Experimentally validated continuous-time repetitive control of non-minimum phase plants with a prescribed degree of stability

This paper considers the application of continuous-time repetitive control to non-minimum phase plants in a continuous-time model predictive control setting. In particular, it is shown how some critical performance problems associated with repetitive control of such plants can be avoided by use of predictive control with a prescribed degree of stability. The results developed are first illustrated by simulation studies and then through experimental tests on a non-minimum phase electro-mechanical system

Dimension of posets with planar cover graphs excluding two long incomparable chains

It has been known for more than 40 years that there are posets with planar cover graphs and arbitrarily large dimension. Recently, Streib and Trotter proved that such posets must have large height. In fact, all known constructions of such posets have two large disjoint chains with all points in one chain incomparable with all points in the other. Gutowski and Krawczyk conjectured that this feature is necessary. More formally, they conjectured that for every $k\geq 1$, there is a constant $d$ such that if $P$ is a poset with a planar cover graph and $P$ excludes $\mathbf{k}+\mathbf{k}$, then $\dim(P)\leq d$. We settle their conjecture in the affirmative. We also discuss possibilities of generalizing the result by relaxing the condition that the cover graph is planar.Comment: New section on connections with graph minors, small correction

The aromatic amino acid hydroxylase genes AAH1 and AAH2 in Toxoplasma gondii contribute to transmission in the cat

The Toxoplasma gondii genome contains two aromatic amino acid hydroxylase genes, AAH1 and AAH2 encode proteins that produce L-DOPA, which can serve as a precursor of catecholamine neurotransmitters. It has been suggested that this pathway elevates host dopamine levels thus making infected rodents less fearful of their definitive Felidae hosts. However, L-DOPA is also a structural precursor of melanins, secondary quinones, and dityrosine protein crosslinks, which are produced by many species. For example, dityrosine crosslinks are abundant in the oocyst walls of Eimeria and T. gondii, although their structural role has not been demonstrated, Here, we investigated the biology of AAH knockout parasites in the sexual reproductive cycle within cats. We found that ablation of the AAH genes resulted in reduced infection in the cat, lower oocyst yields, and decreased rates of sporulation. Our findings suggest that the AAH genes play a predominant role during infection in the gut of the definitive feline host

A computationally universal phase of quantum matter

We provide the first example of a symmetry protected quantum phase that has universal computational power. Throughout this phase, which lives in spatial dimension two, the ground state is a universal resource for measurement based quantum computation.Comment: 5 + 2 page

Determining All Universal Tilers

A universal tiler is a convex polyhedron whose every cross-section tiles the plane. In this paper, we introduce a certain slight-rotating operation for cross-sections of pentahedra. Based on a selected initial cross-section and by applying the slight-rotating operation suitably, we prove that a convex polyhedron is a universal tiler if and only if it is a tetrahedron or a triangular prism.Comment: 18 pages, 12 figure

Therapeutic Effect of Targeting Branched-Chain Amino Acid Catabolic Flux in Pressure-Overload Induced Heart Failure.

Background Branched-chain amino acid (BCAA) catabolic defect is an emerging metabolic hallmark in failing hearts in human and animal models. The therapeutic impact of targeting BCAA catabolic flux under pathological conditions remains understudied. Methods and Results BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid), a small-molecule inhibitor of branched-chain ketoacid dehydrogenase kinase, was used to enhance BCAA catabolism. After 2 weeks of transaortic constriction, mice with significant cardiac dysfunctions were treated with vehicle or BT2. Serial echocardiograms showed continuing pathological deterioration in left ventricle of the vehicle-treated mice, whereas the BT2-treated mice showed significantly preserved cardiac function and structure. Moreover, BT2 treatment improved systolic contractility and diastolic mechanics. These therapeutic benefits appeared to be independent of impacts on left ventricle hypertrophy but associated with increased gene expression involved in fatty acid utilization. The BT2 administration showed no signs of apparent toxicity. Conclusions Our data provide the first proof-of-concept evidence for the therapeutic efficacy of restoring BCAA catabolic flux in hearts with preexisting dysfunctions. The BCAA catabolic pathway represents a novel and potentially efficacious target for treatment of heart failure

Mice with endogenous TDP‐43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis

TDP-43 (encoded by the gene TARDBP) is an RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, how TARDBP mutations trigger pathogenesis remains unknown. Here, we use novel mouse mutants carrying point mutations in endogenous Tardbp to dissect TDP-43 function at physiological levels both in vitro and in vivo. Interestingly, we find that mutations within the C-terminal domain of TDP-43 lead to a gain of splicing function. Using two different strains, we are able to separate TDP-43 loss- and gain-of-function effects. TDP-43 gain-of-function effects in these mice reveal a novel category of splicing events controlled by TDP-43, referred to as "skiptic" exons, in which skipping of constitutive exons causes changes in gene expression. In vivo, this gain-of-function mutation in endogenous Tardbp causes an adult-onset neuromuscular phenotype accompanied by motor neuron loss and neurodegenerative changes. Furthermore, we have validated the splicing gain-of-function and skiptic exons in ALS patient-derived cells. Our findings provide a novel pathogenic mechanism and highlight how TDP-43 gain of function and loss of function affect RNA processing differently, suggesting they may act at different disease stages. Keywords: ALS; cryptic exon; skiptic exon; splicing; TDP-4