Schwingungsverhalten von Walzanlagen

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Use of linear feedback to control relaxation oscillations in a metal-passivation model

A method of linear feedback is shown to be applicable to the control or suppression of spontaneously occurring relaxation oscillations in a two-dimensional model for the passivation of a metal surface exposed to an aqueous medium. For the operating conditions selected, these oscillations are characterized by a large limit cycle within the state space of the electrochemical system. A physically plausible control is used, involving feedback of a linear combination of two measurable quantities to a controllable parameter. The control acts to stabilize an otherwise unstable fixed point without changing its state space coordinates. Addition of the control to the system's dynamics also results in the appearance of two new fixed points, one of which is stable, the other unstable. The control is found to be extremely robust; when applied, even when the system is far from a fixed point, stabilization onto one or the other of the two stable fixed points occurs quickly. Which of the two it approaches depends upon the state space coordinates of the system on the limit cycle at the time the control is initiated. Stabilization onto the fixed point of the free system, from any point on the limit cycle, can be achieved using a combination of free and controlled dynamics. Release of the control causes the system to return to its oscillatory dynamics. Other linear-feedback-based approaches to control also are briefly considered, such as feeding back the time derivative of a measurable quantity to a controllable parameter.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49083/2/ms6607.pd

Intramuscular inflammatory and resolving lipid profile responses to an acute bout of resistance exercise in men

Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. Lipid mediators including classical arachidonic acid-derived eicosanoids (e.g. prostaglandins and leukotrienes) and more recently identified specialized pro-resolving-mediator metabolites of the omega-3 fatty acids play essential roles in initiation, self-limitation, and active resolution of acute inflammatory responses. In this study, we examined the bioactive lipid mediator profile of human skeletal muscle at rest and following acute resistance exercise. Twelve male subjects completed a single bout of maximal isokinetic unilateral knee extension exercise and muscle biopsies were taken from the m.vastus lateralis before and at 2, 4, and 24 h of recovery. Muscle tissue lipid mediator profile was analyzed via liquid chromatography–mass spectrometry (LC-MS)-based targeted lipidomics. At 2 h postexercise, there was an increased intramuscular abundance of cyclooxygenase (COX)-derived thromboxanes (TXB2: 3.33 fold) and prostaglandins (PGE2: 2.52 fold and PGF2α: 1.77 fold). Resistance exercise also transiently increased muscle concentrations of lipoxygenase (LOX) pathway-derived leukotrienes (12-Oxo LTB4: 1.49 fold and 20-COOH LTB4: 2.91 fold), monohydroxy-eicosatetraenoic acids (5-HETE: 2.66 fold, 12-HETE: 2.83 fold, and 15-HETE: 1.69 fold) and monohydroxy-docosahexaenoic acids (4-HDoHE: 1.69 fold, 7-HDoHE: 1.58 fold and 14-HDoHE: 2.35 fold). Furthermore, the abundance of CYP pathway-derived epoxy- and dihydroxy-eicosatrienoic acids was increased in 2 h postexercise biopsies (5,6-EpETrE: 2.48 fold, 11,12-DiHETrE: 1.66 fold and 14,15-DiHETrE: 2.23 fold). These data reveal a range of bioactive lipid mediators as present within human skeletal muscle tissue and demonstrate that acute resistance exercise transiently stimulates the local production of both proinflammatory eicosanoids and pathway markers in specialized proresolving mediator biosynthesis circuits

Un "simposio di sapienza e affetto"

Muscle hypertrophy occurs following increased protein synthesis, which requires activation of the ribosomal complex. Additionally, increased translational capacity via elevated ribosomal RNA (rRNA) synthesis has also been implicated in resistance training-induced skeletal muscle hypertrophy. The time course of ribosome biogenesis following resistance exercise (RE) and the impact exerted by differing recovery strategies remains unknown. In the present study, the activation of transcriptional regulators, the expression levels of pre-rRNA, and mature rRNA components were measured through 48 h after a single-bout RE. In addition, the effects of either low-intensity cycling (active recovery, ACT) or a cold-water immersion (CWI) recovery strategy were compared. Nine male subjects performed two bouts of high-load RE randomized to be followed by 10 min of either ACT or CWI. Muscle biopsies were collected before RE and at 2, 24, and 48 h after RE. RE increased the phosphorylation of the p38-MNK1-eIF4E axis, an effect only evident with ACT recovery. Downstream, cyclin D1 protein, total eIF4E, upstream binding factor 1 (UBF1), and c-Myc proteins were all increased only after RE with ACT. This corresponded with elevated abundance of the pre-rRNAs (45S, ITS-28S, ITS-5.8S, and ETS-18S) from 24 h after RE with ACT. In conclusion, coordinated upstream signaling and activation of transcriptional factors stimulated pre-rRNA expression after RE. CWI, as a recovery strategy, markedly blunted these events, suggesting that suppressed ribosome biogenesis may be one factor contributing to the impaired hypertrophic response observed when CWI is used regularly after exercise

Isotope or mass encoding of combinatorial libraries

Background: Combinatorial chemistry using solid-phase synthesis is a rapidly developing technology that can result in a significant reduction in the time required to find and optimize lead compounds. The application of this approach to traditional medicinal chemistry has led to the construction of libraries of small organic molecules on resin beads. A major difficulty in developing large combinatorial libraries is the lack of a facile encoding and decoding methodology to identify active compounds.Results: Several encoding schemes are described which use the ability of mass spectrometry to ascertain isotopic distributions. Molecular tags are attached to resin beads in parallel or on the linker used for chemical library synthesis. The tags are encoded via a controlled ratio of a number of stable isotopes on the tagging molecules, and range from a single to a complex isotopic distribution.Conclusions: A novel coding scheme is described that is useful for the generation of large encoded combinatorial libraries. The code can be cleaved after assay and analyzed by mass spectrometry in an automated fashion. An important element of the combinatorial discovery process is the ability to extract the structure-activity relationship (SAR) information made available by library screening. The speed and sensitivity of the mass-encoding scheme has the potential to determine the full SAR for a given library

Acute Resistance Exercise Induces Sestrin2 Phosphorylation and p62 Dephosphorylation in Human Skeletal Muscle

Sestrins (1, 2, 3) are a family of stress-inducible proteins capable of attenuating oxidative stress, regulating metabolism, and stimulating autophagy. Sequestosome1 (p62) is also a stress-inducible multifunctional protein acting as a signaling hub for oxidative stress and selective autophagy. It is unclear whether Sestrin and p62Ser403 are regulated acutely or chronically by resistance exercise (RE) or training (RT) in human skeletal muscle. Therefore, the acute and chronic effects of RE on Sestrin and p62 in human skeletal muscle were examined through two studies. In Study 1, nine active men (22.1 ± 2.2 years) performed a bout of single-leg strength exercises and muscle biopsies were collected before, 2, 24, and 48 h after exercise. In Study 2, 10 active men (21.3 ± 1.9 years) strength trained for 12 weeks (2 days per week) and biopsies were collected pre- and post-training. Acutely, 2 h postexercise, phosphorylation of p62Ser403 was downregulated, while there was a mobility shift of Sestrin2, indicative of increased phosphorylation. Forty-eight hours postexercise, the protein expression of both Sestrin1 and total p62 increased. Chronic exercise had no impact on the gene or protein expression of Sestrin2/3 or p62, but Sestrin1 protein was upregulated. These findings demonstrated an inverse relationship between Sestrin2 and p62 phosphorylation after a single bout of RE, indicating they are transiently regulated. Contrarily, 12 weeks of RT increased protein expression of Sestrin1, suggesting that despite the strong sequence homology of the Sestrin family, they are differentially regulated in response to acute RE and chronic RT

Novel n-3 Docosapentaneoic Acid-Derived Pro-resolving Mediators Are Vasculoprotective and Mediate the Actions of Statins in Controlling Inflammation

“This is a post-peer-review, pre-copyedit version of a chapter published in Advances in Experimental Medicine and Biology book series (AEMB, volume 1161). The final publication is available athttps://doi.org/10.1007/978-3-030-21735-8_7

Activation of the KATP channel by Mg-nucleotide interaction with SUR1

The mechanism of adenosine triphosphate (ATP)-sensitive potassium (KATP) channel activation by Mg-nucleotides was studied using a mutation (G334D) in the Kir6.2 subunit of the channel that renders KATP channels insensitive to nucleotide inhibition and has no apparent effect on their gating. KATP channels carrying this mutation (Kir6.2-G334D/SUR1 channels) were activated by MgATP and MgADP with an EC50 of 112 and 8 µM, respectively. This activation was largely suppressed by mutation of the Walker A lysines in the nucleotide-binding domains of SUR1: the remaining small (∼10%), slowly developing component of MgATP activation was fully inhibited by the lipid kinase inhibitor LY294002. The EC50 for activation of Kir6.2-G334D/SUR1 currents by MgADP was lower than that for MgATP, and the time course of activation was faster. The poorly hydrolyzable analogue MgATPγS also activated Kir6.2-G334D/SUR1. AMPPCP both failed to activate Kir6.2-G334D/SUR1 and to prevent its activation by MgATP. Maximal stimulatory concentrations of MgATP (10 mM) and MgADP (1 mM) exerted identical effects on the single-channel kinetics: they dramatically elevated the open probability (PO > 0.8), increased the mean open time and the mean burst duration, reduced the frequency and number of interburst closed states, and eliminated the short burst states. By comparing our results with those obtained for wild-type KATP channels, we conclude that the MgADP sensitivity of the wild-type KATP channel can be described quantitatively by a combination of inhibition at Kir6.2 (measured for wild-type channels in the absence of Mg2+) and activation via SUR1 (determined for Kir6.2-G334D/SUR1 channels). However, this is not the case for the effects of MgATP

Removal of <i>p16</i> ^<i>INK4</i> Expressing Cells in Late Life has Moderate Beneficial Effects on Skeletal Muscle Function in Male Mice.

Aging results in the progressive accumulation of senescent cells in tissues that display loss of proliferative capacity and acquire a senescence-associated secretory phenotype (SASP). The tumor suppressor, p16 INK4A , which slows the progression of the cell cycle, is highly expressed in most senescent cells and the removal of p16-expressing cells has been shown to be beneficial to tissue health. Although much work has been done to assess the effects of cellular senescence on a variety of different organs, little is known about the effects on skeletal muscle and whether reducing cellular senescent load would provide a therapeutic benefit against age-related muscle functional decline. We hypothesized that whole-body ablation of p16-expressing cells in the advanced stages of life in mice would provide a therapeutic benefit to skeletal muscle structure and function. Treatment of transgenic p16-3MR mice with ganciclovir (GCV) from 20 to 26 months of age resulted in reduced p16 mRNA levels in muscle. At 26 months of age, the masses of tibialis anterior, extensor digitorum longus, gastrocnemius and quadriceps muscles were significantly larger in GCV-treated compared with vehicle-treated mice, but this effect was limited to male mice. Maximum isometric force for gastrocnemius muscles was also greater in GCV-treated male mice compared to controls. Further examination of muscles of GCV- and vehicle-treated mice showed fewer CD68-positive macrophages present in the tissue following GCV treatment. Plasma cytokine levels were also measured with only one, granulocyte colony stimulating factor (G-CSF), out of 22 chemokines analyzed was reduced in GCV-treated mice. These findings show that genetic ablation of p16+ senescent cells provides moderate and sex specific therapeutic benefits to muscle mass and function