Carbon based substrates for interfacing neurons: Comparing pristine with functionalized carbon nanotubes effects on cultured neuronal networks

Pristine (as prepared) carbon nanotube (CNT) based substrates have been widely used to grow and interface neurons in culture. Nerve cells normally differentiate on CNTs and the synaptic networks, newly formed at the interface with this material, usually show an improved robustness in signal transfer. However manipulation of pristine CNTs is often prevented by their low dispersibility and tendency to aggregate in most solvents. This issue can be at least partially solved by adding solubilizing groups to the surface of CNT, which also helps improving their biocompatibility. It becomes therefore of crucial importance to determine whether chemically manipulated CNTs may maintain their performance in improving nerve signaling. Here we study and compare the impact in vitro on neuronal signaling of two classes of chemically modified multiwalled CNTs in reference to pristine CNTs, which are known to be a substrate able to boost neuronal growth and communication. We found that the extent of functionalization and the nature of the functional groups on MWNT sidewalls affect the conductivity and the biological effects of the final derivatives. This information is important for the future design of biointegrated devices

Cakes That Bake Cakes: Dynamic Computation in CakeML

We have extended the verified CakeML compiler with a new language primitive, Eval, which permits evaluation of new CakeML syntax at runtime. This new implementation supports an ambitious form of compilation at runtime and dynamic execution, where the original and dynamically added code can share (higher-order) values and recursively call each other. This is, to our knowledge, the first verified run-Time environment capable of supporting a standard LCF-style theorem prover design. Modifying the modern CakeML compiler pipeline and proofs to support a dynamic computation semantics was an extensive project. We review the design decisions, proof techniques, and proof engineering lessons from the project, and highlight some unexpected complications

Predictors of Adherence to Stroke Prevention in the BALKAN-AF Study:A Machine-Learning Approach

Background  Compared with usual care, guideline-adherent stroke prevention strategy, based on the ABC (Atrial fibrillation Better Care) pathway, is associated with better outcomes. Given that stroke prevention is central to atrial fibrillation (AF) management, improved efforts to determining predictors of adherence with ‘A’ (avoid stroke) component of the ABC pathway are needed. Purpose  We tested the hypothesis that more sophisticated methodology using machine learning (ML) algorithms could do this. Methods  In this post-hoc analysis of the BALKAN-AF dataset, ML algorithms and logistic regression were tested. The feature selection process identified a subset of variables that were most relevant for creating the model. Adherence with the ‘A’ criterion of the ABC pathway was defined as the use of oral anticoagulants (OAC) in patients with AF with a CHA (2) DS (2) -VASc score of 0 (male) or 1 (female). Results  Among 2,712 enrolled patients, complete data on ‘A’-adherent management were available in 2,671 individuals (mean age 66.0 ± 12.8; 44.5% female). Based on ML algorithms, independent predictors of ‘A-criterion adherent management’ were paroxysmal AF, center in capital city, and first-diagnosed AF. Hypertrophic cardiomyopathy, chronic kidney disease with chronic dialysis, and sleep apnea were independently associated with a lower likelihood of ‘A’-criterion adherent management. ML evaluated predictors of adherence with the ‘A’ criterion of the ABC pathway derived an area under the receiver-operator curve of 0.710 (95%CI 0.67–0.75) for random forest with fine tuning. Conclusions  Machine learning identified paroxysmal AF, treatment center in the capital city, and first-diagnosed AF as predictors of adherence to the A pathway; and hypertrophic cardiomyopathy, chronic kidney disease with chronic dialysis, and sleep apnea as predictors of non adherence

Free energy barrier for melittin reorientation from a membrane-bound state to a transmembrane state

An important step in a phospholipid membrane pore formation by melittin antimicrobial peptide is a reorientation of the peptide from a surface into a transmembrane conformation. In this work we perform umbrella sampling simulations to calculate the potential of mean force (PMF) for the reorientation of melittin from a surface-bound state to a transmembrane state and provide a molecular level insight into understanding peptide and lipid properties that influence the existence of the free energy barrier. The PMFs were calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We observe that the free energy barrier is reduced when the P/L ratio increased. In addition, we study the cooperative effect; specifically we investigate if the barrier is smaller for a second melittin reorientation, given that another neighboring melittin was already in the transmembrane state. We observe that indeed the barrier of the PMF curve is reduced in this case, thus confirming the presence of a cooperative effect

Electromagnetic monitoring of the Earth's interior in the frame of the MEM Project

The MEM Project (Magnetic and Electric fields Monitoring) was activated in the INGV Observatory of L’Aquila since 2004. The principal purpose of the project is to create in Central Italy a network of observatories to monitoring the electromagnetic signals in the frequency band [0.001 Hz - 100 kHz]. This band includes natural signals (magnetic pulsations of magnetospheric origin, Earth-ionosphere resonance mode signals, atmospheric noise, and so on) and artificial signals (power line emissions, VLF radio transmissions, and so on). The innovative characteristic of the project is the approach chosen to study the complex problem concerning the representation of the spatial and temporal distributions of the electromagnetic fields in the band of interest. Both the distributions can be represented by some parameters containing the locations and the characteristics of the sources of the electromagnetic signals. When all the stations will be in operation the wide-band interferometry will be applied. Combining the simultaneous observations of the electromagnetic field measured in the stations of the network, we will be able to obtain detailed information about the investigated electromagnetic sources. A new measurement system has been developed to fulfil these requirements focusing on the automation of the measurements. The system is designed for long term recording of the electromagnetic fields in a wide frequency band. In the frequency band [1Hz - 100 kHz] the three components of the magnetic field and the three components of atmospheric electric field are processed in real time using DSP (Digital Signal Processing) techniques. In the frequency band [0.001 - 25]Hz the two components of the telluric field and the three components of the magnetic field are recorded as sampled (100Hz). One of the main scientific objectives of the MEM project is the long term monitoring of the geodynamical processes, such as the earthquakes, by the calculation of the Poynting vector, and the analysis of the magnetic transfer functions and impedance tensor. In the next years this kind of analysis can be useful to underline the possible correlation between the geodynamical processes and the local magnetic field anomalies

Safety evaluation of conditionally immortalized cells for renal replacement therapy

Contains fulltext : 208411.pdf (publisher's version ) (Open Access)End-stage kidney disease represents irreversible kidney failure. Dialysis and transplantation, two main treatment options currently available, present various drawbacks and complications. Innovative cell-based therapies, such as a bioartificial kidney, have not reached the clinic yet, mostly due to safety and/or functional issues. Here, we assessed the safety of conditionally immortalized proximal tubule epithelial cells (ciPTECs) for bioartificial kidney application, by using in vitro assays and athymic nude rats. We demonstrate that these cells do not possess key properties of oncogenically transformed cells, including anchorage-independent growth, lack of contact inhibition and apoptosis-resistance. In late-passage cells we did observe complex chromosomal abnormalities favoring near-tetraploidy, indicating chromosomal instability. However, time-lapse imaging of ciPTEC-OAT1, confined to a 3D extracellular matrix (ECM)-based environment, revealed that the cells were largely non-invasive. Furthermore, we determined the viral integration sites of SV40 Large T antigen (SV40T), human telomerase (hTERT) and OAT1 (SLC22A6), the transgenes used for immortalization and cell function enhancement. All integrations sites were found to be located in the intronic regions of endogenous genes. Among these genes, early endosome antigen 1 (EEA1) involved in endocytosis, and BCL2 Like 1 (BCL2L1) known for its role in regulating apoptosis, were identified. Nevertheless, both gene products appeared to be functionally intact. Finally, after subcutaneous injection in athymic nude rats we show that ciPTEC-OAT1 lack tumorigenic and oncogenic effects in vivo, confirming the in vitro findings. Taken together, this study lays an important foundation towards bioartificial kidney (BAK) development by confirming the safety of the cell line intended for incorporation