Alginate hydrogel has a negative impact on in vitro collagen 1 deposition by fibroblasts

Hydrogels have been widely investigated as 3D culture substrates because of their reported structural similarity to the extracellular matrix (ECM). Limited ECM deposition, however, occurs within these materials, so the resulting “tissues” bear little resemblance to those found in the body. Here matrix deposition by fibroblasts encapsulated within a calcium alginate (Ca-alg) hydrogel was investigated. Although the cells transcribed mRNA for coll Iα over a period of 3 weeks, very little collagen protein deposition was observed within the gel by histology or immunohistochemistry (IHC). Although molecular diffusion demonstrated charge dependency, this did not prevent the flux of both positively and negative charged amino acids through the gel, suggesting that the absence of ECM could not be attributed to substrate limitation. The flux of protein, however, was charge-dependent as proteins with a net negative charge passed quickly through the Ca-alg into the medium. The minimal collagen deposition within the Ca-alg was attributed to a combination of rapid movement of negatively charged procollagen through the gel and steric hindrance of fibril formation

Decoupled Sampling-Based Motion Planning for Multiple Autonomous Marine Vehicles

There is increasing interest in the deployment and operation of multiple autonomous marine vehicles (AMVs) for a number of challenging scientific and commercial operational mission scenarios. Some of the missions, such as geotechnical surveying and 3D marine habitat mapping, require that a number of heterogeneous vehicles operate simultaneously in small areas, often in close proximity of each other. In these circumstances safety, reliability, and efficient multiple vehicle operation are key ingredients for mission success. Additionally, the deployment and operation of multiple AMVs at sea are extremely costly in terms of the logistics and human resources required for mission supervision, often during extended periods of time. These costs can be greatly minimized by automating the deployment and initial steering of a vehicle fleet to a predetermined configuration, in preparation for the ensuing mission, taking into account operational constraints. This is one of the core issues addressed in the scope of the Widely Scalable Mobile Underwater Sonar Technology project (WiMUST), an EU Horizon 2020 initiative for underwater robotics research. WiMUST uses a team of cooperative autonomous ma- rine robots, some of which towing streamers equipped with hydrophones, acting as intelligent sensing and communicat- ing nodes of a reconfigurable moving acoustic network. In WiMUST, the AMVs maintain a fixed geometric formation through cooperative navigation and motion control. Formation initialization requires that all the AMVs start from scattered positions in the water and maneuver so as to arrive at required target configuration points at the same time in a completely au- tomatic manner. This paper describes the decoupled prioritized vehicle motion planner developed in the scope of WiMUST that, together with an existing system for trajectory tracking, affords a fleet of vehicles the above capabilities, while ensuring inter- vehicle collision and streamer entanglement avoidance. Tests with a fleet of seven marine vehicles show the efficacy of the system planner developed.Peer reviewe

Simulated Galaxy Interactions as Probes of Merger Spectral Energy Distributions

We present the first systematic comparison of ultraviolet-millimeter spectral energy distributions (SEDs) of observed and simulated interacting galaxies. Our sample is drawn from the Spitzer Interacting Galaxy Survey, and probes a range of galaxy interaction parameters. We use 31 galaxies in 14 systems which have been observed with Herschel, Spitzer, GALEX, and 2MASS. We create a suite of GADGET-3 hydrodynamic simulations of isolated and interacting galaxies with stellar masses comparable to those in our sample of interacting galaxies. Photometry for the simulated systems is then calculated with the SUNRISE radiative transfer code for comparison with the observed systems. For most of the observed systems, one or more of the simulated SEDs match reasonably well. The best matches recover the infrared luminosity and the star formation rate of the observed systems, and the more massive systems preferentially match SEDs from simulations of more massive galaxies. The most morphologically distorted systems in our sample are best matched to simulated SEDs close to coalescence, while less evolved systems match well with SEDs over a wide range of interaction stages, suggesting that an SED alone is insufficient to identify interaction stage except during the most active phases in strongly interacting systems. This result is supported by our finding that the SEDs calculated for simulated systems vary little over the interaction sequence.Comment: 24 pages, 16 figures, 2 tables, accepted for publication in ApJ. Animations of the evolution of the simulated SEDs can be found at http://www.cfa.harvard.edu/~llanz/sigs_sim.htm

IL-21 receptor expression in human tendinopathy

The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward and early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly up regulated by proinflammatory cytokines (TNFα/IL-1β) in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy

Platelet microvesicles (microparticles) in cardiac surgery

SIGNIFICANT POSTOPERATIVE BLEEDING is a common risk of cardiac surgery, with approximately 3.5% of patients requiring surgical re-exploration.1 Re-exploration is associated with adverse outcomes, including infections, ischemia, and increased 30-day mortality.2 Similar adverse outcomes are related to erythrocyte transfusions associated with cardiac surgery,3 in addition to the immunologic and administrative hazards of transfusion.4 These risks are important because the majority of patients undergoing cardiac surgery receive a blood transfusion despite the lack of evidence to support liberal transfusion strategies.5 The frequency and significance of bleeding after cardiac surgery warrant investigation of the hematologic changes throughout the procedure. This review focuses on the (patho)physiology of platelet-derived microvesicles in the setting of cardiovascular surgery, a developing area in the understanding of the control of coagulation

Acidosis slows electrical conduction through the atrio-ventricular node

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis

Origin of ferroelectricity in the multiferroic barium fluorides BaMF4

We present a first principles study of the series of multiferroic barium fluorides with the composition BaMF4, where M is Mn, Fe, Co, or Ni. We discuss trends in the structural, electronic, and magnetic properties, and we show that the ferroelectricity in these systems results from the "freezing in" of a single unstable polar phonon mode. In contrast to the case of the standard perovskite ferroelectrics, this structural distortion is not accompanied by charge transfer between cations and anions. Thus, the ferroelectric instability in the multiferroic barium fluorides arises solely due to size effects and the special geometrical constraints of the underlying crystal structure.Comment: 8 pages, 6 figures, 3 table

Vaccinia Virus Gene B7R Encodes an 18-kDa Protein That is Resident in the Endoplasmic Reticulum and Affects Virus Virulence

AbstractThis paper presents a characterisation of vaccinia virus (VV) gene B7R that was predicted to encode a polypeptide of 182 amino acids with an N-terminal signal peptide. In vitro transcription and translation analysis showed the B7R gene product was a 21-kDa protein that, in the presence of microsomes, was processed into an 18-kDa mature form. The 18-kDa form associated with the microsomal membranes and was within the lumen of the vesicle where it was inaccessible to exogenous protease or an antibody raised against the B7R C terminus. Within VV-infected cells, the 18-kDa form of B7R was detected late during infection in the endoplasmic reticulum where it colocalised with protein disulphide isomerase. The B7R protein was detected neither in the culture supernatant nor associated with virus particles. A virus deletion mutant lacking the B7R gene and a revertant virus were constructed. Compared to wild-type and revertant viruses, the deletion mutant replicated normally in cell culture and had unaltered virulence in a murine intranasal model of infection. However, the deletion mutant was attenuated in a murine intradermal model where it induced a smaller lesion than the control viruses

Dose de-escalation of intrapleural tissue plasminogen activator therapy for pleural infection. The alteplase dose assessment for Pleural infection Therapy project

Rationale: Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA. The first of several planned studies is presented here. Objectives: To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Methods: Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C-reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. Results: We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22–58] to 16% [8–31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247–2,984] over 72 h of therapy; P <  0.05) and a reduction in blood C-reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent surgery. Three patients (4.9%) received blood transfusions for gradual pleural blood loss; none were hemodynamically compromised. Pain requiring escalation of analgesia affected 36% of patients; none required cessation of therapy. Conclusions: These pilot data suggest that a starting dose of 5 mg of tPA administered intrapleurally twice daily in combination with 5 mg of DNase for the treatment of pl

Preschool children's vision screening in New Zealand: a retrospective evaluation of referral accuracy

Langeslag-Smith MA, Vandal AC, Briane V, et al. Preschool children's vision screening in New Zealand: a retrospective evaluation of referral accuracy. BMJ Open 2015;5:e009207. doi: 10.1136/bmjopen-2015-009207Objectives To assess the accuracy of preschool vision screening in a large, ethnically diverse, urban population in South Auckland, New Zealand. Design Retrospective longitudinal study. Methods B4 School Check vision screening records (n=5572) were compared with hospital eye department data for children referred from screening due to impaired acuity in one or both eyes who attended a referral appointment (n=556). False positive screens were identified by comparing screening data from the eyes that failed screening with hospital data. Estimation of false negative screening rates relied on data from eyes that passed screening. Data were analysed using logistic regression modelling accounting for the high correlation between results for the two eyes of each child. Primary outcome measure Positive predictive value of the preschool vision screening programme. Results Screening produced high numbers of false positive referrals, resulting in poor positive predictive value (PPV=31%, 95% CI 26% to 38%). High estimated negative predictive value (NPV=92%, 95% CI 88% to 95%) suggested most children with a vision disorder were identified at screening. Relaxing the referral criteria for acuity from worse than 6/9 to worse than 6/12 improved PPV without adversely affecting NPV. Conclusions The B4 School Check generated numerous false positive referrals and consequently had a low PPV. There is scope for reducing costs by altering the visual acuity criterion for referral.This work was supported by the Arthur D Bronlund Trust, CCRep and University of Auckland Faculty Research Development Fund Grants (3704420)