Modular Lie algebras and the Gelfand-Kirillov conjecture

Let g be a finite dimensional simple Lie algebra over an algebraically closed field of characteristic zero. We show that if the Gelfand-Kirillov conjecture holds for g, then g has type A_n, C_n or G_2.Comment: 20 page

Singularity, complexity, and quasi--integrability of rational mappings

We investigate global properties of the mappings entering the description of symmetries of integrable spin and vertex models, by exploiting their nature of birational transformations of projective spaces. We give an algorithmic analysis of the structure of invariants of such mappings. We discuss some characteristic conditions for their (quasi)--integrability, and in particular its links with their singularities (in the 2--plane). Finally, we describe some of their properties {\it qua\/} dynamical systems, making contact with Arnol'd's notion of complexity, and exemplify remarkable behaviours.Comment: Latex file. 17 pages. To appear in CM

Generalized biomolecular modeling and design with RoseTTAFold All-Atom

Deep learning methods have revolutionized protein structure prediction and design but are currently limited to protein-only systems. We describe RoseTTAFold All-Atom (RFAA) which combines a residue-based representation of amino acids and DNA bases with an atomic representation of all other groups to model assemblies containing proteins, nucleic acids, small molecules, metals, and covalent modifications given their sequences and chemical structures. By fine tuning on denoising tasks we obtain RFdiffusionAA, which builds protein structures around small molecules. Starting from random distributions of amino acid residues surrounding target small molecules, we design and experimentally validate, through crystallography and binding measurements, proteins that bind the cardiac disease therapeutic digoxigenin, the enzymatic cofactor heme, and the light harvesting molecule bilin

The death receptor 3/TL1A pathway is essential for efficient development of antiviral CD4? and CD8? T-cell immunity

Death receptor 3 (DR3, TNFRSF25), the closest family relative to tumor necrosis factor receptor 1, promotes CD4+ T-cell-driven inflammatory disease. We investigated the in vivo role of DR3 and its ligand TL1A in viral infection, by challenging DR3-deficient (DR3KO) mice and their DR3WT littermates with the β-herpesvirus murine cytomegalovirus or the poxvirus vaccinia virus. The phenotype and function of splenic T-cells were analyzed using flow cytometry and molecular biological techniques. We report surface expression of DR3 by naive CD8+ T cells, with TCR activation increasing its levels 4-fold and altering the ratio of DR3 splice variants. T-cell responses were reduced up to 90% in DR3KO mice during acute infection. Adoptive transfer experiments indicated this was dependent on T-cell-restricted expression of DR3. DR3-dependent CD8+ T-cell expansion was NK and CD4 independent and due to proliferation, not decreased cell death. Notably, impaired immunity in DR3KO hosts on a C57BL/6 background was associated with 4- to 7-fold increases in viral loads during the acute phase of infection, and in mice with suboptimal NK responses was essential for survival (37.5%). This is the first description of DR3 regulating virus-specific T-cell function in vivo and uncovers a critical role for DR3 in mediating antiviral immunity.—Twohig, J. P., Marsden, M., Cuff, S. M., Ferdinand, J. R., Gallimore, A. M., Perks, W. V., Al-Shamkhani, A., Humphreys, I. R., Wang, E. C. Y. The death receptor 3/TL1A pathway is essential for efficient development of antiviral CD4+ and CD8+ T-cell immunity

Fidelity of implementation of the Strengthening Families Programme 10-14 UK in Wales UK: a mixed-method process evaluation within a randomised controlled trial

Background: A current pragmatic randomised controlled trial of the Strengthening Families Programme (SFP) is evaluating impacts on family functioning, alcohol use and other outcomes. This presentation describes a mixed-method process evaluation which explored how SFP was delivered by local and statutory bodies in seven areas of Wales.<p></p> Methods: Interviews and self-report data from SFP staff; observation of SFP sessions; and routine data from each area were used to assess the extent to which SFP was implemented with fidelity. Descriptive analyses of quantitative data were conducted with appropriate tests of significance and reliability. A thematic framework was developed for coding and analysis of qualitative data. Variation within and between quantitative and qualitative results was discussed leading to alternative hypotheses which guided further analysis to reveal underlying implementation processes. Overall findings were explained using Negotiated Order Theory.<p></p> Preliminary Results: 56 seven-week programmes were delivered to 330 families. Fidelity to the programme manual was generally high: 67% of staff reports indicated 80% or more of SFP activities were delivered with high fidelity. Between areas, the proportion of high-fidelity activities varied from 55% to 77%. This was partly explained by the extent of pre-session preparation for SFP facilitators. Fidelity to implementation guidelines also varied. Standards for staffing numbers and consistency were attained in 97% of programmes; this high rate was assisted by support from SFP co-ordinators’ colleagues at times when the intended process of recruiting staff from other agencies proved unworkable.<p></p> Conclusions: While SFP content was delivered with reasonably high fidelity overall, analysis has identified some implementation processes which were not entirely as intended. Mixed-methods analysis performed a crucial function in elucidating how deviation from specified processes could sometimes be useful (in maintaining staffing standards) and sometimes less beneficial (in delivering content with fidelity). A theoretical approach offered insights into interpersonal and organisational interactions underlying SFP implementation which may be useful for other pragmatic trials