Epigenetic Activation of the Mouse T Cell Receptor Beta Recombination Center

Lymphocytes are the work horses of adaptive immunity. Compared to the B lymphocyte lineage, early stage progenitors of T lymphocytes maintain considerable potential for differentiation into other hematopoietic lineages. T lineage commitment requires the continuous coordination of transcription factors (TFs) by Notch1 signaling after multi-potent progenitors (MPPs) migrate to thymus. One of the first hall marks of T lineage commitment is expression of the T cell receptor β (TCRβ), which is encoded by the Tcrb locus following its assembly by V(D)J recombination, a somatic shuffling of the genome that joins one V, one D, and one J gene segment. Tcrb assembly is initiated at its recombination center (RC), composed of two DβJβ clusters. Tcrb-RC exhibits features of regulatory regions called super-enhancers (SEs), which are characterized by high level of active histone mark, H3K27ac, and by clusters of binding for TFs involved in cell fate decisions. A key Tcrb-RC enhancer, called Eβ, harbors two composite ETS1-RUNX1 binding motifs, which widely exist in regulatory elements for genes involved in T lymphopoiesis. ETS1 is sharply upregulated during T cell lineage commitment and recruits constitutively expressed RUNX1 to Eβ. However, the independent roles of these two TFs remain unclear, especially since both are potent transactivators. In this study, I have shown that both ETS1 and RUNX1 are sufficient to independently activate Eβ in extrachromosomal reporter substrates. However, ETS1 by itself fails to activate Eβ in its native chromosomal context. By contrast, RUNX1 is sufficient to activate the endogenous Eβ element and its neighboring 25 kb region independently from ETS1. In addition, RUNX1 is sufficient to mediate long-range promoter-Eβ interactions, nucleosome clearance, and robust transcription throughout the Tcrb recombination center (RC). We also find that a RUNX1 domain, termed the negative regulatory domain for DNA binding (NRDB), can compensate for loss of ETS1 binding at adjacent sites. Thus, we have defined independent roles for RUNX1 in the activation of a T cell developmental enhancer, as well as its ability to mediate specific changes in chromatin landscapes that accompany long-range induction of RC promoters

Reinterpreting the Dougong joint: a systematic review of robotic technologies for the assembly of timber joinery

The Dougong (brackets set) is a traditional Chinese capital used to transfer the roof load to the columns. Besides its historical significance, it is also known for its anti-seismic and environmentally friendly properties. This paper investigates which existing digital design and fabrication technologies are suitable for the automated assembly and production of the Dougong joint by reviewing relevant research. The paper systematically reviews and comparatively analyses 23 articles filtered through 1,774 publications searched by using the keywords ‘timber’, ‘digital fabrication’, and ‘robot’ in the databases Scopus, CumlnCAD, ScienceDirect, Engineer Village, IEEE and Semantic Scholar. Our findings include a comparative analysis chart evaluating workflows, tools and technologies on their suitability for the robotic reinterpretation of the Dougong, as well as the proposal of a novel design for fabrication workflow for that particular purpose, which is verified through the design and fabrication of a timber column fragment

Association between Tumor necrosis factor-alpha gene polymorphisms and prostate cancer risk: a meta-analysis

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is an important inflammatory cytokine that may play a role in controlling the progression of prostate cancer. Two common polymorphisms in the TNF-α gene, −308G/A and −238C/T, have been suggested to alter the risk for prostate cancer, but the results have been inconclusive so far. In order to obtain a better understanding of the effects of these two polymorphisms on prostate cancer risk, all available studies were considered in a meta-analysis. METHODS: We conducted a comprehensive literature search in the Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature database (CBM), and the China National Knowledge Infrastructure (CNKI). The associations were evaluated by calculating the pooled odds ratio (OR) with 95% confidence interval (95% CI). RESULTS: In this meta-analysis, we included 14 studies with 5,757 patients and 6,137 control subjects for the TNF-α-308G/A polymorphism and 1,967 patients and 2,004 control subjects for the TNF-α-238C/T polymorphism. A significantly increased prostate cancer risk was found to be associated with the TNF-α-308C/T polymorphism in studies with healthy volunteers (AA + AG vs. GG: OR = 1.531, 95% CI = 1.093–2.145; P = 0.013; AG vs. GG: OR = 1.477, 95% CI = 1.047–2.085; P = 0.026). No significant association was found between the TNF-α-238G/A polymorphism and prostate cancer risk in the overall or subgroup analyses. There was no risk of publication bias in this meta-analysis. CONCLUSIONS: Our results suggest that while the TNF-α-238G/A polymorphism may not be associated with prostate cancer the TNF-α-308C/T polymorphism may significantly contribute to prostate cancer susceptibility in healthy volunteers. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/162928812011630

A diffusion MRI-based spatiotemporal continuum of the embryonic mouse brain for probing gene-neuroanatomy connections

The embryonic mouse brain undergoes drastic changes in establishing basic anatomical compartments and laying out major axonal connections of the developing brain. Correlating anatomical changes with gene-expression patterns is an essential step toward understanding the mechanisms regulating brain development. Traditionally, this is done in a cross-sectional manner, but the dynamic nature of development calls for probing gene-neuroanatomy interactions in a combined spatiotemporal domain. Here, we present a four-dimensional (4D) spatiotemporal continuum of the embryonic mouse brain from E10.5 to E15.5 reconstructed from diffusion magnetic resonance microscopy (dMRM) data. This study achieved unprecedented high-definition dMRM at 30- to 35-µm isotropic resolution, and together with computational neuroanatomy techniques, we revealed both morphological and microscopic changes in the developing brain. We transformed selected gene-expression data to this continuum and correlated them with the dMRM-based neuroanatomical changes in embryonic brains. Within the continuum, we identified distinct developmental modes comprising regional clusters that shared developmental trajectories and similar gene-expression profiles. Our results demonstrate how this 4D continuum can be used to examine spatiotemporal gene-neuroanatomical interactions by connecting upstream genetic events with anatomical changes that emerge later in development. This approach would be useful for large-scale analysis of the cooperative roles of key genes in shaping the developing brain

Rethinking the Brick: developing a file to fabrication framework for mortar-free, robotic masonry wall assembly

This design-led research investigates the development of a file-to-fabrication framework for mortar-free robotic assembly of masonry walls. In particular, we describe, test and evaluate an algorithmic method enabling the robotic assembly or custom-made, complex, interlocking brick structures which don’t require the use of mortar or adhesives but their stability relies only on their geometric properties. We evaluate the process by conducting three design experiments. Our findings highlight the advantages and challenges of the proposed framework focusing on the relationship between the geometry of the individual bricks and the overall structure as well as the tolerances related to the interlocking mechanism

Rethinking the Brick: developing a file to fabrication framework for mortar-free, robotic masonry wall assembly

This design-led research investigates the development of a file-to-fabrication framework for mortar-free robotic assembly of masonry walls. In particular, we describe, test and evaluate an algorithmic method enabling the robotic assembly or custom-made, complex, interlocking brick structures which don’t require the use of mortar or adhesives but their stability relies only on their geometric properties. We evaluate the process by conducting three design experiments. Our findings highlight the advantages and challenges of the proposed framework focusing on the relationship between the geometry of the individual bricks and the overall structure as well as the tolerances related to the interlocking mechanism

A Computational Framework for Parametric Design and Robotic Fabrication of the Dougong joint

The Dougong (brackets set) is a traditional Chinese capital used to transfer the load of the roof to a column. It is known for its anti-seismic properties, sustainability, and cultural significance. This paper introduces a framework for parametric design and robotic fabrication of the Dougong, thus it can be utilised in contemporary architecture. The framework incorporates topology optimisation, voxelisation, multi-objective optimisation and robotic assembly and is verified by designing and assembling a timber frame column out of Dougong units. Our findings highlight the potential of utilising the Dougong in contemporary design as well as a strategy to reduce the tolerances of robotically assembled tenon-mortise elements

Blockchain-based power trading system for microgrid

Direct trading between entities in the microgrid is the trend of micro-grid electricity trading. However, the lack of trust and endorsement among multiple entities in micro-grids makes it difficult to complete direct electricity transactions, which limits the green energy efficiency. To solve this problem, firstly, a blockchain-based microgrid power transaction level model and power transaction process management process are proposed. Secondly, an access interface between the microgrid smart terminal and the blockchain is designed to realize the connection between the blockchain and the underlying equipment. The system is implemented in an island microgrid, which realizes the peer-to-peer trading between power suppliers and users. The system builds a bridge among entities in microgrid and makes the power trading open, transparent and traceable