Endothelial Cells Potentiate Interferon-γ Production in a Novel Tripartite Culture Model of Human Cerebral Malaria

We have established a novel in vitro co-culture system of human brain endothelial cells (HBEC), Plasmodium falciparum parasitised red blood cells (iRBC) and peripheral blood mononuclear cells (PBMC), in order to simulate the chief pathophysiological lesion in cerebral malaria (CM). This approach has revealed a previously unsuspected pro-inflammatory role of the endothelial cell through potentiating the production of interferon (IFN)-γ by PBMC and concurrent reduction of interleukin (IL)-10. The IFN-γ increased the expression of CXCL10 and intercellular adhesion molecule (ICAM)-1, both of which have been shown to be crucial in the pathogenesis of CM. There was a shift in the ratio of IL-10:IFN-γ protein from >1 to <1 in the presence of HBEC, associated with the pro-inflammatory process in this model. For this to occur, a direct contact between PBMC and HBEC, but not PBMC and iRBC, was necessary. These results support HBEC playing an active role in the pathogenesis of CM. Thus, if these findings reflect the pathogenesis of CM, inhibition of HBEC and PBMC interactions might reduce the occurrence, or improve the prognosis, of the condition. © 2013 Khaw et al

Cloud computing and validation of expandable in silico livers

<p>Abstract</p> <p>Background</p> <p>In Silico Livers (ISLs) are works in progress. They are used to challenge multilevel, multi-attribute, mechanistic hypotheses about the hepatic disposition of xenobiotics coupled with hepatic responses. To enhance ISL-to-liver mappings, we added discrete time metabolism, biliary elimination, and bolus dosing features to a previously validated ISL and initiated re-validated experiments that required scaling experiments to use more simulated lobules than previously, more than could be achieved using the local cluster technology. Rather than dramatically increasing the size of our local cluster we undertook the re-validation experiments using the Amazon EC2 cloud platform. So doing required demonstrating the efficacy of scaling a simulation to use more cluster nodes and assessing the scientific equivalence of local cluster validation experiments with those executed using the cloud platform.</p> <p>Results</p> <p>The local cluster technology was duplicated in the Amazon EC2 cloud platform. Synthetic modeling protocols were followed to identify a successful parameterization. Experiment sample sizes (number of simulated lobules) on both platforms were 49, 70, 84, and 152 (cloud only). Experimental indistinguishability was demonstrated for ISL outflow profiles of diltiazem using both platforms for experiments consisting of 84 or more samples. The process was analogous to demonstration of results equivalency from two different wet-labs.</p> <p>Conclusions</p> <p>The results provide additional evidence that disposition simulations using ISLs can cover the behavior space of liver experiments in distinct experimental contexts (there is in silico-to-wet-lab phenotype similarity). The scientific value of experimenting with multiscale biomedical models has been limited to research groups with access to computer clusters. The availability of cloud technology coupled with the evidence of scientific equivalency has lowered the barrier and will greatly facilitate model sharing as well as provide straightforward tools for scaling simulations to encompass greater detail with no extra investment in hardware.</p

The lived experience of involuntary community treatment: a qualitative study of mental health consumers and carers

Objective: To describe the lived experiences of people subject to community treatment orders (CTOs) and their carers. Method: We recruited 11 participants (five mental health consumers and six carers) through consumer and carer networks in NSW, Australia, to take part in interviews about their experiences. We analysed the interview data set using established qualitative methodologies. Results: The lived experiences were characterised by ‘access’ concerns, ‘isolation’, ‘loss and trauma’, ‘resistance and resignation’ and ‘vulnerability and distress’. The extent and impact of these experiences related to the severity of mental illness, the support available for people with mental illnesses and their carers, the social compromises associated with living with mental illness, and the challenges of managing the relationships necessitated by these processes. Conclusions: The lived experience of CTOs is complex: it is one of distress and profound ambivalence. The distress is an intrinsic aspect of the experience of severe mental illness, but it also emerges from communication gaps, difficulty obtaining optimal care and accessing mental health services. The ambivalence arises from an acknowledgement that while CTOs are coercive and constrain autonomy, they may also be beneficial. These findings can inform improvements to the implementation of CTOs and the consequent experiences. Keywords: carer, community treatment order, interview, involuntary treatment, mental health, patient experience, qualitative researchsupported by the Mental Health, Drug and Alcohol Office (MHDAO) of NSW Health of Australia

Hysteresis phenomenon in turbulent convection

Coherent large-scale circulations of turbulent thermal convection in air have been studied experimentally in a rectangular box heated from below and cooled from above using Particle Image Velocimetry. The hysteresis phenomenon in turbulent convection was found by varying the temperature difference between the bottom and the top walls of the chamber (the Rayleigh number was changed within the range of $10^7 - 10^8$). The hysteresis loop comprises the one-cell and two-cells flow patterns while the aspect ratio is kept constant ($A=2 - 2.23$). We found that the change of the sign of the degree of the anisotropy of turbulence was accompanied by the change of the flow pattern. The developed theory of coherent structures in turbulent convection (Elperin et al. 2002; 2005) is in agreement with the experimental observations. The observed coherent structures are superimposed on a small-scale turbulent convection. The redistribution of the turbulent heat flux plays a crucial role in the formation of coherent large-scale circulations in turbulent convection.Comment: 10 pages, 9 figures, REVTEX4, Experiments in Fluids, 2006, in pres

Super-Resolution Reconstruction of Remote Sensing Images Using Multifractal Analysis

Satellite remote sensing (RS) is an important contributor to Earth observation, providing various kinds of imagery every day, but low spatial resolution remains a critical bottleneck in a lot of applications, restricting higher spatial resolution analysis (e.g., intra-urban). In this study, a multifractal-based super-resolution reconstruction method is proposed to alleviate this problem. The multifractal characteristic is common in Nature. The self-similarity or self-affinity presented in the image is useful to estimate details at larger and smaller scales than the original. We first look for the presence of multifractal characteristics in the images. Then we estimate parameters of the information transfer function and noise of the low resolution image. Finally, a noise-free, spatial resolution-enhanced image is generated by a fractal coding-based denoising and downscaling method. The empirical case shows that the reconstructed super-resolution image performs well in detail enhancement. This method is not only useful for remote sensing in investigating Earth, but also for other images with multifractal characteristics

Measuring persistent and transient energy efficiency in the US

The promotion of US energy efficiency policy is seen as a very important activity. Generally, the level of energy efficiency of a country or state is approximated by energy intensity, commonly calculated as the ratio of energy use to GDP. However, energy intensity is not an accurate proxy for energy efficiency given that changes in energy intensity are a function of changes in several factors including the structure of the economy, climate, efficiency in the use of resources, behaviour and technical change. The aim of this paper is to measure persistent and transient energy efficiency for the whole economy of 49 states in the US using a stochastic frontier energy demand approach. A total US energy demand frontier function is estimated using panel data for 49 states over the period 1995 to 2009 using two panel data models: the Mundlak version of the random effects model (which estimates the persistent part of the energy efficiency) and the true random effects model (which estimates the transient part of the energy efficiency). The analysis confirms that energy intensity is not a good indicator of energy efficiency, whereas, by controlling for a range of economic and other factors, the measures of energy efficiency obtained via the approach adopted here are. Moreover, the estimates show that although for some states energy intensity might give a reasonable indication of a state’s relative energy efficiency, this is not the case for all states.ISSN:1570-646XISSN:1570-647

The Competition of Charge Remote and Charge Directed Fragmentation Mechanisms in Quaternary Ammonium Salt Derivatized Peptides—An Isotopic Exchange Study

Derivatization of peptides as quaternary ammonium salts (QAS) is a promising method for sensitive detection by electrospray ionization tandem mass spectrometry (Cydzik et al. J. Pept. Sci.2011, 17, 445–453). The peptides derivatized by QAS at their N-termini undergo fragmentation according to the two competing mechanisms – charge remote (ChR) and charge directed (ChD). The absence of mobile proton in the quaternary salt ion results in ChR dissociation of a peptide bond. However, Hofmann elimination of quaternary salt creates an ion with one mobile proton leading to the ChD fragmentation. The experiments on the quaternary ammonium salts with deuterated N-alkyl groups or amide NH bonds revealed that QAS derivatized peptides dissociate according to the mixed ChR-ChD mechanism. The isotopic labeling allows differentiation of fragments formed according to ChR and ChD mechanisms

Injectable gellan gum hydrogels with autologous cells for the treatment of rabbit articular cartilage defects

In this work, the ability of gellan gum hydrogels coupled with autologous cells to regenerate rabbit full-thickness articular cartilage defects was tested. Five study groups were defined: (a) gellangumwith encapsulated chondrogenic predifferentiated rabbit adipose stem cells (ASCþGF); (b) gellan gum with encapsulated nonchondrogenic predifferentiated rabbit adipose stem cells (ASC); (c) gellan gum with encapsulated rabbit articular chondrocytes (AC) (standard control); (d) gellan gum alone (control); (e) empty defect (control). Fullthickness articular cartilage defects were created and the gellangum constructs were injected and left for 8 weeks. The macroscopic aspect of the explants showed a progressive increase of similarity with the lateral native cartilage, stable integration at the defect site, more pronouncedly in the cell-loaded constructs. Tissue scoring showed that ASCþGF exhibited the best results regarding tissue quality progression. Alcian blue retrieved similar results with a better outcome for the cell-loaded constructs. Regarding real-time PCR analyses, ASCþGF had the best progression with an upregulation of collagen type II and aggrecan, and a downregulation of collagen type I. Gellan gum hydrogels combined with autologous cells constitute a promising approach for the treatment of articular cartilage defects, and adipose derived cellsmayconstitute a valid alternative to currently used articular chondrocytes.J. T. Oliveira acknowledge the Portuguese Foundation for Science and Technology (FCT) for his grant (SFRH/BD17135/2004). The authors thank the medical and technical staff of the Institute for Biomedical Sciences Abel Salazar (ICBAS) of the University of Porto, Portugal and the Institute for Health and Life Sciences (ICVS) of the University of Minho, Portugal. The authors also thank Dr. Patricia Malafaya, Cristina Correia, and Rui Pereira, for their help with the histological scoring. This work was carried out under the scope of the European NoE EXPERTISSUES, and partially supported by the European Project HIPPOCRATES

JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles.

International audienceJASPAR (http://jaspar.genereg.net) is an open-access database storing curated, non-redundant transcription factor (TF) binding profiles representing transcription factor binding preferences as position frequency matrices for multiple species in six taxonomic groups. For this 2016 release, we expanded the JASPAR CORE collection with 494 new TF binding profiles (315 in vertebrates, 11 in nematodes, 3 in insects, 1 in fungi and 164 in plants) and updated 59 profiles (58 in vertebrates and 1 in fungi). The introduced profiles represent an 83% expansion and 10% update when compared to the previous release. We updated the structural annotation of the TF DNA binding domains (DBDs) following a published hierarchical structural classification. In addition, we introduced 130 transcription factor flexible models trained on ChIP-seq data for vertebrates, which capture dinucleotide dependencies within TF binding sites. This new JASPAR release is accompanied by a new web tool to infer JASPAR TF binding profiles recognized by a given TF protein sequence. Moreover, we provide the users with a Ruby module complementing the JASPAR API to ease programmatic access and use of the JASPAR collection of profiles. Finally, we provide the JASPAR2016 R/Bioconductor data package with the data of this release