the future?” and action knowledge deals with “how can we solve the problem?” Production of these 3 different types of knowledge is usually linked in an iterative process in the course of the research supported in an NRP.
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This article synthesizes findings from a review of the state of research on sustainable land management in Kyrgyzstan and Tajikistan and from an analysis of the interface between research and action. Using the Global Land Project (GLP 2005) analytical framework, we analyzed the distribution of 131 selected publications (including a clearly defined set of local and international academic and gray literature) across the framework's components and links in a social–ecological system. There is a strong emphasis in the literature on the impact of changes in land use and management on ecosystems; however, there is little research on the implications for ecosystem services. This finding is opposed to that of a similar analysis of publications at the global scale (Björnsen Gurung et al 2012). Another major gap was the lack of research on Kyrgyzstan and Tajikistan regarding the influence of global factors on social and ecological systems, despite social, economic, and political integration into global structures since the collapse of the Soviet Union and the increasing influence of climate change. Our analysis disaggregated academic literature published in the region and international academic literature, revealing stark differences. These differences are partly attributable to the legacy of the late Soviet era principle of “rational use of land resources,” which fit the planned economy but lacks approaches for decentralized resource governance. Finally, the emphasis of research on systems knowledge, the lack of transdisciplinary research, and the critical feedback of stakeholders at a regional sustainable land management forum suggest that actionable sustainable land management research on Kyrgyzstan and Tajikistan is rare. Recommendations are made for targeted, application-focused, multistakeholder research and knowledge sharing, including local and international researchers as well as practitioners, policy-makers, and land users.