989 resultados para Immunoglobulin Light Chains
Resumo:
El panorama global está cambiando, y esto influye sobre la forma en la que entendemos y tratamos de alcanzar un desarrollo humano sostenible. El crecimiento de la población conlleva una mayor presión sobre los recursos, pero también supone una mayor cantidad de mano de obra y de talento; la concentración en áreas urbanas está cambiando las dinámicas sociales y desafiando los canales de comercialización tradicionales, pero también genera nuevos mercados y fomenta la innovación; los cambios en la economía global están reduciendo los tradicionales desequilibrios de poder entre los países occidentales y el resto del mundo; y las crecientes interconexiones crean nuevos riesgos pero también oportunidades para lanzar iniciativas de alcance global. Todas estas tendencias nos están obligando a repensar qué es el desarrollo humano y de qué manera deberíamos afrontar el reto de la pobreza. Es comúnmente aceptado que la globalización implica interdependencia y que, para conseguir un desarrollo humano sostenible, la colaboración entre actores de distintos ámbitos es necesaria. Se observa una creciente convergencia de temas, intereses y soluciones en torno al desarrollo sostenible, incluso en diferentes países y sectores, lo que está facilitando la colaboración estratégica entre empresas, gobiernos y sociedad civil. Existen pocas duda a día de hoy sobre el papel fundamental que las empresas deben desempeñar en la transición mundial hacia la sostenibilidad ambiental y la erradicación de la pobreza. Las empresas están evolucionando desde un enfoque tradicional centrado en la maximización de beneficios económicos hacia un enfoque holístico que integra la sostenibilidad y la responsabilidad social como parte del núcleo de negocio de las compañías. En el ámbito medioambiental, muchas empresas ya han comenzado a actuar y tratan de reducir sus emisiones, sus desechos y su consumo de energía. Sin embargo la contribución de las empresas a la reducción de la pobreza no está tan clara. Actualmente en torno a 1,2 miles de millones de personas viven en situación de extrema pobreza. La mayoría de estas personas aún vive en zonas rurales donde la mayor parte de la población activa trabaja en el sector agrícola. Por lo tanto, mejorar las oportunidades y reducir los riesgos de los productores más vulnerables en el sector de la agricultura puede ser un motor de desarrollo rural y reducción de la pobreza, especialmente en países de bajo nivel de desarrollo cuyas economías están fundamentalmente basadas en la agricultura. Algunas empresas comienzan a incluir a los pobres en sus operaciones como consumidores, proveedores y emprendedores. Esta tesis se centra en las potenciales oportunidades relacionadas con la incorporación sostenible de los pobres como proveedores de productos y/o de mano de obra. La colaboración entre empresas y productores vulnerables de países en desarrollo es un tema relativamente nuevo y todavía poco estudiado. La pregunta que guía esta tesis es: “¿Cómo pueden las empresas facilitar la inclusión sostenible en cadenas de suministro de productores vulnerables de los países menos desarrollados?”. Para responder a la pregunta anterior, la autora ha aplicado una metodología de casos de estudio. Esta metodología se considera apropiada porque la investigación sobre cadenas de suministro inclusivas es todavía escasa y porque es necesario entender en profundidad un fenómeno de la vida real, y para ello es fundamental conocer su contexto. En primer lugar, se realiza una revisión de literatura para identificar las proposiciones y los constructos teóricos que guiarán la posterior recogida de datos. La revisión de literatura se divide en dos partes: una más general que explora la dimensión social de la sostenibilidad en cadenas de suministro, y una más específica que se centra en la incorporación de los pobres como proveedores en cadenas de suministro. A lo largo de la última década, ha habido un crecimiento exponencial de los estudios académicos sobre la sostenibilidad de las cadenas de suministro, pero la mayoría de los esfuerzos se han dirigido hacia la dimensión medioambiental de la sostenibilidad. Por lo tanto la revisión de literatura, que se presenta en la Sección 3.1 (página 35) y que profundiza en la sostenibilidad social de las cadenas de suministro, puede considerarse una contribución en sí misma. Esta revisión de literatura revela que la investigación sobre aspectos sociales en cadenas de suministro está cobrando impulso en distintas áreas de conocimiento, principalmente en los ámbitos de investigación sobre “gestión de cadenas de suministro”, “responsabilidad social corporativa” y “estudios del desarrollo”. La investigación existente sobre sostenibilidad social de cadenas de suministro se centra en tres temas: aclarar la definición de sostenibilidad social; analizar la implementación de estrategias de sostenibilidad social en cadenas de suministro; y estudiar el apoyo de las em presas líderes a proveedores vulnerables para facilitar su transición hacia la sostenibilidad. Un marco conceptual que resume los principales hallazgos de esta primera parte de la revisión de literatura es planteado en la Figura 7 (página 48). No obstante, en el área de investigación que está emergiendo en torno a la sostenibilidad social de las cadenas de suministro, los estudios relacionados con la reducción de la pobreza son aún escasos. Además se aprecia una falta de contribuciones desde y sobre los países menos desarrollados, así como una clara tendencia a reflejar la visión de las empresas líderes de las cadenas de suministro, olvidando la perspectiva de los proveedores. La segunda parte de la revisión de literatura presentada en la Sección 3.2 (página 51) profundiza en tres líneas de investigación que exploran, desde distintas perspectivas, la inclusión de los pobres en cadenas de suministro. Estas líneas son “Global Value Chains” (GVC), “Base of the Pyramid” (BoP) y “Sustainable Supply Chain Management” (SSCM). La investigación en GVC analiza las cadenas de suministro desde la perspectiva de la globalización económica y el comercio internacional, poniendo especial énfasis en las implicaciones para los países en desarrollo y las comunidades vulnerables. GVC caracteriza las cadenas de suministro según la forma en la que son gobernadas, las oportunidades de mejora que existen para los productores que forman parte de la cadena y el grado de inclusión o exclusión de las comunidades más pobres y vulnerables. La investigación en BoP explora las relaciones comerciales entre empresas y comunidades pobres. La premisa fundamental del concepto BoP es la posibilidad de combinar la generación de beneficios con la reducción de la pobreza. La propuesta original es que mediante la venta de productos y servicios a las comunidades pobres de países en desarrollo, la pobreza puede ser reducida al tiempo que las empresas incrementan sus beneficios, especialmente las grandes empresas multinacionales. Esta idea ha ido evolucionando y, a día de hoy, los investigadores BoP consideran la incorporación de los pobres no sólo como consumidores sino también como empleados, proveedores y co-creadores. La investigación en SSCM ha estado fundamentalmente orientada al estudio de la dimensión medioambiental de la sostenibilidad de cadenas de suministro. Sin embargo, la creciente externalización de la producción a países en desarrollo y las demandas de los grupos de interés para que las empresas aborden todos los aspectos de la sostenibilidad han llevado a los académicos de SSCM a reconocer la importancia de integrar asuntos relacionados con la reducción de la pobreza en sus investigaciones. Algunos estudios comienzan a apuntar los principales retos a los que se enfrentan las empresas para colaborar con productores vulnerables en sus cadenas de suministro. Estos retos son: falta de comunicación, altos costes de transacción y el incremento de la complejidad de las operaciones. Las contribuciones de estas tres líneas de investigación son complementarias para el estudio de las cadenas de suministro inclusivas. Sin embargo, raramente han sido consideradas conjuntamente, ya que pertenecen a ámbitos de conocimiento distintos. Esta tesis integra las aportaciones de GVC, BoP y SSCM en un marco conceptual para la creación y gestión de cadenas de suministro inclusivas. Este marco conceptual para cadenas de suministro inclusivas queda representado en la Figura 9 (página 68). El marco conceptual refleja las motivaciones que llevan a las empresas a colaborar con productores vulnerables, los retos a los que se enfrentan al hacerlo, y los caminos o estrategias que están siguiendo para construir y operar cadenas de suministro inclusivas de manera que sean beneficiosas tanto para la empresa como para los productores vulnerables. A fin de validar y refinar el marco conceptual propuesto, tres casos de estudio se llevan a cabo. Las cadenas de suministro analizadas por los casos de estudio pertenecen al sector agrícola y sus principales proveedores se encuentran en países de África subsahariana. Múltiples métodos de recolección de datos y triangulación son utilizados para mejorar la fiabilidad de los datos. La autora desarrolló trabajos de campo en Senegal, Etiopía y Tanzania. Estos viajes permitieron enriquecer el proceso de recogida de información mediante entrevistas semiestructuradas y conversaciones informales con los principales actores de la cadena de suministro y mediante la observación directa de los procesos y las interacciones entre productores vulnerables y empresas. El Caso de estudio A (Sección 5.1 en página 96) es un caso de estudio único. Analiza la cadena de suministro local de verduras en Senegal. La organización focal es Manobi, una empresa senegalesa que provee servicios de bajo coste a emprendedores locales del sector agrícola. El Caso de estudio A proporciona un interesante análisis del funcionamiento de una cadena de suministro local en un país en desarrollo y muestra como la provisión de servicios profesionales puede mejorar el desempeño de productores vulnerables. El Caso de estudio B (Sección 5.2 en página 122) es un caso de estudio único. Analiza la cadena de suministro global de flor cortada con origen en Etiopía. La organización focal es EHPEA, la Asociación Etíope de Productores y Exportadores Hortícolas, cuya misión es promover y salvaguardar la posición competitiva del sector agrícola etíope en el mercado global. El Caso de estudio B ayuda a comprender mejor la perspectiva de los proveedores respecto a los requerimiento de sostenibilidad del mercado global. También muestra cómo la inclusión de los productores en el proceso de desarrollo de un estándar privado facilita su implementación posterior. El Caso de estudio C (Sección 5.3 en página 143) es un caso de estudio múltiple. Analiza la cadena de suministro global de café especial con origen en Tanzania. Las organizaciones focales son comerciantes que conectan de manera directa a pequeños agricultores de café en países en desarrollo con empresas tostadoras de café en países desarrollados. El Caso de estudio C muestra cómo un pequeño agricultor puede proveer un producto “premium” al mercado global, y participar en un segmento diferenciado del mercado a través de una cadena de suministro transparente y eficiente. Las aportaciones empíricas de los casos de estudio ayudan a validar y mejorar el marco conceptual sobre cadenas de suministro inclusivas (ver discusión en el Capítulo 6 en página 170). El resultado es la propuesta de una nueva versión del marco conceptual representado en la Figura 40 (página 195). Los casos de estudio también proporcionan interesantes aportaciones en relación a la gestión de cadenas de suministro inclusivas y muestran las perspectivas de distintos actores implicados. Esta tesis arroja luz sobre el papel de las empresas en la creación y la gestión de cadenas de suministro inclusivas llevando a cabo una revisión de literatura multidisciplinar y analizando tres casos de estudio en países africanos. Como resultado, esta tesis presenta una serie de contribuciones empíricas y teóricas al ámbito de investigación emergente en torno a las cadenas de suministro inclusivas (Capítulo 7). Esta tesis también pretende ser útil a profesionales que deseen facilitar la incorporación de los pobres como proveedores en condiciones justas y beneficiosas. ABSTRACT The global outlook is changing, and this is influencing the way we understand and try to achieve sustainable human development. Population growth entails increasing pressure over resources, but it also provides greater workforce and talent; concentration in urban areas is changing social dynamics and challenging traditional marketing channels, but also creating news markets and driving innovation; the global economy shift is rebalancing the traditional power imbalance between Western countries and the rest of the world, making new opportunities to arise; and interconnections and global interdependence create new risks but also opportunities for launching initiatives with a global reach. All these trends are impelling us to rethink what development is and in which way poverty alleviation should be approached. It is generally agreed that globalization implies interdependence and, in order to achieve sustainable human development, collaboration of all actors is needed. A convergence of issues, interests and solutions related to sustainable development is being observed across countries and sectors, encouraging strategic collaboration among companies, governments and civil society. There is little doubt nowadays about the crucial role of the private sector in the world’s path towards environmental sustainability and poverty alleviation. Businesses are evolving from a “business as usual” stance to a more sustainable and responsible approach. In the environmental arena, many companies have already “walk the talk”, implementing environmental management systems and trying to reduce emissions and energy consumption. However, regarding poverty alleviation, their contribution is less clear. There are around 1.2 billion people living in extreme poverty. Most of this people still live in rural areas where the agricultural sector employs a big part of the active population. Therefore, improving opportunities and reducing risks for vulnerable producers in the agri-food sector can be a primary engine of rural development and poverty alleviation, particularly in the poor, agriculture-based economies of least developed countries. Some companies are beginning to include the poor into their operations as consumers, suppliers and entrepreneurs. This thesis focuses specifically on the potential opportunities related to the sustainable incorporation of the poor as suppliers of products and/or labor. Business collaboration with vulnerable producers in developing countries is a relatively new trend and it is still understudied. The overall question guiding this thesis is: “How can businesses facilitate the sustainable inclusion of vulnerable producers from least developed countries into supply chains?”. In order to answer the research question, the author has applied a case study research strategy. This methodology is considered appropriate because research about inclusive supply chains is still at an early stage, and because there is a need to understand a real-life phenomenon in depth, but such understanding encompasses important contextual conditions. First, a literature review is conducted, in order to identify the research propositions and theoretical constructs that will guide the data collection. The literature review is divided in two parts: a more general one that explores the social dimension of sustainability of supply chains, and a more specific one that focuses on the incorporation of the poor as suppliers in supply chains. During the last decade, there has been an exponential growth of studies in the field of supply chain sustainability, but research efforts have traditionally been directed towards the analysis of the environmental dimension. Therefore, the literature review presented in Section 3.1 (page 35) that delves into social sustainability of supply chains can be considered a contribution in itself. This literature review reveals that the investigation of social issues in supply chains is gaining momentum and comes from different academic disciplines, namely Supply Chain Management, Corporate Social Responsibility and Development Studies. Existing research about social sustainability of supply chains focuses on three issues: clarify the definition of social sustainability; analyze the implementation of social sustainability strategies in supply chains; and study lead companies’ support to vulnerable suppliers in their transition towards sustainability. A conceptual framework that outlines the main findings that emerge from this first part of literature review is proposed in Figure 7 (page 48). Nevertheless, in this nascent field of social sustainability of supply chains, studies related to poverty alleviation are still scarce. Moreover, a lack of contributions from and about least developed countries has been observed, as well as a tendency to reflect on the lead firms’ standpoint, neglecting the suppliers’ perspective. The second part of the literature review (Section 3.2 in page 51) delves into three research streams that are exploring the inclusion of the poor into supply chains from different viewpoints. These research streams are Global Value Chains (GVC), Base of the Pyramid (BoP) and Sustainable Supply Chain Management (SSCM). GVC research discusses the dynamics of economic globalization and international trade, putting special emphasis in the implications for developing countries and vulnerable communities. GVC characterizes supply chains by the way they are governed, the upgrading opportunities that exist for producers in the chain and the degree of inclusion or exclusion of impoverished communities. BoP research explores trading relationships between businesses and impoverished communities. The core premise of the BoP concept is the possibility to combine profits with poverty alleviation. The original BoP proposition is that by marketing innovative products and services to poor communities in developing countries, poverty would be reduced and companies would increase their benefits, especially multinational companies. This idea has evolved to consider the incorporation of the poor to business activities not only as consumers, but also as employees, entrepreneurs and co-creators. The SSCM school of thought has mainly focused on studying the environmental dimension of supply chain sustainability, neglecting the consideration of the social perspective. However, in recent years, increasing outsourcing of production to developing countries and stakeholders’ demands for a more holistic approach to business sustainability have led SSCM scholars to acknowledge the importance of integrating poverty concerns in this field’s research agenda. Some SSCM studies identify the main operational challenges for companies which engage with vulnerable suppliers in their supply chains: missing communication, higher transactional and operational costs and increased complexity. Contributions from these three research streams are complementary for the study of inclusive supply chains. However, they have been rarely considered together, since they belong to different research areas. This thesis seeks to play a dovetailing role in this scenario by proposing a conceptual framework for creating and operating inclusive supply chains that builds on contributions from GVC, SSCM and BoP research. This framework for inclusive supply chains is depicted in Figure 9 (page 68), and explains the motivations that drive businesses to collaborate with vulnerable suppliers, the chal lenges they face in doing so, and the pathways they are following in order to build and operate inclusive supply chains profitably for both buying companies and vulnerable suppliers. In order to validate and refine the proposed framework, three case studies are carried out. The supply chains analyzed by the case studies belong to the agri-food sector and source from Sub-Saharan African countries. Multiple data collection methods and triangulation are used in order to improve reliability of findings. The author carried out field work in Senegal, Ethiopia and Tanzania. These travels enriched the data collection process, providing semi-structured interviews and informal conversations with the main actors in the supply chains, as well as direct observation of processes and interactions among companies and vulnerable suppliers. Case study A (Section 5.1 in page 96) is a single case study. It analyzes a local supply chain in Senegal providing vegetables to the local market. The focal organization is Manobi, a Senegalese inclusive business which provides affordable ICT services to local entrepreneurs in the agri-food sector. Case study A provides interesting insights into the dynamics of local supply chains and how professional services can help to improve their performance. Case study B (Section 5.2 in page 122) is a single case study. It analyzes a global supply chain with origin in Ethiopia providing cut flowers to the global commodity market. The focal organization is EHPEA, Ethiopian Horticulture Producers and Exporters Association, whose mission is to promote and safeguard the competitive position of the Ethiopian horticulture sector within the global market. Case study B helps to better understand the suppliers’ perspective regarding global market sustainability requirements and shows how the inclusion of suppliers in the process of development of a private standard has a positive impact in its implementation. Case study C (Section 5.3 in page 143) is a multiple case study. It analyzes a global supply chain with origin in Tanzania providing coffee to the global niche market of specialty coffee. The focal organizations are traders who are directly connecting smallholder coffee farmers in developing countries to coffee roasters in developed countries. Case study C shows how smallholder farmers can supply a premium product and be incorporated in a differentiated market segment through a transparent and efficient supply chain. The empirical findings from the case studies help to validate and refine the conceptual framework (see discussion in Chapter 6). The proposal of a new version of the conceptual framework is depicted in Figure 40 (page 195). The case studies also provide interesting insights related to the management of inclusive supply chains and show the perspectives of the different actors involved. This thesis sheds some light on the role of businesses in the creation and operation of inclusive supply chains by carrying out a cross-disciplinary literature review and analyzing three case studies in African countries. In doing so, this thesis presents a series of theoretical and empirical contributions to the emerging academic field of inclusive supply chains (Chapter 7). This thesis also intends to be useful to practitioners willing to improve the incorporation of the poor as suppliers in fair and profitable conditions.
Resumo:
A large superfamily of transmembrane receptors control cellular responses to diverse extracellular signals by catalyzing activation of specific types of heterotrimeric GTP-binding proteins. How these receptors recognize and promote nucleotide exchange on G protein α subunits to initiate signal amplification is unknown. The three-dimensional structure of the transducin (Gt) α subunit C-terminal undecapeptide Gtα(340–350) IKENLKDCGLF was determined by transferred nuclear Overhauser effect spectroscopy while it was bound to photoexcited rhodopsin. Light activation of rhodopsin causes a dramatic shift from a disordered conformation of Gtα(340–350) to a binding motif with a helical turn followed by an open reverse turn centered at Gly-348, a helix-terminating C capping motif of an αL type. Docking of the NMR structure to the GDP-bound x-ray structure of Gt reveals that photoexcited rhodopsin promotes the formation of a continuous helix over residues 325–346 terminated by the C-terminal helical cap with a unique cluster of crucial hydrophobic side chains. A molecular mechanism by which activated receptors can control G proteins through reversible conformational changes at the receptor–G protein interface is demonstrated.
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Chemical cross-linking is a potentially useful technique for probing the architecture of multiprotein complexes. However, analyses using typical bifunctional cross-linkers often suffer from poor yields, and large-scale modification of nucleophilic side chains can result in artifactual results attributable to structural destabilization. We report here the de novo design and development of a type of protein cross-linking reaction that uses a photogenerated oxidant to mediate rapid and efficient cross-linking of associated proteins. The process involves brief photolysis of tris-bipyridylruthenium(II) dication with visible light in the presence of the electron acceptor ammonium persulfate and the proteins of interest. Very high yields of cross-linked products can be obtained with irradiation times of <1 second. This chemistry obviates many of the problems associated with standard cross-linking reagents.
Resumo:
Methods of structural and statistical analysis of the relation between the sequence and secondary and three-dimensional structures are developed. About 5000 secondary structures of immunoglobulin molecules from the Kabat data base were predicted. Two statistical analyses of amino acids reveal 47 universal positions in strands and loops. Eight universally conservative positions out of the 47 are singled out because they contain the same amino acid in > 90% of all chains. The remaining 39 positions, which we term universally alternative positions, were divided into five groups: hydrophobic, charged and polar, aromatic, hydrophilic, and Gly-Ala, corresponding to the residues that occupied them in almost all chains. The analysis of residue-residue contacts shows that the 47 universal positions can be distinguished by the number and types of contacts. The calculations of contact maps in the 29 antibody structures revealed that residues in 24 of these 47 positions have contacts only with residues of antiparallel beta-strands in the same beta-sheet and residues in the remaining 23 positions always have far-away contacts with residues from other beta-sheets as well. In addition, residues in 6 of the 47 universal positions are also involved in interactions with residues of the other variable or constant domains.
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Several lines of evidence indicate that immunoglobulin-bound prolactin found in human serum is not a conventional complex between an anti-prolactin antibody and prolactin but a different type of association of prolactin with the Fab portion of IgG heavy chains. The complex of prolactin with IgG was purified from serum by anti-human prolactin affinity chromatography and was shown to contain close to 1 mole of N epsilon-(gamma-glutamyl)lysine crosslinks per mole of complex, a characteristic feature in structures crosslinked by transglutaminase. Interestingly, the complex caused a proliferation of cells from a subset of patients with chronic lymphocytic leukemia, while it was inactive in a cell proliferation prolactin bioassay. By contrast, human prolactin stimulated the proliferation of cells in the bioassay but had no effect on the complex-responsive cells from the patients. Competition studies with prolactin and free Fc fragment of IgG demonstrated a necessity for engaging both the prolactin and the immunoglobulin receptors for proliferation. More importantly, competition for the growth response by free prolactin and IgG suggests both possible reasons for the slow growth of this neoplasm as well as avenues for control of the disease.
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A large body of evidence supports a role of oxidative stress in Alzheimer disease (AD) and in cerebrovascular disease. A vascular component might be critical in the pathophysiology of AD, but there is a substantial lack of data regarding the simultaneous behavior of peripheral antioxidants and biomarkers of oxidative stress in AD and vascular dementia (VaD). Sixty-three AD patients, 23 VaD patients and 55 controls were included in the study. We measured plasma levels of water-soluble (vitamin C and uric acid) and lipophilic (vitamin E, vitamin A, carotenoids including lutein, zeaxanthin, β-cryptoxanthin, lycopene, α- and β-carotene) antioxidant micronutrients as well as levels of biomarkers of lipid peroxidation [malondialdehyde (MDA)] and of protein oxidation [immunoglobulin G (IgG) levels of protein carbonyls and dityrosine] in patients and controls. With the exception of β-carotene, all antioxidants were lower in demented patients as compared to controls. Furthermore, AD patients showed a significantly higher IgG dityrosine content as compared to controls. AD and VaD patients showed similar plasma levels of plasma antioxidants and MDA as well as a similar IgG content of protein carbonyls and dityrosine. We conclude that, independent of its nature - vascular or degenerative - dementia is associated with the depletion of a large spectrum of antioxidant micronutrients and with increased protein oxidative modification. This might be relevant to the pathophysiology of dementing disorders, particularly in light of the recently suggested importance of the vascular component in AD development. Copyright © 2004 S. Karger AG, Basel.
Resumo:
Humoral and cells surface molecules of the mammalian immune system, grouped into the Immunoglobulin Gene Superfamily, share protein structure and gene sequence homologies with molecules found among diverse phylogenetic groups. In histocompatibility studies, the gorgonian coral Swiftia exserta has recently demonstrated specific alloimmunity with memory (Salter-Cid and Bigger, 1991. Biological Bulletin Vol 181). In an attempt to shed light on the origins of this gene family and the evolution of the vertebrate immune response, genomic DNA from Swiftia exserta was isolated, purified, and analyzed by Southern blot hybridization with mouse gene probes corresponding to two molecules of the Immunoglobulin Gene Superfamily, the Thy-1 antigen, and the alpha-3 domain of the MHC Class I histocompatibility marker. Hybridizations were conducted under low to non-stringent conditions to allow binding of mismatched homologs that may exist between the mouse gene probes and the Swiftia DNA. Removal of non-specific binding (sequences less than 70% homologous) occurred in washing steps. Results show that with the probes selected, the method chosen, and the conditions applied, no evidence of sequences of 70% or greater homology to the mouse Thy-1 or MHC Class I alpha-3 genes exist in Swiftia exserta genome.
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Rapid technological advances and liberal trade regimes permit functional reintegration of dispersed activities into new border-spanning business networks variously referred to as global value chains (GVCs). Given that the gains of a country from GVCs depend on the activities taking place in its jurisdiction and their linkages to global markets, this study starts by providing a descriptive overview of China’s economic structure and trade profile. The first two chapters of this paper demonstrate what significant role GVCs have played in China’s economic growth, evident in enhanced productivity, diversification, and sophistication of China’s exports, and how these economic benefits have propelled China’s emergence as the world’s manufacturing hub in the past two decades. However, benefits from GVC participation – in particular technological learning, knowledge building, and industrial upgrading – are not automatic. What strategies would help Chinese industries engage with GVCs in ways that are deemed sustainable in the long run? What challenges and related opportunities China would face throughout the implementation process? The last two chapters of this paper focus on implications of GVCs for China’s industrial policy and development. Chapter Three examines how China is reorienting its manufacturing sector toward the production of higher value-added goods and expanding its service sector, both domestically and internationally; while Chapter Four provides illustrative policy recommendations on dealing with the positive and negative outcomes triggered by GVCs, within China and beyond the country’s borders. To the end, this study also hopes to shed some light on the lessons and complexities that arise from GVC participation for other developing countries.
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A RET network consists of a network of photo-active molecules called chromophores that can participate in inter-molecular energy transfer called resonance energy transfer (RET). RET networks are used in a variety of applications including cryptographic devices, storage systems, light harvesting complexes, biological sensors, and molecular rulers. In this dissertation, we focus on creating a RET device called closed-diffusive exciton valve (C-DEV) in which the input to output transfer function is controlled by an external energy source, similar to a semiconductor transistor like the MOSFET. Due to their biocompatibility, molecular devices like the C-DEVs can be used to introduce computing power in biological, organic, and aqueous environments such as living cells. Furthermore, the underlying physics in RET devices are stochastic in nature, making them suitable for stochastic computing in which true random distribution generation is critical.
In order to determine a valid configuration of chromophores for the C-DEV, we developed a systematic process based on user-guided design space pruning techniques and built-in simulation tools. We show that our C-DEV is 15x better than C-DEVs designed using ad hoc methods that rely on limited data from prior experiments. We also show ways in which the C-DEV can be improved further and how different varieties of C-DEVs can be combined to form more complex logic circuits. Moreover, the systematic design process can be used to search for valid chromophore network configurations for a variety of RET applications.
We also describe a feasibility study for a technique used to control the orientation of chromophores attached to DNA. Being able to control the orientation can expand the design space for RET networks because it provides another parameter to tune their collective behavior. While results showed limited control over orientation, the analysis required the development of a mathematical model that can be used to determine the distribution of dipoles in a given sample of chromophore constructs. The model can be used to evaluate the feasibility of other potential orientation control techniques.
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Purpose: Prompted by the extensive biases in the immunoglobulin (IG) gene repertoire of splenic marginal-zone lymphoma (SMZL), supporting antigen selection in SMZL ontogeny, we sought to investigate whether antigen involvement is also relevant post-transformation.
Experimental Design: We conducted a large-scale subcloning study of the IG rearrangements of 40 SMZL cases aimed at assessing intraclonal diversification (ID) due to ongoing somatic hypermutation (SHM).
Results: ID was identified in 17 of 21 (81%) rearrangements using the immunoglobulin heavy variable (IGHV)1-2*04 gene versus 8 of 19 (40%) rearrangements utilizing other IGHV genes (P= 0.001). ID was also evident in most analyzed IG light chain gene rearrangements, albeit was more limited compared with IG heavy chains. Identical sequence changes were shared by subclones from different patients utilizing the IGHV1-2*04 gene, confirming restricted ongoing SHM profiles. Non-IGHV1-2*04 cases displayed both a lower number of ongoing SHMs and a lack of shared mutations (per group of cases utilizing the same IGHV gene).
Conclusions: These findings support ongoing antigen involvement in a sizable portion of SMZL and further argue that IGHV1-2*04 SMZL may represent a distinct molecular subtype of the disease.
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The ability to rearrange the germ-line DNA to generate antibody diversity is an essential prerequisite for the production of a functional repertoire. While this is essential to prevent infections, it also represents the "Achilles heel" of the B-cell lineage, occasionally leading to malignant transformation of these cells by translocation of protooncogenes into the immunoglobulin (Ig) loci. However, in evolutionary terms this is a small price to pay for a functional immune system. The study of the configuration and rearrangements of the Ig gene loci has contributed extensively to our understanding of the natural history of development of myeloma. In addition to this, the analysis of Ig gene rearrangements in B-cell neoplasms provides information about the clonal origin of the disease, prognosis, as well as providing a clinical useful tool for clonality detection and minimal residual disease monitoring. Herein, we review the data currently available on both Ig gene rearrangements and protein patterns seen in myeloma with the aim of illustrating how this knowledge has contributed to our understanding of the pathobiology of myeloma.
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BACKGROUND AND OBJECTIVE: Molecular analysis by PCR of monoclonally rearranged immunoglobulin (Ig) genes can be used for diagnosis in B-cell lymphoproliferative disorders (LPD), as well as for monitoring minimal residual disease (MRD) after treatment. This technique has the risk of false-positive results due to the "background" amplification of similar rearrangements derived from polyclonal B-cells. This problem can be resolved in advance by additional analyses that discern between polyclonal and monoclonal PCR products, such as the heteroduplex analysis. A second problem is that PCR frequently fails to amplify the junction regions, mainly due to somatic mutations frequently present in mature (post-follicular) B-cell lymphoproliferations. The use of additional targets (e.g. Ig light chain genes) can avoid this problem. DESIGN AND METHODS: We studied the specificity of heteroduplex PCR analysis of several Ig junction regions to detect monoclonal products in samples from 84 MM patients and 24 patients with B cell polyclonal disorders. RESULTS: Using two distinct VH consensus primers (FR3 and FR2) in combination with one JH primer, 79% of the MM displayed monoclonal products. The percentage of positive cases was increased by amplification of the Vlamda-Jlamda junction regions or kappa(de) rearrangements, using two or five pairs of consensus primers, respectively. After including these targets in the heteroduplex PCR analysis, 93% of MM cases displayed monoclonal products. None of the polyclonal samples analyzed resulted in monoclonal products. Dilution experiments showed that monoclonal rearrangements could be detected with a sensitivity of at least 10(-2) in a background with >30% polyclonal B-cells, the sensitivity increasing up to 10(-3) when the polyclonal background was
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Bettini et al (2006 Nat. Nanotechnol. 1 182-5) reported the first experimental realization of linear atomic chains (LACs) composed of different atoms (Au and Ag). The different contents of Au and Ag were observed in the chains from what was found in the bulk alloys, which raises the question of what the wire composition is, if it is in equilibrium with a bulk alloy. In this work we address the thermodynamic driving force for species fractionation in LACs under tension, and we present the density-functional theory results for Ag-Au chain alloys. A pronounced stabilization of the wires with an alternating Ag-Au sequence is observed, which could be behind the experimentally observed Au enrichment in LACs from alloys with high Ag content.
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Current data indicate that the size of high-density lipoprotein (HDL) may be considered an important marker for cardiovascular disease risk. We established reference values of mean HDL size and volume in an asymptomatic representative Brazilian population sample (n=590) and their associations with metabolic parameters by gender. Size and volume were determined in HDL isolated from plasma by polyethyleneglycol precipitation of apoB-containing lipoproteins and measured using the dynamic light scattering (DLS) technique. Although the gender and age distributions agreed with other studies, the mean HDL size reference value was slightly lower than in some other populations. Both HDL size and volume were influenced by gender and varied according to age. HDL size was associated with age and HDL-C (total population); non- white ethnicity and CETP inversely (females); HDL-C and PLTP mass (males). On the other hand, HDL volume was determined only by HDL-C (total population and in both genders) and by PLTP mass (males). The reference values for mean HDL size and volume using the DLS technique were established in an asymptomatic and representative Brazilian population sample, as well as their related metabolic factors. HDL-C was a major determinant of HDL size and volume, which were differently modulated in females and in males.
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The presence of calcium, iron, and zinc bound to human milk secretory IgA (sIgA) was investigated. The sIgA components were first separated by two-dimensional polyacrylamide gel electrophoresis and then identified by electrospray ionization-tandem mass spectrometry (ESI MS MS). The metal ions were detected by flame atomic absorption spectrometry after acid mineralization of the spots. The results showed eight protein spots corresponding to the IgA heavy chain constant region. Another spot was identified as the transmembrane secretory component. Calcium was bound to both the transmembrane component and the heavy chain constant region, while zinc was bound to the heavy chain constant region and iron was not bound with the identified proteins. The association of a metal ion with a protein is important for a number of reasons, and therefore, the findings of the present study may lead to a better understanding of the mechanisms of action and of additional roles that sIgA and its components play in human milk.