MARTINI coarse-grained model for poly-ε-caprolactone in acetone-water mixtures

In this work we present the development of a MARTINI-type coarse-graining (CG) model for poly-ε-caprolactone (PCL) dissolved in a solvent binary mixture of acetone and water. A thermodynamic/conformational procedure is adopted to build up the CG model of the system, starting from the standard MARTINI force field. The single CG bead is parametrized upon solvation free energy calculations, whereas the conformation of the whole polymer chain is optimized using the radius of gyration values calculated at different chain lengths. The model is then able to reproduce the correct thermodynamics of the system, as well as the conformation of single PCL chains, especially in pure water and acetone. The results obtained here are then used to simulate the interactions between multiple longer PCL chains in solution. The model developed here can be used in the future to achieve deeper insight into the dynamics of the polymer self-assembly

Seismic retrofit of an existing reinforced concrete building with buckling-restrained braces

Background: The seismic retrofitting of frame structures using hysteretic dampers is a very effective strategy to mitigate earthquake-induced risks. However, its application in current practice is rather limited since simple and efficient design methods are still lacking, and the more accurate time-history analysis is time-consuming and computationally demanding. Aims: This paper develops and applies a seismic retrofit design method to a complex real case study: An eight-story reinforced concrete residential building equipped with buckling-restrained braces. Methods: The design method permits the peak seismic response to be predicted, as well as the dampers to be added in the structure to obtain a uniform distribution of the ductility demand. For that purpose, a pushover analysis with the first mode load pattern is carried out. The corresponding story pushover curves are first idealized using a degrading trilinear model and then used to define the SDOF (Single Degree-of-Freedom) system equivalent to the RC frame. The SDOF system, equivalent to the damped braces, is designed to meet performance criteria based on a target drift angle. An optimal damper distribution rule is used to distribute the damped braces along the elevation to maximize the use of all dampers and obtain a uniform distribution of the ductility demand. Results: The effectiveness of the seismic retrofit is finally demonstrated by non-linear time-history analysis using a set of earthquake ground motions with various hazard levels. Conclusion: The results proved the design procedure is feasible and effective since it achieves the performance objectives of damage control in structural members and uniform ductility demand in dampers

Effect of different good solvents in flash nano-precipitation via multi-scale population balance modeling-CFD coupling approach

A computational and modeling approach is used to highlight the key factors that affect polymer nanoparticles (NP) formation in flash nano-precipitation (FNP), when the good solvent, e.g., acetone, is replaced by acetonitrile, tetrahydrofuran and tert-butanol. A population balance model is coupled with computational fluid dynamics to study the kinetics effects on FNP. The mean NP size is predicted in terms of mean radius of gyration via the Flory law of real polymers. The effect of different good solvents is modeled in terms of solute–solvent interactions, using the Flory–Huggins theory and Hansen solubility parameters. Promising results show how the proposed methodology is able to investigate the role played by different good solvents, analyzing single factors at the time. A deep insight into both the dynamics of mixing and the dynamics of aggregation is therefore reached and the main mechanisms involved are pointed out, showing a good agreement with experimental data

Effect of the good solvent nature in flash nano-precipitation via population balance modelling and computational fluid dynamics coupling approach

The effect of the good solvent nature on polymer nano-particles (NP) formation in flash nano-precipitation is here investigated through a combined population balance model-computational fluid dynamics approach (PBM-CFD). Four good solvents are considered: acetone, acetonitrile, tetrahydrofuran and tert-butanol and the different resulting mean NP size is predicted in terms of mean radius of gyration via the Flory law of real polymers. Good solvents effects are here modelled in terms of solute–solvent interactions, using the Flory–Huggins theory and the Hansen solubility parameters. In this way, kinetics and thermodynamics are intertwined in a unique modelling tool. Our results show that the proposed methodology is able to predict the role played by the different good solvents, analysing single factors at the time. More specifically, the dynamics of mixing is decoupled from the dynamics of aggregation achieving a deeper insight into the fundamental fluid properties which affect the final NP size, pointing out the main mechanisms involved and showing a good agreement with experimental data

Simulation of macromolecule self-assembly in solution: a multiscale approach

One of the most common processes to produce polymer nanoparticles is to induce self-assembly by using the solvent-displacement method, in which the polymer is dissolved in a "good" solvent and the solution is then mixed with an "anti-solvent". The polymer ability to self-assemble in solution is therefore determined by its structural and transport properties in solutions of the pure solvents and at the intermediate compositions. In this work, we focus on poly-ε-caprolactone (PCL) which is a biocompatible polymer that finds widespread application in the pharmaceutical and biomedical fields, performing simulation at three different scales using three different computational tools: full atomistic molecular dynamics (MD), population balance modeling (PBM) and computational fluid dynamics (CFD). Simulations consider PCL chains of different molecular weight in solution of pure acetone (good solvent), of pure water (anti-solvent) and their mixtures, and mixing at different rates and initial concentrations in a confined impinging jets mixer (CIJM). Our MD simulations reveal that the nano-structuring of one of the solvents in the mixture leads to an unexpected identical polymer structure irrespectively of the concentration of the two solvents. In particular, although in pure solvents the behavior of the polymer is, as expected, very different, at intermediate compositions, the PCL chain shows properties very similar to those found in pure acetone as a result of the clustering of the acetone molecules in the vicinity of the polymer chain. We derive an analytical expression to predict the polymer structural properties in solution at different solvent compositions and use it to formulate an aggregation kernel to describe the self-assembly in the CIJM via PBM and CFD. Simulations are eventually validated against experiments

Nanoparticles production in continuous flow devices - Modelling and experimental insights into continuous flow-based processes

In this work, a general overview on nanoparticles formation processes is given from both modelling and experimental points of view. The key mechanisms are presented and identified, despite some of them are still under debate. Experiments investigated the effect of different good solvents, as well as the role played by the presence of active principles, and more detailed confirmations have been found out thanks to modelling efforts. Population balance modelling and computational fluid dynamics simulations got a deeper insight into the mechanisms and the good solvent effects that lead to nanoparticles formation. Simulations results confirm the trends experimentally observed. Future investigations can be carried out by means of classical molecular dynamics, in order to gain a better understanding of the nanoparticle’s formation dynamics

Targeted rapid amplification of cDNA ends (T-RACE)—an improved RACE reaction through degradation of non-target sequences

Amplification of the 5′ ends of cDNA, although simple in theory, can often be difficult to achieve. We describe a novel method for the specific amplification of cDNA ends. An oligo-dT adapter incorporating a dUTP-containing PCR primer primes first-strand cDNA synthesis incorporating dUTP. Using the Cap finder approach, another distinct dUTP containing adapter is added to the 3′ end of the newly synthesized cDNA. Second-strand synthesis incorporating dUTP is achieved by PCR, using dUTP-containing primers complimentary to the adapter sequences incorporated in the cDNA ends. The double-stranded cDNA-containing dUTP serves as a universal template for the specific amplification of the 3′ or 5′ end of any gene. To amplify the ends of cDNA, asymmetric PCR is performed using a single gene-specific primer and standard dNTPs. The asymmetric PCR product is purified and non-target transcripts containing dUTP degraded by Uracil DNA glycosylase, leaving only those transcripts produced during the asymmetric PCR. Subsequent PCR using a nested gene-specific primer and the 3′ or 5′ T-RACE primer results in specific amplification of cDNA ends. This method can be used to specifically amplify the 3′ and 5′ ends of numerous cDNAs from a single cDNA synthesis reaction

Analysis of surface wettability effect on nucleate boiling with a diffuse interface method

Multi-phase systems with phase-change phenomena, in particular boiling, are common in many industrial applications, including power generation plants and thermal management of high-power and high-dissipation-rate micro-devices which would burn out if not cooled properly. Due to the non-equilibrium thermodynamics and the complexity of coupling the heat and mass transfer in phase-change and surface processes, these systems are difficult to describe accurately. Although experiments have been conducted to study boiling, its mechanisms and heat transfer characteristics are still not understood completely. We simulate pool boiling using the diffuse interface method (DIM) embedded in our home-grown “TPLS” solver. This method allows the imposition of a boundary condition to prescribe wettability removing the stress singularity at the three-phase contact line, thus enabling us to analyse the role of surface features on heat transfer coefficient, bubble growth and bubble departures. Our framework also allows simulation of populations of bubbles and analyse bubble interactions at varied bubble sizes for different wettabilities as a function of superheat. We compare our simulations with our nucleate boiling experiments using FC72 on silicon surfaces. Our simulations show the importance of surface tension on departure conditions, suggesting a higher heat transfer coefficient in hydrophilic cases. Conversely, we have found limited bubble growth rate on hydrophobic surfaces. In hydrophobic cases, the larger amount of residual vapour left on the heater surface after bubble departure limits the coolability of the substrate but it might promote the growth of forming bubbles subsequentlyEMBOSS Projec

Regional pressure and temperature differences across the injured human brain : comparisons between intraparenchymal and ventricular measurements

Introduction: Intraparenchymal, multimodality sensors are commonly used in the management of patients with severe traumatic brain injury (TBI). The ‘gold standard’, based on accuracy, reliability and cost for intracranial pressure (ICP) monitoring is within the cerebral ventricle (external strain gauge). There are no standards yet for intracerebral temperature monitoring and little is known of temperature differences between brain tissue and ventricle. The aim of the study therefore was to determine pressure and temperature differences at intraparenchymal and ventricular sites during five days of continuous neurominitoring. Methods: Patients with severe TBI requiring emergency surgery. Inclusion criteria: patients who required ICP monitoring were eligible for recruitment. Two intracerebral probe types were used: a) intraventricular, dual parameter sensor (measuring pressure, temperature) with inbuilt catheter for CSF drainage: b) multiparameter intraparenchymal sensor measuring pressure, temperature and oxygen partial pressure. All sensors were inserted during surgery and under aseptic conditions. Results: Seventeen patients, 12 undergoing neurosurgery (decompressive craniectomy n=8, craniotomy n=4) aged 21–78 years were studied. Agreement of measures for 9540 brain tissue-ventricular temperature ‘pairs’ and 10,291 brain tissue-ventricular pressure ‘pairs’ were determined using mixed model to compare mean temperature and pressure for longitudinal data. There was no significant overall difference for mean temperature (p=0.92) or mean pressure readings (p=0.379) between tissue and ventricular sites. With 95.8% of paired temperature readings within 2SD (−0.4 to 0.4°C) differences in temperature between brain tissue and ventricle were clinically insignificant. For pressure, 93.5% of readings pairs fell within the 2SD range (−9.4756 to 7.8112 mmHg) (Fig. 2). However, for individual patients, agreement for mean tissue-ventricular pressure differences was poor on occasions. Conclusions: There is good overall agreement between paired temperature measurements obtained from deep white matter and brain ventricle in patients with and without early neurosurgery. For paired ICP measurements, 93.5% of readings were within 2SD of mean difference. Whilst the majority of paired readings were comparable (within 10mmHg) clinically relevant tissue-ventricular dissociations were noted. Further work is required to unravel the events responsible for short intervals of pressure dissociation before tissue pressure readings can be definitively accepted as a reliable surrogate for ventricular pressure.</p

Quick and Clean Cloning: A Ligation-Independent Cloning Strategy for Selective Cloning of Specific PCR Products from Non-Specific Mixes

We have developed an efficient strategy for cloning of PCR products that contain an unknown region flanked by a known sequence. As with ligation-independent cloning, the strategy is based on homology between sequences present in both the vector and the insert. However, in contrast to ligation-independent cloning, the cloning vector has homology with only one of the two primers used for amplification of the insert. The other side of the linearized cloning vector has homology with a sequence present in the insert, but nested and non-overlapping with the gene-specific primer used for amplification. Since only specific products contain this sequence, but none of the non-specific products, only specific products can be cloned. Cloning is performed using a one-step reaction that only requires incubation for 10 minutes at room temperature in the presence of T4 DNA polymerase to generate single-stranded extensions at the ends of the vector and insert. The reaction mix is then directly transformed into E. coli where the annealed vector-insert complex is repaired and ligated. We have tested this method, which we call quick and clean cloning (QC cloning), for cloning of the variable regions of immunoglobulins expressed in non-Hodgkin lymphoma tumor samples. This method can also be applied to identify the flanking sequence of DNA elements such as T-DNA or transposon insertions, or be used for cloning of any PCR product with high specificity