Human Knockout Carriers: Dead, Diseased, Healthy, or Improved?

Whole-genome and whole-exome sequence data from large numbers of individuals reveal that we all carry many variants predicted to inactivate genes (knockouts). This discovery raises questions about the phenotypic consequences of these knockouts and potentially allows us to study human gene function through the investigation of homozygous loss-of-function carriers. Here, we discuss strategies, recent results, and future prospects for large-scale human knockout studies. We examine their relevance to studying gene function, population genetics, and importantly, the implications for accurate clinical interpretations

Estimating α-Rank from A Few Entries with Low Rank Matrix Completion

Multi-agent evaluation aims at the assessment of an agent's strategy on the basis of interaction with others. Typically, existing methods such as α-rank and its approximation still require to exhaustively compare all pairs of joint strategies for an accurate ranking, which in practice is computationally expensive. In this paper, we aim to reduce the number of pairwise comparisons in recovering a satisfying ranking for n strategies in two-player meta-games, by exploring the fact that agents with similar skills may achieve similar payoffs against others. Two situations are considered: the first one is when we can obtain the true payoffs; the other one is when we can only access noisy payoff. Based on these formulations, we leverage low-rank matrix completion and design two novel algorithms for noise-free and noisy evaluations respectively. For both of these settings, we theorize that O(nr log n) (n is the number of agents and r is the rank of the payoff matrix) payoff entries are required to achieve sufficiently well strategy evaluation performance. Empirical results on evaluating the strategies in three synthetic games and twelve real world games demonstrate that strategy evaluation from a few entries can lead to comparable performance to algorithms with full knowledge of the payoff matrix

Learning to Identify Top Elo Ratings: A Dueling Bandits Approach

The Elo rating system is widely adopted to evaluate the skills of (chess) game and sports players. Recently it has been also integrated into machine learning algorithms in evaluating the performance of computerised AI agents. However, an accurate estimation of the Elo rating (for the top players) often requires many rounds of competitions, which can be expensive to carry out. In this paper, to improve the sample efficiency of the Elo evaluation (for top players), we propose an efficient online match scheduling algorithm. Specifically, we identify and match the top players through a dueling bandits framework and tailor the bandit algorithm to the gradient-based update of Elo. We show that it reduces the per-step memory and time complexity to constant, compared to the traditional likelihood maximization approaches requiring O(t) time. Our algorithm has a regret guarantee of Õ(√T), sublinear in the number of competition rounds and has been extended to the multidimensional Elo ratings for handling intransitive games. We empirically demonstrate that our method achieves superior convergence speed and time efficiency on a variety of gaming tasks

New environmental dependent modelling with Gaussian particle filtering based implementation for ground vehicle tracking

This paper proposes a new domain knowledge aided Gaussian particle filtering based approach for the ground vehicle tracking application. Firstly, a new form of modelling is proposed to reflect the influences of different types of environmental domain knowledge on the vehicle dynamic: i) a non-Markov jump model is applied with multiple models while transition probabilities between models are environmental dependent ii) for a particular model, both the constraints and potential forces obtained from the surrounding environment have been applied to refine the vehicle state distribution. Based on the proposed modelling approach, a Gaussian particle filtering based method is developed to implement the related Bayesian inference for the target state estimation. Simulation studies from multiple Monte Carlo simulations confirm the advantages of the proposed method over traditional ones, from both the modelling and implementation aspects

Vortex-induced Shear Polaritons

Hyperbolic shear polaritons (HShPs) emerge with widespread attention as a new class of polariton modes with broken symmetry due to shear lattices. In this letter, we find a new mechanism of generating HShPs. When utilizing vortex waves as excitation sources of hyperbolic materials without off-diagonal elements, HShPs will appear. In addition, this asymmetric HShPs can be recovered as symmetric modes away from the source, with a critical transition mode between the left-skewed and right-skewed HShPs, via tuning the magnitude of the off-diagonal imaginary component and controlling the topological charge of vortex source. It is worth mentioning that we explore the influence of parity of topological charges on the field distribution and demonstrate these exotic phenomena from numerical and analytical perspectives. Our results will promote new opportunities for both HShPs and vortex waves, widening the horizon for various hyperbolic materials based on vortex sources and offering a new degree of freedom to control various kinds of polaritons

The evolutionary history of new zealand deschampsia is marked by long-distance dispersal, endemism, and hybridization

The contrasting evolutionary histories of endemic versus related cosmopolitan species provide avenues to understand the spatial drivers and limitations of biodiversity. Here, we investigated the evolutionary history of three New Zealand endemic Deschampsia species, and how they are related to cosmopolitan D. cespitosa. We used RADseq to test species delimitations, infer a dated species tree, and investigate gene flow patterns between the New Zealand endemics and the D. cespitosa populations of New Zealand, Australia and Korea. Whole plastid DNA analysis was performed on a larger worldwide sampling. Morphometrics of selected characters were applied to New Zealand sampling. Our RADseq review of over 55 Mbp showed the endemics as genetically well-defined from each other. Their last common ancestor with D. cespitosa lived during the last ten MY. The New Zealand D. cespitosa appears in a clade with Australian and Korean samples. Whole plastid DNA analysis revealed the endemics as members of a southern hemisphere clade, excluding the extant D. cespitosa of New Zealand. Both data provided strong evidence for hybridization between D. cespitosa and D. chapmanii. Our findings provide evidence for at least two migration events of the genus Deschampsia to New Zealand and hybridization between D. cespitosa and endemic taxa.Fil: Xue, Yali. Universidad de Viena; AustriaFil: Greimler, Josef. Universidad de Viena; AustriaFil: Paun, Ovidiu. Universidad de Viena; AustriaFil: Ford, Kerry A.. Allan Herbarium; Nueva ZelandaFil: Barfuss, Michael H. J.. Universidad de Viena; AustriaFil: Chiapella, Jorge Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentin

The evolutionary history of new zealand deschampsia is marked by long-distance dispersal, endemism, and hybridization

The contrasting evolutionary histories of endemic versus related cosmopolitan species provide avenues to understand the spatial drivers and limitations of biodiversity. Here, we investigated the evolutionary history of three New Zealand endemic Deschampsia species, and how they are related to cosmopolitan D. cespitosa. We used RADseq to test species delimitations, infer a dated species tree, and investigate gene flow patterns between the New Zealand endemics and the D. cespitosa populations of New Zealand, Australia and Korea. Whole plastid DNA analysis was performed on a larger worldwide sampling. Morphometrics of selected characters were applied to New Zealand sampling. Our RADseq review of over 55 Mbp showed the endemics as genetically well-defined from each other. Their last common ancestor with D. cespitosa lived during the last ten MY. The New Zealand D. cespitosa appears in a clade with Australian and Korean samples. Whole plastid DNA analysis revealed the endemics as members of a southern hemisphere clade, excluding the extant D. cespitosa of New Zealand. Both data provided strong evidence for hybridization between D. cespitosa and D. chapmanii. Our findings provide evidence for at least two migration events of the genus Deschampsia to New Zealand and hybridization between D. cespitosa and endemic taxa.Fil: Xue, Yali. Universidad de Viena; AustriaFil: Greimler, Josef. Universidad de Viena; AustriaFil: Paun, Ovidiu. Universidad de Viena; AustriaFil: Ford, Kerry A.. Allan Herbarium; Nueva ZelandaFil: Barfuss, Michael H. J.. Universidad de Viena; AustriaFil: Chiapella, Jorge Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentin

Replication of the Association of a MET Variant with Autism in a Chinese Han Population

Background: Autism is a common, severe and highly heritable neurodevelopmental disorder in children, affecting up to 100 children per 10,000. The MET gene has been regarded as a promising candidate gene for this disorder because it is located within a replicated linkage interval, is involved in pathways affecting the development of the cerebral cortex and cerebellum in ways relevant to autism patients, and has shown significant association signals in previous studies. Principal Findings: Here, we present new ASD patient and control samples from Heilongjiang, China and use them in a case-control and family-based replication study of two MET variants. One SNP, rs38845, was successfully replicated in a case-control association study, but failed to replicate in a family-based study, possibly due to small sample size. The other SNP, rs1858830, failed to replicate in both case-control and family-based studies. Conclusions: This is the first attempt to replicate associations in Chinese autism samples, and our result provides evidence that MET variants may be relevant to autism susceptibility in the Chinese Han population

Adaptive Fault-Tolerant Control of A Two-car High-speed Train Model with Inter-car Flexible Link and Traction Actuator Failures

This paper studies the adaptive fault-tolerant tracking control problem for the high-speed trains with intercar flexible link and traction actuator failures. This study is focused on a benchmark model which, as a main dynamic unit of the CRH (China Railway High-speed) train, is a two-car dynamic system with a flexible link between two cars, for which the input acts on the second car and the output is the speed of the first car. This model is under parameter uncertainties and subject to uncertain actuator failures. For such an underactuated system, to ensure the first car tracking a desired speed trajectory, a coordinate transformation method is employed to decompose the system model into a control dynamics subsystem and a zero dynamics subsystem. Stability analysis is conducted to show that such a zero dynamic system is Lyapunov stable and is partially input-to-state stable. An adaptive fault-tolerant control scheme is developed which is able to ensure the closedloop system signal boundedness and desired speed tracking, in the presence of the unknown system parameters and actuator failures. Simulation results from a realistic train dynamic model are presented to verify the desired adaptive control system performance