On the transferability of three water models developed by adaptive force matching

Water is perhaps the most simulated liquid. Recently three water models have been developed following the adaptive force matching (AFM) method that provides excellent predictions of water properties with only electronic structure information as a reference. Compared to many other electronic structure based force fields that rely on fairly sophisticated energy expressions, the AFM water models use point-charge based energy expressions that are supported by most popular molecular dynamics packages. An outstanding question regarding simple force fields is whether such force fields provide reasonable transferability outside of their conditions of parameterization. A survey of three AFM water models, B3LYPD-4F, BLYPSP-4F, and WAIL are provided for simulations under conditions ranging from the melting point up to the critical point. By including ice-Ih configurations in the training set, the WAIL potential predicts the melting temperate, TM, of ice-Ih correctly. Without training for ice, BLYPSP-4F underestimates TM by about 15 K. Interestingly, the B3LYPD-4F model gives a TM 14 K too high. The overestimation of TM by B3LYPD-4F mostly likely reflects a deficiency of the B3LYP reference. The BLYPSP-4F model gives the best estimate of the boiling temperature TB and is arguably the best potential for simulating water in the temperature range from TM to TB. None of the three AFM potentials provides a good description of the critical point. Although the B3LYPD-4F model gives the correct critical temperature TC and critical density, there are good reasons to believe the agreement is reached fortuitously. Links to Gromacs input files for the three water models are provided at the end of the paper.Comment: 25 pages, 2 figure

Algorithms and systems for home telemonitoring in biomedical applications

During the past decades, the interest of the healthcare community shifted from the simple treatment of the diseases towards the prevention and maintenance of a healthy lifestyle. This approach is associated to a reduced cost for the Health Systems, having to face the constantly increased expenditures due to the reduced mortality for chronical diseases and to the progressive population ageing. Nevertheless, the high costs related to hospitalization of patients for monitoring procedures that could be better performed at home hamper the full implementation of this approach in a traditional way. Information and Communication Technology can provide a solution to implement a care model closer to the patient, crossing the physical boundaries of the hospitals and thus allowing to reach also those patients that, for a geographical or social condition, could not access the health services as other luckier subjects. This is the case of telemonitoring systems, whose aim is that of providing monitoring services for some health-related parameters at a distance, by means of custom-designed electronic devices. In this thesis, the specific issues associated to two telemonitoring applications are presented, along with the proposed solutions and the achieved results. The first telemonitoring application considered is the fetal electrocardiography. Non-invasive fetal electrocardiography is the recording of the fetal heart electrical activity using electrodes placed on the maternal abdomen. It can provide important diagnostic parameters, such as the beat-to-beat heart rate variability, whose recurring analysis would be useful in assessing and monitoring fetal health during pregnancy. Long term electrocardiographic monitoring is sustained by the absence of any collateral effects for both the mother and the fetus. This application has been tackled from several perspectives, mainly acquisition and processing. From the acquisition viewpoint a study on different skin treatments, disposable commercial electrodes and textile electrodes has been performed with the aim of improving the signal acquisition quality, while simplifying the measurement setup. From the processing viewpoint, different algorithms have been developed to allow extracting the fetal ECG heart rate, starting from an on-line ICA algorithm or exploiting a subtractive approach to work on recordings acquired with a reduced number of electrodes. The latter, took part to the international "Physionet/Computing in Cardiology Challenge" in 2013 entering into the top ten best-performing open-source algorithms. The improved version of this algorithm is also presented, which would mark the 5th and 4th position in the final ranking related to the fetal heart rate and fetal RR interval measurements performance, reserved to the open-source challenge entries, taking into account both official and unofficial entrants. The research in this field has been carried out in collaboration with the Pediatric Cardiology Unit of the Hospital G. Brotzu in Cagliari, for the acquisition of non-invasive fetal ECG signals from pregnant voluntary patients. The second telemonitoring application considered is the telerehabilitation of the hand. The execution of rehabilitation exercises has been proven to be effective in recovering hand functionality in a wide variety of invalidating diseases, but the lack of standardization and continuous medical control cause the patients neglecting this therapeutic procedures. Telemonitoring the rehabilitation sessions would allow the physician to closely follow the patients' progresses and compliance to the prescribed adapted exercises. This application leads to the development of a sensorized telerehabilitation system for the execution and objective monitoring of therapeutic exercises at the patients' home and of the telemedicine infrastructure that give the physician the opportunity to monitor patients' progresses through parameters summarizing the patients' performance. The proposed non-CE marked medical device, patent pending, underwent a clinical trial, reviewed and approved by the Italian Public Health Department, involving 20 patients with Rheumatoid Arthritis and 20 with Systemic Sclerosis randomly assigned to the experimental or the control arm, enrolled for 12 weeks in a home rehabilitation program. The trial, carried out with the collaboration of the Rheumatology Department of the Policlinico Universitario of Cagliari, revealed promising results in terms of hand functionality recovering, highlighting greater improvements for the patients enrolled in the experimental arm, that use the proposed telerehabilitation system, with respect to those of the control arm, which perform similar rehabilitation exercises using common objects

Kinetics of Brownian Transport

The rate of progress of Brownian processes is not easily quantifiable. An importantmeasure of the ”speed” of Brownian motion is themean first-passage time (FPT) to a given distance. FPTs exist in various flavours including exit- and transition-path times, which, for instance, can be used to quantify the length of reaction paths in folding transitions inmolecules such as DNA. Due to their inherently stochastic nature, measurements of any FPTs require repeated experiments under controlled conditions. In my thesis, I systematically explore FPTs in various contexts using a custom-built automated holographic optical tweezers (HOT) setup. More precisely, I investigate transition- and exit-path-time symmetries in equilibrium systems and demonstrate the breakdown of the symmetry in out-of-equilibriumsystems. Experimental data from folding DNA-hairpins show that the principles established on the mesoscale extend well into the molecular regime. In Kramers escape problem, the reciprocal of the escape rate corresponds to the time of first-passage to leave the initial state. A lower bound for the achievable FPT, e.g. of the reaction coordinate of a folding molecule, therefore corresponds to a speed-limit of the ensemble reaction rate. Using my setup, I show that certain barrier shapes can substantially lower the escape time across the barrier without changing the overall energy balance. This result has deep implications for reaction kinetics, e.g. in protein folding. Furthermore, I investigate the role of entropic forces in Brownian transport, show that hydrodynamic drag plays a crucial role in Brownian motion in confined systems, and give an experimental realisation of Fick-Jacobs theory. The thermodynamic applications of HOTs considered here necessitate the creation of fine-tuned optical landscapes, which requires precise phase-retrieval to compute the necessary holograms. In order to address this problem, I explore novel algorithms based on deep conditional generative models and test whether such models can assist in finding holograms for a given desired light distribution. I compare several differentmodels, including conditional generative-adversarial networks and conditional variational autoencoders, which are trained on data sets sampled on the HOT setup. Furthermore, I propose a novel forward-loss-minimising architecture and demonstrate its excellent performance on both validation and artificially-created test data sets.European Training Network (ETN) Grant No. 674979-NANOTRANS Winton Programme for the Physics of Sustainabilit

Ab initio Prediction of the Conformation of Solvated and Adsorbed Proteins

Proteins are among the most important groups of biomolecules, with their biological functions ranging from structural elements to signal transducers between cells. Apart from their biological role, phenomena related to protein behaviour in solutions and at solid interfaces can find a broad range of engineering applications such as in biomedical implants, scaffolds for artificial tissues, bioseparations, biomineralization and biosensors. For both biological and engineering applications, the functionality of a protein is directly related to its three-dimensional structure (i.e. conformation). Methods such as homology and threading that depend on a large database of existing experimental knowledge are the most popular means of predicting the conformation of proteins in their native environment. Lack of sufficient experimentally-derived information for non-native environments such as general solutions and solid interfaces prevents these knowledge-based methods being used for such environments. Resort must, instead, be made to so-called ab initio methods that rely upon knowledge of the primary sequence of the protein, its environment, and the physics of the interatomic interactions. The development of such methods for non-native environments is in its infancy – this thesis reports on the development of such a method and its application to proteins in water and at gas/solid and water/solid interfaces. After introducing the approach used – which is based on evolutionary algorithms (EAs) – we first report a study of polyalanine adsorbed at a gas/solid interface in which a switching behaviour is observed that, to our knowledge, has never been reported before. The next section reports work that shows the combination of the Langevin dipole (LD) solvent method with the Amber potential energy (PE) model is able to yield solvation energies comparable to those of more sophisticated methods at a fraction of the cost, and that the LD method is able to capture effects that arise from inhomogenities in the water structure such as H-bond bridges. The third section reports a study that shows that EA performance and optimal control parameters vary substantially with the PE model. The first three parts form the basis of the last part of the thesis, which reports pioneering work on predicting ab initio the conformation of proteins in solutions and at water/solid interfaces

Towards a mesoscale rheology model for aqueous particulate suspensions

Particulate suspensions are ubiquitous and diverse; pharmaceutical formulations, biological fluids, magma and foodstuffs are just few of numerous examples. In many cases, the flow behaviour (rheology) of the suspension is critical to its function. A key rheological property is viscosity; a measure of a substance’s resistance to flow. This work aims to understand molecular-level mechanisms responsible for determining flow behaviour in moderately dense suspensions; 35% particles by volume (i.e., volume fraction 0.35). The industrial application of interest to this thesis is catalysis; namely, the ‘washcoat’, a key component in the performance of catalytic converters. A typical washcoat formulation is an aqueous suspension, comprising a high surface-area support powder, an active catalyst material, together with organic additives and certain salts used to optimise properties of the washcoat; including its flow behaviour. Of these components, this work investigates ‘salt-specific effects’; i.e. the influence of differing salt-types. Investigation is conducted at molecular and macroscopic resolution via simulations and experiments, respectively. The research approach probes the constituents of a suspension: the aqueous phase, the particle-aqueous phase interface, and particle interactions. Molecular dynamics simulations are employed as the foundation of this analysis, with experiments - rheology, nuclear magnetic resonance and dynamic light scattering - utilised alongside. A final set of rheology experiments is conducted on particulate suspensions of 35% volume fraction, in pure water and the aqueous salt solutions of interest. At all stages of analysis, results suggest that macroscopic behaviours are a cumulative manifestation of phenomena at molecular resolution. However, such phenomena are varied; the challenge lies in identifying which mechanisms are relevant to the behaviour of interest, how they work together, and how they manifest cumulatively. Towards a mesoscale rheology model for aqueous particulate suspensions, results are discussed in terms of input for such a model, which would predict rheology as a function of particle loading, ionic strength and possibly other factors, in future work

NASA patent abstracts bibliography: A continuing bibliography. Section 2: Indexes (supplement 04)

For abstract, see N74-20609

Multiscale modeling of metal nanoparticles for biotechnological applications

Functionalized metal nanoparticles are supramolecular assemblies that are gaining increasing attention in biomedicine due to their broad-spectrum applicability. In this context, understanding the nano-biointerface is critical for implementing nanoparticles into medical practices, yet the structure-function relation of functionalized metal nanoparticles remains puzzling. This work discusses the design of metal nanoparticles with targeted applications from three focal points: structural modeling, method development, and biomolecular interactions. First, the NanoModeler webserver is introduced for the standardized building and parametrizing of metal nanoparticles for simulations at atomistic and coarse-grained resolutions. Second, a theoretical model is formulated to characterize the surface of charged nanoparticles, which, when combined with mesoscale simulations, clarifies the fundamental principles that enable colloidal stability at physiological conditions. Third, atomistic and coarse-grained simulations were combined to describe, at the molecular level, the non- disruptive cellular permeabilization induced by membranotropic nanoparticles to facilitate intracellular cargo delivery. The multilayered work presented here comprehends new online tools, physics-based methods, and molecular insights that expand our understanding of the structure-function relation in metal nanoparticles and contribute to the design of safe and effective nanoparticle-based therapeutic agents