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B-spline neural networks based PID controller for Hammerstein systems
A new PID tuning and controller approach is introduced for Hammerstein systems based on input/output data. A B-spline neural network is used to model the nonlinear static function in the Hammerstein system. The control signal is composed of a PID controller together with a correction term. In order to update the control signal, the multi-step ahead predictions of the Hammerstein system based on the B-spline neural networks and the associated Jacobians matrix are calculated using the De Boor algorithms including both the functional and derivative recursions. A numerical example is utilized to demonstrate the efficacy of the proposed approaches
Receptor tyrosine kinase activation of RhoA is mediated by AKT phosphorylation of DLC1
We report several receptor tyrosine kinase (RTK) ligands increase RhoA-guanosine triphosphate (GTP) in untransformed and transformed cell lines and determine this phenomenon depends on the RTKs activating the AKT serine/threonine kinase. The increased RhoA-GTP results from AKT phosphorylating three serines (S298, S329, and S567) in the DLC1 tumor suppressor, a Rho GTPase-activating protein (RhoGAP) associated with focal adhesions. Phosphorylation of the serines, located N-terminal to the DLC1 RhoGAP domain, induces strong binding of that N-terminal region to the RhoGAP domain, converting DLC1 from an open, active dimer to a closed, inactive monomer. That binding, which interferes with the interaction of RhoA-GTP with the RhoGAP domain, reduces the hydrolysis of RhoA-GTP, the binding of other DLC1 ligands, and the colocalization of DLC1 with focal adhesions and attenuates tumor suppressor activity. DLC1 is a critical AKT target in DLC1-positive cancer because AKT inhibition has potent antitumor activity in the DLC1-positive transgenic cancer model and in a DLC1-positive cancer cell line but not in an isogenic DLC1-negative cell line
Altered hip muscle forces during gait in people with patellofemoral osteoarthritis
Objectives: The study aimed to (1) assess whether higher vasti (VASTI), gluteus medius (GMED), gluteus maximus (GMAX) and gluteus minimus (GMIN) forces are associated with participant characteristics (lower age, male gender) and clinical characteristics (lower radiographic disease severity, lower symptom severity and higher walking speed); and (2) determine whether hip and knee muscle forces are lower in people with patellofemoral joint (PFJ) osteoarthritis (OA) compared to those without PFJ OA. Design: Sixty participants with PFJ OA and 18 (asymptomatic, no radiographic OA) controls ≥40 years were recruited from the community or via referrals. A three-dimensional musculoskeletal model was used in conjunction with optimisation theory to calculate lower-limb muscle forces during walking. Associations of peak muscle forces with participant and clinical characteristics were conducted using Pearson's r or independent t-tests and between-group comparisons of mean peak muscle forces performed with walking speed as a covariate. Results: Peak muscle forces were not significantly associated with participant, symptomatic or radiographic-specific characteristics. Faster walking speed was associated with higher VASTI muscle force in the PFJ OA (r = 0.495; P < 0.001) and control groups (r = 0.727; P = 0.001) and higher GMAX muscle force (r = 0.593; P = 0.009) in the control group only. Individuals with PFJ OA (N = 60) walked with lower GMED and GMIN muscle forces than controls (N = 18): GMED, mean difference 0.15 [95% confidence interval (CI): 0.01 to 0.29] body weight (BW); GMIN, 0.03 [0.01 to 0.06] BW. No between-group differences were observed in VASTI or GMAX muscle force: VASTI, 0.10 [-0.11 to 0.31] BW; GMAX, 0.01 [-0.11 to 0.09] BW. Conclusion: Individuals with PFJ OA ambulate with lower peak hip abductor muscle forces than their healthy counterparts
The Microarcsecond Sky and Cosmic Turbulence
Radio waves are imprinted with propagation effects from ionized media through
which they pass. Owing to electron density fluctuations, compact sources
(pulsars, masers, and compact extragalactic sources) can display a wide variety
of scattering effects. These scattering effects, particularly interstellar
scintillation, can be exploited to provide *superresolution*, with achievable
angular resolutions (<~ 1 microarcsecond) far in excess of what can be obtained
by very long baseline interferometry on terrestrial baselines. Scattering
effects also provide a powerful sub-AU probe of the microphysics of the
interstellar medium, potentially to spatial scales smaller than 100 km, as well
as a tracer of the Galactic distribution of energy input into the interstellar
medium through a variety of integrated measures. Coupled with future gamma-ray
observations, SKA observations also may provide a means of detecting fainter
compact gamma-ray sources. Though it is not yet clear that propagation effects
due to the intergalactic medium are significant, the SKA will either detect or
place stringent constraints on intergalactic scattering.Comment: 20 pages, 8 figures in 8 PostScript files, to appear in "Science with
the Square Kilometer Array," eds. C. Carilli and S. Rawlings, New Astronomy
Reviews (Elsevier: Amsterdam
Structure and reactivity of Trypanosoma brucei pteridine reductase: inhibition by the archetypal antifolate methotrexate
The protozoan Trypanosoma brucei has a functional pteridine reductase (TbPTR1), an NADPH-dependent short-chain reductase that participates in the salvage of pterins, which are essential for parasite growth. PTR1 displays broad-spectrum activity with pterins and folates, provides a metabolic bypass for inhibition of the trypanosomatid dihydrofolate reductase and therefore compromises the use of antifolates for treatment of trypanosomiasis. Catalytic properties of recombinant TbPTR1 and inhibition by the archetypal antifolate methotrexate have been characterized and the crystal structure of the ternary complex with cofactor NADP(+) and the inhibitor determined at 2.2 Å resolution. This enzyme shares 50% amino acid sequence identity with Leishmania major PTR1 (LmPTR1) and comparisons show that the architecture of the cofactor binding site, and the catalytic centre are highly conserved, as are most interactions with the inhibitor. However, specific amino acid differences, in particular the placement of Trp221 at the side of the active site, and adjustment of the β6-α6 loop and α6 helix at one side of the substrate-binding cleft significantly reduce the size of the substrate binding site of TbPTR1 and alter the chemical properties compared with LmPTR1. A reactive Cys168, within the active site cleft, in conjunction with the C-terminus carboxyl group and His267 of a partner subunit forms a triad similar to the catalytic component of cysteine proteases. TbPTR1 therefore offers novel structural features to exploit in the search for inhibitors of therapeutic value against African trypanosomiasis
(Sub)mm Interferometry Applications in Star Formation Research
This contribution gives an overview about various applications of (sub)mm
interferometry in star formation research. The topics covered are molecular
outflows, accretion disks, fragmentation and chemical properties of low- and
high-mass star-forming regions. A short outlook on the capabilities of ALMA is
given as well.Comment: 20 pages, 7 figures, in proceedings to "2nd European School on Jets
from Young Star: High Angular Resolution Observations". A high-resolution
version of the paper can be found at
http://www.mpia.de/homes/beuther/papers.htm
Post-Newtonian Gravitational Radiation
1 Introduction 2 Multipole Decomposition 3 Source Multipole Moments 4
Post-Minkowskian Approximation 5 Radiative Multipole Moments 6 Post-Newtonian
Approximation 7 Point-Particles 8 ConclusionComment: 46 pages, in Einstein's Field Equations and Their Physical
Implications, B. Schmidt (Ed.), Lecture Notes in Physics, Springe
Hidden Voices of Black Men
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66982/2/10.1177_002193479402500102.pd
A Model for the Development of the Rhizobial and Arbuscular Mycorrhizal Symbioses in Legumes and Its Use to Understand the Roles of Ethylene in the Establishment of these two Symbioses
We propose a model depicting the development of nodulation and arbuscular mycorrhizae. Both processes are dissected into many steps, using Pisum sativum L. nodulation mutants as a guideline. For nodulation, we distinguish two main developmental programs, one epidermal and one cortical. Whereas Nod factors alone affect the cortical program, bacteria are required to trigger the epidermal events. We propose that the two programs of the rhizobial symbiosis evolved separately and that, over time, they came to function together. The distinction between these two programs does not exist for arbuscular mycorrhizae development despite events occurring in both root tissues. Mutations that affect both symbioses are restricted to the epidermal program. We propose here sites of action and potential roles for ethylene during the formation of the two symbioses with a specific hypothesis for nodule organogenesis. Assuming the epidermis does not make ethylene, the microsymbionts probably first encounter a regulatory level of ethylene at the epidermis–outermost cortical cell layer interface. Depending on the hormone concentrations there, infection will either progress or be blocked. In the former case, ethylene affects the cortex cytoskeleton, allowing reorganization that facilitates infection; in the latter case, ethylene acts on several enzymes that interfere with infection thread growth, causing it to abort. Throughout this review, the difficulty of generalizing the roles of ethylene is emphasized and numerous examples are given to demonstrate the diversity that exists in plants
Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.
Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health
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