Membranous glomerulonephritis in the mouse

Membranous glomerulonephritis in the mouse. Glomerulonephritis was induced in C57.B110 mice by a single injection of rabbit IgG against homologous, pronase-digested, renal tubular antigens. The heterologous phase was characterized by a transient increase of glomerular permeability with fixation of rabbit IgG to the capillary walls, in a linear or fine-granular pattern, and to the brush borders of the proximal tubuli. The autologous phase was marked by the immune response to the injected protein, during which subepithelial immune deposits, consisting of mouse IgG1, rabbit IgG, and mouse C3 developed. Small amounts were still present at 1 year after the injection of antiserum. The antibody response of the mice correlated with the development and resolution of the deposits. None of the mice developed a nephrotic syndrome. Control mice treated with normal rabbit IgG did not show immune deposits in their kidneys at any stage despite a comparable antibody response to rabbit IgG. Immunoelectronmicroscopy showed that the rabbit antibodies fixed directly to an antigen in the cell membrane of the glomerular visceral epithelium. It seems, therefore, likely that in situ formation of subepithelial immune complexes occurred in the autologous phase by fixation of mouse immunoglobulins to rabbit IgG already present in the glomerular wall.Glomérulonéphrite extra-membraneuse chez la souris. Une glomérulonéphrite a été induite chez des souris C57.B110 par une injection unique d'IgG de lapin contre des antigènes tubulaires rénaux homologues, digérés par de la pronase. La phase hétérologue était caractérisée par une augmentation transitoire de la perméabilité glomérulaire avec fixation d'IgG de lapin aux parois capillaires, d'une façon linéaire ou finement granuleuse, et aux bordures en brosse des tubules proximaux. La phase autologue était marquée par la réponse immune à la protéine injectée, pendant laquelle des dépôts immuns sous-épithéliaux, consistant en de l'IgG1 de souris, de l'IgG de lapin et du C3 de souris, se sont développés. Il en restait encore de faibles quantités 1 an après l'injection de l'antisérum. La réponse anticorps des souris était corrélée avec le développement et la disparition des dépôts. Aucune des souris n'a développé de syndrome néphrotique. Les souris contrôles traitées avec de l'IgG de lapin normal n'ont pas eu de dépôts immuns dans le rein à aucun stade, malgré une réponse anticorps aux IgG de lapin comparable. La microscopie immuno-électronique a montré que les anticorps de lapin se fixaient directement à un antigène situé sur la membrane des cellules de l'épithélium viscéral glomérulaire. Il semble donc probable que la formation in situ de complexes immuns sous-épithéliaux est survenue à la phase autologue par fixation d'immunoglobulines de souris à de l'IgG de lapin déjà présente dans la paroi glomérulaire

A High Luminosity e+e- Collider to study the Higgs Boson

A strong candidate for the Standard Model Scalar boson, H(126), has been discovered by the Large Hadron Collider (LHC) experiments. In order to study this fundamental particle with unprecedented precision, and to perform precision tests of the closure of the Standard Model, we investigate the possibilities offered by An e+e- storage ring collider. We use a design inspired by the B-factories, taking into account the performance achieved at LEP2, and imposing a synchrotron radiation power limit of 100 MW. At the most relevant centre-of-mass energy of 240 GeV, near-constant luminosities of 10^34 cm^{-2}s^{-1} are possible in up to four collision points for a ring of 27km circumference. The achievable luminosity increases with the bending radius, and for 80km circumference, a luminosity of 5 10^34 cm^{-2}s^{-1} in four collision points appears feasible. Beamstrahlung becomes relevant at these high luminosities, leading to a design requirement of large momentum acceptance both in the accelerating system and in the optics. The larger machine could reach the top quark threshold, would yield luminosities per interaction point of 10^36 cm^{-2}s^{-1} at the Z pole (91 GeV) and 2 10^35 cm^{-2}s^{-1} at the W pair production threshold (80 GeV per beam). The energy spread is reduced in the larger ring with respect to what is was at LEP, giving confidence that beam polarization for energy calibration purposes should be available up to the W pair threshold. The capabilities in term of physics performance are outlined.Comment: Submitted to the European Strategy Preparatory Group 01-04-2013 new version as re-submitted to PRSTA

High-throughput Proteomics Identifies THEMIS2 as Independent Biomarker of Treatment-free Survival in Untreated CLL

It remains challenging in chronic lymphocytic leukemia (CLL) to distinguish between patients with favorable and unfavorable time-to-first treatment (TTFT). Additionally, the downstream protein correlates of well-known molecular features of CLL are not always clear. To address this, we selected 40 CLL patients with TTFT ≤24 months and compared their B cell intracellular protein expression with 40 age- and sex-matched CLL patients with TTFT &gt;24 months using mass spectrometry. In total, 3268 proteins were quantified in the cohort. Immunoglobulin heavy-chain variable (IGHV) mutational status and trisomy 12 were most impactful on the CLL proteome. Comparing cases to controls, 5 proteins were significantly upregulated, whereas 3 proteins were significantly downregulated. Of these, only THEMIS2, a signaling protein acting downstream of the B cell receptor, was significantly associated with TTFT, independently of IGHV and TP53 mutational status (hazard ratio, 2.49 [95% confidence interval, 1.62-3.84]; P &lt; 0.001). This association was validated on the mRNA and protein level by quantitative polymerase chain reaction and ELISA, respectively. Analysis of 2 independently generated RNA sequencing and mass spectrometry datasets confirmed the association between THEMIS2 expression and clinical outcome. In conclusion, we present a comprehensive characterization of the proteome of untreated CLL and identify THEMIS2 expression as a putative biomarker of TTFT.</p

A sense of change: media designers and artists communicating about complexity in social-ecological systems

To take on the current and future challenges of global environmental change, fostering a widespread societal understanding of and engagement with the complex dynamics that characterize interacting human and natural systems is essential. Current science communication methods struggle with a number of specific challenges associated with communicating about complex systems. In this study we report on two collaborative processes, a short workshop and longer course, that aimed to harness the insights of interactive media designers and artists to overcome these challenges. The two processes resulted in 86 new interactive media concepts which were selected by the participants and organizers using set criteria and then evaluated using the same criteria by a panel of communication and media design experts and a panel of complex systems scientists using the same criteria. The top eight concepts are discussed in this paper. These concepts fell into the categories of serious games, group interaction concepts, and social media storytelling. The serious games focused directly on complex systems characteristics and were evaluated to be intuitive and engaging designs that combined transparency and complexity well. The group interaction concepts focused mostly on feedbacks and nonlinearity but were fully developed and tested in the workshops, and evaluated as engaging, accessible, and easy to implement in workshops and educational settings. The social media storytelling concepts involved less direct interactions with system dynamics but were seen as highly accessible to large scale audiences. The results of this study show the potential of interdisciplinary collaboration between complex systems scientists, designers, and artists. The results and process discussed in this paper show the value of more structural engagement of interactive media designers and artist communities in the development of communication tools about human and natural systems change

Limit on Bs0B^0_s oscillation using a jet charge method

A lower limit is set on the B_{s}^{0} meson oscillation parameter \Delta m_{s} using data collected from 1991 to 1994 by the ALEPH detector. Events with a high transverse momentum lepton and a reconstructed secondary vertex are used. The high transverse momentum leptons are produced mainly by b hadron decays, and the sign of the lepton indicates the particle/antiparticle final state in decays of neutral B mesons. The initial state is determined by a jet charge technique using both sides of the event. A maximum likelihood method is used to set a lower limit of \, \Delta m_{s}. The 95\% confidence level lower limit on \Delta m_s ranges between 5.2 and 6.5(\hbar/c^{2})~ps^{-1} when the fraction of b quarks from Z^0 decays that form B_{s}^{0} mesons is varied from 8\% to 16\%. Assuming that the B_{s}^{0} fraction is 12\%, the lower limit would be \Delta m_{s} 6.1(\hbar/c^{2})~ps^{-1} at 95\% confidence level. For x_s = \Delta m_s \, \tau_{B_s}, this limit also gives x_s 8.8 using the B_{s}^{0} lifetime of \tau_{B_s} = 1.55 \pm 0.11~ps and shifting the central value of \tau_{B_s} down by 1\sigma

Measurement of the Bs0^0_s lifetime and production rate with Ds−l+^-_s l^+ combinations in Z decays

The lifetime of the \bs meson is measured in approximately 3 million hadronic Z decays accumulated using the ALEPH detector at LEP from 1991 to 1994. Seven different \ds decay modes were reconstructed and combined with an opposite sign lepton as evidence of semileptonic \bs decays. Two hundred and eight \dsl candidates satisfy selection criteria designed to ensure precise proper time reconstruction and yield a measured \bs lifetime of \mbox{\result .} Using a larger, less constrained sample of events, the product branching ratio is measured to be \mbox{\pbrresult