Tracking, b-tagging and measurement of the b-jet production cross section with the ATLAS detector

The Standard Model of elementary particle physics was developed to describe the fundamental particles which constitute matter and the interactions between them. The Large Hadron Collider (LHC) at CERN in Geneva was built to solve some of the remaining open questions in the Standard Model and to explore physics beyond it, by colliding two proton beams at world-record centre-of-mass energies. The ATLAS experiment is designed to reconstruct particles and their decay products originating from these collisions. The precise reconstruction of particle trajectories plays an important role in the identification of particle jets which originate from bottom quarks (b-tagging). This thesis describes the step-wise commissioning of the ATLAS track reconstruction and b-tagging software and one of the first measurements of the b-jet production cross section in pp collisions at sqrt(s)=7 TeV with the ATLAS detector. The performance of the track reconstruction software was studied in great detail, first using data from cosmic ray showers and then collisions at sqrt(s)=900 GeV and 7 TeV. The good understanding of the track reconstruction software allowed a very early deployment of the b-tagging algorithms. First studies of these algorithms and the measurement of the b-tagging efficiency in the data are presented. They agree well with predictions from Monte Carlo simulations. The b-jet production cross section was measured with the 2010 dataset recorded by the ATLAS detector, employing muons in jets to estimate the fraction of b-jets. The measurement is in good agreement with the Standard Model predictions.

Naive B-cell trafficking is shaped by local chemokine availability and LFA-1-independent stromal interactions.

It is not known how naive B cells compute divergent chemoattractant signals of the T-cell area and B-cell follicles during in vivo migration. Here, we used two-photon microscopy of peripheral lymph nodes (PLNs) to analyze the prototype G-protein-coupled receptors (GPCRs) CXCR4, CXCR5, and CCR7 during B-cell migration, as well as the integrin LFA-1 for stromal guidance. CXCR4 and CCR7 did not influence parenchymal B-cell motility and distribution, despite their role during B-cell arrest in venules. In contrast, CXCR5 played a nonredundant role in B-cell motility in follicles and in the T-cell area. B-cell migration in the T-cell area followed a random guided walk model, arguing against directed migration in vivo. LFA-1, but not α4 integrins, contributed to B-cell motility in PLNs. However, stromal network guidance was LFA-1 independent, uncoupling integrin-dependent migration from stromal attachment. Finally, we observed that despite a 20-fold reduction of chemokine expression in virus-challenged PLNs, CXCR5 remained essential for B-cell screening of antigen-presenting cells. Our data provide an overview of the contribution of prototype GPCRs and integrins during naive B-cell migration and shed light on the local chemokine availability that these cells compute.

B cell memory and idiotype network regulation

This investigation examined the clonal dynamics of B-cell expression and evaluated the role of idiotype network interactions in shaping the expressed secondary B-cell repertoire. Three interrelated experimental approaches were applied. The first approach was designed to distinguish between regulatory influences controlled by the major histocompatibility complex (MHC) and regulatory influences controlled by non-MHC factors including the idiotype network. This approach consisted of studies on the clonal dynamics and heterogeneity of the expressed IgG antibody repertoire of BALB/c mice. The second approach involved the analysis of the clonal dynamics of antibody responses of outbred rabbits. This analysis was coupled with studies to detect the occurrence and activity of constituents of the idiotype network. In the third approach the transfer of rabbit lymphocytes from immunized donors to MHC matched naive recipients was used to examine the effects of recipient non-MHC immunoregulatory influences on the expression of donor memory B-cells. Although many memory B cells were unaffected by non-MHC influences, these data show that non-MHC immunoregulatory influences can affect the expression of B-cells in the secondary response of inbred mice and outbred rabbits. The results also indicate that most IgG antibody responses are heterogeneous and are characterized by a stable group of dominant clonotypes. Clonal dominance and B-cell memory were found to be established early in an immune response. The expression of B memory clones appeared to be favored over the expression of virgin B cells. The injection of anti-tetanus antibody induced the antigen independent production of anti-tetanus antibody, probably through idiotypic mechanisms. These results demonstrate that both antibody and antigen can affect the expressed B-ceIl repertoire. Thus, idiotypic interactions are capable of influencing the expression of B-cells and these findings support the existence and function of an idiotype network with strong immunoregulatory potential. ^

Retention in care of HIV-infected pregnant and lactating women starting art under Option B+ in rural Mozambique.

OBJECTIVE In 2013, Mozambique adopted Option B+, universal lifelong antiretroviral therapy (ART) for all pregnant and lactating women, as national strategy for prevention of mother-to-child transmission of HIV. We analyzed retention in care of pregnant and lactating women starting Option B+ in rural northern Mozambique. METHODS We compared ART outcomes in pregnant ("B+pregnant"), lactating ("B+lactating") and non-pregnant-non-lactating women of childbearing age starting ART after clinical and/or immunological criteria ("own health") between July 2013 and June 2014. Lost to follow-up was defined as no contact >180 days after the last visit. Multivariable competing risk models were adjusted for type of facility (type 1 vs. peripheral type 2 health center), age, WHO stage and time from HIV diagnosis to ART. RESULTS Over 333 person-years of follow-up (of 243 "B+pregnant", 65″B+lactating" and 317 "own health" women), 3.7% of women died and 48.5% were lost to follow-up. "B+pregnant" and "B+lactating" women were more likely to be lost in the first year (57% vs. 56.9% vs. 31.6%; p<0.001) and to have no follow-up after the first visit (42.4% vs. 29.2% vs. 16.4%; p<0.001) than "own health" women. In adjusted analyses, risk of being lost to follow-up was higher in "B+pregnant" (adjusted subhazard ratio [asHR]: 2.77; 95% CI: 2.18-3.50; p<0.001) and "B+lactating" (asHR: 1.94; 95% CI: 1.37-2.74; p<0.001). Type 2 health center was the only additional significant risk factor for loss to follow-up. CONCLUSIONS Retaining pregnant and lactating women in option B+ ART was poor; losses to follow-up were mainly early. The success of Option B+ for prevention of mother-to-child transmission of HIV in rural settings with weak health systems will depend on specific improvements in counseling and retention measures, especially at the beginning of treatment. This article is protected by copyright. All rights reserved.

A critical role of Lyn and Fyn for B cell responses to CD38 ligation and interleukin 5

CD38 ligation on mouse B cells by CS/2, an anti-mouse CD38 mAb, induced proliferation, interleukin 5 (IL-5) receptor α chain expression, and tyrosine phosphorylation of Bruton tyrosine kinase (Btk) from wild-type, but not from X chromosome-linked, immunodeficient mice. B cells from fyn-deficient (Fyn−/−) and lyn-deficient (Lyn−/−) mice showed an impaired response to mAb CS/2 for proliferation and IL-5 receptor α chain expression, and B cells from fyn/lyn double-deficient (Fyn/Lyn−/−) mice did not respond at all to mAb CS/2. The Btk activation by CD38 ligation was observed in B cells from Fyn−/− mice, and it was severely impaired in B cells from Lyn−/− and Fyn/Lyn−/− mice. CD38 expression on B cells from three mutant strains was comparable to that on control B cells. We infer from these results that both Fyn and Lyn are required and that their signals are synergistic for B cell triggering after CD38 ligation. Lyn is upstream of Btk activation in the CD38 signaling. Stimulation of B cells with IL-5 together with CD38 ligation induces not only IgM but also IgG1 secretion. Analysis of the synergistic effects of IL-5 and CD38 ligation on IgG1 secretion revealed the impaired IgG1 secretion of B cells from Lyn−/− and Fyn/Lyn−/− mice. These data imply that Lyn is involved in B cell triggering by CD38 ligation plus IL-5 for isotype switching.

Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice

The tetraspanin CD81 is ubiquitously expressed and associated with CD19 on B lymphocytes and with CD4 and CD8 on T lymphocytes. Analysis of mice with disrupted CD81 gene reveals normal T cells but a distinct abnormality in B cells consisting of decreased expression of CD19 and severe reduction in peritoneal B-1 cells. CD81-deficient B cells responded normally to surface IgM crosslinking, but had severely impaired calcium influx following CD19 engagement. CD81-deficient mice had increased serum IgM and IgA and an exaggerated antibody response to the type II T independent antigen TNP-Ficoll. These results suggest that CD81 is important for CD19 signaling and B cell function.

Independent evolution of the prochlorophyte and green plant chlorophyll a/b light-harvesting proteins

The prochlorophytes are oxygenic prokaryotes differing from other cyanobacteria by the presence of a light-harvesting system containing both chlorophylls (Chls) a and b and by the absence of phycobilins. We demonstrate here that the Chl a/b binding proteins from all three known prochlorophyte genera are closely related to IsiA, a cyanobacterial Chl a-binding protein induced by iron starvation, and to CP43, a constitutively expressed Chl a antenna protein of photosystem II. The prochlorophyte Chl a/b protein (pcb) genes do not belong to the extended gene family encoding eukaryotic Chl a/b and Chl a/c light-harvesting proteins. Although higher plants and prochlorophytes share common pigment complements, their light-harvesting systems have evolved independently.

Coexistence of phycoerythrin and a chlorophyll a/b antenna in a marine prokaryote.

Prochlorococcus marinus CCMP 1375, a ubiquitous and ecologically important marine prochlorophyte, was bound to possess functional genes coding for the alpha and beta subunits of a phycobiliprotein. The latter is similar to phycoerythrins (PE) from marine Synechococcus cyanobacteria and bind a phycourobilin-like pigment as the major chromophore. However, differences in the sequences of the alpha and beta chains compared with known PE subunits and the presence of a single bilin attachment site on the alpha subunit designate it as a novel PE type, which we propose naming PE-III. P. marinus is the sole prokaryotic organisms known so far that contains chlorophylls a and b as well as phycobilins. These data strongly suggest that the common ancestor of prochlorophytes and the Synechococcus cyanobacteria contained phycobilins. Flow cytometric data from the tropical Pacific Ocean provide evidence that deep populations of Prochlorococcus possess low amounts of a PE-like pigment, which could serve either in light harvesting or nitrogen storage or both.

Tumor dormancy and cell signaling: anti-mu-induced apoptosis in human B-lymphoma cells is not caused by an APO-1-APO-1 ligand interaction.

Signal transduction initiated by crosslinking of antigen-specific receptors on T- and B-lymphoma cells induces apoptosis. In T-lymphoma cells, such crosslinking results in upregulation of the APO-1 ligand, which then interacts with induced or constitutively expressed APO-1, thereby triggering apoptosis. Here we show that crosslinking the membrane immunoglobulin on human lymphoma cells (Daudi) (that constitutively express APO-1) does not induce synthesis of APO-1 ligand. Further, a noncytotoxic fragment of anti-APO-1 antibody that blocks T-cell-receptor-mediated apoptosis in T-lymphoma cells does not block anti-mu-induced apoptosis. Hence, in B-lymphoma cells, apoptosis induced by signaling via membrane IgM is not mediated by the APO-1 ligand.

Synthesis of Chromen[4,3-b]pyrrolidines by Intramolecular 1,3-Dipolar Cycloadditions of Azomethine Ylides: An Experimental and Computational Assessment of the Origin of Stereocontrol

Azomethine ylides, generated from imine-derived O-cinnamyl or O-crotonyl salicylaldeyde and α-amino acids, undergo intramolecular 1,3-dipolar cycloaddition, leading to chromene[4,3-b]pyrrolidines. Two reaction conditions are used: (a) microwave-assisted heating (200 W, 185 °C) of a neat mixture of reagents, and (b) conventional heating (170 °C) in PEG-400 as solvent. In both cases, a mixture of two epimers at the α-position of the nitrogen atom in the pyrrolidine nucleus was formed through the less energetic endo-approach (B/C ring fusion). In many cases, the formation of the stereoisomer bearing a trans-arrangement into the B/C ring fusion was observed in high proportions. Comprehensive computational and kinetic simulation studies are detailed. An analysis of the stability of transient 1,3-dipoles, followed by an assessment of the intramolecular pathways and kinetics are also reported.

Collaboration and Engagement Throughout The Supply Chain : The Role of Government

Collaboration is acknowledged as a key to continued growth in the Australian construction industry. Government, as a major industry client, has an important role to play with respect to fostering collaboration and ensuring the global competitiveness of the industry. The paper draws upon data collected for the Construction 2020 study and aims to demonstrate that government can a) help to break down the adversarial situation that currently exists between clients, project managers and subcontractors; and b) allow the supply chain to collaborate more effectively in terms of satisfying the relational and financial needs of all parties. Government can also provide a clear set of guidelines (backed up by a functional dispute resolution system) that will promote confidence with respect to forging relationships. Thus, the paper will discuss the way in which public policy can be more closely aligned with actual industry needs in order to promote greater collaboration.

Social justice and high-quality human services : visioning the place of a contemporary professional association

The current world situation is plagued by “wicked problems” and a widespread sense of “things are going to get worse”. We confront the almost imponderable consequences of global habitat destruction and climate change, as well as the meltdown of the financial markets with their largely yet to be seen damage to the “real economy”. These things will have considerable negative impacts on the social system and people's lives, particularly the disadvantaged and socially excluded, and require innovative policy and program responses delivered by caring, intelligent, and committed practitioners. These gargantuan issues put into perspective the difficulties that confront social, welfare, and community work today. Yet, in times of trouble, social work and human services tend to do well. For example, although Australian Social Workers and Welfare and Community Workers have experienced phenomenal job growth over the past 5 years, they also have good prospects for future growth and above average salaries in the seventh and sixth deciles, respectively (Department of Education, Employment and Workplace Relations, 2008). I aim to examine the host of reasons why the pursuit of social justice and high-quality human services is difficult to attain in today's world and then consider how the broadly defined profession of social welfare practitioners may collectively take action to (a) respond in ways that reassert our role in compassionately assisting the downtrodden and (b) reclaim the capacity to be a significant body of professional expertise driving social policy and programs. For too long social work has responded to the wider factors it confronts through a combination of ignoring them, critiquing from a distance, and concentrating on the job at hand and our day-to-day responsibilities. Unfortunately, “holding the line” has proved futile and, little by little, the broad social mandate and role of social welfare has altered until, currently, most social programs entail significant social surveillance of troublesome or dangerous groups, rather than assistance. At times it almost seems like the word “help” has been lost in the political and managerial lexicon, replaced by “manage” and “control”. Our values, beliefs, and ethics are under real threat as guiding principles for social programs.

Raman spectroscopic study of the magnesium carbonate minerals– artinite and dypingite

Magnesium minerals are important in the understanding of the concept of geosequestration. The two hydrated hydroxy magnesium carbonate minerals artinite and dypingite have been studied by Raman spectroscopy. Intense bands are observed at 1092 cm-1 for artinite and at 1120 cm-1 for dypingite attributed CO32- ν1 symmetric stretching mode. The CO32- ν3 antisymmetric stretching vibrations are extremely weak and are observed at1412 and 1465 cm-1 for artinite and at 1366, 1447 and 1524 cm-1 for dypingite. Very weak Raman bands at 790 cm-1 for artinite and 800 cm-1 for dypingite are assigned to the CO32- ν2 out-of-plane bend. The Raman band at 700 cm-1 of artinite and at 725 and 760 cm-1 of dypingite are ascribed to CO32- ν2 in-plane bending mode. The Raman spectrum of artinite in the OH stretching region is characterised by two sets of bands: (a) an intense band at 3593 cm-1 assigned to the MgOH stretching vibrations and (b) the broad profile of overlapping bands at 3030 and 3229 cm-1 attributed to water stretching vibrations. X-ray diffraction studies show the minerals are disordered. This is reflected in the difficulty of obtaining Raman spectra of reasonable quality and explains why the Raman spectra of these minerals have not been previously or sufficiently described.