Probing DNA conformational changes with high temporal resolution by Tethered Particle Motion

The Tethered Particle Motion (TPM) technique informs about conformational changes of DNA molecules, e.g. upon looping or interaction with proteins, by tracking the Brownian motion of a particle probe tethered to a surface by a single DNA molecule and detecting changes of its amplitude of movement. We discuss in this context the time resolution of TPM, which strongly depends on the particle-DNA complex relaxation time, i.e. the characteristic time it takes to explore its configuration space by diffusion. By comparing theory, simulations and experiments, we propose a calibration of TPM at the dynamical level: we analyze how the relaxation time grows with both DNA contour length (from 401 to 2080 base pairs) and particle radius (from 20 to 150~nm). Notably we demonstrate that, for a particle of radius 20~nm or less, the hydrodynamic friction induced by the particle and the surface does not significantly slow down the DNA. This enables us to determine the optimal time resolution of TPM in distinct experimental contexts which can be as short as 20~ms.Comment: Improved version, to appear in Physical Biology. 10 pages + 10 pages of supporting materia

Photoreceptor Outer Segment-like Structures in Long-Term 3D Retinas from Human Pluripotent Stem Cells.

The retinal degenerative diseases, which together constitute a leading cause of hereditary blindness worldwide, are largely untreatable. Development of reliable methods to culture complex retinal tissues from human pluripotent stem cells (hPSCs) could offer a means to study human retinal development, provide a platform to investigate the mechanisms of retinal degeneration and screen for neuroprotective compounds, and provide the basis for cell-based therapeutic strategies. In this study, we describe an in vitro method by which hPSCs can be differentiated into 3D retinas with at least some important features reminiscent of a mature retina, including exuberant outgrowth of outer segment-like structures and synaptic ribbons, photoreceptor neurotransmitter expression, and membrane conductances and synaptic vesicle release properties consistent with possible photoreceptor synaptic function. The advanced outer segment-like structures reported here support the notion that 3D retina cups could serve as a model for studying mature photoreceptor development and allow for more robust modeling of retinal degenerative disease in vitro

Landslide Detection in Real-Time Social Media Image Streams

Lack of global data inventories obstructs scientific modeling of and response to landslide hazards which are oftentimes deadly and costly. To remedy this limitation, new approaches suggest solutions based on citizen science that requires active participation. However, as a non-traditional data source, social media has been increasingly used in many disaster response and management studies in recent years. Inspired by this trend, we propose to capitalize on social media data to mine landslide-related information automatically with the help of artificial intelligence (AI) techniques. Specifically, we develop a state-of-the-art computer vision model to detect landslides in social media image streams in real time. To that end, we create a large landslide image dataset labeled by experts and conduct extensive model training experiments. The experimental results indicate that the proposed model can be deployed in an online fashion to support global landslide susceptibility maps and emergency response

Integrin αvβ8-mediated TGF-β activation by effector regulatory T sells is essential for suppression of T-Cell-mediated inflammation

Regulatory T (Treg) cells play a pivotal role in suppressing self-harmful T cell responses, but how Treg cells mediate suppression to maintain immune homeostasis and limit responses during inflammation is unclear. Here we show that effector Treg cells express high amounts of the integrin αvβ8, which enables them to activate latent transforming growth factor-β (TGF-β). Treg-cell-specific deletion of integrin αvβ8 did not result in a spontaneous inflammatory phenotype, suggesting that this pathway is not important in Treg-cell-mediated maintenance of immune homeostasis. However, Treg cells lacking expression of integrin αvβ8 were unable to suppress pathogenic T cell responses during active inflammation. Thus, our results identify a mechanism by which Treg cells suppress exuberant immune responses, highlighting a key role for effector Treg-cell-mediated activation of latent TGF-β in suppression of self-harmful T cell responses during active inflammation

Late gadolinium enhancement CMR in primary mitral regurgitation.

AIMS: The appropriate timing for surgery in severe asymptomatic primary mitral regurgitation (MR) remains controversial. It has been shown that late gadolinium enhancement on cardiovascular magnetic resonance (LGE CMR), which may identify myocardial fibrosis, is associated with a worse outcome in various cardiomyopathies. We sought to investigate the prevalence and significance of delayed enhancement in primary MR. METHODS: We prospectively included 41 patients with at least moderate primary MR and without overt signs of left ventricular (LV) dysfunction. Patients with evidence of coronary artery disease, arrhythmias or significant concomitant valvular disease were excluded. All patients were scheduled for transthoracic echocardiography and LGE CMR. RESULTS: A total of 39 patients had interpretable LGE CMR images. Among them, 12 (31%) had late contrast uptake of the LV wall. LGE CMR showed an infarct pattern in three patients, a pattern of mid-wall fibrosis in seven patients and two patients had a combined pattern. Patients with delayed enhancement on CMR had significant higher LV diameters (LV end-systolic diameter 39 +/- 4 vs. 34 +/- 5 mm, P = 0.002; LV end-diastolic diameter 57 +/- 5 vs. 50 +/- 5 mm, P = 0.001). There was a trend towards a higher indexed left atrial volume (55 +/- 21 vs. 44 +/- 13 mL/m(2), P = 0.06). By contrast, there was no significant association between myocardial contrast uptake and age, LV ejection fraction and MR severity. CONCLUSION: Left ventricular remodelling seems to be associated with the presence of delayed enhancement on CMR in primary MR. Further data are needed to determine whether LGE CMR can predict a less favourable outcome or could improve risk stratification in asymptomatic primary MR

Co-doped Dy3+ and Pr3+ Ga5Ge20Sb10S65 fibers for mid-infrared broad emission

Rare earth ion doped materials are means to obtain cost-effective infrared light sources, with enough brilliance for applications such as gas sensing. Within a sulfide matrix, the simultaneous luminescence of both Pr3+ and Dy3+ in the Ga5Ge20Sb10S65 glass is reported. The use of these two rare earths is giving rise to a broad continuous luminescence in the 2.2–5.5 µm wavelength range, which could be used as a mid-infrared light source for gas-sensing applications. The demonstration of CO2 and CH4 detection using a fiber drawn from these materials is reported

Expression and regulation of drug transporters in vertebrate neutrophils.

There remains a need to identify novel pro-resolution drugs for treatment of inflammatory disease. To date, there are no neutrophil-specific anti-inflammatory treatments in clinical use, perhaps due to our lack of understanding of how drugs access this complex cell type. Here we present the first comprehensive description and expression of both major classes of drug transporters, SLC and ABC, in resting human blood neutrophils. Moreover, we have studied the expression of these carriers in the tractable model system, the zebrafish (Danio rerio), additionally examining the evolutionary relationship between drug transporters in zebrafish and humans. We anticipate that this will be a valuable resource to the field of inflammation biology and will be an important asset in future anti-inflammatory drug design

Legal situation and current practice of waste incineration bottom ash utilisation in Europe

Almost 500 municipal solid waste incineration plants in the EU, Norway, and Switzerland generate about 17.6 Mt/a of incinerator bottom ash (IBA). IBA contains minerals and metals. Metals are mostly separated and sold to the scrap market and minerals are either disposed of in landfills or utilised in the construction sector. Since there is no uniform regulation for IBA utilisation at EU level, countries developed own rules with varying requirements for utilisation. As a result from a cooperation network between European experts an up-to-date overview of documents regulating IBA utilisation is presented. Furthermore, this work highlights the different requirements that have to be considered. Overall, 51 different parameters for the total content and 36 different parameters for the emission by leaching are defined. An analysis of the defined parameter reveals that leaching parameters are significantly more to be considered compared to total content parameters. In order to assess the leaching behaviour nine different leaching tests, including batch tests, up-flow percolation tests and one diffusion test (monolithic materials) are in place. A further discussion of leaching parameters showed that certain countries took over limit values initially defined for landfills for inert waste and adopted them for IBA utilisation. The overall utilisation rate of IBA in construction works is approximately 54 wt.%. It is revealed that the rate of utilisation does not necessarily depend on how well regulated IBA utilisation is, but rather seems to be a result of political commitment for IBA recycling and economically interesting circumstances

A near-real-time global landslide incident reporting tool demonstrator using social media and artificial intelligence

The development of a system that monitors social media continuously for general landslide-related content using a landslide classification model to identify and retain the most relevant information is described and validated. The system harvests photographs in real-time from these data and tags each image as landslide or not-landslide. A training model was developed with input from computer scientists, geologists (landslide specialists) and social media specialists to establish a large image dataset that has then been applied to the live Twitter data stream. The preliminary model was developed by training a convolutional neural network on the dataset. Quantitative verification of the system's performance during a real-world deployment shows that the system can detect landslide reports with Precision = 76%. The demonstrator model is currently running live https://landslide-aidr.qcri.org/service.php; the next stage of development will incorporate stakeholder and user feedback