Full metastable asymptotic of the Fisher information

We establish an expansion by Gamma-convergence of the Fisher information relative to the reference measure exp(-beta V), where V is a generic multiwell potential and beta goes to infinity. The expansion reveals a hierarchy of multiple scales reflecting the metastable behavior of the underlying overdamped Langevin dynamics: distinct scales emerge and become relevant depending on whether one considers probability measures concentrated on local minima of V, probability measures concentrated on critical points of V, or generic probability measures on R^d. We thus fully describe the asymptotic behavior of minima of the Fisher information over regular sets of probabilities. The analysis mostly relies on spectral properties of diffusion operators and the related semiclassical Witten Laplacian and covers also the case of a compact smooth manifold as underlying space.Comment: 24 pages. Typos correcte

A metaheuristic multi-criteria optimisation approach to portfolio selection

Portfolio selection is concerned with selecting from of a universe of assets the ones in which one wishes to invest and the amount of the investment. Several criteria can be used for portfolio selection, and the resulting approaches can be classified as being either active or passive. The two approaches are thought to be mutually exclusive, but some authors have suggested combining them in a unified framework. In this work, we define a multi-criteria optimisation problem in which the two types of approaches are combined, and we introduce a hybrid metaheuristic that combines local search and quadratic programming to obtain an approximation of the Pareto set. We experimentally analyse this approach on benchmarks from two different instance classes: these classes refer to the same indexes, but they use two different return representations. Results show that this metaheuristic can be effectively used to solve multi-criteria portfolio selection problems. Furthermore, with an experiment on a set of instances coming from a different financial scenario, we show that the results obtained by our metaheuristic are robust with respect to the return representation used

Lipid-Nanodiscs Formed by Paramagnetic Polymers for Fast NMR Data Acquisition

Membrane proteins are critical components of any cell, and their malfunction is associated with numerous diseases. For this reason, they represent a primary target for various drugs on the market, but both academic and pharmaceutical research is hindered by the challenges associated with obtaining stable and functioning samples. Artificial lipid membranes are crucial for the investigation of membrane proteins because of their ability to simulate the amphipathic native-like environment of the cell membrane. Recent studies have shown the dramatic advantages of using lipid/nanodiscs as compared to other types of membrane mimetics. While the nanodiscs prepared using scaffold proteins, peptides, and proteins have their advantages and limitations; there is significant interest in synthetic polymers because of the broad scope and feasibilities. Macromolecules such as copolymers of styrene and maleic acid (SMA) interact with lipids forming stable discoidal nanoparticles made of bilayer patches wrapped by the polymeric belt. These copolymers have also been used to extract membrane proteins directly from their native environment and isolate them into nanodiscs without using detergents. Despite the many successes reported in the literature, copolymer-nanodiscs still show several limitations, and new formulations are under development. The Ramamoorthy research group focused on the hydrophilic functionalization of a low molecular-weight SMA copolymer. This approach allowed for the tuning and enhancement of these polymers, particularly in the field of nuclear magnetic resonance (NMR) spectroscopy. NMR is widely employed to study nanodiscs reconstituted membrane proteins but suffers from its intrinsic low sensitivity, which necessitates long data acquisition times. Paramagnetic resonance enhancement is among the strategies that have been used to enhance the sensitivity of NMR by reducing the spin-lattice relaxation or T1, a key parameter in assessing the duration of the required data acquisition. However, PRE requires the introduction of PRE-agents in the sample that could alter the sample's stability and function. This thesis reports a novel PRE-agent that does not involve (i) direct labeling of membrane proteins, (ii) the alteration of the surrounding lipid composition, or (iii) the presence of free metal ions in the sample. Specifically, SMA-EA-DOTA copolymer allows the chelation of paramagnetic ions directly in the copolymer-lipid nanodiscs' outer rim without contaminating the nanodiscs' constituents such as lipids and proteins, enabling T1-reduction. A variety of lanthanide ions are investigated to quantify the PRE effects and for use in nanodiscs-enabled studies on membrane systems. Since nanodiscs-forming copolymers act, de facto, as macromolecular detergents, this thesis also investigates the relationship between the critical micelle concentration (c.m.c.) of a set of SMA-copolymers and their ability to form nanodiscs. It was found that the interaction with phospholipids alters the copolymers' c.m.c. values, and the existence of an equilibrium between the «free» or «micellar» copolymer chains and the «nanodiscs-bound» copolymer chains. Because of this equilibrium, the thesis speculates the possibility of substituting inexpensive copolymers after membrane proteins isolation and purification with paramagnetically-tagged copolymers for magnetic resonance studies. Aside from PRE-NMR, membrane proteins reconstituted in paramagnetically-labeled nanodiscs, such as SMA-EA-DOTA, ST-10, ST-100, and mixed formulations, can be studied using other biophysical techniques including electron paramagnetic resonance and dynamic nuclear polarization NMR. Finally, paramagnetically-tagged copolymer nanodiscs can find new applications outside the biophysical and biochemical fields. For instance, these bioinspired paramagnetic nanoparticles might find applications in the fields of drug delivery and magnetic resonance imaging as macromolecular contrast agents for better diagnosis of solid tumors.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/168073/1/gdimauro_1.pd

Secondary metabolites with ecologic and medicinal implications in Anthemis cretica subsp. petraea from Majella National Park

Anthemis cretica subsp. petraea (Ten.) Greuter is a plant belonging to the Asteraceae family and endemic of central Italy. In this paper, the first analysisof the ethanolic fraction of samples collected in the Majella National Park is reported. Seven compounds were isolated and identified namely parthenolide (1), 9α-acetoxyparthenolide (2), tamarixetin (3), 7-hydroxycoumarin (4), 4'-hydroxyacetophenone (5), leucanthemitol (conduritol F) (6),and proto-quercitol (7). Isolation of the compounds was achieved by means ofcolumn chromatography (CC), while their identification was achieved through spectroscopic and spectrometric techniques. The presence of these compounds is of great relevance. Compounds 1 and 2 are chemosystematic markers of the family, thus confirming the correct botanical classification of the species. Conversely, compounds 3, 5,and 7 were identified for the first time in the species and, instead, confirm the tendency of endemic entities to develop characteristic metabolite patterns in respect to cosmopolite species. Moreover, the presence of compounds 6 and 7 has ecologic implications and may be linked to this taxon’s adaption to dry environments. The production of these osmolytes may, in fact, represent the reason why this species is able to survive in extreme conditions of aridity. Lastly, from a medicinal standpoint, the isolated compounds are endowed with interesting biological activities and may justify, on a molecular base, the widespread traditional uses of the Anthemis species, as well as a basis for the use ofthe subspecies petraea

Bioinspired, Sizeâ Tunable Selfâ Assembly of Polymerâ Lipid Bilayer Nanodiscs

Polymerâ based nanodiscs are valuable tools in biomedical research that can offer a detergentâ free solubilization of membrane proteins maintaining their native lipid environment. Herein, we introduce a novel ca. 1.6â kDa SMAâ based polymer with styrene:maleic acid moieties that can form nanodiscs containing a planar lipid bilayer which are useful to reconstitute membrane proteins for structural and functional studies. The physicochemical properties and the mechanism of formation of polymerâ based nanodiscs are characterized by light scattering, NMR, FTâ IR, and TEM. A remarkable feature is that nanodiscs of different sizes, from nanometer to subâ micrometer diameter, can be produced by varying the lipidâ toâ polymer ratio. The smallâ size nanodiscs (up to ca. 30â nm diameter) can be used for solution NMR spectroscopy studies whereas the magneticâ alignment of macroâ nanodiscs (diameter of > ca. 40â nm) can be exploited for solidâ state NMR studies on membrane proteins.Discrete bilayers: Lipid bilayer nanodiscs of different size are formed by using modified styrene maleic acid coâ polymer. The smallâ size nanodiscs (up to ca. 30â nm diameter) can be used for solution NMR spectroscopy studies, whereas the magnetic alignment of largeâ size nanodiscs (or macroâ nanodiscs with a diameter of >40â nm) can be exploited for solidâ state NMR studies on membrane proteins.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138344/1/anie201705569.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138344/2/anie201705569_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138344/3/anie201705569-sup-0001-misc_information.pd

Communicating Seismic Risk Information: The Effect of Risk Comparisons on Risk Perception Sensitivity

Communicating seismic risk to individuals can be difficult for an institution because it involves providing technical and scientific information, including the low probability of an adverse event, that is not always easy to understand. One way to facilitate understanding of low probabilities is to provide comparisons with the probability of occurrence of other more familiar events. In a randomized trials experiment, we investigated the effect of providing individuals with a set of risk comparisons on their sensitivity to different levels of seismic risk (1 in 100, 1 in 1,000, and 1 in 10,000). The findings show that providing risk comparisons increased individual risk sensitivity to information about the likelihood of experiencing a seismic event. Our findings are explained by the evaluability hypothesis, which states that a single probability value is better understood if the recipient is given some reference data to evaluate it. Our results have implications for disaster risk communication, providing ways to increase risk awareness and, consequently, disaster prevention

Imaging techniques in Veterinary Medicine. Part I: Radiography and Ultrasonography

In Veterinary Medicine all the Imaging techniques are used and described but, due to organizational, managerial and, mostly, economical reasons, Radiography and Ultrasonography are the most used. Veterinary Radiology teaching has a relatively small number of educational credits in the degree courses but, nowday, educational opportunities are remarkably increased thanks to a number of post-degree courses and masters, organized both by the universities and private veterinary associations. The relevance of Diagnostic Imaging is particularly true in Veterinary Medicine, in which Radiology could be considered “indispensable” for diagnosis, prognosis and follow up. Furthermore, it should not be forgotten that the diagnostic image represents a “document” and, has a relevant role in legal medical debats. In this first part, Radiography and Ultrasonography are described

Memristor Circuits for Simulating Neuron Spiking and Burst Phenomena

Since the introduction of memristors, it has been widely recognized that they can be successfully employed as synapses in neuromorphic circuits. This paper focuses on showing that memristor circuits can be also used for mimicking some features of the dynamics exhibited by neurons in response to an external stimulus. The proposed approach relies on exploiting multistability of memristor circuits, i.e., the coexistence of infinitely many attractors, and employing a suitable pulse-programmed input for switching among the different attractors. Specifically, it is first shown that a circuit composed of a resistor, an inductor, a capacitor and an ideal charge-controlled memristor displays infinitely many stable equilibrium points and limit cycles, each one pertaining to a planar invariant manifold. Moreover, each limit cycle is approximated via a first-order periodic approximation analytically obtained via the Describing Function (DF) method, a well-known technique in the Harmonic Balance (HB) context. Then, it is shown that the memristor charge is capable to mimic some simplified models of the neuron response when an external independent pulse-programmed current source is introduced in the circuit. The memristor charge behavior is generated via the concatenation of convergent and oscillatory behaviors which are obtained by switching between equilibrium points and limit cycles via a properly designed pulse timing of the current source. The design procedure takes also into account some relationships between the pulse features and the circuit parameters which are derived exploiting the analytic approximation of the limit cycles obtained via the DF method

Physical Implementation of a Tunable Memristor-based Chua's Circuit

Nonlinearity is a central feature in demanding computing applications that aim to deal with tasks such as optimization or classification. Furthermore, the consensus is that nonlinearity should not be only exploited at the algorithm level, but also at the physical level by finding devices that incorporate desired nonlinear features to physically implement energy, area and/or time efficient computing applications. Chaotic oscillators are one type of system powered by nonlinearity, which can be used for computing purposes. In this work we present a physical implementation of a tunable Chua's circuit in which the nonlinear part is based on a nonvolatile memristive device. Device characterization and circuit analysis serve as guidelines to design the circuit and results prove the possibility to tune the circuit oscillatory response by electrically programming the device.Comment: Accepted by IEEE 48th European Solid State Circuits Conference (ESSCIRC 2022

Chua's Circuit With Tunable Nonlinearity Based on a Nonvolatile Memristor: Design and Realization

Nonvolatile memristive devices display nonlinear characteristics suitable for implementing circuits exhibiting oscillations or more complex dynamic behaviors, including chaos. However, the results presented in related works are mostly limited to simulations and employing ideal memristor models whose resistance is governed by a charge-flux relation that is not connected to real devices, thus hindering the realization of such nonlinear oscillators. In this work, we present the framework for the physical implementation of a tunable memristor Chua's circuit, which is based on a nonvolatile memristive device that provides the nonlinear conductance required by the circuit and the possibility to tune it for the purpose of selecting among different oscillation patterns. We first establish design guidelines to guarantee complex oscillations in the tunable memristor Chua's circuit. Further, we physically implement the circuit after characterizing and modeling the tunable current-voltage characteristic of a real device. Our circuit successfully generates different oscillation patterns just by programming the nonvolatile memristive device to different states. The devised design guidelines and device modeling were used to extend the experimental work and draw further requirements for device properties for a successful circuit implementation