Cooperative melting in double-stranded peptide chains through local mechanical interactions.

The separation of double-stranded peptide chains can occur in two ways: cooperatively or non-cooperatively. These two regimes can be driven either by chemical or thermal effects, or through non-local mechanical interactions. Here, we show explicitly that local mechanical interactions in biological systems may regulate the stability, the reversibility, and the cooperative/non-cooperative character of the debonding transition. We show that this transition is characterized by a single parameter depending on an internal length scale. Our theory describes a wide range of melting transitions found in biological systems such as protein secondary structures, microtubules and tau proteins, and DNA molecules. In these cases, the theory gives the critical force as a function of the chain length and its elastic properties. Our theoretical results provide quantitative predictions for known experimental effects that appear in different biological and biomedical fields.

Growth of a flexible fibre in a deformable ring.

We study the equilibrium configurations related to the growth of an elastic fibre in a confining flexible ring. This system represents a paradigm for a variety of biological, medical, and engineering problems. We consider a simplified geometry in which initially the container is a circular ring of radius R. Quasi-static growth is then studied by solving the equilibrium equations as the fibre length l increases, starting from l = 2R. Considering both the fibre and the ring as inextensible and unshearable, we find that beyond a critical length, which depends on the relative bending stiffness, the fibre buckles. Furthermore, as the fibre grows further it folds, distorting the ring until it induces a break in mirror symmetry at l > 2πR. We get that the equilibrium shapes depend only on two dimensionless parameters: the length ratio µ = l/R and the bending stiffnesses ratio κ. These findings are also supported by finite element simulation. Finally we experimentally validate the theoretical results showing a very good quantitative prediction of the observed buckling and folding regimes at variable geometrical parameters.

A predictive model for the thermomechanical melting transition of double stranded DNA.

By extending the classical Peyrard-Bishop model, we are able to obtain a fully analytical description for the mechanical response of DNA under stretching at variable values of temperature, number of base pairs and intrachains and interchains bonds stiffness. In order to compare elasticity and temperature effects, we first analyze the system in the zero temperature mechanical limit, important to describe several experimental effects including possible hysteresis. We then analyze temperature effects in the framework of equilibrium Statistical Mechanics. In particular, we obtain an analytical expression for the temperature-dependent melting force and unzipping assigned displacement in the thermodynamical limit, also depending on the relative stability of intra vs. inter molecular bonds. Such results coincide with the purely mechanical model in the limit of zero temperature and with the denaturation temperature that we obtain with the classical transfer integral method. Based on our analytical results, we obtain explicitly phase diagrams and cooperativity parameters, where also discreteness effect can be accounted for. The obtained results are successfully applied in reproducing the thermomechanical experimental melting of DNA and the response of DNA hairpins. Due to the generality of the model, exemplified in the proposed analysis of both overstretching and unzipping experiments, we argue that the proposed approach can be extended to other thermomechanically induced molecular melting phenomena. STATEMENT OF SIGNIFICANCE: We obtain a fully analytical description of the complex wiggly energy landscape of two stranded macromolecules under unzipping loading. Based on Equilibrium Statistical Mechanics, we describe the combined thermomechanical effects and the melting transition of double stranded molecules such as nucleic acids. This is proved by quantitatively predicting the experimental behavior of both melting of DNA and DNA hairpins opening. While analytical results have been previously attained under special conditions on the relative stiffness of the covalent vs. non-covalent bonds of the base pairs, our model is completely general in this respect, thus representing a tool in the perspective of the design at the molecular scale. We show that the obtained model can be fully inscribed in the theory of phase transitions giving a new interpretation of the thermomechanical behavior of double stranded molecules.

Simons Observatory: broadband metamaterial antireflection cuttings for large-aperture alumina optics.

We present the design, fabrication, and measured performance of metamaterial antireflection cuttings (ARCs) for large-format alumina filters operating over more than an octave of bandwidth to be deployed at the Simons Observatory (SO). The ARC consists of subwavelength features diced into the optic's surface using a custom dicing saw with near-micrometer accuracy. The designs achieve percent-level control over reflections at angles of incidence up to 20∘. The ARCs were demonstrated on four 42 cm diameter filters covering the 75 to 170 GHz band and a 50 mm diameter prototype covering the 200 to 300 GHz band. The reflection and transmission of these samples were measured using a broadband coherent source that covers frequencies from 20 GHz to 1.2 THz. These measurements demonstrate percent-level control over reflectance across the targeted pass-bands and a rapid reduction in transmission as the wavelength approaches the length scale of the metamaterial structure where scattering dominates the optical response. The latter behavior enables use of the metamaterial ARC as a scattering filter in this limit.

Simons Observatory HoloSim-ML: machine learning applied to the efficient analysis of radio holography measurements of complex optical systems.

Near-field radio holography is a common method for measuring and aligning mirror surfaces for millimeter and sub-millimeter telescopes. In instruments with more than a single mirror, degeneracies arise in the holography measurement, requiring multiple measurements and new fitting methods. We present HoloSim-ML, a Python code for beam simulation and analysis of radio holography data from complex optical systems. This code uses machine learning to efficiently determine the position of hundreds of mirror adjusters on multiple mirrors with few micrometer accuracy. We apply this approach to the example of the Simons Observatory 6 m telescope.

A coarse-grained mechanical model for folding and unfolding of tropoelastin with possible mutations.

We propose a simple general framework to predict folding, native states, energy barriers, protein unfolding, as well as mutation induced diseases and other protein structural analyses. The model should not be considered as an alternative to classical approaches (Molecular Dynamics or Monte Carlo) because it neglects low scale details and rather focuses on global features of proteins and structural information. We aim at the description of phenomena that are out of the range of classical molecular modeling approaches due to the large computational cost: multimolecular interactions, cyclic behavior under variable external interactions, and similar. To demonstrate the effectiveness of the approach in a real case, we focus on the folding and unfolding behavior of tropoelastin and its mutations. Specifically, we derive a discrete mechanical model whose structure is deduced based on a coarse graining approach that allows us to group the amino acids sequence in a smaller number of `equivalent' masses. Nearest neighbor energy terms are then introduced to reproduce the interaction of such amino acid groups. Nearest and non-nearest neighbor energy terms, inter and intra functional blocks are phenomenologically added in the form of Morse potentials. As we show, the resulting system reproduces important properties of the folding-unfolding mechanical response, including the monotonic and cyclic force-elongation behavior, representing a physiologically important information for elastin. The comparison with the experimental behavior of mutated tropoelastin confirms the predictivity of the model. STATEMENT OF SIGNIFICANCE: Classical approaches to the study of phenomena at the molecular scale such as Molecular Dynamics (MD) represent an incredible tool to unveil mechanical and conformational properties of macromolecules, in particular for biological and medical applications. On the other hand, due to the computational cost, the time and spatial scales are limited. Focusing of the real case of tropoelastin, we propose a new approach based on a careful coarse graining of the system, able to describe the overall properties of the macromolecule and amenable of extension to larger scale effects (protein bundles, protein-protein interactions, cyclic loading). The comparison with tropoelastin behavior, also for mutations, is very promising.

The Simons Observatory: modeling optical systematics in the Large Aperture Telescope.

We present geometrical and physical optics simulation results for the Simons Observatory Large Aperture Telescope. This work was developed as part of the general design process for the telescope, allowing us to evaluate the impact of various design choices on performance metrics and potential systematic effects. The primary goal of the simulations was to evaluate the final design of the reflectors and the cold optics that are now being built. We describe nonsequential ray tracing used to inform the design of the cold optics, including absorbers internal to each optics tube. We discuss ray tracing simulations of the telescope structure that allow us to determine geometries that minimize detector loading and mitigate spurious near-field effects that have not been resolved by the internal baffling. We also describe physical optics simulations, performed over a range of frequencies and field locations, that produce estimates of monochromatic far-field beam patterns, which in turn are used to gauge general optical performance. Finally, we describe simulations that shed light on beam sidelobes from panel gap diffraction.

The influence of device handles in single-molecule experiments.

We deduce a fully analytical model to predict the artifacts of the device handles in single molecule force spectroscopy experiments. As we show, neglecting the handle stiffness can lead to crucial overestimation or underestimation of the stability properties and unfolding thresholds of multistable molecules.

Gravitational collapse of Mount Etna's southeastern flank.

The southeastern flank of Etna volcano slides into the Ionian Sea at rates of centimeters per year. The prevailing understanding is that pressurization of the magmatic system, and not gravitational forces, controls flank movement, although this has also been proposed. So far, it has not been possible to separate between these processes, because no data on offshore deformation were available until we conducted the first long-term seafloor displacement monitoring campaign from April 2016 until July 2017. Unprecedented seafloor geodetic data reveal a >4-cm slip along the offshore extension of a fault related to flank kinematics during one 8-day-long event in May 2017, while displacement on land peaked at ~4 cm at the coast. As deformation increases away from the magmatic system, the bulk of Mount Etna's present continuous deformation must be driven by gravity while being further destabilized by magma dynamics. We cannot exclude flank movement to evolve into catastrophic collapse, implying that Etna's flank movement poses a much greater hazard than previously thought. The hazard of flank collapse might be underestimated at other coastal and ocean island volcanoes, where the dynamics of submerged flanks are unknown.

Global positioning system survey data for active seismic and volcanic areas of eastern Sicily, 1994 to 2013.

This work presents and describes a 20-year long database of GPS data collected by geodetic surveys over the seismically and volcanically active eastern Sicily, for a total of more than 6300 measurements. Raw data were initially collected from the various archives at the Istituto Nazionale di Geofisica e Vulcanologia, Sezione di Catania-Osservatorio Etneo and organized in a single repository. Here, quality and completeness checks were performed, while all necessary supplementary information were searched, collected, validated and organized together with the relevant data. Once all data and information collections were completed, raw binary data were converted into the universal ASCII RINEX format; all data are provided in this format with the necessary information for precise processing. In order to make the data archive readily consultable, we developed software allowing the user to easily search and obtain the needed data by simple alphanumeric and geographic queries.

Real Time Tracking of Magmatic Intrusions by means of Ground Deformation Modeling during Volcanic Crises.

Volcano observatories provide near real-time information and, ultimately, forecasts about volcano activity. For this reason, multiple physical and chemical parameters are continuously monitored. Here, we present a new method to efficiently estimate the location and evolution of magmatic sources based on a stream of real-time surface deformation data, such as High-Rate GPS, and a free-geometry magmatic source model. The tool allows tracking inflation and deflation sources in time, providing estimates of where a volcano might erupt, which is important in understanding an on-going crisis. We show a successful simulated application to the pre-eruptive period of May 2008, at Mount Etna (Italy). The proposed methodology is able to track the fast dynamics of the magma migration by inverting the real-time data within seconds. This general method is suitable for integration in any volcano observatory. The method provides first order unsupervised and realistic estimates of the locations of magmatic sources and of potential eruption sites, information that is especially important for civil protection purposes.

Luminex technology for anti-HLA antibody screening: evaluation of performance and of impact on laboratory routine.

The recent introduction of new technologies such as Luminex has provided alternative methods to the Complement Dependent Cytotoxicity (CDC) test for HLA specific antibody detection. In this study we compared the results obtained with CDC to those obtained using a Luminex method with the aim of evaluating the impact of this new technology on antibody screening policies in our transplant setting.A total of 1,421 sera, acquired from patients on the waiting list for a kidney transplant or following transplantation, were tested by both methodologies. CDC was performed using a whole lymphocyte population comprising a panel of 52 cells. The percentage panel reactive antibodies (PRA) and antibody specificity were evaluated using Lambda Scan Analysis software. For the Luminex method sera screening and identification of antibody specificity were carried out using the LABScreen Mixed and LABScreen PRA respectively. The overall concordance between the results obtained using the CDC and the Luminex methods was 85%. HLA antibody specificity was confirmed in 96% of the sera which tested positive using the Luminex system and serum positivity corresponded with a previous sensitisation event in these individuals. Using the Luminex method 18% of patients on the waiting list were considered and managed as sensitised as compared to 7% when testing with CDC alone. The Luminex method was able to detect a number of antibody specificities significantly more frequently than the CDC method and in addition the CDC method failed to detect some of the antibody specificities detected by the Luminex system. Based on this comparison study we have incorporated the Luminex methodology into our screening strategy.