Antigen presenting capacity of murine splenic myeloid cells

BACKGROUND: The spleen is an important site for hematopoiesis. It supports development of myeloid cells from bone marrow-derived precursors entering from blood. Myeloid subsets in spleen are not well characterised although dendritic cell (DC) subsets are clearly defined in terms of phenotype, development and functional role. Recently a novel dendritic-like cell type in spleen named ‘L-DC’ was distinguished from other known dendritic and myeloid cells by its distinct phenotype and developmental origin. That study also redefined splenic eosinophils as well as resident and inflammatory monocytes in spleen. RESULTS: L-DC are shown to be distinct from known splenic macrophages and monocyte subsets. Using a new flow cytometric procedure, it has been possible to identify and isolate L-DC in order to assess their functional competence and ability to activate T cells both in vivo and in vitro. L-DC are readily accessible to antigen given intravenously through receptor-mediated endocytosis. They are also capable of CD8(+) T cell activation through antigen cross presentation, with subsequent induction of cytotoxic effector T cells. L-DC are MHCII(−) cells and unable to activate CD4(+) T cells, a property which clearly distinguishes them from conventional DC. The myeloid subsets of resident monocytes, inflammatory monocytes, neutrophils and eosinophils, were found to have varying capacities to take up antigen, but were uniformly unable to activate either CD4(+) T cells or CD8(+) T cells. CONCLUSION: The results presented here demonstrate that L-DC in spleen are distinct from other myeloid cells in that they can process antigen for CD8(+) T cell activation and induction of cytotoxic effector function, while both L-DC and myeloid subsets remain unable to activate CD4(+) T cells. The L-DC subset in spleen is therefore distinct as an antigen presenting cell

New Cyclometalating Ligands for Emissive Iridium(III) Complexes for OLED Applications

The literature surrounding the design of iridium(III) complexes for OLED applications is summarised, with a particular focus on tuning the colour of the emission via structural modification. In this thesis a new family of sulfone-containing ligands was synthesised, with the aim of blue-shifting the emission of the resultant iridium complexes compared to the parent complex, FIrpic. Introduction of a sulfone unit to key positions on dfppy resulted in a blue-shift of 10 nm compared to FIrpic, due to the lowering of the HOMO with respect to the LUMO. This series of complexes was then extended to include complexes which contain fewer aromatic fluorines, including a ‘fluorine-free’ complex, as these are known to make the complexes unstable in devices. To blue-shift the emission further a new ancillary ligand was synthesised and combined with some of the sulfone ligands to produce complexes. Devices fabricated in the Department of Physics retained the blue emission observed in solution and performed comparably with FIrpic. Donor-acceptor chromophoric ligands were also synthesised to investigate the solvent dependent dual emission properties of the resultant complexes. The donor and acceptor components were varied, producing complexes with differing degrees of dual emission character in solution, which is tentatively assigned to the prescence of a ligand based CT state. While the complexes did not display dual emission properties in the solid state, devices fabricated in the Department of Physics showed favourable performances as blue emitters compared to a FIrpic device. New complexes with oxazoline- and oxazole- based ancillary ligands were also synthesised which showed an unusual HOMO-LUMO distribution. The emission colour of the complexes was tuned via introduction of substituents on to both the ancillary and the cyclometalating ligand, and the complexes’ performance in OLED devices was investigated. Finally, hexadentate tripodal ligands were synthesised based on known cyclometalating ligands, and the tripodal complexes were synthesised with the aim of enhancing complex stability and reducing quenching relative to their tris-bidentate analogues. The synthesis and photophysical properties of these materials are discussed. The complexes displayed comparable or superior PLQYs and lifetimes to the parent/related complexes, and the 1H NMR data suggested some limited motion in solution

Archiving and disseminating integrative structure models.

Limitations in the applicability, accuracy, and precision of individual structure characterization methods can sometimes be overcome via an integrative modeling approach that relies on information from all available sources, including all available experimental data and prior models. The open-source Integrative Modeling Platform (IMP) is one piece of software that implements all computational aspects of integrative modeling. To maximize the impact of integrative structures, the coordinates should be made publicly available, as is already the case for structures based on X-ray crystallography, NMR spectroscopy, and electron microscopy. Moreover, the associated experimental data and modeling protocols should also be archived, such that the original results can easily be reproduced. Finally, it is essential that the integrative structures are validated as part of their publication and deposition. A number of research groups have already developed software to implement integrative modeling and have generated a number of structures, prompting the formation of an Integrative/Hybrid Methods Task Force. Following the recommendations of this task force, the existing PDBx/mmCIF data representation used for atomic PDB structures has been extended to address the requirements for archiving integrative structural models. This IHM-dictionary adds a flexible model representation, including coarse graining, models in multiple states and/or related by time or other order, and multiple input experimental information sources. A prototype archiving system called PDB-Dev ( https://pdb-dev.wwpdb.org ) has also been created to archive integrative structural models, together with a Python library to facilitate handling of integrative models in PDBx/mmCIF format

Facilitated extinction of appetitive instrumental conditioning following excitotoxic lesions of the core or the medial shell subregion of the nucleus accumbens in rats

The nucleus accumbens has been implicated in the control of goal-directed behaviour, including instrumental conditioning. Here, we evaluated the effect of N-methyl-d-aspartate (NMDA)-induced excitotoxic lesions restricted to either the core or the medial shell subregions of the nucleus accumbens (NAC) on extinction in rats using a trial discrete fixed ratio-5 (FR-5) appetitive operant procedure. Neither core nor shell lesions of the NAC affected the acquisition of instrumental responding. Both lesions facilitated the cessation of responding when the instrumental act no longer yielded reinforcement. Our results suggest that both the NAC core and medial shell contribute to the control of extinction learning of appetitively motivated instrumental behaviou

Double-dimer condensation and the PT-DT correspondence

We resolve an open conjecture from algebraic geometry, which states that two generating functions for plane partition-like objects (the "box-counting" formulae for the Calabi-Yau topological vertices in Donaldson-Thomas theory and Pandharipande-Thomas theory) are equal up to a factor of MacMahon's generating function for plane partitions. The main tools in our proof are a Desnanot-Jacobi-type condensation identity, and a novel application of the tripartite double-dimer model of Kenyon-Wilson.Comment: 91 pages, 15 figures. This is the full version of the FPSAC extended abstract arXiv:2012.0848

Climate Benefits Tenure Costs: The Economic Case for Securing Indigenous Land Rights in the Amazon

A new report offers evidence that the modest investments needed to secure land rights for indigenous communities will generate billions in returns—economically, socially and environmentally—for local communities and the world's changing climate. The report, Climate Benefits, Tenure Costs: The Economic Case for Securing Indigenous Land Rights, quantifies for the first time the economic value of securing land rights for the communities who live in and protect forests, with a focus on Colombia, Brazil, and Bolivia

Optimization's Neglected Normative Commitments

Optimization is offered as an objective approach to resolving complex, real-world decisions involving uncertainty and conflicting interests. It drives business strategies as well as public policies and, increasingly, lies at the heart of sophisticated machine learning systems. A paradigm used to approach potentially high-stakes decisions, optimization relies on abstracting the real world to a set of decision(s), objective(s) and constraint(s). Drawing from the modeling process and a range of actual cases, this paper describes the normative choices and assumptions that are necessarily part of using optimization. It then identifies six emergent problems that may be neglected: 1) Misspecified values can yield optimizations that omit certain imperatives altogether or incorporate them incorrectly as a constraint or as part of the objective, 2) Problematic decision boundaries can lead to faulty modularity assumptions and feedback loops, 3) Failing to account for multiple agents' divergent goals and decisions can lead to policies that serve only certain narrow interests, 4) Mislabeling and mismeasurement can introduce bias and imprecision, 5) Faulty use of relaxation and approximation methods, unaccompanied by formal characterizations and guarantees, can severely impede applicability, and 6) Treating optimization as a justification for action, without specifying the necessary contextual information, can lead to ethically dubious or faulty decisions. Suggestions are given to further understand and curb the harms that can arise when optimization is used wrongfully.Comment: 14 pages, 1 figure, presentation at FAccT2

Planning the Future of North American Cold-Formed Steel Design Standards

Growth in cold-formed steel structures has long been tied to developing and advancing the engineering standards that govern their use in construction. The American Iron and Steel Institute (AISI) has taken a leadership role in this activity in North America since 1946. Conventional standards providing closed-formed solutions to member capacity, such as the recently completed suite of AISI Standards in 2015 and 2016. These standards have reached an impressive level of maturity given the complexity of designing entire (building) structural systems out of steel that is rarely greater than 2mm thick. However, the demands on the structural engineer designing cold-formed steel have evolved. System performance, resilience, and sustainability all present new challenges, while changing processes in construction and the integration of simulation tools in design alter engineering workflows and open up new opportunities. Cold-formed steel standards need to evolve to meet these demands and leverage new workflows. The Strategic Planning Committee of the AISI Standards Council facilitated a process that defined areas of focus (vision statements) for the AISI specification writing committees and then facilitated a process to generate prioritized issues for the subcommittees to address. Taken together the lists provide a snapshot of the needed work to evolve cold-formed steel standards, and in turn enable next-generation cold-formed steel structural systems. This paper provides a description of the strategic planning process and its significant outcomes, which will guide the efforts of AISI standards development over the next code development cycle and beyond