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The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies., Wellcome Trust (London, England) (Core Award 090532/Z/09/Z), Wellcome Trust (London, England) (Senior Investigator Award 095552/Z/11/Z ), Wellcome Trust (London, England) (WT095908), Wellcome Trust (London, England) (WT109497), Wellcome Trust (London, England) (WT098051), Wellcome Trust (London, England) (WT086084/Z/08/Z), Wellcome Trust (London, England) (WT100956/Z/13/Z ), Wellcome Trust (London, England) (WT097307), Wellcome Trust (London, England) (WT0855322/Z/08/Z ), Wellcome Trust (London, England) (WT090770/Z/09/Z ), Wellcome Trust (London, England) (Major Overseas program in Vietnam grant 089276/Z.09/Z), Medical Research Council (Great Britain) (grant G0801823), Biotechnology and Biological Sciences Research Council (Great Britain) (grant BB/I02593X/1), Biotechnology and Biological Sciences Research Council (Great Britain) (grant BB/I021213/1), Zhongguo ke xue ji shu qing bao yan jiu suo. Office of 863 Programme of China (2012AA02A201), National Basic Research Program of China (2011CB809201), National Basic Research Program of China (2011CB809202), National Basic Research Program of China (2011CB809203), National Natural Science Foundation of China (31161130357), Shenzhen Municipal Government of China (grant ZYC201105170397A), Canadian Institutes of Health Research (grant 136855), Quebec Ministry of Economic Development, Innovation, and Exports (PSR-SIIRI-195), Germany. Bundesministerium für Bildung und Forschung (0315428A), Germany. Bundesministerium für Bildung und Forschung (01GS08201), Germany. Bundesministerium für Bildung und Forschung (BMBF-EPITREAT grant 0316190A), Deutsche Forschungsgemeinschaft (Emmy Noether Grant KO4037/1-1), Beatriu de Pinos Program (2006 BP-A 10144), Beatriu de Pinos Program (2009 BP-B 00274), Spanish National Institute for Health (grant PRB2 IPT13/0001-ISCIII-SGEFI/FEDER), Japan Society for the Promotion of Science (fellowship number PE13075), Marie Curie Actions Career Integration (grant 303772), Fonds National Suisse del la Recherche, SNSF, Scientifique (31003A_130342), National Center for Biotechnology Information (U.S.) (U54HG3067), National Center for Biotechnology Information (U.S.) (U54HG3273), National Center for Biotechnology Information (U.S.) (U01HG5211), National Center for Biotechnology Information (U.S.) (U54HG3079), National Center for Biotechnology Information (U.S.) (R01HG2898), National Center for Biotechnology Information (U.S.) (R01HG2385), National Center for Biotechnology Information (U.S.) (RC2HG5552), National Center for Biotechnology Information (U.S.) (U01HG6513), National Center for Biotechnology Information (U.S.) (U01HG5214), National Center for Biotechnology Information (U.S.) (U01HG5715), National Center for Biotechnology Information (U.S.) (U01HG5718), National Center for Biotechnology Information (U.S.) (U01HG5728), National Center for Biotechnology Information (U.S.) (U41HG7635), National Center for Biotechnology Information (U.S.) (U41HG7497), National Center for Biotechnology Information (U.S.) (R01HG4960), National Center for Biotechnology Information (U.S.) (R01HG5701), National Center for Biotechnology Information (U.S.) (R01HG5214), National Center for Biotechnology Information (U.S.) (R01HG6855), National Center for Biotechnology Information (U.S.) (R01HG7068), National Center for Biotechnology Information (U.S.) (R01HG7644), National Center for Biotechnology Information (U.S.) (DP2OD6514), National Center for Biotechnology Information (U.S.) (DP5OD9154), National Center for Biotechnology Information (U.S.) (R01CA166661), National Center for Biotechnology Information (U.S.) (R01CA172652), National Center for Biotechnology Information (U.S.) (P01GM99568), National Center for Biotechnology Information (U.S.) (R01GM59290), National Center for Biotechnology Information (U.S.) (R01GM104390), National Center for Biotechnology Information (U.S.) (T32GM7790), National Center for Biotechnology Information (U.S.) (R01HL87699), National Center for Biotechnology Information (U.S.) (R01HL104608), National Center for Biotechnology Information (U.S.) (T32HL94284), National Center for Biotechnology Information (U.S.) (HHSN268201100040C), National Center for Biotechnology Information (U.S.) (HHSN272201000025C), Lundbeck Foundation (grant R170-2014-1039, Simons Foundation (SFARI award SF51), National Science Foundation (U.S.) (Research Fellowship DGE-1147470)

Description of meta-analysis, enrichment analyses, and novel candidates found in this study. (DOCX 182 kb)

Solid oxide fuel cell (SOFC) has emerged as a promising technology in the family of clean electricity generation methods. However, it is challenging to control the output voltage at the desired value due to the strong nonlinearity, slow dynamics and actuator saturation. The biggest difficulty comes from the constraint on the fuel utilization in a transient response. This paper is dedicated to develop an engineering friendly control structure to fulfill the comprehensive objectives. A basic PI feedback controller is utilized to accommodate the nonlinearity. The dynamic response is accelerated via a feedforward action. A compensation block is designed to satisfy the constraint requirement. The simulation shows that the resulting performance is similar to that of the latest model predictive control (MPC) design, demonstrating that the various difficulties can be effectively handled under the framework of conventional control.

Mixed-phase TiO2 nanostructures are synthesized by hydrothermal treatment of anodized TiO2 nanotubes. The growth of rutile nanorods on the anatase nanotubes can greatly expedite the electron–hole separation and transportation, enhance the light absorption, and also increase the surface area. When used for photocatalytic water splitting, more than three-fold enhancement in photocurrent density is observed for mixed-phase TiO2 nanostructures, relative to pristine TiO2 nanotubes.

This paper proposed an improved primary air (PA) control strategy for the purpose of bed-inventory balance in Circulating Fluidized Bed (CFB) boiler with pant-leg structure. An active disturbance rejection controller (ADRC) is used to estimate the bed-inventory deviation of two legs as well the internal and external disturbances, and then eliminate them by regulating the setpoints of PA flowrates of two sides in the furnace. The experiment conducted on a 600MWe CFB power plant simulation platform shows that the proposed control scheme can quickly balance the bed-inventory and decrease the overturn risk compared with traditional PI control system.

In this paper, a dynamic model of a single effect LiBr-H2O absorption chiller has been developed to explore the transient characteristics for the purpose of control design. Dynamic performance of the absorption chiller is tested to determine an appropriate control strategy. Active disturbance rejection control (ADRC) is implemented to achieve cooling capacity control and disturbance rejection. Comparison with conventional PID control shows that ADRC delivers better performance when different disturbances occur.

We describe the variation in copy number of a ~ 10 kb region overlapping the long intergenic noncoding RNA (lincRNA) gene, TTTY22, within the IR3 inverted repeat on the short arm of the human Y chromosome, leading to individuals with 0–3 copies of this region in the general population. Variation of this CNV is common, with 266 individuals having 0 copies, 943 (including the reference sequence) having 1, 23 having 2 copies, and two having 3 copies, and was validated by breakpoint PCR, fibre-FISH, and 10× Genomics Chromium linked-read sequencing in subsets of 1234 individuals from the 1000 Genomes Project. Mapping the changes in copy number to the phylogeny of these Y chromosomes previously established by the Project identified at least 20 mutational events, and investigation of flanking paralogous sequence variants showed that the mutations involved flanking sequences in 18 of these, and could extend over > 30 kb of DNA. While either gene conversion or double crossover between misaligned sister chromatids could formally explain the 0–2 copy events, gene conversion is the more likely mechanism, and these events include the longest non-allelic gene conversion reported thus far. Chromosomes with three copies of this CNV have arisen just once in our data set via another mechanism: duplication of 420 kb that places the third copy 230 kb proximal to the existing proximal copy. Our results establish gene conversion as a previously under-appreciated mechanism of generating copy number changes in humans and reveal the exceptionally large size of the conversion events that can occur.

The output voltage control of the Solid Oxide Fuel Cell (SOFC) is challenging due to the strong nonlinearity, modelling uncertainty, the dramatic change of the external current load and constraints on the amplitudes and change rates of the actuator. Besides, the desired range of the fuel utilization is another difficult for the control strategy. In this paper, Active disturbance rejection control (ADRC) is proposed to handle the nonlinearity, uncertainty and the external disturbance, and physical feedforward is designed to speed up the response of the whole system and keep the fuel utilization in the desired range. Instead of the SOFC model, the design of physical feedforward is based on the definition of fuel utilization which is featured by simplicity, generality and effectiveness. Simulation results show that the proposed control strategy has smaller variation range of the fuel utilization, shorter time of the changing process of the output voltage and better robustness than others control strategies.

The active disturbance rejection control (ADRC) framework gives birth to a new concept, the modified plant (MP), describing the dynamics after the total disturbance is estimated and cancelled approximately. Ideally the modified plant is in integral form, to greatly simplify and fix the controller design, even though actual plant contains higher-order dynamics or dead time. This paper investigates that when such processes are modified into the integral, how the parameters of the extended state observer (ESO) impact on the dynamic characteristics and stability of the MP. Frequency-domain analyses show that the MP can gradually approach the integral form through parameters tuning. However, it should be cautious that an aggressive set of parameters may lead to an unstable modified plant in the presence of order mismatch.

New Guinea shows human occupation since ~50 thousand years ago (ka), independent adoption of plant cultivation ~10 ka, and great cultural and linguistic diversity today. We performed genome-wide single-nucleotide polymorphism genotyping on 381 individuals from 85 language groups in Papua New Guinea and find a sharp divide originating 10 to 20 ka between lowland and highland groups and a lack of non-New Guinean admixture in the latter. All highlanders share ancestry within the last 10 thousand years, with major population growth in the same period, suggesting population structure was reshaped following the Neolithic lifestyle transition. However, genetic differentiation between groups in Papua New Guinea is much stronger than in comparable regions in Eurasia, demonstrating that such a transition does not necessarily limit the genetic and linguistic diversity of human societies.

The Canaanites inhabited the Levant region during the Bronze Age and established a culture which became influential in the Near East and beyond. However, the Canaanites, unlike most other ancient Near Easterners of this period, left few surviving textual records and thus their origin and relationship to ancient and present-day populations remain unclear. In this study, we sequenced five whole-genomes from ~3,700-year-old individuals from the city of Sidon, a major Canaanite city-state on the Eastern Mediterranean coast. We also sequenced the genomes of 99 individuals from present-day Lebanon to catalogue modern Levantine genetic diversity. We find that a Bronze Age Canaanite-related ancestry was widespread in the region, shared among urban populations inhabiting the coast (Sidon) and inland populations (Jordan) who likely lived in farming societies or were pastoral nomads. This Canaanite-related ancestry derived from mixture between local Neolithic populations and eastern migrants genetically related to Chalcolithic Iranians. We estimate, using linkage-disequilibrium decay patterns, that admixture occurred 6,600-3,550 years ago, coinciding with massive population movements in the mid-Holocene triggered by aridification ~4,200 years ago. We show that present-day Lebanese derive most of their ancestry from a Canaanite-related population, which therefore implies substantial genetic continuity in the Levant since at least the Bronze Age. In addition, we find Eurasian ancestry in the Lebanese not present in Bronze Age or earlier Levantines. We estimate this Eurasian ancestry arrived in the Levant around 3,750-2,170 years ago during a period of successive conquests by distant populations such as the Persians and Macedonians.

It is difficult to control the output voltage of the Solid Oxide Fuel Cells (SOFCs) because of the system nonlinearity, load disturbance and various constraints on the actuators and the fuel utilization rate. To overcome these difficulties, this paper proposed a multiple model predictive control scheme. The nonlinearity is addressed by using multiple models that are linearized at different operating conditions. The disturbance is accommodated by directly sending the load current information to the optimizer. And the constraints are naturally handled by formulating a constrained optimization problem. The simulation results show the effectiveness of the proposed strategy.

This paper proposes a linear active disturbance rejection control (LADRC) for gird-connected inverter with LCL filter to deal with parameters variation, internal coupling and external disturbance. Relative degree of plant is used to design LADRC and on the basis of relationship between LADRCs parameters and bandwidth, the parameters tuning are sum up in several guidable points. It is demonstrated that LADRC presents a good dynamic performances, high disturbance rejection and extremely robust to parameters variation in Matlab/Simulink.

Linear active disturbance rejection control (LADRC) has been paid much attention in academic and industrial fields. However, the selection of the order for LADRC controller design and the choice of parameter b0 in system correcting are key facts which are still being faced by designer. In this paper, an effective method about how to select the order of LADRC and the parameter b0 is given first. Frequency analysis often used by engineers for designing controller, the normal transfer function form of LADRC is constructed, so the loop gain, close loop transfer function and disturbance transfer function to a general high-order system are presented and can be easily used. The example shows that the proposed method is easy to apply and verified the lower-order LADRC can obtain the better effective than PID and high-order LADRC, and the frequency response analysis of a thermal power plant is elaborated and the simulation result indicates that LADRC has a strong robustness against the large variation of parameters in the plant mode.

Control of output voltage is critical for the power quality of solid oxide fuel cells (SOFCs), which is, however, challenging due to electrochemical nonlinearity, load disturbances, modelling uncertainties, and actuator constraints. Moreover, the fuel utilization rate should be limited within a safety range during the voltage regulation transient. The current research is usually appealing to model predictive control (MPC) by formulating the difficulties into a constrained optimization problem, but its huge computational complexity makes it formidable for real-time implementation in practice. To this end, this paper aims to develop a combined control structure, with basic function blocks, to fulfill the objectives with minor computation. Firstly, the disturbance, nonlinearity and uncertainties are lumped as a total disturbance, which is estimated and mitigated by active disturbance rejection controller (ADRC). Secondly, a feed-forward controller is introduced to improve the load disturbance rejection response. Finally, the constraints are satisfied by designing a cautious switching strategy. The simulation results show that the nominal performance of the proposed strategy is comparable to MPC. In the presence of parameter perturbation, the proposed strategy shows a better performance than MPC.

State of Charge (SOC) estimation has always been a key issue in the Battery Management System (BMS). This paper proposes a simple modified Luenberger observer to estimate the state of charge of the lithium-ion battery. Nonlinearity of battery equivalent circuit model is approximated at each step. Simulation results show that this simple modified Luenberger observer achieves satisfactory estimation accuracy, while still remains the advantage of low computational complexity. The robustness of this proposed estimation algorithm is demonstrated by Monte-Carlo method, and the estimation output sensitivity to model parameters variations is also revealed through sensitivity analysis.

Furnace pressure control is one of the most significant loop in thermal power plant. The stable pressure in furnace guarantees the safety and efficiency of combustion. The frequent disturbances in combustion and multi-loop coupling make it difficult to continuously maintain an anticipated furnace pressure. This paper applied low-order Active Disturbance Rejection Control (ADRC) to furnace pressure control. Through simulation and experiment in a genuine 1000MW power plant, the effectiveness of ADRC is demonstrated on this kind of processes characterized by fast response, frequently disturbed and uncertain dynamic performance.

In this paper, Maclaurin expansion and Pade approximation are utilized to handle the RHP zeros in the simplified decoupling control and the choosing strategy is given. To improve the robustness of each loop, Active Disturbance Rejection Control (ADRC) is adopted as a good solution which can estimate and compensate the total disturbances by the extended state observer (ESO). Besides, the stability region of the closed loop with ADRC is calculated to benefit for the parameters tuning and μ-analysis is used to analyze the robustness with different controllers. The simulation results demonstrate the advantage of ADRC based simplified decoupling in tracking performance and robustness.

The human Y chromosome provides a fertile ground for structural rearrangements owing to its haploidy and high content of repeated sequences. The methodologies used for copy number variation (CNV) studies have developed over the years. Low-throughput techniques based on direct observation of rearrangements were developed early on, and are still used, often to complement array-based or sequencing approaches which have limited power in regions with high repeat content and specifically in the presence of long, identical repeats, such as those found in human sex chromosomes. Some specific rearrangements have been investigated for decades; because of their effects on fertility, or their outstanding evolutionary features, the interest in these has not diminished. However, following the flourishing of large-scale genomics, several studies have investigated CNVs across the whole chromosome. These studies sometimes employ data generated within large genomic projects such as the DDD study or the 1000 Genomes Project, and often survey large samples of healthy individuals without any prior selection. Novel technologies based on sequencing long molecules and combinations of technologies, promise to stimulate the study of Y-CNVs in the immediate future.

Absorbers for visible and near-infrared light are realized by depositing a thin iron layer on arrays of cones which are replicated from a porous template. The replicated conic structure itself is of several micrometers and ineffective at antireflection, but the subsequent deposition of iron on top generates nano-meter-size columnar structures, and thus broadband absorption enhancement is achieved.

Arctic populations live in an environment characterized by extreme cold and the absence of plant foods for much of the year and are likely to have undergone genetic adaptations to these environmental conditions in the time they have been living there. Genome-wide selection scans based on genotype data from native Siberians have previously highlighted a 3 Mb chromosome 11 region containing 79 protein-coding genes as the strongest candidates for positive selection in Northeast Siberians. However, it was not possible to determine which of the genes might be driving the selection signal. Here, using whole-genome high-coverage sequence data, we identified the most likely causative variant as a nonsynonymous G>A transition (rs80356779; c.1436C>T [p.Pro479Leu] on the reverse strand) in CPT1A, a key regulator of mitochondrial long-chain fatty-acid oxidation. Remarkably, the derived allele is associated with hypoketotic hypoglycemia and high infant mortality yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in our Northeast Siberian sample. We provide evidence of one of the strongest selective sweeps reported in humans; this sweep has driven this variant to high frequency in circum-Arctic populations within the last 6–23 ka despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment.

Summary: Runs of homozygosity (RoHs) are genomic stretches of a diploid genome that show identical alleles on both chromosomes. Longer RoHs are unlikely to have arisen by chance but are likely to denote autozygosity, whereby both copies of the genome descend from the same recent ancestor. Early tools to detect RoH used genotype array data, but substantially more information is available from sequencing data. Here, we present and evaluate BCFtools/RoH, an extension to the BCFtools software package, that detects regions of autozygosity in sequencing data, in particular exome data, using a hidden Markov model. By applying it to simulated data and real data from the 1000 Genomes Project we estimate its accuracy and show that it has higher sensitivity and specificity than existing methods under a range of sequencing error rates and levels of autozygosity. Availability and implementation: BCFtools/RoH and its associated binary/source files are freely available from https://github.com/samtools/BCFtools. Contact: vn2@sanger.ac.uk or pd3@sanger.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.

A new type of entrained flow gasifier with membrane wall and two-stage oxygen supply is being developed in China. The fraction of the secondary oxygen in total oxygen (FSO) is an important parameter for this kind of gasifier. A dynamic reduced order model (ROM) based on a reactor network model (RNM) is developed for this gasifier, which is used to investigate the effects of FSO on the slag layer thickness profile on the wall and explore the potential of FSO in dynamic slag control. The ROM adopts a flexible RNM blocking method, which varies with FSO to account for the influence of FSO on the flow pattern in the gasifier. Available industrial data was used to validate the model and a detailed sensitivity analysis for the calculation of slag layer thickness was performed. Static analyses show that FSO has a marked effect on the slag thickness distribution and higher FSO leads to lower heat loss through the wall. Finally, a slag control system, which introduced FSO as an auxiliary regulator, is proposed. Dynamic simulation shows that the new control system offers an improved performance in slag control and can broaden the regulating range of operating temperature.

Decentralized Robust Feedback Linearization (DRFL) approach based on integrity for multivariable systems is presented. It uses a model observer to compensate the non-modeled dynamics, system uncertainties, and external disturbances of a system. Firstly, the existence of DRFL controllers with integrity is examined. Then, stable regions of each DRFL controller parameters are calculated, and some parameters are obtained by placing suitable closed-loop poles, for meeting the design specifications for the whole control system. The proposed method is applied to an illustrative example. Results demonstrate that DRFL control is feasible and robust for complicated multivariable systems.

A new control solution based on a unique active disturbance rejection control (ADRC) paradigm is proposed for the ALSTOM gasifier control problem. In the new control method, the disturbances, including unknown dynamics and external disturbances to the system, are treated as an augmented state that is estimated and then eliminated in real-time. A first-order ADRC scheme for the ALSTOM gasifier is designed. The simulation results show that the new control method is superior to the PI solution by Simm and Xue in terms of the integral of the absolute error of gas pressure disturbance tests at 0% load, the no-overshoot peak value of the gas temperature and the short time for the bed mass to return to the set point during a ramping test, and the ability to reject large coal quality disturbances.

We present 42 new Y-chromosomal sequences from diverse Indian tribal and non-tribal populations, including the Jarawa and Onge from the Andaman Islands, which are analysed within a calibrated Y-chromosomal phylogeny incorporating South Asian (in total 305 individuals) and worldwide (in total 1286 individuals) data from the 1000 Genomes Project. In contrast to the more ancient ancestry in the South than in the North that has been claimed, we detected very similar coalescence times within Northern and Southern non-tribal Indian populations. A closest neighbour analysis in the phylogeny showed that Indian populations have an affinity towards Southern European populations and that the time of divergence from these populations substantially predated the Indo-European migration into India, probably reflecting ancient shared ancestry rather than the Indo-European migration, which had little effect on Indian male lineages. Among the tribal populations, the Birhor (Austro-Asiatic-speaking) and Irula (Dravidian-speaking) are the nearest neighbours of South Asian non-tribal populations, with a common origin in the last few millennia. In contrast, the Riang (Tibeto-Burman-speaking) and Andamanese have their nearest neighbour lineages in East Asia. The Jarawa and Onge shared haplogroup D lineages with each other within the last ~7000 years, but had diverged from Japanese haplogroup D Y-chromosomes ~53000 years ago, most likely by a split from a shared ancestral population. This analysis suggests that Indian populations have complex ancestry which cannot be explained by a single expansion model. Funding was provided by the joint Spain–India bilateral grant PRI-PIBIN-2011-0942 and BFU2016-77961-P (AEI/ FEDER, UE) both awarded by the Ministerio de Economía y Competitividad (Spain) and with the support of Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2014 SGR 866). Anders Bergström, YaliXue and Chris Tyler-Smith were supported by The Wellcome Trust (Grant 098051)

Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of twelve anthropometric traits associated with height, body mass and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. Seventy-one percent of signals reside within genes and fine-mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits, and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically-relevant discoveries across the frequency spectrum.

Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans., Facultad de Ciencias Naturales y Museo

In this paper, an active disturbance rejection control (ADRC) with tracking differentiator (TD) solution is proposed and tested on a certain four operating condition model. The proposed system with a cascaded control scheme is constructed based on a linear Active disturbance rejection controller (LADRC) with parameters optimized under a modified fruit fly algorithm. The tracking performance could be improved by the tracking differentiator with flexible damping. The simulation results indicate that the proposed strategy could effectively balance rapid and stable responses.

High-coverage whole-genome sequence studies have so far focused on a limited number1 of geographically restricted populations2, 3, 4, 5, or been targeted at specific diseases, such as cancer6. Nevertheless, the availability of high- resolution genomic data has led to the development of new methodologies for inferring population history7, 8, 9 and refuelled the debate on the mutation rate in humans10. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record11, and admixture between AMHs and Neanderthals predating the main Eurasian expansion12, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75, 000 years ago.

This paper derived a model for the superheated steam temperature based on the open-loop step response. A cascaded control structure based on disturbance observer (DOB) is proposed to accommodate the control difficulties. The simulation results show the great performance improvement compared with the conventional cascaded control structure. This paper is a preliminary research to the cascaded DOB control structure. Much improvement, theoretic analysis and experimental demonstration will be carried out in the future.

Due to the long-time engineering practice, the existing PID controllers and their parameters contain the valuable information about the models of the industrial processes. Such information is absorbed to simplify the design and tuning process of the active disturbance rejection controller (ADRC) in this study. If one channel of the multivariable system is stabilized by PID, then ADRC can be built to replace the PID scheme, and the ADRC parameters can be calculated from the PID parameters. This technique can be operated channel by channel until all channels are stabilized by ADRC, which is verified by simulations. Moreover, the simulations imply that the presented ADRC design and tuning method can generate the feasible parameters efficiently for the plants with unknown models.

Active disturbance rejection control (ADRC) is applied in fluidized bed combustor (FBC) facing some control difficulty. By analyzing the difficulties, ADRC controllers are designed for the power loop and the bed temperature loop of FBC system. The simulation demonstrates both loops with ADRC have a better tracking speed and a stronger robustness, the power loop can inhibit the input and output disturbance quickly and the temperature loop has a slight advantage in disturbance rejection. Besides, manipulated variables is analyzed by the phase diagrams.

The conventional direct energy balance (DEB) based PI control can fulfill the fundamental tracking requirements of the coal-fired power plant. However, it is challenging to deal with the cases when the coal quality variation is present. To this end, this paper introduces the active disturbance rejection control (ADRC) to the DEB structure, where the coal quality variation is deemed as a kind of unknown disturbance that can be estimated and mitigated promptly. Firstly, the nonlinearity of a recent power plant model is analyzed based on the gap metric, which provides guidance on how to set the pressure set-point in line with the power demand. Secondly, the approximate decoupling effect of the DEB structure is analyzed based on the relative gain analysis in frequency domain. Finally, the synthesis of the DEB based ADRC control system is carried out based on multi-objective optimization. The optimized ADRC results show that the integrated absolute error (IAE) indices of the tracking performances in both loops can be simultaneously improved, in comparison with the DEB based PI control and H∞ control system. The regulation performance in the presence of the coal quality variation is significantly improved under the ADRC control scheme. Moreover, the robustness of the proposed strategy is shown comparable with the H∞ control.

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.

Scally, A. et al., Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution. © 2012 Macmillan Publishers Limited. All rights reserved., This research was supported in part by Wellcome Trust grants WT062023(toJ.H.,K.B.,S.F.,A.J.V.,P.F.),WT089066(toR.D.),WT077192(toR.D.,S.M., A.K.-K., J.T.S., W.W.), WT077009 (to Y.X., B.Y., Q.A., Y.C., C.T.-S.), WT077198 (to G.K.L.) and 075491/Z/04 (to G.L.); EMBL grants (to P.C.S., P.F.); scholarships from the Gates Cambridge Trust (to G.E.J. and T.D.O’C.); an MRC Special Fellowship in Biomedical Informatics (toA.S.);funding from the Lundbeck Foundation(toA.H.);the Academy of Finland and the Emil Aaltonen Foundation(toT.L.);a Marie Curie fellowship(toT.M.-B.); the European Community’s Seventh Framework Programme (FP7/2007-2013)/ ERC Starting Grant(StG_20091118)(toT.M.-B.);an FPI grant from the Spanish Ministry of Education (BES-2010-032251) (to J.P.-M.); a BBSRC Doctoral Training Grant (to S.H.M.); grants from the UK Medical Research Council (to A.H., S.M., C.P.P.); the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health(to J.C.M.);the Danish Council for Independent Research, Natural Sciences,grant no.09-062535(toK.M.,M.H.S.);a Commonwealth Scholarship (to M.C.W.); the Swiss National Science Foundation, Louis Jeantet Foundation (to E.T.D.); an ERC Starting Grant and an EMBO Young Investigator Award, Hutchinson Whampoa (to D.T.O.); NHGRI support (to W.C.W.); support from BIOBASE GmbH (to E.V.B., P.D.S., M.M., A.D.P., K.S., D.N.C.); US National Science Foundation grant DGE-0739133(toW.W.);NHGRIU54HG003079(toR.K.W.);NIHgrantHG002385(to E.E.E). E.E.E. is an investigator of the Howard Hughes Medical Institute.

Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies, but the generalizability of such findings remains unknown. Here we genotype 1,267 individuals from a Greek population isolate on the Illumina HumanExome Beadchip, in search of functional coding variants associated with lipids traits. We find genome-wide significant evidence for association between R19X, a functional variant in APOC3, with increased high-density lipoprotein and decreased triglycerides levels. Approximately 3.8% of individuals are heterozygous for this cardioprotective variant, which was previously thought to be private to the Amish founder population. R19X is rare (, Isolated populations may empower genetic association studies of complex traits. Here, the authors identify a rare cardioprotective APOC3 variant in a Greek population isolate and highlight the value of using population isolates to detect rare variants that confer disease risk.

Heterozygous mutations within homozygous sequences descended from a recent common ancestor offer a way to ascertain de novo mutations (DNMs) across multiple generations. Using exome sequences from 3,222 British-Pakistani individuals with high parental relatedness, we estimate a mutation rate of 1. 45 ± 0.05 × 10−8 per base pair per generation in autosomal coding sequence, with a corresponding noncrossover gene conversion rate of 8.75 ± 0.05 × 10−6 per base pair per generation. This is at the lower end of exome mutation rates previously estimated in parent-offspring trios, suggesting that post-zygotic mutations contribute little to the human germline mutation rate. We found frequent recurrence of mutations at polymorphic CpG sites, and an increase in C to T mutations in a 5’ CCG 3’ → 5’ CTG 3’ context in the Pakistani population compared to Europeans, suggesting that mutational processes have evolved rapidly between human populations.

High-altitude adaptation in Tibetans is influenced by introgression of a 32.7-kb haplotype from the Denisovans, an extinct branch of archaic humans, lying within the endothelial PAS domain protein 1 (EPAS1), and has also been reported in Sherpa. We genotyped 19 variants in this genomic region in 1507 Eurasian individuals, including 1188 from Bhutan and Nepal residing at altitudes between 86 and 4550 m above sea level. Derived alleles for five SNPs characterizing the core Denisovan haplotype (AGGAA) were present at high frequency not only in Tibetans and Sherpa, but also among many populations from the Himalayas, showing a significant correlation with altitude (Spearman’s correlation coefficient = 0.75, p value 3.9 × 10−11). Seven East- and South-Asian 1000 Genomes Project individuals shared the Denisovan haplotype extending beyond the 32-kb region, enabling us to refine the haplotype structure and identify a candidate regulatory variant (rs370299814) that might be interacting in an additive manner with the derived G allele of rs150877473, the variant previously associated with high-altitude adaptation in Tibetans. Denisovan-derived alleles were also observed at frequencies of 3–14 % in the 1000 Genomes Project African samples. The closest African haplotype is, however, separated from the Asian high-altitude haplotype by 22 mutations whereas only three mutations, including rs150877473, separate the Asians from the Denisovan, consistent with distant shared ancestry for African and Asian haplotypes and Denisovan adaptive introgression. Electronic supplementary material The online version of this article (doi:10.1007/s00439-016-1641-2) contains supplementary material, which is available to authorized users.

We have assessed the numbers of potentially deleterious variants in the genomes of apparently healthy humans by using (1) low-coverage whole-genome sequence data from 179 individuals in the 1000 Genomes Pilot Project and (2) current predictions and databases of deleterious variants. Each individual carried 281–515 missense substitutions, 40–85 of which were homozygous, predicted to be highly damaging. They also carried 40–110 variants classified by the Human Gene Mutation Database (HGMD) as disease-causing mutations (DMs), 3–24 variants in the homozygous state, and many polymorphisms putatively associated with disease. Whereas many of these DMs are likely to represent disease-allele-annotation errors, between 0 and 8 DMs (0–1 homozygous) per individual are predicted to be highly damaging, and some of them provide information of medical relevance. These analyses emphasize the need for improved annotation of disease alleles both in mutation databases and in the primary literature; some HGMD mutation data have been recategorized on the basis of the present findings, an iterative process that is both necessary and ongoing. Our estimates of deleterious-allele numbers are likely to be subject to both overcounting and undercounting. However, our current best mean estimates of ∼400 damaging variants and ∼2 bona fide disease mutations per individual are likely to increase rather than decrease as sequencing studies ascertain rare variants more effectively and as additional disease alleles are discovered.

the paper presents our recent research work in study of a novel multivariable coordinate control for a 600MW supercritical (SC) power plant process. The nonlinear mathematical model of the plant is briefly described in the paper. Then, a control strategy is designed which is based on Generalized Model Predictive Control (MPC) theory and tested within small load changes. But the MPC alone performs well only within small load changes even with consideration of constant disturbance and measurement noises in prediction algorithm. We then propose a dynamic compensator in parallel with the MPC to track large load changes. Because the model has been identified with on-site closed loop data, the multivariable optimal control signals have been used as a correction to the reference of the plant local controls instead of direct control signal applications. The simulation results have shown good performance of the controller in response to some load changes. Furthermore, it has been proved that the plant dynamic response can be improved by increasing the coal grinding capability and pulverized coal discharging through the implemented coal mill controllers. The benefit from this study is to provide convinced methodology to improve the SC power plant dynamic response for fulfilment of National Grid Code (NGC) requirements.

Defective Gene Detective Identifying genes that give rise to diseases is one of the major goals of sequencing human genomes. However, putative loss-of-function genes, which are often some of the first identified targets of genome and exome sequencing, have often turned out to be sequencing errors rather than true genetic variants. In order to identify the true scope of loss-of-function genes within the human genome, MacArthur et al. (p. 823 ; see the Perspective by Quintana-Murci ) extensively validated the genomes from the 1000 Genomes Project, as well as an additional European individual, and found that the average person has about 100 true loss-of-function alleles of which approximately 20 have two copies within an individual. Because many known disease-causing genes were identified in “normal” individuals, the process of clinical sequencing needs to reassess how to identify likely causative alleles.

This survey presents the application of force feedback in aviation. In modern fly-by-wire control system, actuator rate limit is the primary source of PIO II (Pilot Induced Oscillation II). The combination of smart-cue and smart-gain method can alleviate PIO II effectively, and consequently enhance the flight safety. The recent research of applying force feedback in aviation demonstrates that it is worthy of theoretical exploration and extensive utilization.

Beta-defensins are a family of multifunctional genes with roles in defense against pathogens, reproduction, and pigmentation. In humans, six beta-defensin genes are clustered in a repeated region which is copy-number variable (CNV) as a block, with a diploid copy number between 1 and 12. The role in host defense makes the evolutionary history of this CNV particularly interesting, because morbidity due to infectious disease is likely to have been an important selective force in human evolution, and to have varied between geographical locations. Here, we show CNV of the beta-defensin region in chimpanzees, and identify a beta-defensin block in the human lineage that contains rapidly evolving noncoding regulatory sequences. We also show that variation at one of these rapidly evolving sequences affects expression levels and cytokine responsiveness of DEFB103, a key inhibitor of influenza virus fusion at the cell surface. A worldwide analysis of beta-defensin CNV in 67 populations shows an unusually high frequency of high-DEFB103-expressing copies in East Asia, the geographical origin of historical and modern influenza epidemics, possibly as a result of selection for increased resistance to influenza in this region. Hum Mutat 32:743–750, 2011. © 2011 Wiley-Liss, Inc.

Model-based algorithms are generally employed in active control of combustion oscillations. Since practical combustion processes consist of complex thermal and acoustic couplings, their accurate models and parameters may not be obtained in advance economically, a model free controller is necessary for the control of thermoacoustic instabilities. Active compensation based control algorithm is applied in the suppression of combustion instabilities. Tuning the controller parameters on line, the amplitudes of the acoustic waves can be modulated to desired values. Simulations performed on a control oriented, typical longitudinal oscillations combustor model illustrate the controllers’ capability to attenuate combustion oscillations.

An increasing penetration of renewable energy may bring significant challenges to a power system due to its inherent intermittency. To achieve a sustainable future for renewable energy, a conventional power plant is required to be able to change its power output rapidly for a grid balance purpose. However, the rapid power change may result in the boiler operating in a dangerous manner. To this end, this paper aims to improve boiler control performance via a data-driven control strategy, namely Active Disturbance Rejection Control (ADRC). For practical implementation, a tuning method is developed for ADRC controller parameters to maximize its potential in controlling a boiler operating in different conditions. Based on a Monte Carlo simulation, a Probabilistic Robustness (PR) index is subsequently formulated to represent the controller’s sensitivity to the varying conditions. The stability region of the ADRC controller is depicted to provide the search space in which the optimal group of parameters is searched for based on the PR index. Illustrative simulations are performed to verify the efficacy of the proposed method. Finally, the proposed method is experimentally applied to a boiler’s secondary air control system successfully. The results of the field application show that the proposed ADRC based on PR can ensure the expected control performance even though it works in a wider range of operating conditions. The field application depicts a promising future for the ADRC controller as an alternative solution in the power industry to integrate more renewable energy into the power grid.

Based on the baseline PI control structure, the control parameters of non-linear ALSTOM gasifier benchmark problem are optimized. Firstly, taking all the input and output limits under three load conditions as constraints, the relative IAE indices at six scenarios are calculated and optimized by using multi-objective optimization algorithm NSGA-II. A set of non-dominated solutions are obtained which facilitate the further improvement on the performance under coal quality change. Then among those non-dominated solutions, the solution with best coal quality flexibility comes to the fore through a selection procedure. The simulation results show that the optimization and selection procedure presented in this paper improves the baseline PI control performance with better dynamic responses and coal quality flexibility.

We have examined the male-specific phylogeography of the Levant and its surroundings by analyzing Y-chromosomal haplogroup distributions using 5,874 samples (885 new) from 23 countries. The diversity within some of these haplogroups was also examined. The Levantine populations showed clustering in SNP and STR analyses when considered against a broad Middle-East and North African background. However, we also found a coastal-inland, east-west pattern of diversity and frequency distribution in several haplogroups within the small region of the Levant. Since estimates of effective population size are similar in the two regions, this strong pattern is likely to have arisen mainly from differential migrations, with different lineages introduced from the east and west.