Data Compression Concepts and Algorithms and Their Applications to Bioinformatics

Data compression at its base is concerned with how information is organized in data. Understanding this organization can lead to efficient ways of representing the information and hence data compression. In this paper we review the ways in which ideas and approaches fundamental to the theory and practice of data compression have been used in the area of bioinformatics. We look at how basic theoretical ideas from data compression, such as the notions of entropy, mutual information, and complexity have been used for analyzing biological sequences in order to discover hidden patterns, infer phylogenetic relationships between organisms and study viral populations. Finally, we look at how inferred grammars for biological sequences have been used to uncover structure in biological sequences

Data Compression Concepts and Algorithms and Their Applications to Bioinformatics

Data compression at its base is concerned with how information is organized in data. Understanding this organization can lead to efficient ways of representing the information and hence data compression. In this paper we review the ways in which ideas and approaches fundamental to the theory and practice of data compression have been used in the area of bioinformatics. We look at how basic theoretical ideas from data compression, such as the notions of entropy, mutual information, and complexity have been used for analyzing biological sequences in order to discover hidden patterns, infer phylogenetic relationships between organisms and study viral populations. Finally, we look at how inferred grammars for biological sequences have been used to uncover structure in biological sequences

Astrophysical Ionizing Radiation and the Earth: A Brief Review and Census of Intermittent Intense Sources

Cosmic radiation backgrounds are a constraint on life, and their distribution will affect the Galactic Habitable Zone. Life on Earth has developed in the context of these backgrounds, and characterizing event rates will elaborate the important influences. This in turn can be a base for comparison with other potential life-bearing planets. In this review we estimate the intensities and rates of occurrence of many kinds of strong radiation bursts by astrophysical entities ranging from gamma-ray bursts at cosmological distances to the Sun itself. Many of these present potential hazards to the biosphere: on timescales long compared with human history, the probability of an event intense enough to disrupt life on the land surface or in the oceans becomes large. We enumerate the known sources of radiation and characterize their intensities at the Earth and rates or upper limits on these quantities. When possible, we estimate a "lethal interval", our best estimate of how often a major extinction-level event is probable given the current state of knowledge; we base these estimates on computed or expected depletion of stratospheric ozone. In general, moderate level events are dominated by the Sun, but the far more severe infrequent events are probably dominated by gamma-ray bursts and supernovae. We note for the first time that so-called "short-hard" gamma-ray bursts are a substantial threat, comparable in magnitude to supernovae and greater than that of the higher-luminosity long bursts considered in most past work. Given their precursors, short bursts may come with little or no warning.Comment: to be published in Astrobiolog

Modeling of Masonry Structures at Multiple Scales

Zdivo je materiál použitý ve většině stavebních památek na celém světě. Spolehlivé nástroje pro analýzu zděných konstrukcí jsou zapotřebí nejen pro vyhodnocení jejich seismické zranitelnosti, ale také při návrhu opatření směřujících k obnovení či zvýšení únosnosti existujících budov, které si zaslouží ochranu. Zdivo je nelineární, heterogenní a anizotropní materiál, jehož vlastnosti silně závisejí na základních stavebních jednotkách, tedy blocích (cihlách) a maltě, a na jejich prostorovém uspořádání. Pro simulaci mechanického chování zděných konstrukcí byla vyvinuta řada modelů, které se liší mírou rozlišení. Pro velké konstrukce vede snaha o výpočetní efektivitu ke zjednodušeným modelům, charakterizovaným rozdělením zděných stěn na makroprvky. Významným zástupcem této skupiny modelů je metoda ekvivalentního rámu. Její podstatou je nahrazení zděné stěny idealizovaným rámem, přičemž panely jsou modelovány jako nosníky charakterizované odpovídajícím mechanickým chováním. Míra rozlišení může být zvýšena tím, že se každý makroprvek uvažuje jako homogenizované kontinuum s vlastnostmi, které reprodukují celkovou odezvu určitého výseku heterogenní mikrostruktury. Formulace vhodného konstitutivního zákona ale není lehkou úlohou. Tento zákon by měl fenomenologicky reprodukovat mechanické chování materiálu, včetně vzniku tahových trhlin, smykového pokluzu, drcení v tlaku a dalších jevů. Navíc tento přístup vyžaduje těžkopádnou identifikaci mechanických parametrů, které není vždy snadné určit na základě běžných laboratorních testů materiálu. K popisu role základních stavebních jednotek a jejich interakce může posloužit model formulovaný na mikroúrovni, který explicitně bere v úvahu jednotlivé bloky, maltu a rozhraní mezi nimi. Tato práce se zabývá zděnými konstrukcemi na několika úrovních rozlišení. Problémy s formulací modelů ekvivalentního rámu v případě nepravidelného rozmístění otvorů se zkoumají na základě porovnání výsledků pro ekvivalentní rámy s výsledky získanými metodou konečných prvků, o které lze předpokládat, že lépe postihuje skutečné chování nepravidelných stěn. Provedená parametrická analýza zděných pilířů modelovaných jako homogenizované kontinuum je zaměřena na posouzení vlivu tvaru a svislého tlakového zatížení na nelineární statické chování. Pozornost se pak přesouvá na jemnější úrovně rozlišení, na nichž se zkoumá lokalizace nepružného přetváření, která ovlivňuje konstitutivní zákony pro modelování zdiva na makro a mikroúrovni. Provádí se lokalizační analýza ortotropního makroskopického modelu formulovaného podle teorie plasticity s více plochami plasticity, v jejímž rámci jsou odvozeny analytické podmínky lokalizace potvrzené simulacemi metodou konečných prvků. V závěru je vyvinut mikromechanický model pro pravidelné zdivo a pomocí něj se na reprezentativním objemu materiálu analyzují lokalizační vlastnosti, ovlivněné velikostí tohoto objemu a předpokládanými směry periodicityMasonry represents the material used in the great majority of the world building heritage structures. Reliable tools for analysis of masonry structures are needed not only for seismic vulnerability assessment but also to properly design interventions to restore and strengthen existing buildings, which deserve to be preserved. Masonry is a nonlinear, heterogeneous, and anisotropic material whose properties strongly depend on its microstructure, typically composed of two phases, blocks and mortar, and on the way it is assembled. To simulate the mechanical behavior of masonry structures, numerous models have been developed, characterized by different detailing levels. For large structures, the need for computational efficiency leads to simplified models characterized by the subdivision of masonry walls in macro-elements. A notable example of this group of models is the equivalent-frame method, which consists of identifying the masonry wall with an ideal frame, where panels are modeled as beams characterized by proper mechanical behavior. The detailing level can be increased by considering each macro-element as a homogenized continuum, assuming that, at the scale of representation, masonry can be treated as a continuum having mechanical properties that reproduce the overall response of a certain portion of the heterogeneous microstructure. However, the formulation of a suitable constitutive law is not an easy task. It should phenomenologically reproduce the material mechanics, including tension cracking, shear sliding, compressive crushing, and many other aspects. Moreover, this approach requires a cumbersome identification of mechanical parameters that are not always easy to determine from basic experimental tests on the material. To consider the role of each constituent and the effects of their interactions, a microscale model can be set up, where blocks, mortar joints, and mortar-block interfaces are represented explicitly. In this work, masonry structures are studied at several detailing levels. An issue affecting equivalent-frame models, namely the presence of irregularity in the wall opening layout, is addressed by comparing equivalent-frame results with finite-element ones, which are assumed to better represent the actual behavior of irregular walls. A parametric analysis on masonry piers, modeled as a homogenized continuum, is carried out, aimed to assess the influence of the height-to-width ratio and the vertical compression load on the nonlinear static behavior. The focus is then shifted to finer scales. The localization analysis of an orthotropic macro-scale model in the framework of multi-surface plasticity is presented, deriving analytical localization conditions corroborated by finite element simulations. Finally, a microscale model for regular masonry is developed to analyze the localization properties of the representative volume element, also by investigating the role of its size and periodicity directions

A single cell based model for cell divisions with spontaneous topology changes

The development of multicellular organisms is accompanied by the formation of tis- sues of precise shapes, sizes and topologies. Remarkable similarities between tissue topologies, in particular proliferating epithelial topologies, in various species suggest that the mechanisms that govern the formation of tissues are conserved among species. To understand these mechanisms various models have been developed. In this thesis, we present a novel mechanical model for cell divisions and tissue for- mation. The model accounts for cell mechanics and cell-cell adhesion. In our model, each cell is treated individually, thus the changes in cell’s shape and its local rearrange- ments occur naturally as a response to the evolving cellular environment and cell-cell interactions. We introduce the processes of cell growth and divisions and numerically simulate tissue proliferation. As tissue grows starting from few cells, we follow the dynamics of the tissue growth and cell packing topologies. The outcomes are com- pared with experimental observations in Drosophila wing growth. Our model accounts for the exponential decay of the mitotic index and reproduces commonly observed cell packing topologies in proliferating epithelia. Next, we consider two biologically relevant division schemes, namely, division through asymmetric division plane and division by Hertwig’s rule. We study the im- pact of division planes on tissue growth and show that the division plane may affect cell packing topologies. Development of the tissue is accompanied by cellular rearrange- ments. We vary the extent of cellular rearrangements and analyse their effects on tissue topology. We find that when cells are allowed to move freely, more organized packing topologies emerge

Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use

Biological Nanowires: Integration of the silver(I) base pair into DNA with nanotechnological and synthetic biological applications

Modern computing and mobile device technologies are now based on semiconductor technology with nanoscale components, i.e., nanoelectronics, and are used in an increasing variety of consumer, scientific, and space-based applications. This rise to global prevalence has been accompanied by a similarly precipitous rise in fabrication cost, toxicity, and technicality; and the vast majority of modern nanotechnology cannot be repaired in whole or in part. In combination with looming scaling limits, it is clear that there is a critical need for fabrication technologies that rely upon clean, inexpensive, and portable means; and the ideal nanoelectronics manufacturing facility would harness micro- and nanoscale fabrication and self-assembly techniques. The field of molecular electronics has promised for the past two decades to fill fundamental gaps in modern, silicon-based, micro- and nanoelectronics; yet molecular electronic devices, in turn, have suffered from problems of size, dispersion and reproducibility. In parallel, advances in DNA nanotechnology over the past several decades have allowed for the design and assembly of nanoscale architectures with single-molecule precision, and indeed have been used as a basis for heteromaterial scaffolds, mechanically-active delivery mechanisms, and network assembly. The field has, however, suffered for lack of meaningful modularity in function: few designs to date interact with their surroundings in more than a mechanical manner. As a material, DNA offers the promise of nanometer resolution, self-assembly, linear shape, and connectivity into branched architectures; while its biological origin offers information storage, enzyme-compatibility and the promise of biologically-inspired fabrication through synthetic biological means. Recent advances in DNA chemistry have isolated and characterized an orthogonal DNA base pair using standard nucleobases: by bridging the gap between mismatched cytosine nucleotides, silver(I) ions can be selectively incorporated into the DNA helix with atomic resolution. The goal of this thesis is to explore how this approach to “metallize” DNA can be combined with structural DNA nanotechnology as a step toward creating electronically-functional DNA networks. This work begins with a survey of applications for such a transformative technology, including nanoelectronic component fabrication for low-resource and space-based applications. We then investigate the assembly of linear Ag+-functionalized DNA species using biochemical and structural analyses to gain an understanding of the kinetics, yield, morphology, and behavior of this orthogonal DNA base pair. After establishing a protocol for high yield assembly in the presence of varying Ag+ functionalization, we investigate these linear DNA species using electrical means. First a method of coupling orthogonal DNA to single-walled carbon nanotubes (SWCNTs) is explored for self-assembly into nanopatterned transistor devices. Then we carry out scanning tunneling microscope (STM) break junction experiments on short polycytosine, polycationic DNA duplexes and find increased molecular conductance of at least an order of magnitude relative to the most conductive DNA analog. With an understanding of linear species from both a biochemical and nanoelectronic perspective, we investigate the assembly of nonlinear Ag+-functionalized DNA species. Using rational design principles gathered from the analysis of linear species, a de novo mathematical framework for understanding generalized DNA networks is developed. This provides the basis for a computational model built in Matlab that is able to design DNA networks and nanostructures using arbitrary base parity. In this way, DNA nanostructures are able to be designed using the dC:Ag+:dC base pair, as well as any similar nucleobase or DNA-inspired system (dT:Hg2+:dT, rA:rU, G4, XNA, LNA, PNA, etc.). With this foundation, three general classes of DNA tiles are designed with embedded nanowire elements: single crossover Holliday junction (HJ) tiles, T-junction (TJ) units, and double crossover (DX) tile pairs and structures. A library of orthogonal chemistry DNA nanotechnology is described, and future applications to nanomaterials and circuit architectures are discussed