Domain value mutation and other techniques for constraint satisfaction problems

The term Constraint Satisfaction Problem (CSP) refers to a class of NP-complete problems, a collection of difficult problems for which no fast solution is known. The standard definition of a CSP involves variables, values, and constraints: each variable must be assigned a value from a designated group of possible values (also known as the variable’s domain), while a constraint on a set of variables indicates permissible combinations of values for these variables. Given a CSP, an important objective is to query whether it has a solution — an assignment of each variable to a value such that all constraints are satisfied. Solving a CSP usually requires chronological backtracking search that interleaves variable assignments with various kinds of inferences in order to reduce the search space. This dissertation comprises two parts. The first part deals with a modification of the classical CSP model that allows a value to be broken up and multiple values to be combined. The second part deals with generalized arc consistency algorithms. Both parts share a common theme in that extensional constraints --‐ the most basic expression possible for constraints --- play the central role. Despite being an important class, extensional constraints have received much less attention recently as most efforts have been channelled toward identifying new types of specialized constraints and coming up with corresponding algorithms. Regardless, improvements to algorithms for extensional constraints are more fundamental. This dissertation will attempt to improve existing techniques and algorithms for extensional constraints by examining them critically from the bottom up and approaching them from a novel direction

Proceedings of the NASA Conference on Space Telerobotics, volume 1

The theme of the Conference was man-machine collaboration in space. Topics addressed include: redundant manipulators; man-machine systems; telerobot architecture; remote sensing and planning; navigation; neural networks; fundamental AI research; and reasoning under uncertainty

Badanie samorzutnych reakcji inwersji chiralnej i peptyzacji wybranych aminokwasów białkowych

The aim of this PhD thesis was investigation of the oscillating reactions of amino acids carried out in vitro, with the amino acids dissolved in aqueous or aqueous-organic solutions and kept under the mild external conditions (i.e., at 21±2oC, normally considered as the room temperature). This investigation demonstrated susceptibility of the examined amino acids to spontaneously undergo the enantiomerization and condensation processes. Moreover, it was shown that the spontaneous chiral inversion and condensation take place in the parallel. Investigations with use of the thin-layer chromatography coupled with mass spectrometry (TLC-MS) demonstrated the parallel processes of spontaneous enantiomerization and condensation with such amino acids, as L-cysteine and L-methionine. Moreover, enantiomerization of L-methionine was confirmed with use of polarimetry. Condensation of these two amino acids was also demonstrated with use of the high-performance liquid chromatography (HPLC) applied in continuous mode. Application of continuous mode to tracing concentration changes of the amino acids of interest pointed out to the non-linear nature of these processes, whereas the presence of the newly formed peptides was confirmed with use of the high-performance liquid chromatography coupled with mass spectrometry (MS). Similar investigations with use of HPLC-DAD and HPLC-ELSD were carried out for L-phenylalanine, L-phenylglycine, and the binary solutions of L-phenylalanine-L-hydroxyproline, L-cysteine-L-phenylalanine, and L-cysteine-L-phenylglycine. Amino acids in the binary systems also undergo the oscillating concentration changes, yet with the amplitudes different from those observed in the monocomponent solutions. In the course of the studies, it was shown that the peptides spontaneously formed in the solutions self-organize into the peptide nano- and microstructures, and the shape of these structures depends on the functional groups of amino acids. Owing to its thiol group, cysteine is able to form the disulfide bridges and assume spherical structures, while the phenylalanine-derived peptides organize in the micro- and nanofibers. Investigation of peptide structures was carried out with use of the scanning electron microscopy (SEM). At an initial stage, the precipitation of peptide structures was monitored with use of turbidimetry. Owing to application of this technique, it was shown that certain L-amino acids assume the circadian rhythm of the oscillations, which does not happen with their D- or DL-counterparts. Peptide structures originating from the spontaneous oscillatory reactions of amino acids could probably find applications in nanotechnology, nanobiotechnology, and nanomedicine

Acoustic and Elastic Waves: Recent Trends in Science and Engineering

The present Special Issue intends to explore new directions in the field of acoustics and ultrasonics. The interest includes, but is not limited to, the use of acoustic technology for condition monitoring of materials and structures. Topics of interest (among others): • Acoustic emission in materials and structures (without material limitation) • Innovative cases of ultrasonic inspection • Wave dispersion and waveguides • Monitoring of innovative materials • Seismic waves • Vibrations, damping and noise control • Combination of mechanical wave techniques with other types for structural health monitoring purposes. Experimental and numerical studies are welcome

Development and application of liquid-observed vapor exchange NMR to study dehydrated protein structure and protection at the residue-level

Life on Earth evolved in the oceans, and therefore the stability, dynamics, and function of proteins – the molecules that carry out the majority of life’s processes – are intricately linked to the properties of liquid water. However, despite decades of research, our understanding of the fundamental interaction between proteins and water remains surprisingly limited, in part because we have been unable to study, at adequate resolution, what happens to proteins when water is removed. Such technological boundaries have also hindered our understanding of how molecules known as excipients protect proteins from the destructive effects of dehydration, which is important in the context of protein-based drugs such as insulin and vaccines. For my dissertation work, I sought to help fill these knowledge gaps by developing Liquid-Observed Vapor Exchange (LOVE) NMR, a solution NMR technique that provides residue-level information on the structure and interactions of dehydrated proteins. My dissertation begins with a brief overview and contextualization of what we do and do not know about dehydrated protein structure and mechanisms of dehydration protection (Chapter 1), and then goes into the initial proof-of-concept experiments for LOVE NMR, which show that LOVE NMR reports on the fraction of dried protein population for which a given residue is protected from exchange with D2O vapor, and that this fraction is related to the amount of local structure and/or inter-molecular interactions in the dry state (Chapter 2). I then applied LOVE NMR to uncover water’s variable role in the mutation-induced (de)stabilization of two different proteins (Chapter 3) and to probe the importance of surface-area, charge-patterning, and electrostatic interactions in protein dehydration protection by two distinct disordered proteins from desiccation-tolerant animals (Chapter 4). Finally, in Chapter 5 I suggest strategies to increase the accuracy and precision of LOVE NMR and deepen our understanding of the results it produces. Overall, the results presented in this dissertation demonstrate the potential of LOVE NMR to provide new insights into protein-water and protein-excipient interactions.Doctor of Philosoph

Summary of Research 1994

The views expressed in this report are those of the authors and do not reflect the official policy or position of the Department of Defense or the U.S. Government.This report contains 359 summaries of research projects which were carried out under funding of the Naval Postgraduate School Research Program. A list of recent publications is also included which consists of conference presentations and publications, books, contributions to books, published journal papers, and technical reports. The research was conducted in the areas of Aeronautics and Astronautics, Computer Science, Electrical and Computer Engineering, Mathematics, Mechanical Engineering, Meteorology, National Security Affairs, Oceanography, Operations Research, Physics, and Systems Management. This also includes research by the Command, Control and Communications (C3) Academic Group, Electronic Warfare Academic Group, Space Systems Academic Group, and the Undersea Warfare Academic Group

Development of a Novel, Microemulsion System for the Simultaneous Delivery of Hydrophilic and Hydrophobic Active Pharmaceutical Ingredients (APIs)

Concurrent chronic disease and ensuing multi-morbidity are a debilitating reality for millions of Canadians. This adversity is compounded by increased pill burden and decreased patient adherence. Microemulsions (MEs) serve as a potential multi-drug therapy solution. MEs are thermodynamically stable, colloidal systems whose oil and water compositions and nano-sized droplets have the potential to facilitate simultaneous hydrophilic and lipophilic drug delivery, while improving bioavailability. However, the area of multi-drug delivery using ME technology is largely unexplored and unfulfilled. In order to develop a ME capable of simultaneous multi-drug delivery, emulsifying agents as the heart of these systems must be investigated. In this work, the potential for multi-drug delivery using ME systems was explored with a particular focus on emulsifying agent properties conducive to this purpose. A prenatal supplement comprised of eleven active pharmaceutical ingredients (APIs) of varying hydro- and lipophilicity was selected as a proof of concept. Five non-ionic surfactants were subjected to extensive ternary phase diagram (TPD) mapping with a medium chain triglyceride, Miglyol 812 in order to identify regions of monophasic microemulsion formation. Optimization was performed via critical micelle concentration determination and the hydrophilic-lipophilic deviation (HLD) equation. A final microemulsion comprised of 3:1 Polysorbate 80:Cremophor RH 40 surfactant, Miglyol 812 and water in a surfactant:oil:water (S:O:W) ratio of 50:40:10, was identified as optimal for monophasic, microemulsion formation. Eleven active pharmaceutical ingredients- five lipophilic (Vitamins A, D, E, K and docosahexaenoic acid) and six hydrophilic (Vitamins B1, B2, B3, B6, B9, B12) were then successfully incorporated. The resulting microemulsion was determined to be of a bicontinuous nature and after 100x aqueous dilution, spherical droplets were identified via TEM with a diameter of 164 ± 37 nm, a charge of -14.1 ± 2.2 mV and a low viscosity of 1.04 ± 0.04 mPa/s. Twelve additional non-ionic surfactants were screened for possible use in the formulation. Polysorbate 81, with 15 less ethylene oxide head groups but equivalent carbon chain length to Polysorbate 80, was identified as most promising based on droplet diameter and zeta potential. Thus, this type of multi-drug formulation appeared to be tolerable to larger changes in non-ionic surfactant head group than hydrocarbon chain length; Hydrophilic-lipophilic balance (HLB), in contrast, appeared to have little to no effect. Two additional drug-loaded microemulsion formulations comprised of 3:1 Polysorbate 81:Cremophor RH 40 surfactant, Miglyol 812 oil and water in S:O:W ratios of 40:50:10 and 50:40:10, resulted in droplet diameters of 94 ± 15 nm and 81 ± 2.4 nm, and zeta potential values of -17 ± 4 mV and -23 ± 6 mV, respectively after 100x aqueous dilution. All final multi-drug loaded MEs demonstrated >70% dissolution improvement of folic acid and >90% dissolution improvement of riboflavin in 50 mM phosphate buffer (pH 7.4) as compared to a commercial prenatal supplement in suspension form. Overall, it was demonstrated that the process of TPD mapping, HLD optimization and careful surfactant screening was instrumental in the successful development of a multi-drug microemulsion system with the potential to treat concurrent, chronic diseases in a single dose