Flow Perfusion Co-culture of Human Mesenchymal Stem Cells and Endothelial Cells on Biodegradable Polymer Scaffolds

In this study, we investigated the effect of flow perfusion culture on the mineralization of co-cultures of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs). Osteogenically precultured hMSCs were seeded onto electrospun scaffolds in monoculture or a 1:1 ratio with HUVECs, cultured for 7 or 14 days in osteogenic medium under static or flow perfusion conditions, and the resulting constructs were analyzed for cellularity, alkaline phosphatase (ALP) activity and calcium content. In flow perfusion, constructs with monocultures of hMSCs demonstrated higher cellularity and calcium content, but lower ALP activity compared to corresponding static controls. ALP activity was enhanced in co-cultures under flow perfusion conditions, compared to hMSCs alone; however unlike the static controls, the calcium content of the co-cultures in flow perfusion was not different from the corresponding hMSC monocultures. The data suggest that co-cultures of hMSCs and HUVECs did not contribute to enhanced mineralization compared to hMSCs alone under the flow perfusion conditions investigated in this study. However, flow perfusion culture resulted in an enhanced spatial distribution of cells and matrix compared to static cultures, which were limited to a thin surface layer

Responsive and In situ-forming chitosan scaffolds for bone tissue engineering applications : an overview of the last decade

The use of bioabsorbable polymeric scaffolds is being investigated for use in bone tissue engineering applications, as their properties can be tailored to allow them to degrade and integrate at optimal rates as bone remodelling is completed. The main goal of this review is to highlight the “intelligent” properties exhibited by chitosan scaffolds and their use in the bone tissue engineering field. To complement the fast evolution of the bone tissue engineering field, it is important to propose the use of responsive scaffolds and take advantage of bioinspired materials and their properties as emerging technologies. There is a growing interest and need for new biomaterials, such as “smart”/responsive materials with the capability to respond to changes in the in vivo environment. This review will provide an overview of strategies that can modulate bone tissue regeneration by using in situ-forming scaffolds

Design of a High-Throughput Flow Perfusion Bioreactor System for Tissue Engineering

Flow perfusion culture is used in many areas of tissue engineering and offers several key advantages. However, one challenge to these cultures is the relatively low-throughput nature of perfusion bioreactors. Here, a flow perfusion bioreactor with increased throughput was designed and built for tissue engineering. This design uses an integrated medium reservoir and flow chamber in order to increase the throughput, limit the volume of medium required to operate the system, and simplify the assembly and operation

Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation: Special Report of the Intergovernmental Panel on Climate Change

This Special Report on Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation (SREX) has been jointly coordinated by Working Groups I (WGI) and II (WGII) of the Intergovernmental Panel on Climate Change (IPCC). The report focuses on the relationship between climate change and extreme weather and climate events, the impacts of such events, and the strategies to manage the associated risks. The IPCC was jointly established in 1988 by the World Meteorological Organization (WMO) and the United Nations Environment Programme (UNEP), in particular to assess in a comprehensive, objective, and transparent manner all the relevant scientific, technical, and socioeconomic information to contribute in understanding the scientific basis of risk of human-induced climate change, the potential impacts, and the adaptation and mitigation options. Beginning in 1990, the IPCC has produced a series of Assessment Reports, Special Reports, Technical Papers, methodologies, and other key documents which have since become the standard references for policymakers and scientists.This Special Report, in particular, contributes to frame the challenge of dealing with extreme weather and climate events as an issue in decisionmaking under uncertainty, analyzing response in the context of risk management. The report consists of nine chapters, covering risk management; observed and projected changes in extreme weather and climate events; exposure and vulnerability to as well as losses resulting from such events; adaptation options from the local to the international scale; the role of sustainable development in modulating risks; and insights from specific case studies

HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail

To avoid immune recognition by cytotoxic T lymphocytes (CTLs), human immunodeficiency virus (HIV)-1 Nef disrupts the transport of major histocompatibility complex class I molecules (MHC-I) to the cell surface in HIV-infected T cells. However, the mechanism by which Nef does this is unknown. We report that Nef disrupts MHC-I trafficking by rerouting newly synthesized MHC-I from the trans-Golgi network (TGN) to lysosomal compartments for degradation. The ability of Nef to target MHC-I from the TGN to lysosomes is dependent on expression of the μ1 subunit of adaptor protein (AP) AP-1A, a cellular protein complex implicated in TGN to endolysosomal pathways. We demonstrate that in HIV-infected primary T cells, Nef promotes a physical interaction between endogenous AP-1 and MHC-I. Moreover, we present data that this interaction uses a novel AP-1 binding site that requires amino acids in the MHC-I cytoplasmic tail. In sum, our evidence suggests that binding of AP-1 to the Nef–MHC-I complex is an important step required for inhibition of antigen presentation by HIV

Determining the Magnetic Field Orientation of Coronal Mass Ejections from Faraday Rotation

We describe a method to measure the magnetic field orientation of coronal mass ejections (CMEs) using Faraday rotation (FR). Two basic FR profiles, Gaussian-shaped with a single polarity or "N"-like with polarity reversals, are produced by a radio source occulted by a moving flux rope depending on its orientation. These curves are consistent with the Helios observations, providing evidence for the flux-rope geometry of CMEs. Many background radio sources can map CMEs in FR onto the sky. We demonstrate with a simple flux rope that the magnetic field orientation and helicity of the flux rope can be determined 2-3 days before it reaches Earth, which is of crucial importance for space weather forecasting. An FR calculation based on global magnetohydrodynamic (MHD) simulations of CMEs in a background heliosphere shows that FR mapping can also resolve a CME geometry curved back to the Sun. We discuss implementation of the method using data from the Mileura Widefield Array (MWA).Comment: 22 pages with 9 figures, accepted for publication in Astrophys.

Correlation between energetic ion enhancements and heliospheric current sheet crossings in the outer heliosphere

Voyagers 1 and 2 observed highly-variable beams of energetic ions in the foreshock region upstream of the termination shock (TS). At Voyager 2 (V2), the ion intensities are generally not related to the plasma properties. At Voyager 1 (V1), the beams are often coincident with crossings of the heliospheric current sheet (HCS). The V1 intensity peaks occur when the HCS is crossed from negative to positive magnetic polarities and V1 is within a few AU of the TS. Two mechanisms are considered: current sheet drift and streaming of ions from the TS along magnetic field lines which are parallel to the HCS. The current sheet drift hypothesis predicts that enhancements observed at V2 will occur when the HCS is crossed in the opposite direction, from positive to negative magnetic polarity, since V2 is at southern heliolatitudes

Teaching Geophysics with a Vertical-Component Seismometer

Earthquakes are some of the more dramatic expressions of the dynamics of our planet. The sudden release of stress built up slowly by tectonic or volcanic processes often has far-reaching consequences, and can be measured (in classrooms) around the world. This is one reason why designing and building seismometers has been a popular activity,1,2 and why different versions of “Seismometer in Schools” projects thrive in the United States, Australia, and Europe. We present a cheap, robust, and easy-to-build seismometer—called the TC1 —to measure seismic displacements in the vertical direction. Its components are easy to obtain and assemble, yet the resulting instrument is accurate enough to record earthquakes from around the globe. The parts list and building instructions of the TC1 seismometer are freely available online. Alternatively, a complete kit can be purchased for around US$300. Assembling the system naturally introduces students to a number of concepts in physics and engineering, while upon completion seismic recordings trigger discussions about the dynamics and internal structure of the Earth. The discussions are fostered by service learning and shared in the network of TC1s called the Z-NET

Investigating a training supporting shared decision making (IT'S SDM 2011): study protocol for a randomized controlled trial

<p/> <p>Background</p> <p>Shared Decision Making (SDM) is regarded as the best practice model for the communicative challenge of decision making about treatment or diagnostic options. However, randomized controlled trials focusing the effectiveness of SDM trainings are rare and existing measures of SDM are increasingly challenged by the latest research findings. This study will 1) evaluate a new physicians' communication training regarding patient involvement in terms of SDM, 2) validate SDM_MASS, a new compound measure of SDM, and 3) evaluate the effects of SDM on the perceived quality of the decision process and on the elaboration of the decision.</p> <p>Methods</p> <p>In a multi-center randomized controlled trial with a waiting control group, 40 physicians from 7 medical fields are enrolled. Each physician contributes a sequence of four medical consultations including a diagnostic or treatment decision.</p> <p>The intervention consists of two condensed video-based individual coaching sessions (15min.) supported by a manual and a DVD. The interventions alternate with three measurement points plus follow up (6 months).</p> <p>Realized patient involvement is measured using the coefficient SDM_MASSdrawn from the Multifocal Approach to the Sharing in SDM (MAPPIN'SDM) which includes objective involvement, involvement as perceived by the patient, and the doctor-patient concordance regarding their judges of the involvement. For validation purposes, all three components of SDM_MASSare supplemented by similar measures, the OPTION observer scale, the Shared Decision Making Questionnaire (SDM-Q) and the dyadic application of the Decisional Conflict Scale (DCS). Training effects are analyzed using t-tests. Spearman correlation coefficients are used to determine convergent validities, the influence of involvement (SDM_MASS) on the perceived decision quality (DCS) and on the elaboration of the decision. The latter is operationalised by the ELAB coefficient from the UP24 (Uncertainty Profile, 24 items version).</p> <p>Discussion</p> <p>Due to the rigorous blinded randomized controlled design, the current trial promises valid and reliable results. On the one hand, we expect this condensed time-saving training to be adopted in clinical routine more likely than previous trainings. On the other hand, the exhaustivity of the MAPPIN'SDM measurement system qualifies it as a reference measure for simpler instruments and to deepen understanding of decision-making processes.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN78716079">ISRCTN78716079</a></p

Synthetic biodegradable hydrogel delivery of demineralized bone matrix for bone augmentation in a rat model

There exists a strong clinical need for a more capable and robust method to achieve bone augmentation, and a system with fine-tuned delivery of demineralized bone matrix (DBM) has the potential to meet that need. As such, the objective of the present study was to investigate a synthetic biodegradable hydrogel for the delivery of DBM for bone augmentation in a rat model. Oligo(poly(ethylene glycol) fumarate) (OPF) constructs were designed and fabricated by varying the content of rat-derived DBM particles (either 1:3, 1:1 or 3:1 DBM:OPF weight ratio on a dry basis) and using two DBM particle size ranges (50–150 or 150–250 μm). The physical properties of the constructs and the bioactivity of the DBM were evaluated. Selected formulations (1:1 and 3:1 with 50–150 μm DBM) were evaluated in vivo compared to an empty control to investigate the effect of DBM dose and construct properties on bone augmentation. Overall, 3:1 constructs with higher DBM content achieved the greatest volume of bone augmentation, exceeding 1:1 constructs and empty implants by 3- and 5-fold, respectively. As such, we have established that a synthetic, biodegradable hydrogel can function as a carrier for DBM, and that the volume of bone augmentation achieved by the constructs correlates directly to the DBM dose