The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

Adversarial Body Shape Search for Legged Robots

We propose an evolutionary computation method for an adversarial attack on the length and thickness of parts of legged robots by deep reinforcement learning. This attack changes the robot body shape and interferes with walking-we call the attacked body as adversarial body shape. The evolutionary computation method searches adversarial body shape by minimizing the expected cumulative reward earned through walking simulation. To evaluate the effectiveness of the proposed method, we perform experiments with three-legged robots, Walker2d, Ant-v2, and Humanoid-v2 in OpenAI Gym. The experimental results reveal that Walker2d and Ant-v2 are more vulnerable to the attack on the length than the thickness of the body parts, whereas Humanoid-v2 is vulnerable to the attack on both of the length and thickness. We further identify that the adversarial body shapes break left-right symmetry or shift the center of gravity of the legged robots. Finding adversarial body shape can be used to proactively diagnose the vulnerability of legged robot walking.Comment: 6 pages, 7 figure

The liquid Miscibility Gap and the Distribution of Silver Between Speiss and Metallic Lead in the Pb-Fe-As, Pb-Cu-As and Pb-Fe-Cu-As System at 1200℃

The liquid miscibility gap and the distribution of silver between speiss and metallic lead for the Pb-Fe-Cu-As quarternary system have been determined at 1200℃. The miscibility gap in the Pb-Fe-As system covered a wide composition range. Molten lead containing a small amount of arsenic equilibrated with the speiss which consisted of iron arsenide with a small quantity of dissolved lead. The miscibility gap in the Pb-Cu-As system was also determined. In this system, the solubility of lead in speiss had a minimum with increasing arsenic content. In the quarternary system, the region of immiscibility was found to be distributed between the above, two, ternary systems on a pseudoternary phase diagram and was dependent on the cu/Fe+Cu ratio in speiss. The arsenic content in molten lead increased sharply beyond a definite quantity of arsenic in speiss. The behaviour of the distribution ratio of silver, K_, defined as wt.% Ag in speiss/wt.% Ag in metallic lead was summarized as follows : (1) In the Pb-Fe-As system, the values for K_ were low when the arsenic content in speiss was below 40% ; but above this range, the values increased sharply. (2) In the Pb-Cu-As system, K_ was around 1.2 for all speiss compositions investigated. (3) In the Pb-Fe-Cu-As system, the value of K_ was distributed between those obtained for the two ternary systems. The distribution ratios of silver derived from practical data agreed well with present work. From these results, a pyrometallurgical process in which lead and precious metals are recovered as bullion and in which arsenic is fixed and discarded as iron arsenide speiss can be proposed

Noninvasive quantification of regional ventricular function in rats: Assessment of serial change and spatial distribution using ultrasound strain analysis

Background: The optimal method for quantitative assessment of regional ventricular function in rats remains unclear. The goal of this study was to investigate the use of ultrasonic strain rate (SR) and strain analysis in evaluating the serial change and spatial distribution of regional contractile function in rats. Methods: In all, 22 anesthetized rats underwent incremental dobutamine infusion (protocol 1) for assessment of serial change or underwent coronary ligation (protocol 2) for assessment of spatial distribution. For protocol 1, the serial change of systolic SR and strain during dobutamine was measured in the posterior myocardium on the short-axis view, and the systolic strain was compared with the percent change in wall thickening. For protocol 2, the spatial distribution of strain profile was analyzed in normal, peripheral ischemic, and central ischemic regions that were identified by myocardial contrast echocardiography. Results: In protocol 1, the incremental dobutamine infusion resulted in a gradual increase in peak systolic SR. In contrast, peak systolic strain increased with low-dose dobutamine but tended to decrease for higher doses of dobutamine. Further, the serial change of peak systolic strain corresponded to changes in percent change in wall thickening, but the strain values were always lower than percent change in wall thickening. In protocol 2, the strain profile indicated postsystolic thickening in the peripheral ischemic region and indicated systolic wall thinning in the central ischemic region. Conclusions: Ultrasonic determination of SR and strain is an accurate and noninvasive method of quantitation of the serial change and spatial distribution of regional contractile function in rats. Copyright 2005 by the American Society of Echocardiography.Hirano T, Asanuma T, Azakami R, Okuda K, Ishikura F, Beppu S. Noninvasive quantification of regional ventricular function in rats: assessment of serial change and spatial distribution using ultrasound strain analysis. J Am Soc Echocardiogr. 2005 Sep;18(9):907-12. doi: 10.1016/j.echo.2005.01.009

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

エンヘンパ プリント アンテナヨウ ループ マイクロストリップ ソシ ノ モーメントホウ ニヨル カイセキ

In this paper, the authors has assumed that the mode of electromagnetic waves is T M_° mode on a surface of the device made by the loop type microstrip element, and then has introduced the procedure of calculation following the moment method one of the solution by the electric computer

E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis

Chronic hepatic damage leads to liver fibrosis, which is characterized by the accumulation of collagen-rich extracellular matrix. However, the mechanism by which E3 ubiquitin ligase is involved in collagen synthesis in liver fibrosis is incompletely understood. This study aimed to explore the involvement of the E3 ubiquitin ligase synoviolin (Syno) in liver fibrosis.The expression and localization of synoviolin in the liver were analyzed in CCl(4)-induced hepatic injury models and human cirrhosis tissues. The degree of liver fibrosis and the number of activated hepatic stellate cells (HSCs) was compared between wild type (wt) and Syno(+/-) mice in the chronic hepatic injury model. We compared the ratio of apoptosis in activated HSCs between wt and Syno(+/-) mice. We also analyzed the effect of synoviolin on collagen synthesis in the cell line from HSCs (LX-2) using siRNA-synoviolin and a mutant synoviolin in which E3 ligase activity was abolished. Furthermore, we compared collagen synthesis between wt and Syno(-/-) mice embryonic fibroblasts (MEF) using quantitative RT-PCR, western blotting, and collagen assay; then, we immunohistochemically analyzed the localization of collagen in Syno(-/-) MEF cells.In the hepatic injury model as well as in cirrhosis, synoviolin was upregulated in the activated HSCs, while Syno(+/-) mice developed significantly less liver fibrosis than in wt mice. The number of activated HSCs was decreased in Syno(+/-) mice, and some of these cells showed apoptosis. Furthermore, collagen expression in LX-2 cells was upregulated by synoviolin overexpression, while synoviolin knockdown led to reduced collagen expression. Moreover, in Syno(-/-) MEF cells, the amounts of intracellular and secreted mature collagen were significantly decreased, and procollagen was abnormally accumulated in the endoplasmic reticulum.Our findings demonstrate the importance of the E3 ubiquitin ligase synoviolin in liver fibrosis

The luxS mutation causes loosely-bound biofilms in Shewanella oneidensis

<p>Abstract</p> <p>Background</p> <p>The <it>luxS </it>gene in <it>Shewanella oneidensis </it>was shown to encode an autoinducer-2 (AI-2)-like molecule, the postulated universal bacterial signal, but the impaired biofilm growth of a <it>luxS </it>deficient mutant could not be restored by AI-2, indicating it might not have a signalling role in this organism.</p> <p>Findings</p> <p>Here, we provide further evidence regarding the metabolic role of a <it>luxS </it>mutation in <it>S. oneidensis</it>. We constructed a <it>luxS </it>mutant and compared its phenotype to a wild type control with respect to its ability to remove AI-2 from the medium, expression of secreted proteins and biofilm formation. We show that <it>S. oneidensis </it>has a cell-dependent mechanism by which AI-2 is depleted from the medium by uptake or degradation at the end of the exponential growth phase. As AI-2 depletion is equally active in the <it>luxS </it>mutant and thus does not require AI-2 as an inducer, it appears to be an unspecific mechanism suggesting that AI-2 for <it>S. oneidensis </it>is a metabolite which is imported under nutrient limitation. Secreted proteins were studied by iTraq labelling and liquid chromatography mass spectrometry (LC-MS) detection. Differences between wild type and mutant were small. Proteins related to flagellar and twitching motility were slightly up-regulated in the <it>luxS </it>mutant, in accordance with its loose biofilm structure. An enzyme related to cysteine metabolism was also up-regulated, probably compensating for the lack of the LuxS enzyme. The <it>luxS </it>mutant developed an undifferentiated, loosely-connected biofilm which covered the glass surface more homogenously than the wild type control, which formed compact aggregates with large voids in between.</p> <p>Conclusions</p> <p>The data confirm the role of the LuxS enzyme for biofilm growth in <it>S. oneidensis </it>and make it unlikely that AI-2 has a signalling role in this organism.</p