Genome-wide screen for genes involved in Caenorhabditis elegans developmentally timed sleep

In Caenorhabditis elegans, Notch signaling regulates developmentally timed sleep during the transition from L4 larval stage to adulthood (L4/A) . To identify core sleep pathways and to find genes acting downstream of Notch signaling, we undertook the first genome-wide, classical genetic screen focused on C. elegans developmentally timed sleep. To increase screen efficiency, we first looked for mutations that suppressed inappropriate anachronistic sleep in adult hsp::osm-11 animals overexpressing the Notch coligand OSM-11 after heat shock. We retained suppressor lines that also had defects in L4/A developmentally timed sleep, without heat shock overexpression of the Notch coligand. Sixteen suppressor lines with defects in developmentally timed sleep were identified. One line carried a new allele of goa-1; loss of GOA-1 Gαo decreased C. elegans sleep. Another line carried a new allele of gpb-2, encoding a Gβ5 protein; Gβ5 proteins have not been previously implicated in sleep. In other scenarios, Gβ5 GPB-2 acts with regulators of G protein signaling (RGS proteins) EAT-16 and EGL-10 to terminate either EGL-30 Gαq signaling or GOA-1 Gαo signaling, respectively. We found that loss of Gβ5 GPB-2 or RGS EAT-16 decreased L4/A sleep. By contrast, EGL-10 loss had no impact. Instead, loss of RGS-1 and RGS-2 increased sleep. Combined, our results suggest that, in the context of L4/A sleep, GPB-2 predominantly acts with EAT-16 RGS to inhibit EGL-30 Gαq signaling. These results confirm the importance of G protein signaling in sleep and demonstrate that these core sleep pathways function genetically downstream of the Notch signaling events promoting sleep

A* Orthogonal Matching Pursuit: Best-First Search for Compressed Sensing Signal Recovery

Compressed sensing is a developing field aiming at reconstruction of sparse signals acquired in reduced dimensions, which make the recovery process under-determined. The required solution is the one with minimum $\ell_0$ norm due to sparsity, however it is not practical to solve the $\ell_0$ minimization problem. Commonly used techniques include $\ell_1$ minimization, such as Basis Pursuit (BP) and greedy pursuit algorithms such as Orthogonal Matching Pursuit (OMP) and Subspace Pursuit (SP). This manuscript proposes a novel semi-greedy recovery approach, namely A* Orthogonal Matching Pursuit (A*OMP). A*OMP performs A* search to look for the sparsest solution on a tree whose paths grow similar to the Orthogonal Matching Pursuit (OMP) algorithm. Paths on the tree are evaluated according to a cost function, which should compensate for different path lengths. For this purpose, three different auxiliary structures are defined, including novel dynamic ones. A*OMP also incorporates pruning techniques which enable practical applications of the algorithm. Moreover, the adjustable search parameters provide means for a complexity-accuracy trade-off. We demonstrate the reconstruction ability of the proposed scheme on both synthetically generated data and images using Gaussian and Bernoulli observation matrices, where A*OMP yields less reconstruction error and higher exact recovery frequency than BP, OMP and SP. Results also indicate that novel dynamic cost functions provide improved results as compared to a conventional choice.Comment: accepted for publication in Digital Signal Processin

Abelian Links, Monopoles and Glueballs in SU(2) Lattice Gauge Theory

We investigate the masses of 0+ and 2+ glueballs in SU(2) lattice gauge theory using abelian projection to the maximum abelian gauge. We calculate glueball masses using both abelian links and monopole operators. Both methods reproduce the known full SU(2) results quantitatively. Positivity problems present in the abelian projection are discussed. We study the dependence of the glueball masses on magnetic current loop size, and find that the 0+ state requires a much greater range of sizes than does the 2+ state.Comment: 18 pages, latex, 4 postscript figure

Query Complexity of Approximate Equilibria in Anonymous Games

We study the computation of equilibria of anonymous games, via algorithms that may proceed via a sequence of adaptive queries to the game's payoff function, assumed to be unknown initially. The general topic we consider is \emph{query complexity}, that is, how many queries are necessary or sufficient to compute an exact or approximate Nash equilibrium. We show that exact equilibria cannot be found via query-efficient algorithms. We also give an example of a 2-strategy, 3-player anonymous game that does not have any exact Nash equilibrium in rational numbers. However, more positive query-complexity bounds are attainable if either further symmetries of the utility functions are assumed or we focus on approximate equilibria. We investigate four sub-classes of anonymous games previously considered by \cite{bfh09, dp14}. Our main result is a new randomized query-efficient algorithm that finds a $O(n^{-1/4})$-approximate Nash equilibrium querying $\tilde{O}(n^{3/2})$ payoffs and runs in time $\tilde{O}(n^{3/2})$. This improves on the running time of pre-existing algorithms for approximate equilibria of anonymous games, and is the first one to obtain an inverse polynomial approximation in poly-time. We also show how this can be utilized as an efficient polynomial-time approximation scheme (PTAS). Furthermore, we prove that $\Omega(n \log{n})$ payoffs must be queried in order to find any $\epsilon$-well-supported Nash equilibrium, even by randomized algorithms

Taiwan's COVID-19 response : the interdependence of state and private sector institutions

During 2020, Taiwan's facemask policy formed a critical part of its relatively successful response to the COVID-19 pandemic. It also served to showcase capacities for coordinated action by state and business actors. This article demonstrates that Taiwan's ability to rapidly increase facemask production called for the government and key industry players to overcome a series of cooperation challenges. The authors show that the effective industry response required concerted action in three domains: the state sector, business–government cooperation, and cooperation among private firms. This article makes two contributions. First, it differentiates the dynamics attached to coordination, commitment and collective action challenges that actors in public and private sectors needed to overcome in order to deliver on the policy. Second, it contributes to the literature by endorsing the view that business–government cooperation and private sector coordination are complementary and interdependent. The findings presented here further illustrate the evolution of Taiwan's state institutions in their capacity to take on new tasks and modes of interaction with private sector actors.Peer reviewe

Tungsten isotope composition of the Acasta Gneiss Complex

AbstractHigh-precision tungsten (182W/184W) isotope measurements on well-characterised mafic and felsic samples of the ca. 3960 Ma Acasta Gneiss Complex (AGC; Northwest Territories, Canada) show radiogenic ε182W values between +0.06 to +0.15. Two ca. 3600 Ma felsic samples from this terrane have ε182W ∼ 0 and are the oldest samples so far documented to have a W isotopic composition indistinguishable from that of the modern mantle. The ε182W data are correlated with ε142Nd (Roth et al., 2014) and we attribute this variability to incomplete metamorphic homogenisation of the 3960 Ma protolith with more recent material in a 3370 Ma tectono-thermal event. Notably, the value of the positive ε182W anomalies seen in the 3960 Ma AGC samples that are least affected by metamorphic homogenisation is comparable to that observed in other early Archean rocks (Isua Supracrustal Belt, Greenland; Nuvvuagittuq Supracrustal Belt, Canada) and the late Archean Kostomuksha komatiites (Karelia). This demonstrates a globally constant signature. We infer that the presence of a pre-late veneer mantle represents the most straightforward interpretation of a uniform distribution of εW182∼+0.15 value in Archean rocks of different ages. We show that such a notion is compatible with independent constraints from highly siderophile element abundances in mafic and ultra-mafic Archean mantle-derived rocks. The absence of anomalous ε182W and ε142Nd so far measured in samples younger than ca. 2800 Ma suggests progressive convective homogenisation of silicate reservoirs. The downward mixing of an upper mantle rich in late-delivered meteoritic material might account for these combined observations

Improvements on Uncertainty Quantification for Node Classification via Distance-Based Regularization

Deep neural networks have achieved significant success in the last decades, but they are not well-calibrated and often produce unreliable predictions. A large number of literature relies on uncertainty quantification to evaluate the reliability of a learning model, which is particularly important for applications of out-of-distribution (OOD) detection and misclassification detection. We are interested in uncertainty quantification for interdependent node-level classification. We start our analysis based on graph posterior networks (GPNs) that optimize the uncertainty cross-entropy (UCE)-based loss function. We describe the theoretical limitations of the widely-used UCE loss. To alleviate the identified drawbacks, we propose a distance-based regularization that encourages clustered OOD nodes to remain clustered in the latent space. We conduct extensive comparison experiments on eight standard datasets and demonstrate that the proposed regularization outperforms the state-of-the-art in both OOD detection and misclassification detection.Comment: Neurips 202

A cell behavior screen: identification, sorting, and enrichment of cells based on motility

BACKGROUND: Identifying and isolating cells with specific behavioral characteristics will facilitate the understanding of the molecular basis regulating these behaviors. Although many approaches exist to characterize cell motility, retrieving cells of specific motility following analysis remains challenging. RESULTS: Cells migrating on substrates coated with fluorescent microspheres generate non-fluorescent tracks as they move and ingest the spheres. The area cleared by each cell allows for quantitation of single cell and population motility; because individual cell fluorescence is proportional to motility, cells can be sorted according to their degree of movement. Using this approach, we sorted a glioblastoma cell line into high motility and low motility populations and found stable differences in motility following sorting. CONCLUSION: We describe an approach to identify, sort, and enrich populations of cells possessing specific levels of motility. Unlike existing assays of cell motility, this approach enables recovery of characterized cell populations, and can enable screens to identify factors that might regulate motility differences even within clonal population of cells

3′,4′-Dihydroxyflavonol Reduces Superoxide and Improves Nitric Oxide Function in Diabetic Rat Mesenteric Arteries

Background: 3',4'-Dihydroxyflavonol (DiOHF) is an effective antioxidant that acutely preserves nitric oxide (NO) activity in the presence of elevated reactive oxygen species (ROS). We hypothesized that DiOHF treatment (7 days, 1 mg/kg per day s.c.) would improve relaxation in mesenteric arteries from diabetic rats where endothelial dysfunction is associated with elevated oxidant stress. Methodology/Principal Findings: In mesenteric arteries from diabetic rats there was an increase in ROS, measured by L-012 and 2',7'-dichlorodihydrofluorescein diacetate fluorescence. NADPH oxidase-derived superoxide levels, assayed by lucigenin chemiluminescence, were also significantly increased in diabetic mesenteric arteries (diabetes, 4892±946 counts/mg versus normal 2486±344 counts/mg, n = 7–10, p<0.01) associated with an increase in Nox2 expression but DiOHF (2094±300 counts/mg, n = 10, p<0.001) reversed that effect. Acetylcholine (ACh)-induced relaxation of mesenteric arteries was assessed using wire myography (pEC50 = 7.94±0.13 n = 12). Diabetes significantly reduced the sensitivity to ACh and treatment with DiOHF prevented endothelial dysfunction (pEC50, diabetic 6.86±0.12 versus diabetic+DiOHF, 7.49±0.13, n = 11, p<0.01). The contribution of NO versus endothelium-derived hyperpolarizing factor (EDHF) to ACh-induced relaxation was assessed by evaluating responses in the presence of TRAM-34+apamin+iberiotoxin or N-nitro-L-arginine+ODQ respectively. Diabetes impaired the contribution of both NO (maximum relaxation, Rmax diabetic 24±7 versus normal, 68±10, n = 9–10, p<0.01) and EDHF (pEC50, diabetic 6.63±0.15 versus normal, 7.14±0.12, n = 10–11, p<0.01) to endothelium-dependent relaxation. DiOHF treatment did not significantly affect the EDHF contribution but enhanced NO-mediated relaxation (Rmax 69±6, n = 11, p<0.01). Western blotting demonstrated that diabetes also decreased expression and increased uncoupling of endothelial NO synthase (eNOS). Treatment of the diabetic rats with DiOHF significantly reduced vascular ROS and restored NO-mediated endothelium-dependent relaxation. Treatment of the diabetic rats with DiOHF also increased eNOS expression, both in total and as a dimer. Conclusions/Significance: DiOHF improves NO activity in diabetes by reducing Nox2-dependent superoxide production and preventing eNOS uncoupling to improve endothelial function

Beyond the quark model of hadrons from lattice QCD

Lattice QCD can give direct information on OZI-violating contributions to mesons. Here we explore the contributions that split flavour singlet and non-singlet meson masses. I discuss in detail the spectrum and decays for scalar mesons (ie including glueball effects). I also review the status of hybrid mesons and their decays.Comment: to appear in proceedings of QNP2002, 3 pages, LATEX, 2 ps figure