A Stochastic Approach to Shortcut Bridging in Programmable Matter

In a self-organizing particle system, an abstraction of programmable matter, simple computational elements called particles with limited memory and communication self-organize to solve system-wide problems of movement, coordination, and configuration. In this paper, we consider a stochastic, distributed, local, asynchronous algorithm for "shortcut bridging", in which particles self-assemble bridges over gaps that simultaneously balance minimizing the length and cost of the bridge. Army ants of the genus Eciton have been observed exhibiting a similar behavior in their foraging trails, dynamically adjusting their bridges to satisfy an efficiency trade-off using local interactions. Using techniques from Markov chain analysis, we rigorously analyze our algorithm, show it achieves a near-optimal balance between the competing factors of path length and bridge cost, and prove that it exhibits a dependence on the angle of the gap being "shortcut" similar to that of the ant bridges. We also present simulation results that qualitatively compare our algorithm with the army ant bridging behavior. Our work gives a plausible explanation of how convergence to globally optimal configurations can be achieved via local interactions by simple organisms (e.g., ants) with some limited computational power and access to random bits. The proposed algorithm also demonstrates the robustness of the stochastic approach to algorithms for programmable matter, as it is a surprisingly simple extension of our previous stochastic algorithm for compression.Comment: Published in Proc. of DNA23: DNA Computing and Molecular Programming - 23rd International Conference, 2017. An updated journal version will appear in the DNA23 Special Issue of Natural Computin

Fast Approximate Geodesics for Deep Generative Models

The length of the geodesic between two data points along a Riemannian manifold, induced by a deep generative model, yields a principled measure of similarity. Current approaches are limited to low-dimensional latent spaces, due to the computational complexity of solving a non-convex optimisation problem. We propose finding shortest paths in a finite graph of samples from the aggregate approximate posterior, that can be solved exactly, at greatly reduced runtime, and without a notable loss in quality. Our approach, therefore, is hence applicable to high-dimensional problems, e.g., in the visual domain. We validate our approach empirically on a series of experiments using variational autoencoders applied to image data, including the Chair, FashionMNIST, and human movement data sets.Comment: 28th International Conference on Artificial Neural Networks, 201

Outbreak of Middle East Respiratory Syndrome at Tertiary Care Hospital, Jeddah, Saudi Arabia, 2014

During March–May 2014, a Middle East respiratory syndrome (MERS) outbreak occurred in Jeddah, Saudi Arabia, that included many persons who worked or received medical treatment at King Fahd General Hospital. We investigated 78 persons who had laboratory-confirmed MERS during March 2–May 10 and documented contact at this hospital. The 78 persons with MERS comprised 53 patients, 16 healthcare workers, and 9 visitors. Among the 53 patients, the most probable sites of acquisition were the emergency department (22 patients), inpatient areas (17), dialysis unit (11), and outpatient areas (3). Infection control deficiencies included limited separation of suspected MERS patients, patient crowding, and inconsistent use of infection control precautions; aggressive improvements in these deficiencies preceded a decline in cases. MERS coronavirus transmission probably was multifocal, occurring in multiple hospital settings. Continued vigilance and strict application of infection control precautions are necessary to prevent future MERS outbreaks

The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters

Unintended Consequences of Conservation Actions: Managing Disease in Complex Ecosystems

Infectious diseases are increasingly recognised to be a major threat to biodiversity. Disease management tools such as control of animal movements and vaccination can be used to mitigate the impact and spread of diseases in targeted species. They can reduce the risk of epidemics and in turn the risks of population decline and extinction. However, all species are embedded in communities and interactions between species can be complex, hence increasing the chance of survival of one species can have repercussions on the whole community structure. In this study, we use an example from the Serengeti ecosystem in Tanzania to explore how a vaccination campaign against Canine Distemper Virus (CDV) targeted at conserving the African lion (Panthera leo), could affect the viability of a coexisting threatened species, the cheetah (Acinonyx jubatus). Assuming that CDV plays a role in lion regulation, our results suggest that a vaccination programme, if successful, risks destabilising the simple two-species system considered, as simulations show that vaccination interventions could almost double the probability of extinction of an isolated cheetah population over the next 60 years. This work uses a simple example to illustrate how predictive modelling can be a useful tool in examining the consequence of vaccination interventions on non-target species. It also highlights the importance of carefully considering linkages between human-intervention, species viability and community structure when planning species-based conservation actions

Mutability and Importance of a Hypermutable Cell Subpopulation that Produces Stress-Induced Mutants in Escherichia coli

In bacterial, yeast, and human cells, stress-induced mutation mechanisms are induced in growth-limiting environments and produce non-adaptive and adaptive mutations. These mechanisms may accelerate evolution specifically when cells are maladapted to their environments, i.e., when they are are stressed. One mechanism of stress-induced mutagenesis in Escherichia coli occurs by error-prone DNA double-strand break (DSB) repair. This mechanism was linked previously to a differentiated subpopulation of cells with a transiently elevated mutation rate, a hypermutable cell subpopulation (HMS). The HMS could be important, producing essentially all stress-induced mutants. Alternatively, the HMS was proposed to produce only a minority of stress-induced mutants, i.e., it was proposed to be peripheral. We characterize three aspects of the HMS. First, using improved mutation-detection methods, we estimate the number of mutations per genome of HMS-derived cells and find that it is compatible with fitness after the HMS state. This implies that these mutants are not necessarily an evolutionary dead end, and could contribute to adaptive evolution. Second, we show that stress-induced Lac+ mutants, with and without evidence of descent from the HMS, have similar Lac+ mutation sequences. This provides evidence that HMS-descended and most stress-induced mutants form via a common mechanism. Third, mutation-stimulating DSBs introduced via I-SceI endonuclease in vivo do not promote Lac+ mutation independently of the HMS. This and the previous finding support the hypothesis that the HMS underlies most stress-induced mutants, not just a minority of them, i.e., it is important. We consider a model in which HMS differentiation is controlled by stress responses. Differentiation of an HMS potentially limits the risks of mutagenesis in cell clones

Maternal Feeding Controls Fetal Biological Clock

BACKGROUND: It is widely accepted that circadian physiological rhythms of the fetus are affected by oscillators in the maternal brain that are coupled to the environmental light-dark (LD) cycle. METHODOLOGY/PRINCIPAL FINDINGS: To study the link between fetal and maternal biological clocks, we investigated the effects of cycles of maternal food availability on the rhythms of Per1 gene expression in the fetal suprachiasmatic nucleus (SCN) and liver using a transgenic rat model whose tissues express luciferase in vitro. Although the maternal SCN remained phase-locked to the LD cycle, maternal restricted feeding phase-advanced the fetal SCN and liver by 5 and 7 hours respectively within the 22-day pregnancy. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that maternal feeding entrains the fetal SCN and liver independently of both the maternal SCN and the LD cycle. This indicates that maternal-feeding signals can be more influential for the fetal SCN and particular organ oscillators than hormonal signals controlled by the maternal SCN, suggesting the importance of a regular maternal feeding schedule for appropriate fetal molecular clockwork during pregnancy

The changing landscape of genetic testing and its impact on clinical and laboratory services and research in Europe

The arrival of new genetic technologies that allow efficient examination of the whole human genome (microarray, next-generation sequencing) will impact upon both laboratories (cytogenetic and molecular genetics in the first instance) and clinical/medical genetic services. The interpretation of analytical results in terms of their clinical relevance and the predicted health status poses a challenge to both laboratory and clinical geneticists, due to the wealth and complexity of the information obtained. There is a need to discuss how to best restructure the genetic services logistically and to determine the clinical utility of genetic testing so that patients can receive appropriate advice and genetic testing. To weigh up the questions and challenges of the new genetic technologies, the European Society of Human Genetics (ESHG) held a series of workshops on 10 June 2010 in Gothenburg. This was part of an ESHG satellite symposium on the 'Changing landscape of genetic testing', co-organized by the ESHG Genetic Services Quality and Public and Professional Policy Committees. The audience consisted of a mix of geneticists, ethicists, social scientists and lawyers. In this paper, we summarize the discussions during the workshops and present some of the identified ways forward to improve and adapt the genetic services so that patients receive accurate and relevant information. This paper covers ethics, clinical utility, primary care, genetic services and the blurring boundaries between healthcare and research

In vitro susceptibility to pyrimethamine of DHFR I164L single mutant Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>Recently, <it>Plasmodium falciparum </it>parasites bearing <it>Pfdhfr </it>I164L single mutation were found in Madagascar. These new mutants may challenge the use of antifolates for the intermittent preventive treatment of malaria during pregnancy (IPTp). Assays with transgenic bacteria suggested that I164L parasites have a wild-type phenotype for pyrimethamine but it had to be confirmed by testing the parasites themselves.</p> <p>Methods</p> <p>Thirty <it>Plasmodium falciparum </it>clinical isolates were collected in 2008 in the south-east of Madagascar. A part of <it>Pfdhfr </it>gene encompassing codons 6 to 206 was amplified by PCR and the determination of the presence of single nucleotide polymorphisms was performed by DNA sequencing. The multiplicity of infection was estimated by using an allelic family-specific nested PCR. Isolates that appeared monoclonal were submitted to culture adaptation. Determination of IC_50sto pyrimethamine was performed on adapted isolates.</p> <p>Results</p> <p>Four different <it>Pfdhfr </it>alleles were found: the 164L single mutant-type (N = 13), the wild-type (N = 7), the triple mutant-type 51I/59R/108N (N = 9) and the double mutant-type 108N/164L (N = 1). Eleven out 30 (36.7%) of <it>P. falciparum </it>isolates were considered as monoclonal infection. Among them, five isolates were successfully adapted in culture and tested for pyrimethamine <it>in vitro </it>susceptibility. The wild-type allele was the most susceptible with a 50% inhibitory concentration (IC₅₀) < 10 nM. The geometric mean of IC₅₀of the three I164L mutant isolates was 6-fold higher than the wild-type with 61.3 nM (SD = 3.2 nM, CI95%: 53.9-69.7 nM). These values remained largely below the IC₅₀of the triple mutant parasite (13,804 nM).</p> <p>Conclusion</p> <p>The IC₅₀s of the I164L mutant isolates were significantly higher than those of the wild-type (6-fold higher) and close from those usually reported for simple mutants S108N (roughly10-fold higher than wild type). Given the observed values, the determination of IC₅₀s directly on parasites did not confirm what has been found on transgenic bacteria. The prevalence increase of the <it>Pfdhfr </it>I164L single mutant parasite since 2006 could be explained by the selective advantage of this allele under sulphadoxine-pyrimethamine pressure. The emergence of highly resistant alleles should be considered in the future, in particular because an unexpected double mutant-type allele S108N/I164L has been already detected.</p

Functional Desaturase Fads1 (Δ5) and Fads2 (Δ6) Orthologues Evolved before the Origin of Jawed Vertebrates

Long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are essential components of biomembranes, particularly in neural tissues. Endogenous synthesis of ARA, EPA and DHA occurs from precursor dietary essential fatty acids such as linoleic and α-linolenic acid through elongation and Δ5 and Δ6 desaturations. With respect to desaturation activities some noteworthy differences have been noted in vertebrate classes. In mammals, the Δ5 activity is allocated to the Fads1 gene, while Fads2 is a Δ6 desaturase. In contrast, teleosts show distinct combinations of desaturase activities (e.g. bifunctional or separate Δ5 and Δ6 desaturases) apparently allocated to Fads2-type genes. To determine the timing of Fads1-Δ5 and Fads2-Δ6 evolution in vertebrates we used a combination of comparative and functional genomics with the analysis of key phylogenetic species. Our data show that Fads1 and Fads2 genes with Δ5 and Δ6 activities respectively, evolved before gnathostome radiation, since the catshark Scyliorhinus canicula has functional orthologues of both gene families. Consequently, the loss of Fads1 in teleosts is a secondary episode, while the existence of Δ5 activities in the same group most likely occurred through independent mutations into Fads2 type genes. Unexpectedly, we also establish that events of Fads1 gene expansion have taken place in birds and reptiles. Finally, a fourth Fads gene (Fads4) was found with an exclusive occurrence in mammalian genomes. Our findings enlighten the history of a crucially important gene family in vertebrate fatty acid metabolism and physiology and provide an explanation of how observed lineage-specific gene duplications, losses and diversifications might be linked to habitat-specific food web structures in different environments and over geological timescales