New insights into dendritic cell biology and histiocytosis through a transgenic tumor model

SUMMARY The effective development of an immune response depends on the careful interplay and the regulation between innate and adaptive immunity. As the dendritic cells (DCs) are equipped with many receptors, such as Toll-like receptors, which can detect the presence of infection by recognizing different component of bacteria, fungi and even viruses, they are the among the first cells to respond to the infection. Upon pathogen challenge, the DCs interpret the innate system activation as a maturation signal, resulting in the migration of the DCS to a draining lymph node site. There, activated DCs present efficiently antigens to naïve T cells, which are in turn activated and initiate adaptive immunity. Therefore, DCs are the main connectors between innate and adaptive immune systems. In addition to be the most efficient antigen- presenting cells, DCs play a central role in the regulation of immune responses and immune tolerance. Despite extensive research, many aspects related to DC biology are still unsolved and/or controversial. The low frequency of DCs in vivo often hamper study of DC biology and in vitro-derived DCs are not suited to address certain questions, such as the development of DC. We sought of transforming in vivo the DCs through the specific expression of an oncogene, in order to obtain unlimited numbers of these cells. To achieve this goal, transgenic mouse lines expressing the SV40 Large T oncogene under the control of the CD1 1 c promoter were generated. These transgenic mice are healthy until the age of three to four months without alterations in the DC biology. Thereafter transgenic mice develop a fatal disease that shows features of a human pathology, named histiocytosis, involving DCs. We demonstrate that the disease development in the transgenic mice correlates with a massive accumulation of transformed DCs in the affected organs. Importantly, transformed DCs are immature and fully conserve their capacity to mature in antigen presenting cells. We observe hyperproliferation of transformed DCs only in the sick transgenic mice. Surprisingly, transformed DCs do not proliferate in vitro, but transfer of the transformed DCs into immunodeficient or tolerant host leads to tumor formation. Altoghether, the transgenic mouse lines we have generated represent a valuable tumor model for human histiocytosis, and provide excellent tools to study DC biology. RESUME Le développement d'une réponse immunitaire efficace dépend d'une minutieuse interaction et régulation entre l'immunité innée et adaptative. Comme les cellules dendritiques (DCs) sont équipées de nombreux récepteurs, tels que les récepteurs Toll-like, qui peuvent détecter la présence d'une infection en reconnaissant différents composants bactériens, issus de champignons ou même viraux, elles sont parmi les premières cellules à répondre à l'infection. Suite à la stimulation induite par le pathogène, les DCs interprètent l'activation du système immunitaire inné comme un signal de maturation, résultant dans la migration des DCs vers le ganglion drainant le site d'infection. Là, les DCs actives présentent efficacement des antigènes aux cellules T, qui sont à leur tour activées et initient les systèmes d'immunité adaptative. Ainsi, les DCs forment le lien principal entre les réponses immunitaires innées et adaptatives. En plus d'être les cellules présentatrices d'antigènes les plus efficaces, les DCs jouent un rôle central dans la régulation du système immunitaire et dans le phénomène de tolérance. Malgré des recherches intensives, de nombreux aspects liés à la biologie des DCs sont encore irrésolus et/ou controversés. La faible fréquence des DCs in vivo gêne souvent l'étude de la biologie de ces cellules et les DCs dérivées in vitro ne sont pas adéquates pour adresser certaines questions, telles que le développement des DCs. Afin d'obtenir des quantités illimitées de DCs, nous avons songé à transformer in vivo les DC grâce à l'expression spécifique d'un oncogène. Afin d'atteindre ce but, nous avons généré des lignées de souris transgéniques qui expriment l'oncogène SV40 Large T sous le contrôle du promoter CD1 le. Ces souris transgéniques sont saines jusqu'à l'âge de trois à quatre mois et ne présentent pas d'altération dans la biologie des DCs. Ensuite, les souris transgéniques développent une maladie présentant les traits caractéristiques d'une pathologie humaine nommée histiocytose, qui implique les DCs. Nous montrons que le développement de cette maladie corrèle avec une accumulation massive des DCs transformées dans les organes touchés. De plus, les DCs transformées sont immatures et conservent leur capacité à différencier en cellules présentatrices d'antigène. Nous observons une hyper-prolifération des DCs transformées seulement dans les souris transgéniques malades. Etonnament, les DC transformées ne prolifèrent pas in vitro, par contre, le transfert des DCs transformées dans des hôtes immuno-déficients ou tolérant conduit à la formation de tumeurs. Globalement, les lignées de souris transgéniques que nous avons générées représentent un modèle valide pour l'histiocytose humaine, et de plus, offrent d'excellents outils pour étudier la biologie des DCs.

Estudi de la connectivitat de l’illa de Menorca

Com a objectius generals: Analitzar la connectivitat ecològica a nivell paisatgístic de Menorca a partir d’una diagnosi que permeti determinar els espais d’interès connector i els punts crítics. Desenvolupar un pla d’acció amb propostes per millorar la connectivitat actual. Objectius específics: Aplicar una metodologia capaç de parametritzar els diferents conceptes relacionats amb la connectivitat ecològica i que sigui aplicable en la planificació territorial. Identificar els espais i elements d’interès per a la correcta circulació dels fluxos ecològics (flora i fauna) i socials, clau pel manteniment del paisatge i de la connectivitat funcional, definint connectors fluvials, espais naturals protegits, matrius (forestal, agrícola i urbana), unitats paisatgístiques, patrimoni arquitectònic i arqueològic, senders i camins ramaders, etc. que permetin determinar Espais o Elements d’Interès Estratègic per a la Connectivitat (EIEC). Definir els punts clau per a la connectivitat i identificar els punts crítics, on les barreres i els elements de fragmentació (carreteres, torrents, sòl urbà, etc.) intercepten els EIEC

Al cap i a la fi, en fi i en definitiva: tres marcadors discursius vehiculadors de la reformulació conclusiva en català

En aquest article analitzem el funcionament de tres marcadors discursius del català en textos escrits que comparteixen el fet que entre els seus components gramaticals hi ha la paraula fi: al cap i a la fi, en fi i en definitiva, per tal de ferneun estudi comparatiu.Tot i que el grau de fixació d’aquestes unitats és elevat —es caracteritzen per la invariablilitat—, la presència del mot fi com a un dels seus elements constitutius influeix decididament en el funcionament semanticopragmàctic d’aquestespeces lèxiques, de manera que en aquests marcadors s’evidencia clarament una interrelació entre la forma i la funció. Tots tres marcadors esdevenen vehiculadors de la reformulació conclusiva en català.

Del discurso a la lexicografía: propuesta de aplicación para los conectores reformulativos

This paper aims at defending the necessity of creating applicationsfrom studies on discourse, so that applied linguistics becomes auseful tool for the society. This work explains briefly what reformulation connectors are and it shows the electronic prototype (than can be consulted by internet) of a tool designed to make the work of lexicographerseasy concerning the entrance of connectors in the dictionaries (ALCOR), by making emphasis on the theoretical base on which it is sustained and on the decisions of application that have been taken into account.

Book vs. Fair Value Accounting in Banking, and Intertemporal Smoothing

The aim of this paper is to examine the pros and cons of book and fair value accounting from the perspective of the theory of banking. We consider the implications of the two accounting methods in an overlapping generations environment. As observed by Allen and Gale(1997), in an overlapping generation model, banks have a role as intergenerational connectors as they allow for intertemporal smoothing. Our main result is that when dividends depend on profits, book value ex ante dominates fair value, as it provides better intertemporal smoothing. This is in contrast with the standard view that states that, fair value yields a better allocation as it reflects the real opportunity cost of assets. Banking regulation play an important role by providing the right incentives for banks to smooth intertemporal consumption whereas market discipline improves intratemporal efficiency.

Les Vies verdes del Vallès

En un moment en que Catalunya i, sobretot, la regió metropolitana de Barcelona, experimenta un procés d'ocupació del territori sense precedents, es especialment important avançar en l'estudi dels possibles connectors existents, el seu reconeixement i la seva delimitació en el planejament territorial, El 13 de juliol de 2004 es va signar i fer públic el Manifest de Sant Celoni pel reconeixement de les vies verdes del Vallès. En aquest manifest es demana, entre altres mesures, el reconeixement i la delimitació en el planejament territorial de 7 grans vies verdes: Obac-Olorda, Sant Llorenç-Collserola, Farell-Marina, Gallifa-Gallecs, Tagamanent-Cellecs, Calma-Corredor, Montseny-Montnegre. Totes aquestes vies exerceixen funcions de connexió ecològica i paisatgística entre les serralades Litoral i Prelitoral i, juntament amb altres espais menys urbanitzats que hi ha al peu de la serralada Prelitoral, integren el sistema d'espais oberts del Vallès. Aquesta ponència presenta, en primer lloc, el marc conceptual on s'inscriu el concepte via verda. En segon lloc, explica els principals antecedents en relació amb les vies verdes del Vallès que apareixen en el Manifest de Sant Celoni, i, finalment l’encaix de les vies verdes del Vallès en el planejament territorial de la regió metropolitana de Barcelona, així com les principals línies estratègiques que es podrien seguir per convertir-les en una realitat

Book vs. fair value accounting in banking and intertemporal smoothing

The aim of this paper is to examine the pros and cons of book and fair value accounting from the perspective of the theory of banking. We consider the implications of the two accounting methods in an overlapping generations environment. As observed by Allen and Gale(1997), in an overlapping generation model, banks have a role as intergenerational connectors as they allow for intertemporal smoothing. Our main result is that when dividends depend on profits, book value ex ante dominates fair value, as it provides better intertemporal smoothing. This is in contrast with the standard view that states that, fair value yields a better allocation as it reflects the real opportunity cost of assets. Banking regulation play an important role by providing the right incentives for banks to smooth intertemporal consumption whereas market discipline improves intratemporal efficiency.

Animal Tissue Response To Mid-Term Electronic Modular Artificial Sphincter Implantation

Introduction and objectives: The AMS 800TM is considered the gold standard for sphincter replacement. However, the one-ring design can erode the urethra and lead to severe complications. A mechanism that could alternatively compress successive segments of the urethra would limit such deleterious outcome. We report 12 weeks animal urethral tissue analysis following implantation of a new modular artificial sphincter. METHODS: The device is composed by three parts: the contractile unit, two rings and an integrated microprocessor. The contractile unit is made of Nitinol fibers. The rings are placed around the urethra to control the flow of urine by squeezing the urethra. They work in a sequential alternative mode and are controlled by a microprocessor connected to an external computer. The computer can reveal specific failure of device components. The device was impkanted in eight male sheep. The rings were positioned around the urethra and the control unit was placed 5cm away. The device was working twenty hours per day; it was open 10min. per hour to allow urination. The animals were sacrificed after 12 weeks. The urethra and the tissues surrounding the control unit were macroscopically and microscopically examined. Two transversal sections crossing the sphincter and two transversal sections crossing the urethra alone were obtained and stained with modified Paragon after resin embedding. Urethra was also embedded in paraffin. The first section was stained with safranin-hematoxylin-eosin, the second section was stained with Masson's Trichrome and the remaining eight sections were available for immunolabelling of the macrophages.Results: The chronic study went uneventful. No clinical infection or pain was observed. The computer registered no specific failure in ring function, Nitinol wires and tube connectors. At explantation, except for a slight grade of lymphocytes in two out of eight specimens, no urethral stricture or atrophy could be observed. Immunohistochemistry confirmed the absence of macrophages. Tissue structure and organization of the urethra with and without artificial sphincter were similar. No migration of the device was observed.Conclusions: The study clearly showed no tissue damage or inflammation of the urethra. Electronic design, preservation of urethral vascularisation and adjustability after implantation are the key ideas to improve the actual AUS. Further studies will be carried out to evaluate this potential.

Investigation of Two Bridge Alternatives for Low Volume Roads, Volume 1 of 2 Concept 1: Precast Steel Beam Units, HR-382, 1997

Recent reports have indicated that 23.5% of the nation's highway bridges are structurally deficient and 17.7% are functionally obsolete. A significant number of these bridges are on the Iowa secondary road system where over 86% of the rural bridge management responsibilities are assigned to the counties. Some of the bridges can be strengthened or otherwise rehabilitated, but many more are in need of immediate replacement. In a recent investigation (HR-365 "Evaluation of Bridge Replacement Alternatives for the County Bridge System") several types of replacement bridges that are currently being used on low volume roads were identified. It was also determined that a large number of counties (69%) have the ability and are interested in utilizing their own forces to design and construct short span bridges. In reviewing the results from HR-365, the research team developed one "new" bridge replacement concept and a modification of a replacement system currently being used. Both of these bridge replacement alternatives were investigated in this study, the results of which are presented in two volumes. This volume (Volume 1) presents the results of Concept 1 - Steel Beam Precast Units. Concept 2 - Modification of the Beam-in-Slab Bridge is presented in Volume 2. Concept 1, involves the fabrication of precast units (two steel beams connected by a concrete slab) by county work forces. Deck thickness is limited so that the units can be fabricated at one site and then transported to the bridge site where they are connected and the remaining portion of the deck placed. Since Concept 1 bridge is primarily intended for use on low-volume roads, the precast units can be constructed with new or used beams. In the experimental part of the investigation, there were three types of static load tests: small scale connector tests, "handling strength" tests, and service and overload tests of a model bridge. Three finite element models for analyzing the bridge in various states of construction were also developed. Small scale connector tests were completed to determine the best method of connecting the precast double-T (PCDT) units. "Handling strength" tests on an individual PCDT unit were performed to determine the strength and behavior of the precast unit in this configuration. The majority of the testing was completed on the model bridge [L=9,750 mm (32 ft), W=6,400 mm (21 ft)] which was fabricated using the precast units developed. Some of the variables investigated in the model bridge tests were number of connectors required to connect adjacent precast units, contribution of diaphragms to load distribution, influence of position of diaphragms on bridge strength and load distribution, and effect of cast-in-place portion of deck on load distribution. In addition to the service load tests, the bridge was also subjected to overload conditions. Using the finite element models developed, one can predict the behavior and strength of bridges similar to the laboratory model as well as design them. Concept 1 has successfully passed all laboratory testing; the next step is to field test it.

Strengthening of Existing Single Span Steel Beam and Concrete Deck Bridges, HR-238, Part 1, 1983

The Phase I research, Iowa Department of Transportation (IDOT) Project HR-214, "Feasibility Study of Strengthening Existing Single Span Steel Beam Concrete Deck Bridges," verified that post-tensioning can be used to provide strengthening of the composite bridges under investigation. Phase II research, reported here, involved the strengthening of two full-scale prototype bridges - one a prototype of the model bridge tested during Phase I and the other larger and skewed. In addition to the field work, Phase II also involved a considerable amount of laboratory work. A literature search revealed that only minimal data existed on the angle-plus-bar shear connectors. Thus, several specimens utilizing angle-plus-bar, as well as channels, studs and high strength bolts as shear connectors were fabricated and tested. To obtain additional shear connector information, the bridge model of Phase I was sawed into four composite concrete slab and steel beam specimens. Two of the resulting specimens were tested with the original shear connection, while the other two specimens had additional shear connectors added before testing. Although orthotropic plate theory was shown in Phase I to predict vertical load distribution in bridge decks and to predict approximate distribution of post-tensioning for right-angle bridges, it was questioned whether the theory could also be used on skewed bridges. Thus, a small plexiglas model was constructed and used in vertical load distribution tests and post-tensioning force distribution tests for verification of the theory. Conclusions of this research are as follows: (1) The capacity of existing shear connectors must be checked as part of a bridge strengthening program. Determination of the concrete deck strength in advance of bridge strengthening is also recommended. (2) The ultimate capacity of angle-plus-bar shear connectors can be computed on the basis of a modified AASHTO channel connector formula and an angle-to-beam weld capacity check. (3) Existing shear connector capacity can be augmented by means of double-nut high strength bolt connectors. (4) Post-tensioning did not significantly affect truck load distribution for right angle or skewed bridges. (5) Approximate post-tensioning and truck load distribution for actual bridges can be predicted by orthotropic plate theory for vertical load; however, the agreement between actual distribution and theoretical distribution is not as close as that measured for the laboratory model in Phase I. (6) The right angle bridge exhibited considerable end restraint at what would be assumed to be simple support. The construction details at bridge abutments seem to be the reason for the restraint. (7) The skewed bridge exhibited more end restraint than the right angle bridge. Both skew effects and construction details at the abutments accounted for the restraint. (8) End restraint in the right angle and skewed bridges reduced tension strains in the steel bridge beams due to truck loading, but also reduced the compression strains caused by post-tensioning.

Totes les vacances són diferents. És més beneficiós fer el descans anual sempre a la mateixa època i recordar-lo

Les vacances, el descans mensual, ens influeixen des del punt de vista psicològic i fisiològic, en vista de dos treballs científics recents que analitzen minuciosament els seus efectes.

Falten vocacions científiques. La davallada d'estudiants contrasta amb la capacitat investigadora a Catalunya.

El desenvolupamnet cientifico-tècnic és una de les àrees amb un valor afegit més alt, per la cual cosa és crucial destinar-hi recursos econòmics i capital humà.

Apologia del pensament. Tant en ciència com en educació és imprescindible tenir temps per pensar

Quan hi ha canvi de govern és habitual trobar cartes obertes en què l'autor expressa la seva opinió amb l'esperança que les seves idees puguin contribuir a la nova acció de govern. Aquí pretenc fer una raonada apologia del pensament

La importància de les vacunes. Un conflicte entre llibertat individual i protecció social

Els grups contraris a les vacunes guanyen adeptes, i la seva actitud comença a ser una amenaça per a la salut publica, atès que contribueix que hi hagi rebrots de malalties que ja s'havien eradicat a Catalunya.

La FP ha de dur a la universitat? La formació professional compleix uns objectius diferents al batxillerat.

Alumnes de formació professional copen els graus dedicats a formar el professorat. La irrupcio d'estudiants de FP deixa fora de la universitat alguns batxillers.