Robust Control Techniques for State Tracking in the Presence of Variable Time Delays

In this paper, a distributed driver-in-the-Ioop and hardware-in-the-Ioop simulator is described with a driver on a motion simulator at the U.S. Army TARDEC Ground Vehicle Simulation Laboratory (GVSL). Realistic power system response is achieved by linking the driver in the GVSL with a full-sized hybrid electric power system located 2,450 miles away at the TARDEC Power and Energy Systems Integration Laboratory (P&E SIL), which is developed and maintained by Science Applications International Corporation (SAIC). The goal is to close the loop between the GVSL and P&E SIL over the Internet to provide a realistic driving experience in addition to realistic power system results. In order to preserve a valid and safe hardware-in-the-Ioop experiment, the states of the GVSL must track the states of the P&E SIL. In a distributed control system utilizing the open Internet, the communications channel is a primary source of uncertainty and delay that can degrade the overall system performance and stability. The presence of a cross-country network delay and the unavoidable differences between the P&E SIL hardware and GVSL model will cause the GVSL states and P&E SIL states to diverge without any additional action. Thus, two robust strategies for state convergence are developed and presented in this paper. The first strategy is a non-linear Sliding Mode control scheme. The second strategy is an H-infinity control scheme. Both schemes are implemented in simulation, and both schemes show promising results for state convergence in the presence of variable cross-country time delays

Groundwater-supported evapotranspiration within glaciated watersheds under conditions of climate change

This paper analyzes the effects of geology and geomorphology on surface-water/-groundwater interactions, evapotranspiration, and recharge under conditions of long-term climatic change. Our analysis uses hydrologic data from the glaciated Crow Wing watershed in central Minnesota, USA, combined with a hydrologic model of transient coupled unsaturated/saturated flow (HYDRAT2D). Analysis of historical water-table (1970–1993) and lake-level (1924–2002) records indicates that larger amplitude and longer period fluctuations occur within the upland portions of watersheds due to the response of the aquifer system to relatively short-term climatic fluctuations. Under drought conditions, lake and water-table levels fell by as much as 2–4 m in the uplands but by 1 m in the lowlands. The same pattern can be seen on millennial time scales. Analysis of Holocene lake-core records indicates that Moody Lake, located near the outlet of the Crow Wing watershed, fell by as much as 4 m between about 4400 and 7000 yr BP. During the same time, water levels in Lake Mina, located near the upland watershed divide, fell by about 15 m. Reconstructed Holocene climate as represented by HYDRAT2D gives somewhat larger drops (6 and 24 m for Moody Lake and Lake Mina, respectively). The discrepancy is probably due to the effect of three-dimensional flow. A sensitivity analysis was also carried out to study how aquifer hydraulic conductivity and land-surface topography can influence water-table fluctuations, wetlands formation, and evapotranspiration. The models were run by recycling a wet year (1985, 87 cm annual precipitation) over a 10-year period followed by 20 years of drier and warmer climate (1976, 38 cm precipitation). Model results indicated that groundwater-supported evapotranspiration accounted for as much as 12% (10 cm) of evapotranspiration. The aquifers of highest hydraulic conductivity had the least amount of groundwater-supported evapotranspiration owing to a deep water table. Recharge was even more sensitive to aquifer hydraulic conductivity, especially in the lowland regions. These findings have important implications for paleoclimatic studies, because the hydrologic response of a surface-water body will vary across the watershed to a given climate signal

Rapid “Open-Source” Engineering of Customized Zinc-Finger Nucleases for Highly Efficient Gene Modification

Summary—Custom-made zinc-finger nucleases (ZFNs) can induce targeted genome modifications with high efficiency in cell types including Drosophila, C. elegans, plants, and humans. A bottleneck in the application of ZFN technology has been the generation of highly specific engineered zincfinger arrays. Here we describe OPEN (Oligomerized Pool ENgineering), a rapid, publicly available strategy for constructing multi-finger arrays, which we show is more effective than the previously published modular assembly method. We used OPEN to construct 37 highly active ZFN pairs which induced targeted alterations with high efficiencies (1 to 50%) at 11 different target sites located within three endogenous human genes (VEGF-A, HoxB13, CFTR), an endogenous plant gene (tobacco SuRA), and a chromosomally-integrated EGFP reporter gene. In summary, OPEN provides an “opensource” method for rapidly engineering highly active zinc-finger arrays, thereby enabling broader practice, development, and application of ZFN technology for biological research and gene therapy

ERBB4 exonic deletions on chromosome 2q34 in patients with intellectual disability or epilepsy

ERBB4 encodes the tyrosine kinase receptor HER4, a critical regulator of normal cell function and neurodevelopmental processes in the brain. One of the key ligands of HER4 is neureglin-1 (NRG1), and the HER4-NRG1 signalling pathway is essential in neural crest cell migration, and neuronal differentiation. Pharmacological inactivation of HER4 has been shown to hasten the progression of epileptogenesis in rodent models, and heterozygous ERBB4 null mice are shown to have cognitive deficits and delayed motor development. Thus far there is only a single case report in the literature of a heterozygous ERBB4 deletion in a patient with intellectual disability (ID). We identified nine subjects from five unrelated families with chromosome 2q34 deletions, resulting in heterozygous intragenic loss of multiple exons of ERBB4, associated with either non-syndromic ID or generalised epilepsy. In one family, the deletion segregated with ID in five affected relatives. Overall, this case series further supports that haploinsufficiency of ERBB4 leads to non-syndromic intellectual disability or epilepsy

The diagnostic utility of clinical exome sequencing in 60 patients with hearing loss disorders: A single‐institution experience

From Wiley via Jisc Publications RouterHistory: received 2020-12-21, rev-recd 2021-04-08, accepted 2021-05-08, pub-electronic 2021-07-05Article version: VoRPublication status: PublishedFunder: Mexico’s National Council of Science and Technology; Grant(s): (CONACyT)‐392996Funder: Peter Mount award (Manchester University NHS Foundation Trust); Grant(s): G70658Funder: Data Driven Award (Manchester University NHS Foundation Trust); Grant(s): NH_SY_020419Funder: Manchester NIHR BRC; Grant(s): BRC‐1215‐20007Funder: Wellcome Trust; Grant(s): 200990/Z/16/

Phenotypic and Genome-Wide Analysis of an Antibiotic-Resistant Small Colony Variant (SCV) of Pseudomonas aeruginosa

Small colony variants (SCVs) are slow-growing bacteria, which often show increased resistance to antibiotics and cause latent or recurrent infections. It is therefore important to understand the mechanisms at the basis of this phenotypic switch.One SCV (termed PAO-SCV) was isolated, showing high resistance to gentamicin and to the cephalosporine cefotaxime. PAO-SCV was prone to reversion as evidenced by emergence of large colonies with a frequency of 10(-5) on media without antibiotics while it was stably maintained in presence of gentamicin. PAO-SCV showed a delayed growth, defective motility, and strongly reduced levels of the quorum sensing Pseudomonas quinolone signal (PQS). Whole genome expression analysis further suggested a multi-layered antibiotic resistance mechanism, including simultaneous over-expression of two drug efflux pumps (MexAB-OprM, MexXY-OprM), the LPS modification operon arnBCADTEF, and the PhoP-PhoQ two-component system. Conversely, the genes for the synthesis of PQS were strongly down-regulated in PAO-SCV. Finally, genomic analysis revealed the presence of mutations in phoP and phoQ genes as well as in the mexZ gene encoding a repressor of the mexXY and mexAB-oprM genes. Only one mutation occurred only in REV, at nucleotide 1020 of the tufA gene, a paralog of tufB, both encoding the elongation factor Tu, causing a change of the rarely used aspartic acid codon GAU to the more common GAC, possibly causing an increase of tufA mRNA translation. High expression of phoP and phoQ was confirmed for the SCV variant while the revertant showed expression levels reduced to wild-type levels.By combining data coming from phenotypic, gene expression and proteome analysis, we could demonstrate that resistance to aminoglycosides in one SCV mutant is multifactorial including overexpression of efflux mechanisms, LPS modification and is accompanied by a drastic down-regulation of the Pseudomonas quinolone signal quorum sensing system

Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds

status: publishe