Developmental gene regulatory network architecture across 500 million years of echinoderm evolution

Evolutionary change in morphological features must depend on architectural reorganization of developmental gene regulatory networks (GRNs), just as true conservation of morphological features must imply retention of ancestral developmental GRN features. Key elements of the provisional GRN for embryonic endomesoderm development in the sea urchin are here compared with those operating in embryos of a distantly related echinoderm, a starfish. These animals diverged from their common ancestor 520-480 million years ago. Their endomesodermal fate maps are similar, except that sea urchins generate a skeletogenic cell lineage that produces a prominent skeleton lacking entirely in starfish larvae. A relevant set of regulatory genes was isolated from the starfish Asterina miniata, their expression patterns determined, and effects on the other genes of perturbing the expression of each were demonstrated. A three-gene feedback loop that is a fundamental feature of the sea urchin GRN for endoderm specification is found in almost identical form in the starfish: a detailed element of GRN architecture has been retained since the Cambrian Period in both echinoderm lineages. The significance of this retention is highlighted by the observation of numerous specific differences in the GRN connections as well. A regulatory gene used to drive skeletogenesis in the sea urchin is used entirely differently in the starfish, where it responds to endomesodermal inputs that do not affect it in the sea urchin embryo. Evolutionary changes in the GRNs since divergence are limited sharply to certain cis-regulatory elements, whereas others have persisted unaltered

The Solution Distribution of Influence Maximization: A High-level Experimental Study on Three Algorithmic Approaches

Influence maximization is among the most fundamental algorithmic problems in social influence analysis. Over the last decade, a great effort has been devoted to developing efficient algorithms for influence maximization, so that identifying the ``best'' algorithm has become a demanding task. In SIGMOD'17, Arora, Galhotra, and Ranu reported benchmark results on eleven existing algorithms and demonstrated that there is no single state-of-the-art offering the best trade-off between computational efficiency and solution quality. In this paper, we report a high-level experimental study on three well-established algorithmic approaches for influence maximization, referred to as Oneshot, Snapshot, and Reverse Influence Sampling (RIS). Different from Arora et al., our experimental methodology is so designed that we examine the distribution of random solutions, characterize the relation between the sample number and the actual solution quality, and avoid implementation dependencies. Our main findings are as follows: 1. For a sufficiently large sample number, we obtain a unique solution regardless of algorithms. 2. The average solution quality of Oneshot, Snapshot, and RIS improves at the same rate up to scaling of sample number. 3. Oneshot requires more samples than Snapshot, and Snapshot requires fewer but larger samples than RIS. We discuss the time efficiency when conditioning Oneshot, Snapshot, and RIS to be of identical accuracy. Our conclusion is that Oneshot is suitable only if the size of available memory is limited, and RIS is more efficient than Snapshot for large networks; Snapshot is preferable for small, low-probability networks.Comment: To appear in SIGMOD 202

The prototype HIV-1 maturation inhibitor, bevirimat, binds to the CA-SP1 cleavage site in immature Gag particles

<p>Abstract</p> <p>Background</p> <p>Bevirimat, the prototype Human Immunodeficiency Virus type 1 (HIV-1) maturation inhibitor, is highly potent in cell culture and efficacious in HIV-1 infected patients. In contrast to inhibitors that target the active site of the viral protease, bevirimat specifically inhibits a single cleavage event, the final processing step for the Gag precursor where p25 (CA-SP1) is cleaved to p24 (CA) and SP1.</p> <p>Results</p> <p>In this study, photoaffinity analogs of bevirimat and mass spectrometry were employed to map the binding site of bevirimat to Gag within immature virus-like particles. Bevirimat analogs were found to crosslink to sequences overlapping, or proximal to, the CA-SP1 cleavage site, consistent with previous biochemical data on the effect of bevirimat on Gag processing and with genetic data from resistance mutations, in a region predicted by NMR and mutational studies to have α-helical character. Unexpectedly, a second region of interaction was found within the Major Homology Region (MHR). Extensive prior genetic evidence suggests that the MHR is critical for virus assembly.</p> <p>Conclusions</p> <p>This is the first demonstration of a direct interaction between the maturation inhibitor, bevirimat, and its target, Gag. Information gained from this study sheds light on the mechanisms by which the virus develops resistance to this class of drug and may aid in the design of next-generation maturation inhibitors.</p

Jamming and Fluctuations in Granular Drag

We investigate the dynamic evolution of jamming in granular media through fluctuations in the granular drag force. The successive collapse and formation of jammed states give a stick-slip nature to the fluctuations which is independent of the contact surface between the grains and the dragged object -- thus implying that the stress-induced collapse is nucleated in the bulk of the granular sample. We also find that while the fluctuations are periodic at small depths, they become "stepped" at large depths, a transition which we interpret as a consequence of the long-range nature of the force chains.Comment: 7 pages, 4 figures, RevTe

U.S. stock market interaction network as learned by the Boltzmann Machine

We study historical dynamics of joint equilibrium distribution of stock returns in the U.S. stock market using the Boltzmann distribution model being parametrized by external fields and pairwise couplings. Within Boltzmann learning framework for statistical inference, we analyze historical behavior of the parameters inferred using exact and approximate learning algorithms. Since the model and inference methods require use of binary variables, effect of this mapping of continuous returns to the discrete domain is studied. The presented analysis shows that binarization preserves market correlation structure. Properties of distributions of external fields and couplings as well as industry sector clustering structure are studied for different historical dates and moving window sizes. We found that a heavy positive tail in the distribution of couplings is responsible for the sparse market clustering structure. We also show that discrepancies between the model parameters might be used as a precursor of financial instabilities.Comment: 15 pages, 17 figures, 1 tabl

Investigation of the effects of time periodic pressure and potential gradients on viscoelastic fluid flow in circular narrow confinements

In this paper we present an in-depth analysis and analytical solution for time periodic hydrodynamic flow (driven by a time-dependent pressure gradient and electric field) of viscoelastic fluid through cylindrical micro- and nanochannels. Particularly, we solve the linearized Poisson–Boltzmann equation, together with the incompressible Cauchy momentum equation under no-slip boundary conditions for viscoelastic fluid in the case of a combination of time periodic pressure-driven and electro-osmotic flow. The resulting solutions allow us to predict the electrical current and solution flow rate. As expected from the assumption of linear viscoelasticity, the results satisfy the Onsager reciprocal relation, which is important since it enables an analogy between fluidic networks in this flow configuration and electric circuits. The results especially are of interest for micro- and nanofluidic energy conversion applications. We also found that time periodic electro-osmotic flow in many cases is much stronger enhanced than time periodic pressure-driven flow when comparing the flow profiles of oscillating PDF and EOF in micro- and nanochannels. The findings advance our understanding of time periodic electrokinetic phenomena of viscoelastic fluids and provide insight into flow characteristic as well as assist the design of devices for lab-on-chip applications

Establishment of a Wolbachia Superinfection in Aedes aegypti Mosquitoes as a Potential Approach for Future Resistance Management.

Wolbachia pipientis is an endosymbiotic bacterium estimated to chronically infect between 40-75% of all arthropod species. Aedes aegypti, the principle mosquito vector of dengue virus (DENV), is not a natural host of Wolbachia. The transinfection of Wolbachia strains such as wAlbB, wMel and wMelPop-CLA into Ae. aegypti has been shown to significantly reduce the vector competence of this mosquito for a range of human pathogens in the laboratory. This has led to wMel-transinfected Ae. aegypti currently being released in five countries to evaluate its effectiveness to control dengue disease in human populations. Here we describe the generation of a superinfected Ae. aegypti mosquito line simultaneously infected with two avirulent Wolbachia strains, wMel and wAlbB. The line carries a high overall Wolbachia density and tissue localisation of the individual strains is very similar to each respective single infected parental line. The superinfected line induces unidirectional cytoplasmic incompatibility (CI) when crossed to each single infected parental line, suggesting that the superinfection would have the capacity to replace either of the single constituent infections already present in a mosquito population. No significant differences in fitness parameters were observed between the superinfected line and the parental lines under the experimental conditions tested. Finally, the superinfected line blocks DENV replication more efficiently than the single wMel strain when challenged with blood meals from viremic dengue patients. These results suggest that the deployment of superinfections could be used to replace single infections and may represent an effective strategy to help manage potential resistance by DENV to field deployments of single infected strains

Optical Propagation and Communication

Contains reports on four research projects.National Science Foundation (Grant ECS81-20637)U.S. Navy - Office of Naval Research (Contract N00014-81-K-0662)U.S. Army Research Office - Durham (Contract DAAG29-80-K-0022)U.S. Navy - Office of Naval Research (Contract N00014-80-C-0941

Unfolding-based Dynamic Partial Order Reduction of Asynchronous Distributed Programs

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