A supervised cooperative learning system for early detection of language disorders

The Quality of Life of a person may depend on early attention to his neurodevel-opment disorders in childhood. Identification of language disorders under the age of six years old can speed up required diagnosis and/or treatment processes. This paper details the enhancement of a Clinical Decision Support System (CDSS) aimed to assist pediatricians and language therapists at early identification and re-ferral of language disorders. The system helps to fine tune the Knowledge Base of Language Delays (KBLD) that was already developed and validated in clinical routine with 146 children. Medical experts supported the construction of Gades CDSS by getting scientific consensus from literature and fifteen years of regis-tered use cases of children with language disorders. The current research focuses on an innovative cooperative model that allows the evolution of the KBLD of Gades through the supervised evaluation of the CDSS learnings with experts¿ feedback. The deployment of the resulting system is being assessed under a mul-tidisciplinary team of seven experts from the fields of speech therapist, neonatol-ogy, pediatrics, and neurology.

The Use of Patents to Assess National Innovation Systems: Evidences from Spanish Biotechnology

Spain’s economy recorded a high rate of growth from the mid-1990s onwards. At the same time, the resources allocated to Research and Development (R&D) grew at a much faster pace than in other European Union (EU) countries. Spain’s growth recorded an average rate of 2.93% from the early 1990s to 2004. Over the same period, the average growth in the EU was 0.46%. This circumstance, together with several sound policy decisions implemented between 2004 and 2009, ushered in a “golden age of Spanish biotechnology”. In terms of the national patent licenses issued by the Spanish Patent and Trademark Office (SPTO) between 2004 and 2009, the number in biotechnology grew from 84 to 151. However, the current economic situation in Spain, along with a series of political decisions taken over the past two or three years to cut spending on R&D, predicts a sharp downturn in the performance of Spanish biotechnology. This scenario makes Spain one of the best places to study the successes and failures of the management of science and allows transfer this experience to the other international regions. We need to analyze the influence of political decisions as a major factor with a bearing on the quality of science. Using patents as an indicator of scientific development, this paper analyzes the evolution of the biotechnology sector in Spain and its relationship with scientific policy and the management of R&D.

Optimal safety incentives in road concession contracts

Changes in the roles of the government and the private sector in the provision of public services along with budget constraints are resulting in an increasing use of the concession approach for financing and managing roads. In the last few years, many of these contracts set up incentives linked to bonuses to encourage the concessionaire to render a better service to the users. Road safety is one the aspects on the basis of which concessionaires can be rewarded according to their performance. The goal of this paper is to evaluate whether road safety incentives are being defined in the right way nowadays in different European countries and also identify what incentives would need to be implemented to achieve a socially optimal road safety level. To that end, we develop a specific incentive for road concession contracts that encourages companies to achieve the optimal level. We apply this methodology to three case studies of concessions recently awarded in order to determine to what extend the incentives they set up are closer or farther to the optimum.

La arquitectura religiosa de Luis Cubillo de Arteaga (1954-1974)

Esta Tesis Doctoral viene a cubrir el vacío existente referido a la arquitectura religiosa de Luis Cubillo de Arteaga, arquitecto conocido fundamentalmente por su aportación a la vivienda social madrileña en los años 50 y 60, pero con una abundante obra sacra. Para ello se ha estudiado la totalidad de su producción, que abarca desde 1954 hasta 1974. La Tesis analiza su arquitectura religiosa desde varios puntos de vista, que incluyen la implantación de los edificios y sus aspectos formales, constructivos y tipológicos, estos últimos especialmente destacados tras las directrices emanadas del Concilio Vaticano II. Previamente se analizan cuatro ámbitos relevantes en la arquitectura religiosa de Cubillo. En primer lugar se estudia la labor de la Dirección General de Asuntos Eclesiásticos, a la que estaba adscrito el arquitecto y para la que realizó sus primeros trabajos. Dentro de ella se expone la evolución del modelo de Seminario entre los años 40 y 60, para analizar la relevancia de la propuesta de Cubillo para el Seminario de Castellón. A continuación se trata la participación de Cubillo en la construcción de la periferia de Madrid, aunque no referida a sus conocidos trabajos sobre vivienda social, sino a los edificios dotacionales. Así mismo se expone una iniciativa hasta ahora inédita de la Comisaría de Ordenación Urbana de Madrid para dotar de centros parroquiales a los nuevos barrios. Un tercer bloque estudia un tema recurrente a finales de los años 50, la integración de las artes en la nueva arquitectura religiosa, propiciada principalmente por José Luis Fernández del Amo. En el caso de Cubillo, las colaboraciones más notables y objeto de estudio en esta Tesis, fueron las realizadas con los artistas Arcadio Blasco y José Luis Sánchez. Por último se describe la situación de la iglesia madrileña posconciliar y su plan de construcción de nuevos templos, en el que jugó un papel muy destacado Cubillo, convertido en arquitecto de confianza de la Oficina Técnica del Arzobispado-------------------------ABSTRACT------------------------------ This Doctoral Thesis fills the emptiness of knowledge about the religious architecture of Luis Cubillo de Arteaga, architect mainly known for his contribution to Madrid's social housing in the 50s and 60s, but with a wide sacred work. To this end it have been studied his entire production, ranging from 1954 to 1974. The thesis discusses his religious architecture from several points of view, including the implementation of the buildings and their formal, constructive and typological aspects, the latter especially important by following the guidelines issued by Vatican II. Previously, four relevant areas in Cubillo’s religious architecture are analyzed. First of all, it’s studied the work of the Department of Ecclesiastical Affairs, to which the architect was assigned and for whom he made his early works. As a part of it, is exposed the evolution of Seminar model between 40s and 60s, to discuss the relevance of Cubillo’s design for the Seminar of Castellón. Next, it´s studied the participation of Cubillo in the construction of the outskirts of Madrid, although not referring to his well known work on social housing, but to the design of the comunitary buildings. It’s also explained an unpublished initiative from Commissariat for Urban Planning of Madrid to provide parish centers to new neighborhoods. A third section examines a recurring theme in the late 50s, the integration of the arts in the new religious architecture, mainly leaded by José Luis Fernández del Amo. For Cubillo, the most notable collaborations, studied in this thesis, were with the artists Arcadio Blasco and José Luis Sánchez. Finally, it´s described the situation of the post-conciliar church in Madrid and its plan to build new temples, with a prominent role of Cubillo, that became in trusted architect of the Technical Office of the Archbishop.

Evaluación de la distribución de riesgos en los distintos modelos de asociación público-privada para la provisión de infraestructura carretera en México

México es de los pocos países en el mundo que ha realizado dos grandes programas para la construcción de autopistas en colaboración con el sector privado. El primero, fue realizado entre 1989 y 1994, con resultados adversos por el mal diseño del esquema de concesiones; y, el segundo con mejores resultados, en operación desde 2003 mediante nuevos modelos de asociación público-privada (APP). El objetivo de la presente investigación es estudiar los modelos de asociación público-privada empleados en México para la provisión de infraestructura carretera, realizando el análisis y la evaluación de la distribución de riesgos entre el sector público y privado en cada uno de los modelos con el propósito de establecer una propuesta de reasignación de riesgos para disminuir el costo global y la incertidumbre de los proyectos. En la primera parte se describe el estado actual del conocimiento de las asociaciones público-privadas para desarrollar proyectos de infraestructura, incluyendo los antecedentes, la definición y las tipologías de los esquemas APP, así como la práctica internacional de programas como el modelo británico Private Finance Initiative (PFI), resultados de proyectos en la Unión Europea y programas APP en otros países. También, se destaca la participación del sector privado en el financiamiento de la infraestructura del transporte de México en la década de 1990. En los capítulos centrales se aborda el estudio de los modelos APP que se han utilizado en el país en la construcción de la red de carreteras de alta capacidad. Se presentan las características y los resultados del programa de autopistas 1989-94, así como el rescate financiero y las medidas de reestructuración de los proyectos concesionados, aspectos que obligaron a las autoridades mexicanas a cambiar la normatividad para la aprobación de los proyectos según su rentabilidad, modificar la legislación de caminos y diseñar nuevos esquemas de colaboración entre el gobierno y el sector privado. Los nuevos modelos APP vigentes desde 2003 son: nuevo modelo de concesiones para desarrollar autopistas de peaje, modelo de proyectos de prestación de servicios (peaje sombra) para modernizar carreteras existentes y modelo de aprovechamiento de activos para concesionar autopistas de peaje en operación a cambio de un pago. De estos modelos se realizaron estudios de caso en los que se determinan medidas de desempeño operativo (niveles de tráfico, costos y plazos de construcción) y rentabilidad financiera (tasa interna de retorno y valor presente neto). En la última parte se efectúa la identificación, análisis y evaluación de los riesgos que afectaron los costos, el tiempo de ejecución y la rentabilidad de los proyectos de ambos programas. Entre los factores de riesgo analizados se encontró que los más importantes fueron: las condiciones macroeconómicas del país (inflación, producto interno bruto, tipo de cambio y tasa de interés), deficiencias en la planificación de los proyectos (diseño, derecho de vía, tarifas, permisos y estimación del tránsito) y aportaciones públicas en forma de obra. Mexico is one of the few countries in the world that has developed two major programs for highway construction in collaboration with the private sector. The first one was carried out between 1989 and 1994 with adverse outcomes due to the wrong design of concession schemes; and, the second one, in operation since 2003, through new public-private partnership models (PPPs). The objective of this research is to study public-private partnership models used in Mexico for road infrastructure provision, performing the analysis and evaluation of risk’s distribution between the public and the private sector in each model in order to draw up a proposal for risk’s allocation to reduce the total cost and the uncertainty of projects. The first part describes the current state of knowledge in public-private partnership to develop infrastructure projects, including the history, definition and types of PPP models, as well as international practice of programs such as the British Private Finance Initiative (PFI) model, results in the European Union and PPP programs in other countries. Also, it stands out the private sector participation in financing of Mexico’s transport infrastructure in 1990s. The next chapters present the study of public-private partnerships models that have been used in the country in the construction of the high capacity road network. Characteristics and outcomes of the highway program 1989-94 are presented, as well as the financial bailout and restructuring measures of the concession projects, aspects that forced the Mexican authorities to change projects regulations, improve road’s legislation and design new schemes of cooperation between the Government and the private sector. The new PPP models since 2003 are: concession model to develop toll highways, private service contracts model (shadow toll) to modernize existing roads and highway assets model for the concession of toll roads in operation in exchange for a payment. These models were analyzed using case studies in which measures of operational performance (levels of traffic, costs and construction schedules) and financial profitability (internal rate of return and net present value) are determined. In the last part, the analysis and assessment of risks that affect costs, execution time and profitability of the projects are carried out, for both programs. Among the risk factors analyzed, the following ones were found to be the most important: country macroeconomic conditions (inflation, gross domestic product, exchange rate and interest rate), deficiencies in projects planning (design, right of way, tolls, permits and traffic estimation) and public contributions in the form of construction works.

Optimización de la agitación de un digestor anaerobio mediante mecánica de fluidos computacional

Debido al gran interés existente en el ahorro y recuperación de energía, y en el deseo de obtener productos que permitan usos beneficiosos del fango procedente de la depuración del agua residual, la digestión anaerobia es el proceso de estabilización de uso más extendido. El tiempo de retención de sólidos es un factor clave en el proceso de digestión anaerobia. En base al tiempo de retención de sólidos, se dimensiona el volumen de los digestores anaerobios para así obtener la reducción de materia orgánica deseada, con la correspondiente producción de biogás. La geometría del digestor y su sistema de agitación deben ser adecuados para alcanzar el tiempo de retención de sólidos de diseño. Los primeros trabajos sobre la agitación de los digestores realizaban únicamente experimentos con trazadores y otros métodos de medición. En otros casos, la mezcla era evaluada mediante la producción de biogás. Estas técnicas tenían el gran hándicap de no conocer lo que sucedía realmente dentro del digestor y sólo daban una idea aproximada de su funcionamiento. Mediante aplicación de la mecánica de fluidos computacional (CFD) es posible conocer con detalle las características del fluido objeto de estudio y, por lo tanto, simular perfectamente el movimiento del fango de un digestor anaerobio. En esta tesis se han simulado mediante CFD diferentes digestores a escala real (unos 2000 m3 de volumen) agitados con bomba/s de recirculación para alcanzar los siguientes objetivos: establecer la influencia de la relación entre el diámetro y la altura, de la pendiente de la solera, del número de bombas y del caudal de recirculación en dichos digestores, definir el campo de velocidades en la masa de fango y realizar un análisis energético y económico. Así, es posible conocer mejor cómo funciona el sistema de agitación de un digestor anaerobio a escala real equipado con bomba/s de recirculación. Los resultados obtenidos muestran que una relación diámetro/altura del digestor por encima de 1 empeora la agitación del mismo y que la pendiente en la solera del digestor favorece que la masa de fango esté mejor mezclada, siendo más determinante la esbeltez del tanque que la pendiente de su solera. No obstante, también es necesario elegir adecuadamente los parámetros de diseño del sistema de agitación, en este caso el caudal de recirculación de fango, para obtener una agitación completa sin apenas zonas muertas. En el caso de un digestor con una geometría inadecuada es posible mejorar su agitación aumentando el número de bombas de recirculación y el caudal de las mismas, pero no se llegará a alcanzar una agitación total de la masa de fango debido a su mal diseño original. Anaerobic digestion is the process for waste water treatment sludge stabilization of more widespread use due to the huge interest in saving and recovering energy and the wish to obtain products that allow beneficial uses for the sludge. The solids retention time is a key factor in the anaerobic digestion. Based on the solids retention time, volume anaerobic digester is sized to obtain the desired reduction in organic matter, with the corresponding production of biogas. The geometry of the digester and the stirring system should be adequate to achieve the design solid retention time. Early works on digesters stirring just performed tracer experiments and other measurement methods. In other cases, mixing was evaluated by biogas production. These techniques had the great handicap of not knowing what really happened inside the digester and they only gave a rough idea of its operation. By application of computational fluid dynamics (CFD), it is possible to know in detail the characteristics of the fluid under study and, therefore, simulate perfectly the sludge movement of an anaerobic digester. Different full-scale digesters (about 2000 m3 of volume) agitated with pump/s recirculation have been simulated by CFD in this thesis to achieve the following objectives: to establish the influence of the relationship between the diameter and height, the slope of the bottom, the number of pumps and the recirculation flow in such digesters, to define the velocity field in the mass of sludge and carry out an energy and economic analysis. Thus, it is possible to understand better how the agitation system of a full-scale anaerobic digester equipped with pump/s recirculation works. The results achieved show that a diameter/height ratio of the digester above 1 worsens its stirring and that the slope of the digester bottom favors that the mass of sludge is better mixed, being more decisive the tank slenderness than the slope of its bottom. However, it is also necessary to select properly the design parameters of the agitation system, in this case the sludge recirculation flow rate, for a complete agitation with little dead zones. In the case of a digester with inadequate geometry, its agitation can be improved by increasing the number of recirculation pumps and flow of them, but it will not reach a full agitation of the mass of sludge because of the poor original design.

O EVANGELHO SEGUNDO DOSTOIÉVSKI UMA ABORDAGEM INTERTEXTUAL DA IMAGEM DE CRISTO NO ROMANCE O IDIOTA

No romance O Idiota, Dostoiévski cria, por meio do príncipe Míchkin, uma personagem com as características do Cristo. Sabe-se que a Bíblia, principalmente o Novo Testamento, acompanhou o escritor desde sua infância até o momento de sua morte. O primeiro capítulo, dedicado ao referencial teórico da pesquisa, lida com o universo da linguagem. Tanto o texto literário quanto a literatura bíblica procedem do mito. Neste sen-tido, religião e literatura se tocam e se aproximam. O segundo capítulo foi escrito na intenção de mostrar como o Cristo e os Evangelhos são temas, motivos e imagens recorrentes na obra de Dostoiévski. A literatura bíblica está presente, com mais ou menos intensidade, em diversas das principais obras do escritor russo e não somente em O Idiota. A hipótese de que Dostoiévski cria um Cristo e um Evangelho por meio de O Idiota é demonstrada na análise do romance, no terceiro capítulo. A tese proposta é: Dostoiévski desenvolve um evangelho literário, por meio de Míchkin, misto de um Cristo russo, ao mesmo tempo divino e humano, mas também idiota e quixotesco. Na dinâmica intertextual entre os Evangelhos bíblicos e O Idiota, entre Cristo e Míchkin, a literatura e o sagrado se revelam, como uma presença divina. Nas cenas e na estruturação do enredo que compõe o romance, Cristo se manifesta nas ações de Míchkin, na luz, na beleza, mas também na tragicidade de uma trajetória deslocada e antinômica. O amor e a compaixão ganham forma e vida na presen-ça do príncipe, vazio de si, servo de todos.

Regulation of F-Actin Binding to Platelet Moesin In Vitro by Both Phosphorylation of Threonine 558 and Polyphosphatidylinositides

Activation of human platelets with thrombin transiently increases phosphorylation at 558threonine of moesin as determined with phosphorylation state-specific antibodies. This specific modification is completely inhibited by the kinase inhibitor staurosporine and maximally promoted by the phosphatase inhibitor calyculin A, making it possible to purify the two forms of moesin to homogeneity. Blot overlay assays with F-actin probes labeled with either [32P]ATP or 125I show that only phosphorylated moesin interacts with F-actin in total platelet lysates, in moesin antibody immunoprecipitates, and when purified. In the absence of detergents, both forms of the isolated protein are aggregated. Phosphorylated, purified moesin co-sediments with α- or β/γ-actin filaments in cationic, but not in anionic, nonionic, or amphoteric detergents. The interaction affinity is high (Kd, ∼1.5 nM), and the maximal moesin:actin stoichiometry is 1:1. This interaction is also observed in platelets extracted with cationic but not with nonionic detergents. In 0.1% Triton X-100, F-actin interacts with phosphorylated moesin only in the presence of polyphosphatidylinositides. Thus, both polyphosphatidylinositides and phosphorylation can activate moesin’s high-affinity F-actin binding site in vitro. Dual regulation by both mechanisms may be important for proper cellular control of moesin-mediated linkages between the actin cytoskeleton and the plasma membrane.

Dynamics of Centromeres during Metaphase–Anaphase Transition in Fission Yeast: Dis1 Is Implicated in Force Balance in Metaphase Bipolar Spindle

In higher eukaryotic cells, the spindle forms along with chromosome condensation in mitotic prophase. In metaphase, chromosomes are aligned on the spindle with sister kinetochores facing toward the opposite poles. In anaphase A, sister chromatids separate from each other without spindle extension, whereas spindle elongation takes place during anaphase B. We have critically examined whether such mitotic stages also occur in a lower eukaryote, Schizosaccharomyces pombe. Using the green fluorescent protein tagging technique, early mitotic to late anaphase events were observed in living fission yeast cells. S. pombe has three phases in spindle dynamics, spindle formation (phase 1), constant spindle length (phase 2), and spindle extension (phase 3). Sister centromere separation (anaphase A) rapidly occurred at the end of phase 2. The centromere showed dynamic movements throughout phase 2 as it moved back and forth and was transiently split in two before its separation, suggesting that the centromere was positioned in a bioriented manner toward the poles at metaphase. Microtubule-associating Dis1 was required for the occurrence of constant spindle length and centromere movement in phase 2. Normal transition from phase 2 to 3 needed DNA topoisomerase II and Cut1 but not Cut14. The duration of each phase was highly dependent on temperature.

Role of Dynactin in Endocytic Traffic: Effects of Dynamitin Overexpression and Colocalization with CLIP-170

The flow of material from peripheral, early endosomes to late endosomes requires microtubules and is thought to be facilitated by the minus end-directed motor cytoplasmic dynein and its activator dynactin. The microtubule-binding protein CLIP-170 may also play a role by providing an early link to endosomes. Here, we show that perturbation of dynactin function in vivo affects endosome dynamics and trafficking. Endosome movement, which is normally bidirectional, is completely inhibited. Receptor-mediated uptake and recycling occur normally, but cells are less susceptible to infection by enveloped viruses that require delivery to late endosomes, and they show reduced accumulation of lysosomally targeted probes. Dynactin colocalizes at microtubule plus ends with CLIP-170 in a way that depends on CLIP-170’s putative cargo-binding domain. Overexpression studies using p150Glued, the microtubule-binding subunit of dynactin, and mutant and wild-type forms of CLIP-170 indicate that CLIP-170 recruits dynactin to microtubule ends. These data suggest a new model for the formation of motile complexes of endosomes and microtubules early in the endocytic pathway.

Staphylococcal protein A: Unfolding pathways, unfolded states, and differences between the B and E domains

We present multiple native and denaturation simulations of the B and E domains of the three-helix bundle protein A, totaling 60 ns. The C-terminal helix (H3) consistently denatures later than either of the other two helices and contains residual helical structure in the denatured state. These results are consistent with experiments suggesting that the isolated H3 fragment is more stable than H1 and H2 and that H3 forms early in folding. Interestingly, the denatured state of the B domain is much more compact than that of the E domain. This sequence-dependent effect on the dimensions of the denatured state and the lack of correlation with structure suggest that the radius of gyration can be a misleading reaction coordinate for unfolding/folding. Various unfolding and refolding events are observed in the denaturation simulations. In some cases, the transitions are facilitated through interactions with other portions of the protein—contact-assisted helix formation. In the native simulations, the E domain is very stable: after 6 ns, the Cα root-mean-square deviation from the starting structure is less than 1.4 Å. In contrast, the native state of the B domain deviates more and its inter-helical angles fluctuate. In apparent contrast, we note that the B domain is thermodynamically more stable than the E domain. The simulations suggest that the increased stability of the B domain may be due to heightened mobility, and therefore entropy, in the native state and decreased mobility/entropy in the more compact denatured state.

Randomised controlled trial comparing effectiveness and acceptability of an early discharge, hospital at home scheme with acute hospital care

Objective: To compare effectiveness and acceptability of early discharge to a hospital at home scheme with that of routine discharge from acute hospital.

The challenge of contracting for technological information

Contracting to provide technological information (TI) is a significant challenge. TI is an unusual commodity in five ways. (i) TI is difficult to count and value; conventional indicators, such as patents and citations, hardly indicate value. TI is often sold at different prices to different parties. (ii) To value TI, it may be necessary to “give away the secret.” This danger, despite nondisclosure agreements, inhibits efforts to market TI. (iii) To prove its value, TI is often bundled into complete products, such as a computer chip or pharmaceutical product. Efficient exchange, by contrast, would involve merely the raw information. (iv) Sellers’ superior knowledge about TI’s value make buyers wary of overpaying. (v) Inefficient contracts are often designed to secure rents from TI. For example, licensing agreements charge more than marginal cost. These contracting difficulties affect the way TI is produced, encouraging self-reliance. This should be an advantage to large firms. However, small research and development firms spend more per employee than large firms, and nonprofit universities are major producers. Networks of organizational relationships, particularly between universities and industry, are critical in transmitting TI. Implicit barter—money for guidance—is common. Property rights for TI are hard to establish. Patents, quite suitable for better mousetraps, are inadequate for an era when we design better mice. Much TI is not patented, and what is patented sets fuzzy demarcations. New organizational forms are a promising approach to contracting difficulties for TI. Webs of relationships, formal and informal, involving universities, start-up firms, corporate giants, and venture capitalists play a major role in facilitating the production and spread of TI.

The cranium of Parapithecus grangeri, an Egyptian Oligocene anthropoidean primate

A nearly complete skull of Parapithecus grangeri from the early Oligocene of Egypt is described. The specimen is relatively undistorted and is undoubtedly the most complete higher primate skull yet found in the African Oligocene, which also makes it the most complete Oligocene primate cranium worldwide. Belonging in superfamily Parapithecoidea, a group regarded by some as the sister group to all other Anthropoidea, this skull reveals important information about the radiation of stem anthropoideans. This cranium is about 15% larger than size estimates based on a fragmentary cranium of its contemporary and close relative Apidium phiomense. It is about the same size as that of the gray gentle lemur, Hapalemur griseus, or of platyrrhines such as the owl monkey, Aotus trivirgatus, or the titi monkey, Callicebus torquatus. Comparatively small orbits and size differences in jaws and teeth show it was both diurnal and dimorphic. This is the only specimen of the species that shows (from sockets) that there were four small upper incisors. Several mandibular specimens of the species establish that there were no permanent lower incisors and that the symphysis was fused. Like other early anthropoideans this species possessed a lower encephalization quotient and less-developed orbital frontality than later anthropoideans. There is full postorbital closure and fusion of the metopic suture, and the ectotympanic forms a rim to the auditory aperture. A probable frontal/alisphenoid contact is a potentially derived resemblance to Catarrhini. A proposed separate genus for the species P. grangeri is not sustained.

Rab4 and cellubrevin define different early endosome populations on the pathway of transferrin receptor recycling.

During receptor mediated endocytosis, at least a fraction of recycling cargo typically accumulates in a pericentriolar cluster of tubules and vesicles. However, it is not clear if these endosomal structures are biochemically distinct from the early endosomes from which they are derived. To better characterize this pericentriolar endosome population, we determined the distribution of two endogenous proteins known to be functionally involved in receptor recycling [Rab4, cellubrevin (Cbvn)] relative to the distribution of a recycling ligand [transferrin (Tfn)] as it traversed the endocytic pathway. Shortly after internalization, Tfn entered a population of early endosomes that contained both Rab4 and Cbvn, demonstrated by triple label immunofluorescence confocal microscopy. Tfn then accumulated in the pericentriolar cluster of recycling vesicles (RVs). However, although these pericentriolar endosomes contained Cbvn, they were strikingly depleted of Rab4. The ability of internalized Tfn to reach the Rab4-negative population was not blocked by nocodazole, although the characteristic pericentriolar location of the population was not maintained in the absence of microtubules. Similarly, Rab4-positive and -negative populations remained distinct in cells treated with brefeldin A, with only Rab4-positive elements exhibiting the extended tubular morphology induced by the drug. Thus, at least with respect to Rab4 distribution, the pathway of Tfn receptor recycling consists of at least two biochemically and functionally distinct populations of endosomes, a Rab4-positive population of early endosomes to which incoming Tfn is initially delivered and a Rab4-negative population of recycling vesicles that transiently accumulates Tfn on its route back to the plasma membrane.