BRCA1 as tumor suppressor: lord without its RING?

BRCA1 is a tumor suppressor with critical roles in the maintenance of genomic stability. It encodes a large protein with an amino-terminal RING domain that possesses ubiquitin-ligase activity. Given the occurrence of numerous cancer-causing mutations within its RING domain, investigators have long suspected that BRCA1's ubiquitin ligase is important for its tumor suppression and DNA repair activities. Using genetically engineered mouse models, two recent studies shed light on this age-old hypothesis

full simulation of a piezoelectric double nozzle flapper pilot valve coupled with a main stage spool valve

Abstract This paper develops a detailed simulation model, realized by the software Simscape, which can be a powerful tool to analyze the performance of a double nozzle flapper valve actuated by a piezoelectric ring bender. The particularity of this valve is that the use of the torque motor and flexure tube is avoided, thus reducing the complexity, manufacturing time and cost of the valve assembly. The model accounts for all the real phenomena present in the valve, such as fluid compressibility and fluid viscosity. The viability of the valve concept is validated by step tests simulated at different valve openings. It is shown that the response time obtained for a supply pressure of 210 bar and necessary to reach 90% of the maximum opening degree (corresponding to a maximum spool position of 1mm and maximum flow rate of 60 l/min) is only 6 ms, which is comparable with typical commercially available double nozzle flapper valves, but with the advantage of having removed critical components such as the torque motor and the flexure tube

More Than a Safety Net: Ethiopia\u27s Flagship Public Works Program Increases Tree Cover

More than one billion people worldwide receive cash or in-kind transfers from social protection programs. In low-income countries, these transfers are often conditioned on participation in labor-intensive public works to rehabilitate local infrastructure or natural resources. Despite their popularity, the environmental impacts of public works programs remain largely undocumented. We quantify the impact on tree cover of Ethiopia\u27s Productive Safety Net Program (PSNP), one of the world\u27s largest and longest-running public works programs, using satellite-based data of tree cover combined with difference-in-differences and inverse probability treatment weighting methodologies. We find that the PSNP increased tree cover by 3.8% between 2005 and 2019, with larger increases in less densely populated areas and on steep-sloped terrain. As increasing tree cover is considered an important strategy to mitigate global warming, our results suggest a win–win potential for social safety net programs with an environmental component

Reading visually embodied meaning from the brain: Visually grounded computational models decode visual-object mental imagery induced by written text

Embodiment theory predicts that mental imagery of object words recruits neural circuits involved in object perception. The degree of visual imagery present in routine thought and how it is encoded in the brain is largely unknown. We test whether fMRI activity patterns elicited by participants reading objects' names include embodied visual-object representations, and whether we can decode the representations using novel computational image-based semantic models. We first apply the image models in conjunction with text-based semantic models to test predictions of visual-specificity of semantic representations in different brain regions. Representational similarity analysis confirms that fMRI structure within ventral-temporal and lateral-occipital regions correlates most strongly with the image models and conversely text models correlate better with posterior-parietal/lateral-temporal/inferior-frontal regions. We use an unsupervised decoding algorithm that exploits commonalities in representational similarity structure found within both image model and brain data sets to classify embodied visual representations with high accuracy (8/10) and then extend it to exploit model combinations to robustly decode different brain regions in parallel. By capturing latent visual-semantic structure our models provide a route into analyzing neural representations derived from past perceptual experience rather than stimulus-driven brain activity. Our results also verify the benefit of combining multimodal data to model human-like semantic representations

Non-Clifford and parallelizable fault-tolerant logical gates on constant and almost-constant rate homological quantum LDPC codes via higher symmetries

We study parallel fault-tolerant quantum computing for families of homological quantum low-density parity-check (LDPC) codes defined on 3-manifolds with constant or almost-constant encoding rate. We derive generic formula for a transversal $T$ gate of color codes on general 3-manifolds, which acts as collective non-Clifford logical CCZ gates on any triplet of logical qubits with their logical-$X$ membranes having a $\mathbb{Z}_2$ triple intersection at a single point. The triple intersection number is a topological invariant, which also arises in the path integral of the emergent higher symmetry operator in a topological quantum field theory: the $\mathbb{Z}_2^3$ gauge theory. Moreover, the transversal $S$ gate of the color code corresponds to a higher-form symmetry supported on a codimension-1 submanifold, giving rise to exponentially many addressable and parallelizable logical CZ gates. We have developed a generic formalism to compute the triple intersection invariants for 3-manifolds and also study the scaling of the Betti number and systoles with volume for various 3-manifolds, which translates to the encoding rate and distance. We further develop three types of LDPC codes supporting such logical gates: (1) A quasi-hyperbolic code from the product of 2D hyperbolic surface and a circle, with almost-constant rate $k/n=O(1/\log(n))$ and $O(\log(n))$ distance; (2) A homological fibre bundle code with $O(1/\log^{\frac{1}{2}}(n))$ rate and $O(\log^{\frac{1}{2}}(n))$ distance; (3) A specific family of 3D hyperbolic codes: the Torelli mapping torus code, constructed from mapping tori of a pseudo-Anosov element in the Torelli subgroup, which has constant rate while the distance scaling is currently unknown. We then show a generic constant-overhead scheme for applying a parallelizable universal gate set with the aid of logical-$X$ measurements.Comment: 40 pages, 31 figure

Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells.

Chemokines have a central role in regulating processes essential to the immune function of T cells, such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the pathogen Toxoplasma gondii in the brains of chronically infected mice. This chemokine boosts T-cell function in two different ways: it maintains the effector T-cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Notably, these statistics are not Brownian; rather, CD8+ T-cell motility in the brain is well described by a generalized Lévy walk. According to our model, this unexpected feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8+ T-cell behaviour is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys, and CXCL10 aids T cells in shortening the average time taken to find rare targets

The quest for greener pastures: evaluating the livelihoods impacts of providing vegetation condition maps to pastoralists in Eastern Africa

The survival of millions of pastoral households in Eastern Africa has become increasingly at risk. Due to mounting socioeconomic and climatic stressors, pastoral households are faced with making migration decisions under increasing uncertainty about resource availability and limited coping strategies. We assess the potential of providing vegetation condition maps to support the migration decision of pastoralists in Ethiopia and Tanzania and the effect of map usage on their herd condition and size. The maps were generated from remotely sensed data using the Normalized Difference Vegetation Index (NDVI) as a proxy for vegetation condition and overlain with pastoralists’ preferred grazing areas. The use of maps for migration decisions was low in both study areas, partly due to challenges in map distribution (26% and 2% in Ethiopia at midline and endline respectively; and 35% and 29% in Tanzania at midline and endline respectively). However, map adopters in both countries reported an overwhelmingly positive experience and found maps accurate and helpful. Map usage was associated with improved animal condition in Tanzania, but we find no causal evidence that map usage affected herd size