Civil society governance decisions: certification organization response to artisanal and small-scale gold mining

Why do global governance organizations enter some economic sectors but not others? A simple model of material incentives suggests that similar organizations should make similar choices. Yet in the empirical realm of jewelry industry governance, similar organizations diverge in their response to artisanal and small-scale gold mining: certification organizations Fairtrade International and the Alliance for Responsible Mining have entered the sector, while the Rainforest Alliance has stayed out. To explain this puzzle and its implications for human development, the project proceeds in two steps. First, it enriches the simple model by taking a discursive institutional approach that traces the process by which norm entrepreneurs, organizational cultures, and network effects shape the sector entry decisions of organizations. Drawing on interview, document, and hyperlink data, the project argues that the interaction of norm entrepreneurs and organizational culture, more than network effects, explains sector entry decisions in the gold governance case. Second, the project uses the details of the certification standards to conduct a decision analysis that estimates their impact on human development. The analysis finds that certification organizations are likely to increase a miner’s income by 41%-79% over the status quo, which may lift some, though not all, miners out of poverty. It further finds that degree of environmental protection as well as which organization is best at providing it depends on the gold price and the governance context. At prices below $26,666, the Alliance is best and competition creates better or equal outcomes than monopolies. At prices above$26,666, however, Fairtrade is best, and competition creates perverse incentives for pollution reduction. This surprising finding suggests that in the realm of global governance, there can be too much of a good thing. The project argues that governance without governments can foster human development, but that better outcomes are possible in the gold mining case. It concludes by recommending that certification organizations do three things to maximize their positive impacts: 1) prevent de-certification, 2) cooperate rather than compete, and 3) aim to be irrelevant, because mining should be a transitory, not permanent, developing country livelihood

Exploring lymphocyte subsets, autoantibodies and the effect of B cell targeted therapies in rheumatic diseases

Nowadays, around 100 different diseases sort under the umbrella of rheumatic diseases(1). They involve different mechanisms and symptoms engaging joints, tendons, ligaments, bones, muscles but also vital organs like the kidneys nervous system and circulation. The diagnoses is dependent on a combination of common clinical manifestations and laboratory findings such as the presence of specific antibodies that target self-antigen (2–4). Rheumatic disease evolves from a complex interplay between genetic, stochastic and environmental factors resulting in a loss of immune tolerance. B-cell targeting agents have proven useful in the treatment of several rheumatic diseases. Rituximab, a chimeric monoclonal antibody targeting CD20, is e.g. used in rheumatoid arthritis (RA) patients who do not respond to tumor necrosis factor (TNF) inhibitors and as off label-rescue treatment in systemic lupus erythematosus (SLE). Additionally, belimumab, a B cell activating factor (BAFF) inhibitor, is the first approved biological drug for SLE. Even though B-cell targeting therapies are commonly used, little is known about the effect of these therapies on disease associated B and T cell subsets, such as age/autoimmune-associated B cells (ABCs) and T follicular helper (Tfh) cells. In paper I, we therefore studied the effect of these two subsets in response to rituximab treatment in SLE patients and found that ABCs are indeed influenced by the treatment while Tfh frequencies stayed similar to baseline. Additionally, we observed a decrease frequency of programmed cell death protein 1 (PD-1) high CD4+ T cells. In paper II, we investigated the effect of belimumab on circulating B and T cell phenotypes in SLE patients using mass cytometry and correlated them with clinical response. Belimumab had rapid effects on B cell subsets of earlier developmental stages such as naïve B cells while late B cell stages, such as memory or plasma cells, decreased later in a gradual manner or did not change upon treatment. Only early immunological changes correlated with disease improvement. High B cell counts at baseline were associated with late or non-responders. Not all patients respond to B-cell targeting therapy, highlighting the heterogenicity of SLE. To develop novel therapies, a better understanding of the underlying mechanisms related to clinical phenotypes is needed. Thus, in paper III, we explored the cytokine profile and the cellular composition in the synovial fluid of lupus arthritis patients, and we found elevated levels of IL-6 and IL-17A in the joint. Furthermore, we found an enrichment of Th17, peripheral helper T cells and EOMES/Granzyme A-expressing T cells in synovial fluid of SLE patients. All in all, indicating a potential role of Th17 cells in the pathogenesis of lupus. In contrast to lupus arthritis, RA patients exhibit a more aggressive form of arthritis, especially in conjunction with anti-citrullinated protein autoantibodies (ACPA). Therefore, in paper IV, we investigated the citrulline-specific B cell population in RA patients using an antigen-tetramer enrichment technology followed by single cell sequencing of the immunoglobulin genes. We discovered that the broad ACPA specificity in RA patients might develop from clonal expansion of a few B cell clones. Furthermore, monoclonal antibodies which originated from citrulline reactive B cells were multi-reactive and able to promote pain-like behavior and joint inflammation in mice. Overall, this thesis explored immunological changes upon B-cell-targeting therapy and pathogenicity in joint inflammation in SLE and seropositive RA patients. We provided new understanding of B-cell targeting therapies on B and T cell subsets in SLE patients as well as the pathogenic mechanism which might be involved in lupus arthritis. Additionally, we examined the citrulline reactive B cell repertoire in RA patients and our data reveal their potential origin

Heterogeneous Gain Forecasting Using Historic Asset Information

Using historic return inputs in a stylized computational financial market, this paper explores how participant outcomes are affected by the degree to which their asset allocation behavior responds to new market information. Findings support the efficient market hypothesis in that no alternate trading rule shows consistent improved outcomes relative to a full market exposure buy-and-hold strategy over the given time period. The only exception occurs briefly at the bottom of the 2008 financial crisis. Market participants that drastically alter market exposure in response to volatile returns, however, do outperform those who alter their exposure less drastically. Furthermore, the trading rules used here appear to offer a tradeoff between risk, return volatility and wealth development that is in-part at odds with efficient market hypothesis

Compliance Training Produces Increases in Skill-Based Assessments in Typically-Developing Children

Early intensive behavioral intervention therapy (EIBIT) practitioners have been documented to use both standardized psychological and behavioral assessments in assessing outcomes of children diagnosed with autism. Assessments are necessary to inform stakeholders if EIBIT is effective, for which children, and under what conditions. However, the extent to which variables like compliance influence the results of existing EIBIT assessments is yet unknown. This study evaluated the influence of compliance training on the results of the Early Learning Measure (ELM), one assessment used in EIBIT. Two participants underwent repeated compliance training sessions followed by re-testing of the ELM assessment. Mean scores on the ELM increased over baseline following compliance training alone for both participants. A compliance reversal training protocol was then conducted. Mean scores on the ELM decreased for one participant and remained stagnant for the second following compliance reversal. The study’s findings support variables like compliance may influence scores on EIBIT assessments and provide a preliminary evidence for the need to systematically manipulate these variables in applied settings

Heterogeneous Gain Forecasting Using Historic Asset Information

Using historic return inputs in a stylized computational financial market, this paper explores how participant outcomes are affected by the degree to which their asset allocation behavior responds to new market information. Findings support the efficient market hypothesis in that no alternate trading rule shows consistent improved outcomes relative to a full market exposure buy-and-hold strategy over the given time period. The only exception occurs briefly at the bottom of the 2008 financial crisis. Market participants that drastically alter market exposure in response to volatile returns, however, do outperform those who alter their exposure less drastically. Furthermore, the trading rules used here appear to offer a tradeoff between risk, return volatility and wealth development that is in-part at odds with efficient market hypothesis

Detecting Repetitions and Periodicities in Proteins by Tiling the Structural Space

The notion of energy landscapes provides conceptual tools for understanding the complexities of protein folding and function. Energy Landscape Theory indicates that it is much easier to find sequences that satisfy the "Principle of Minimal Frustration" when the folded structure is symmetric (Wolynes, P. G. Symmetry and the Energy Landscapes of Biomolecules. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 14249-14255). Similarly, repeats and structural mosaics may be fundamentally related to landscapes with multiple embedded funnels. Here we present analytical tools to detect and compare structural repetitions in protein molecules. By an exhaustive analysis of the distribution of structural repeats using a robust metric we define those portions of a protein molecule that best describe the overall structure as a tessellation of basic units. The patterns produced by such tessellations provide intuitive representations of the repeating regions and their association towards higher order arrangements. We find that some protein architectures can be described as nearly periodic, while in others clear separations between repetitions exist. Since the method is independent of amino acid sequence information we can identify structural units that can be encoded by a variety of distinct amino acid sequences

ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins

A major problem in structural biology is the recognition of errors in experimental and theoretical models of protein structures. The ProSA program (Protein Structure Analysis) is an established tool which has a large user base and is frequently employed in the refinement and validation of experimental protein structures and in structure prediction and modeling. The analysis of protein structures is generally a difficult and cumbersome exercise. The new service presented here is a straightforward and easy to use extension of the classic ProSA program which exploits the advantages of interactive web-based applications for the display of scores and energy plots that highlight potential problems spotted in protein structures. In particular, the quality scores of a protein are displayed in the context of all known protein structures and problematic parts of a structure are shown and highlighted in a 3D molecule viewer. The service specifically addresses the needs encountered in the validation of protein structures obtained from X-ray analysis, NMR spectroscopy and theoretical calculations. ProSA-web is accessible at https://prosa.services.came.sbg.ac.a

Self-Consistent Assignment of Asparagine and Glutamine Amide Rotamers in Protein Crystal Structures

SummaryThe current protein structure database contains unfavorable Asn/Gln amide rotamers in the order of 20%. Here, we derive a set of self-consistent potential functions to identify and correct unfavorable rotamers. Potentials of mean force for all heavy atoms are compiled from a database of high-resolution protein crystal structures. Starting from erroneous data, a refinement-correction cycle quickly converges to a self-consistent set of potentials. The refinement is entirely driven by the deposited structure data and does not involve any assumptions on molecular interactions or any artificial constraints. The refined potentials obtained in this way identify unfavorable rotamers with high confidence. Since the state of Asn/Gln rotamers is largely determined by hydrogen bond interactions, the features of the respective potentials are of interest in terms of molecular interactions, protein structure refinement, and prediction. The Asn/Gln rotamer assignment is available as a public web service intended to support protein structure refinement and modeling