An Algorithm for the Maximum Weight Independent Set Problem on Outerstring Graphs

Outerstring graphs are the intersection graphs of curves that lie inside a disk such that each curve intersects the boundary of the disk. Outerstring graphs are among the most general classes of intersection graphs studied. To date, no polynomial time algorithm is known for any of the classical graph optimization problems on outerstring graphs; in fact, most are NP-hard. It is known that there is an intersection model for any outerstring graph that consists of polygonal arcs attached to a circle. However, this representation may require an exponential number of segments relative to the size of the graph. Given an outerstring graph and an intersection model consisting of polygonal arcs with a total of N segments, we develop an algorithm that solves the Maximum Weight Independent Set problem in O(N³) time. If the polygonal arcs are restricted to single segments, then outersegment graphs result. For outersegment graphs, we solve the Maximum Weight Independent Set problem in O(n³) time where n is the number of vertices in the graph

Age-related deterioration of rod vision in mice

Even in healthy individuals, aging leads to deterioration in visual acuity, contrast sensitivity, visual field, and dark adaptation. Little is known about the neural mechanisms that drive the age-related changes of the retina and, more specifically, photoreceptors. According to one hypothesis, the age-related deterioration in rod function is due to the limited availability of 11-cis-retinal for rod pigment formation. To determine how aging affects rod photoreceptors and to test the retinoid-deficiency hypothesis, we compared the morphological and functional properties of rods of adult and aged B6D2F1/J mice. We found that the number of rods and the length of their outer segments were significantly reduced in 2.5-year-old mice compared with 4-month-old animals. Aging also resulted in a twofold reduction in the total level of opsin in the retina. Behavioral tests revealed that scotopic visual acuity and contrast sensitivity were decreased by twofold in aged mice, and rod ERG recordings demonstrated reduced amplitudes of both a- and b-waves. Sensitivity of aged rods determined from single-cell recordings was also decreased by 1.5-fold, corresponding to not more than 1% free opsin in these photoreceptors, and kinetic parameters of dim flash response were not altered. Notably, the rate of rod dark adaptation was unaffected by age. Thus, our results argue against age-related deficiency of 11-cis-retinal in the B6D2F1/J mouse rod visual cycle. Surprisingly, the level of cellular dark noise was increased in aged rods, providing an alternative mechanism for their desensitization

The Chromatic Aberration of the Eye and its Importance in the Modern World

The human eye has various aberrations that distort the image formed on the retina. Monochromatic aberrations are the distortions present at a single wavelength and chromatic aberrations are wavelength dependent. Longitudinal chromatic aberration (LCA) describes the difference in defocus at different wavelengths. The LCA of the human eye is approximately 2 dioptres (D) across the visible spectrum. Normally we are unaware of these distortions, however, they do play an important role in our vision. The aim of this thesis was to investigate the importance of these aberrations in the context of the modern world. The illuminant spectra that we are exposed to today are quite different from 100 years ago. Because LCA results in a difference in defocus with wavelength this means that the amount of defocus blur in the retinal image will change depending on the spectrum of light. In this thesis findings are reported indicating that there are certain illuminant spectra for which the chromatic fringes due to LCA were more visible. We also investigated how people accommodated to spectra made up of two distinct narrowband LEDs. The findings suggest that people do not accommodate optimally to these spectra. There is also increasing interest in blurring stimuli realistically. This is partly with the emergence of virtual reality, so that 3D scenes appear as realistic as possible, but also has more clinical applications in trialling the effects of different corrective lenses on vision before the lenses are made (or inserted in the case of intraocular lenses). We investigated the importance of including monochromatic aberrations when rendering out of focus stimuli. It seems that monochromatic aberrations do make the stimuli appear more realistic, however, they did not have a significant impact on visual acuity

New opportunities for photon storage and detection: an exploration of a high-efficiency optical quantum memory and the quantum capabilities of the human eye

The field of quantum information has grown in recent years, due to tremendous technological advancements toward quantum networking and quantum computation. Nevertheless, there is still a great need for creative research that explores possibilities for new capabilities. Particularly, we look towards quantum optics research to develop new ways of manipulating and detecting photons. Here, we discuss our efforts toward developing two separate quantum optics experiments that can provide great insight into the development of quantum devices. We begin by discussing our work to investigate the lower threshold of human vision and the eye's potential as a single-photon detector, using a custom-built single-photon source, and a novel two-alternative forced-choice experimental design. Our preliminary findings show promising data that support previous results found from a similar experiment using a somewhat different approach. We then discuss our second project, where we have developed a robust reconfigurable optical delay line quantum memory that compares favorably with competing methods. Our memory is capable of photon storage with an unprecedentedly high time-bandwidth product, high free-space transmission over the range of 10 $\mu$s, and high fidelity. These attributes, plus the memory's capability for multi-mode storage, make this system a strong candidate for a critical component in the large-scale heterogeneous quantum networks we hope to see developed in the next ten years

Zebrafish and mouse models for studying deubiquitinating enzyme genes as candidates for retinal dystrophies

[eng] The retina consists of several structured layers of highly specialized neurons that capture and process light stimuli enabling vision. Such a fine architecture turns retinal differentiation into an extremely complex event that must be accurately regulated. The ubiquitin-proteasome system (UPS) is considered one of the most dynamic and versatile mechanisms of protein regulation in eukaryotic cells. As ubiquitination is reversible, deubiquitinating enzymes (DUBs) play a major regulatory role in the UPS. Despite the importance of proteostasis and the UPS in health and disease, a more comprehensive in-depth analysis of DUB expression and function on particular tissues or organs, such as the retina, is still missing. Combining expression quantification, mRNA localization assays and functional analyses in animal and cellular models, we analyzed the function of several DUB genes in the retina to identify DUBs that regulate important retinal cell mechanisms, explore their relevance in retinal function in health and disease, and finally, posit them as new potential candidate genes for retinal dystrophies. Taking into consideration our results in the expression levels and pattern of DUBs in the retina, we first selected USP45 to perform functional assays in animal models in order to define its role and function in the retina. By morpholino-knockdown of usp45 in zebrafish embryos, our results showed moderate to severe eye morphological defects, eye size reduction, small body size with small tail or without tail, and disruption in notochord formation. There is also defective lamination and formation of the retinal structures, with no distinguishable layers and smaller retinas. Overall, our results supported the relevance of USP45 in the normal development and formation of the vertebrate retina, and we proposed this gene as a good candidate for causing hereditary retinal dystrophies, as later confirmed by other authors in several families. We also selected ATXN3, a DUB gene that causes the dominant polyQ disease Spinocerebellar ataxia type 3 (SCA3), and we aimed to analyze its function in the retina. We showed that depletion of Atxn3 in zebrafish and mice caused retinal morphological and functional alterations with photoreceptor outer segment elongation, cone opsin mislocalization, and cone hyperexcitation upon light stimuli. A pool of ATXN3 resides at the basal body and axoneme of the photoreceptor cilium, where it controls the levels and recruitment of the regulatory proteins KEAP1 and HDAC6. Abrogation of Atxn3 expression causes delayed phagosome maturation in the retinal pigment epithelium. We propose that ATXN3 regulates two relevant biological processes in the retina, ciliogenesis and phagocytosis, by modulating microtubule polymerization and microtubule-dependent retrograde transport, and propose ATXN3 as a causative or modifier gene in retinal/macular dystrophies. We further aimed to explore whether the SCA3 humanized mouse model showed specific retinal phenotype traits. We showed that polyQ-expanded ATXN3 protein formed a high number of progressive pathogenic aggregates in the retinal layers of transgenic Atxn3Q84 mice, and caused a decrease in the number of cone photoreceptors. Optical coherence tomography revealed a general decrease in the thickness of the retinal layers whereas retinal electrophysiological analyses showed a strong decrease in photoreceptor response to light, thus supporting severe retinal dysfunction in Atxn3Q84 mice. Similar analyses in human patients detected a correlation of retinal alterations with the number of CAG repeats and the age of onset of SCA3 symptoms. We propose that retinal alterations detected by non-invasive eye examination and electroretinography tests in SCA3 patients could serve as a valuable early-onset symptom and a biological marker of disease progression. As a conclusion, our work posits several DUB genes as candidates for inherited retinal dystrophies, but further investigation is needed to dissect the function of DUBs in retinal cell differentiation, photoreceptor function, and retinal homeostasis

New Platforms for Optical Biosensing

Physicochemical experimental techniques combined with the specificity of a biological recognition system have resulted in a variety of new analytical devices known as biosensors. Biosensors are under intensive development worldwide because they have many potential applications, e.g. in the fields of clinical diagnostics, food analysis, and environmental monitoring. Much effort is spent on the development of highly sensitive sensor platforms to study interactions on the molecular scale. In the first part, this thesis focuses on exploiting the biosensing application of nanoporous gold (NPG) membranes. NPG with randomly distributed nanopores (pore sizes less than 50 nm) will be discussed here. The NPG membrane shows unique plasmonic features, i.e. it supports both propagating and localized surface plasmon resonance modes (p SPR and l-SPR, respectively), both offering sensitive probing of the local refractive index variation on/in NPG. Surface refractive index sensors have an inherent advantage over fluorescence optical biosensors that require a chromophoric group or other luminescence label to transduce the binding event. In the second part, gold/silica composite inverse opals with macroporous structures were investigated with bio- or chemical sensing applications in mind. These samples combined the advantages of a larger available gold surface area with a regular and highly ordered grating structure. The signal of the plasmon was less noisy in these ordered substrate structures compared to the random pore structures of the NPG samples. In the third part of the thesis, surface plasmon resonance (SPR) spectroscopy was applied to probe the protein-protein interaction of the calcium binding protein centrin with the heterotrimeric G-protein transducin on a newly designed sensor platform. SPR spectroscopy was intended to elucidate how the binding of centrin to transducin is regulated towards understanding centrin functions in photoreceptor cells.Physikochemische instrumentelle Techniken, die mit der Spezifität eines biologischen Erkennungssystems kombiniert sind, resultierten in unzähligen neuen analytischen Geräten bekannt als Biosensoren. In die Entwicklung von Biosensoren wird weltweit viel investiert angesichts der zahlreichen potentiellen Anwendungen, wie z.B. in der klinischen Diagnostik, der Nahrungsmittelanalyse und zur Umweltüberwachung. Hochempfindliche Sensor-Plattfor-men werden benötigt, um Wechselwirkungen auf molekularer Ebene zu studieren. Im ersten Teil der Doktorarbeit werden nanoporöse Gold (NPG)-Membranen im bezug auf ihre biosensorische Anwendung untersucht. NPG Proben mit einer willkürlichen Porengrößenverteilung (Poren von weniger als 50 nm) werden hierzu erforscht. Die NPG Membranen zeigen einzigartige plasmonische Eigenschaften, d.h. propagierende und lokalisierte Oberflächenplasmonresonanzmodi (p-SPR bzw. l-SPR) können gleichzeitig angeregt werden. Beide Moden ermöglichen eine sensitive Detektion der lokalen Brechungsindexveränderung an/im nanoporösen Gold Substrat. Der große Vorteil der Brechungsindexsensoren im Vergleich zu fluoreszenz-optischen Biosensoren besteht darin, daß keine chromophore Gruppe oder Lumineszenzmarkierung zur Detektion benötigt wird. Im zweiten Teil der Arbeit wurden macroporöse, aus Gold und Silica zusammengesetzte inverse Opale auf ihre bio- bzw. chemischen Sensorfähigkeiten hin analysiert. Diese Substrate kombinieren den Vorzug einer großen verfügbaren Oberfläche mit einer hoch geordneten Gitterstruktur. Das Plasmonensignal ist bei einer geordneten Substratstruktur weniger verrauscht als es bei der willkürlichen Anordnung der Poren im NPG der Fall ist. Im dritten Teil der Doktorarbeit wird die Oberfächenplasmonenresonanz (SPR) Spektroskopie angewendet, um die Protein-Protein Wechselwirkung zwischen dem Calcium bindenden Protein Centrin und dem heterotrimeren G-Protein Transducin zu erforschen. Dazu wurde eine neue Sensorplattform entwickelt. Die SPR Spektroskopie sollte aufklären, wie die Bindung des Centrins zum Transducin reguliert wird und zum besseren Verständnis der Centrinfunktionen in den Photorezeptorzellen beitragen

Flight Mechanics/Estimation Theory Symposium, 1990

This conference publication includes 32 papers and abstracts presented at the Flight Mechanics/Estimation Theory Symposium on May 22-25, 1990. Sponsored by the Flight Dynamics Division of Goddard Space Flight Center, this symposium features technical papers on a wide range of issues related to orbit-attitude prediction, determination and control; attitude sensor calibration; attitude determination error analysis; attitude dynamics; and orbit decay and maneuver strategy. Government, industry, and the academic community participated in the preparation and presentation of these papers

The Molecular and Cellular Basis of Retinal Diseases

There are more than 300 genes that have been identified which carry mutations that cause various forms of retinal dysfunction and degeneration, making the study of retinal diseases a subject of high relevance. In this compendium of original and review articles, many of the diseases and pathways associated with disorders of the retina are examined using animal models, to provide the reader with a good overview of current retinal research. Within this volume, you will find research reports on many of the most prominent retinal disorders, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), choroidal neovascularization (CNV), and retinitis pigmentosa (RP). We hope that the work presented here will stimulate new ideas and lead to effective treatments for retinal diseases