Experimental demonstration of an OpenFlow based software-defined optical network employing packet, fixed and flexible DWDM grid technologies on an international multi-domain testbed.

Software defined networking (SDN) and flexible grid optical transport technology are two key technologies that allow network operators to customize their infrastructure based on application requirements and therefore minimizing the extra capital and operational costs required for hosting new applications. In this paper, for the first time we report on design, implementation & demonstration of a novel OpenFlow based SDN unified control plane allowing seamless operation across heterogeneous state-of-the-art optical and packet transport domains. We verify and experimentally evaluate OpenFlow protocol extensions for flexible DWDM grid transport technology along with its integration with fixed DWDM grid and layer-2 packet switching.

Inter-layer traffic engineering with hierarchical-PCE in MPLS-TP over wavelength switched optical networks.

We present the implementation and validation of an Inter-layer Traffic Engineering (TE) architecture based on a hierarchical path computation element (PCE), where the parent PCE is notified of established optical layer Label Switched Paths that induce packet traffic engineering (TE) links, thus not requiring full topology visibility. We summarize the architecture, the control plane extensions and its experimental evaluation in a control plane testbed.

Genetic reporter system for oncogenic Igh-Myc translocations in mice.

The Myc-deregulating chromosomal T(12;15)(Igh-Myc) translocation, the hallmark mutation of inflammation- and interleukin 6-dependent mouse plasmacytoma (PCT), is the premier model of cancer-associated chromosomal translocations because it is the only translocation in mice that occurs spontaneously (B lymphocyte lineage) and with predictably high incidence (approximately 85% of PCT), and has a direct counterpart in humans: Burkitt lymphoma t(8;14)(q24;q32) translocation. Here, we report on the development of a genetic system for the detection of T(12;15)(Igh-Myc) translocations in plasma cells of a mouse strain in which an enhanced green fluorescent protein (GFP)-encoding reporter gene has been targeted to Myc. Four of the PCTs that developed in the newly generated translocation reporter mice, designated iGFP(5'Myc), expressed GFP consequent to naturally occurring T(12;15) translocation. GFP expression did not interfere with tumor development or the deregulation of Myc on derivative 12 of translocation, der (12), because the reporter gene was allocated to the reciprocal product of translocation, der (15). Although the described reporter gene approach requires refinement before T(12;15) translocations can be quantitatively detected in vivo, including in B lymphocyte lineage cells that have not yet completed malignant transformation, our findings provide proof of principle that reporter gene tagging of oncogenes in gene-targeted mice can be used to elucidate unresolved questions on the occurrence, distribution and trafficking of cells that have acquired cancer-causing chromosomal translocations of great relevance for humans.

Contribution of receptor editing to the antibody repertoire.

Receptor editing, clonal deletion, and anergy are the mechanisms by which B cells maintain tolerance to self antigens. To determine the extent to which receptor editing shapes the normal antibody repertoire, we generated an immunoglobulin kappa polymorphism that facilitates the detection of editing of immunoglobulin light chains in vivo. We found that B cells are targeted for editing during a 2-hour delay in development at the pre-BII cell stage, and that about 25% of all antibody molecules are produced by gene replacement. These results suggest that receptor editing represents a major force in shaping the antibody repertoire.

Antibody regulation of B cell development.

Antibodies on the surface of B lymphocytes trigger adaptive immune responses and control a series of antigen-independent checkpoints during B cell development. These physiologic processes are regulated by a complex of membrane immunoglobulin and two signal transducing proteins known as Ig alpha and Ig beta. Here we focus on the role of antibodies in governing the maturation of B cells from early antigen-independent through the final antigen-dependent stages.

[Analysis of preventive behavior for accidents among adolescents in our setting]. / Aproximación a los hábitos de prevención de accidentes del adolescente en nuestro medio.

OBJECTIVE: Our objective was to analyze the preventative behavior for accidents in adolescents in our environment. PATIENTS AND METHODS: The accident preventative behavior of adolescents was studied by means of an anonymous questionnaire distributed to 268 students in a secondary school. A descriptive study regarding hazardous agents was conducted. We studied the relationships between the age, sex, number of siblings and the educational and economic level of the parents. RESULTS: Our study identifies deficiencies in the prevention of burns, traffic accidents and alcohol consumption. We detected the influence of age, sex, number of siblings and sociocultural level of the parents. CONCLUSIONS: The prevalence of a high risk attitude in adolescents suggests that appropriate counseling by pediatricians and appropriate prevention programs should be implemented.

Xenopus Smad7 inhibits both the activin and BMP pathways and acts as a neural inducer.

Smads are proteins that transduce signals on behalf of members of the TGF beta superfamily of growth factors. Recently, inhibitory Smads, Smad6, Smad7, and Dad, were isolated from human, mouse, and fly. These anti-Smads were shown to inhibit TGF beta signaling by stably associating to TGF beta type I receptors or, as it was shown for Smad6, by binding to receptor-activated Smad1. We report the cloning, distribution, and embryological activity of the Xenopus Smad7 (XSmad7). We report that XSmad7 inhibits signaling from the activin and BMP pathways in animal explants although at different thresholds. When expressed in the embryo, low concentrations of XSmad7 dorsalize the ventral mesoderm, thus inducing a secondary axis. At higher concentrations however, XSmad7 inhibits both mesoderm induction and primary axis specification. In addition, we show that XSmad7 acts as a direct neural inducer both in the context of ectodermal explants and in vivo. We discuss the implications of these findings in the biochemical context of the activin and BMP pathways as well as their implications in mesodermal, neural, and axis specification.

Ku80 is required for immunoglobulin isotype switching.

Isotype switching is the DNA recombination mechanism by which antibody genes diversify immunoglobulin effector functions. In contrast to V(D)J recombination, which is mediated by RAG1, RAG2 and DNA double-stranded break (DSB) repair proteins, little is known about the mechanism of switching. We have investigated the role of DNA DSB repair in switch recombination in mice that are unable to repair DSBs due to a deficiency in Ku80 (Ku80(-/-)). B-cell development is arrested at the pro-B cell stage in Ku80(-/-) mice because of abnormalities in V(D)J recombination, and there are no mature B cells. To reconstitute the B-cell compartment in Ku80(-/-) mice, pre-rearranged VB1-8 DJH2 (mu i) and V3-83JK2 (kappa i) genes were introduced into the Ku80(-/-) background (Ku80(-/-)mu i/+kappa i/+). Ku80(-/-)mu i/+ kappai/+ mice develop mature mIgM+ B cells that respond normally to lipopolysaccharide (LPS) or LPS plus interleukin-4 (IL-4) by producing specific germline Ig constant region transcripts and by forming switch region-specific DSBs. However, Ku80(-/-)mu i/+kappa i/+ B cells are unable to produce immunoglobulins of secondary isotypes, and fail to complete switch recombination. Thus, Ku80 is essential for switch recombination in vivo, suggesting a significant overlap between the molecular machinery that mediates DNA DSB repair, V(D)J recombination and isotype switching.

V(D)J recombination in mature B cells: a mechanism for altering antibody responses.

The clonal selection theory states that B lymphocytes producing high-affinity immunoglobulins are selected from a pool of cells undergoing antibody gene mutation. Somatic hypermutation is a well-documented mechanism for achieving diversification of immune responses in mature B cells. Antibody genes were also found to be modified in such cells in germinal centers by recombination of the variable (V), diversity (D), and joining (J) segments. The ability to alter immunoglobulin expression by V(D)J recombination in the selective environment of the germinal center may be an additional mechanism for inactivation or diversification of immune responses.