Extracellular matrix synthesis in vascular disease: hypertension, and atherosclerosis

Extracellular matrix (ECM) within the vascular network provides both a structural and regulatory role. The ECM is a dynamic composite of multiple proteins that form structures connecting cells within the network. Blood vessels are distended by blood pressure and, therefore, require ECM components with elasticity yet with enough tensile strength to resist rupture. The ECM is involved in conducting mechanical signals to cells. Most importantly, ECM regulates cellular function through chemical signaling by controlling activation and bioavail- ability of the growth factors. Cells respond to ECM by remodeling their microenvironment which becomes dys- regulated in vascular diseases such hypertension, restenosis and atherosclerosis. This review examines the cellu- lar and ECM components of vessels, with specific emphasis on the regulation of collagen type I and implications in vascular disease

When Enough Is Not Enough: Screening, Brief Intervention and Referral to Treatment for Hepatitis C in Patients Presenting to the Emergency Department

Chronic hepatitis C viral (HCV)infection is the most common blood‐borne infection affecting at least 3.5 million people in the USA.1 HCV is a public health threat as it can lead to cirrhosis, liver decompensation with variceal bleeding, ascites, hepatic encephalopathy, hepatocellular carcinoma or death.2 The World Health Organization (WHO) estimates that 399,000 individuals died from cirrhosis or hepatocellular carcinoma caused by HCV infection in 2015

Comparison of 20nm silver nanoparticles synthesized with and without a gold core: Structure, dissolution in cell culture media, and biological impact on macrophages

Widespread use of silver nanoparticles raises questions of environmental and biological impact. Many synthesis approaches are used to produce pure silver and silver-shell gold-core particles optimized for specific applications. Since both nanoparticles and silver dissolved from the particles may impact the biological response, it is important to understand the physicochemical characteristics along with the biological impact of nanoparticles produced by different processes. The authors have examined the structure, dissolution, and impact of particle exposure to macrophage cells of two 20 nm silver particles synthesized in different ways, which have different internal structures. The structures were examined by electron microscopy and dissolution measured in Rosewell Park Memorial Institute media with 10% fetal bovine serum. Cytotoxicity and oxidative stress were used to measure biological impact on RAW 264.7 macrophage cells. The particles were polycrystalline, but 20 nm particles grown on gold seed particles had smaller crystallite size with many high-energy grain boundaries and defects, and an apparent higher solubility than 20 nm pure silver particles. Greater oxidative stress and cytotoxicity were observed for 20 nm particles containing the Au core than for 20 nm pure silver particles. A simple dissolution model described the time variation of particle size and dissolved silver for particle loadings larger than 9 μg/ml for the 24-h period characteristic of many in-vitro studies

An endogenous F-box protein regulates ARGONAUTE1 in Arabidopsis thaliana

ARGONAUTE1 (AGO1) mediates microRNA- and small interfering RNA-directed posttranscriptional gene silencing in Arabidopsis thaliana. Mutant alleles of SQUINT (SQN) slightly reduce AGO1 activity and have weak effects on shoot morphology. A screen for mutations that suppress the sqn phenotype produced loss-of-function mutations in the F-box gene FBW2. Mutations in FBW2 not only suppress sqn but also suppress many of the developmental phenotypes of weak, but not null, alleles of AGO1 by increasing AGO1 protein levels. Conversely, over-expression of FBW2 decreases the abundance of the AGO1 protein but not AGO1 messenger RNA, further indicating that FBW2 regulates AGO1 protein levels. fbw2 mutants have no obvious morphological phenotype, but display a reduced sensitivity to abscisic acid (ABA) that can be attributed to increased AGO1 activity. Our results indicate that FBW2 is a novel negative regulator of AGO1 and suggest that it plays a role in ABA signalling and/or response

A Role of Myocardin Related Transcription Factor-A (MRTF-A) in Scleroderma Related Fibrosis.

In scleroderma (systemic sclerosis, SSc), persistent activation of myofibroblast leads to severe skin and organ fibrosis resistant to therapy. Increased mechanical stiffness in the involved fibrotic tissues is a hallmark clinical feature and a cause of disabling symptoms. Myocardin Related Transcription Factor-A (MRTF-A) is a transcriptional co-activator that is sequestered in the cytoplasm and translocates to the nucleus under mechanical stress or growth factor stimulation. Our objective was to determine if MRTF-A is activated in the disease microenvironment to produce more extracellular matrix in progressive SSc. Immunohistochemistry studies demonstrate that nuclear translocation of MRTF-A in scleroderma tissues occurs in keratinocytes, endothelial cells, infiltrating inflammatory cells, and dermal fibroblasts, consistent with enhanced signaling in multiple cell lineages exposed to the stiff extracellular matrix. Inhibition of MRTF-A nuclear translocation or knockdown of MRTF-A synthesis abolishes the SSc myofibroblast enhanced basal contractility and synthesis of type I collagen and inhibits the matricellular profibrotic protein, connective tissue growth factor (CCN2/CTGF). In MRTF-A null mice, basal skin and lung stiffness was abnormally reduced and associated with altered fibrillar collagen. MRTF-A has a role in SSc fibrosis acting as a central regulator linking mechanical cues to adverse remodeling of the extracellular matrix

Learning and Composing Primitive Skills for Dual-Arm Manipulation

In an attempt to confer robots with complex manipulation capabilities, dual-arm anthropomorphic systems have become an important research topic in the robotics community. Most approaches in the literature rely upon a great understanding of the dynamics underlying the system's behaviour and yet offer limited autonomous generalisation capabilities. To address these limitations, this work proposes a modelisation for dual-arm manipulators based on dynamic movement primitives laying in two orthogonal spaces. The modularity and learning capabilities of this model are leveraged to formulate a novel end-to-end learning-based framework which (i) learns a library of primitive skills from human demonstrations, and (ii) composes such knowledge simultaneously and sequentially to confront novel scenarios. The feasibility of the proposal is evaluated by teaching the iCub humanoid the basic skills to succeed on simulated dual-arm pick-and-place tasks. The results suggest the learning and generalisation capabilities of the proposed framework extend to autonomously conduct undemonstrated dual-arm manipulation tasks.Comment: Annual Conference Towards Autonomous Robotic Systems (TAROS19

X-Ray Cone Beam Tomography with Two Tilted Circular Trajectories

Recently 3-D cone-beam tomography has become of interest for the nondestructive evaluation of advanced materials. The main field of application in nondestructive testing is the evaluation of structural ceramics. Study of such materials implies high density resolution and high sensitivity to cracks. In fact, with a single circular source trajectory, when the cone-beam aperture increases, density is underestimated and cone shaped artifacts may appear at interfaces in the sample even at relatively small aperture [1–3]. These artifacts limit the thickness we can examine with a planar source trajectory. To maintain optimal reconstruction accuracy with a circular source trajectory, the angular aperture must remain within ±10°. However Kudo and Saito [4] showed that this limit can be slightly overcome by using a special interpolation of the shadow area. But to examine greater thicknesses and to maintain resolution, we must widen the cone-beam aperture thereby decreasing accuracy. To overcome these aperture limitations, Tuy [5] introduced the double circular source trajectory idea

Visualizing sound emission of elephant vocalizations: evidence for two rumble production types

Recent comparative data reveal that formant frequencies are cues to body size in animals, due to a close relationship between formant frequency spacing, vocal tract length and overall body size. Accordingly, intriguing morphological adaptations to elongate the vocal tract in order to lower formants occur in several species, with the size exaggeration hypothesis being proposed to justify most of these observations. While the elephant trunk is strongly implicated to account for the low formants of elephant rumbles, it is unknown whether elephants emit these vocalizations exclusively through the trunk, or whether the mouth is also involved in rumble production. In this study we used a sound visualization method (an acoustic camera) to record rumbles of five captive African elephants during spatial separation and subsequent bonding situations. Our results showed that the female elephants in our analysis produced two distinct types of rumble vocalizations based on vocal path differences: a nasally- and an orally-emitted rumble. Interestingly, nasal rumbles predominated during contact calling, whereas oral rumbles were mainly produced in bonding situations. In addition, nasal and oral rumbles varied considerably in their acoustic structure. In particular, the values of the first two formants reflected the estimated lengths of the vocal paths, corresponding to a vocal tract length of around 2 meters for nasal, and around 0.7 meters for oral rumbles. These results suggest that African elephants may be switching vocal paths to actively vary vocal tract length (with considerable variation in formants) according to context, and call for further research investigating the function of formant modulation in elephant vocalizations. Furthermore, by confirming the use of the elephant trunk in long distance rumble production, our findings provide an explanation for the extremely low formants in these calls, and may also indicate that formant lowering functions to increase call propagation distances in this species'

Occupational noise exposure and hearing loss: A study on knowledge, attitude and practice among Tanzanian iron and steel workers

We assessed Knowledge Attitude and Practice (KAP) regarding occupational noise exposure, Noise-induced hearing loss, audiometry and use of hearing protection devices among iron and steel factory workers exposed to high noise level. A modified, validated, structured questionnaire was used to collect information from 253 male workers randomly selected from the four factories. The sum scores for each domain of KAP were computed. Scores above 75% were defined as good knowledge and positive attitude. For practice, scores of >50% were defined as good. Independent samples t-test and Chi-squared test were used to analyze association between KAP and continuous/categorical variables respectively. Majority of workers displayed poor knowledge and poor practice (94%), but 76% displayed a positive attitude. Most of the workers (86%) had never been provided with hearing protection devices. The mean scores for attitude and practice differed significantly between the four factories (one-way ANOVA, p < 0.001). Implementation of hearing conservation program with provision of hearing protection devices are suggested.publishedVersio

Simulating Dynamical Features of Escape Panic

One of the most disastrous forms of collective human behaviour is the kind of crowd stampede induced by panic, often leading to fatalities as people are crushed or trampled. Sometimes this behaviour is triggered in life-threatening situations such as fires in crowded buildings; at other times, stampedes can arise from the rush for seats or seemingly without causes. Tragic examples within recent months include the panics in Harare, Zimbabwe, and at the Roskilde rock concert in Denmark. Although engineers are finding ways to alleviate the scale of such disasters, their frequency seems to be increasing with the number and size of mass events. Yet, systematic studies of panic behaviour, and quantitative theories capable of predicting such crowd dynamics, are rare. Here we show that simulations based on a model of pedestrian behaviour can provide valuable insights into the mechanisms of and preconditions for panic and jamming by incoordination. Our results suggest practical ways of minimising the harmful consequences of such events and the existence of an optimal escape strategy, corresponding to a suitable mixture of individualistic and collective behaviour.Comment: For related information see http://angel.elte.hu/~panic, http://www.helbing.org, http://angel.elte.hu/~fij, and http://angel.elte.hu/~vicse