55 research outputs found
Crosstalk in stereoscopic displays
Crosstalk is an important image quality attribute of stereoscopic 3D displays. The research presented in this thesis examines the presence, mechanisms, simulation, and reduction of crosstalk for a selection of stereoscopic display technologies. High levels of crosstalk degrade the perceived quality of stereoscopic displays hence it is important to minimise crosstalk. This thesis provides new insights which are critical to a detailed understanding of crosstalk and consequently to the development of effective crosstalk reduction techniques
A review of snapshot multidimensional optical imaging: Measuring photon tags in parallel
Multidimensional optical imaging has seen remarkable growth in the past decade. Rather than measuring only the two-dimensional spatial distribution of light, as in conventional photography, multidimensional optical imaging captures light in up to nine dimensions, providing unprecedented information about incident photons’ spatial coordinates, emittance angles, wavelength, time, and polarization. Multidimensional optical imaging can be accomplished either by scanning or parallel acquisition. Compared with scanning-based imagers, parallel acquisition–also dubbed snapshot imaging–has a prominent advantage in maximizing optical throughput, particularly when measuring a datacube of high dimensions. Here, we first categorize snapshot multidimensional imagers based on their acquisition and image reconstruction strategies, then highlight the snapshot advantage in the context of optical throughput, and finally we discuss their state-of-the-art implementations and applications
A review of snapshot multidimensional optical imaging: Measuring photon tags in parallel
Multidimensional optical imaging has seen remarkable growth in the past decade. Rather than measuring only the two-dimensional spatial distribution of light, as in conventional photography, multidimensional optical imaging captures light in up to nine dimensions, providing unprecedented information about incident photons’ spatial coordinates, emittance angles, wavelength, time, and polarization. Multidimensional optical imaging can be accomplished either by scanning or parallel acquisition. Compared with scanning-based imagers, parallel acquisition–also dubbed snapshot imaging–has a prominent advantage in maximizing optical throughput, particularly when measuring a datacube of high dimensions. Here, we first categorize snapshot multidimensional imagers based on their acquisition and image reconstruction strategies, then highlight the snapshot advantage in the context of optical throughput, and finally we discuss their state-of-the-art implementations and applications
Dissociation and interpersonal autonomic physiology in psychotherapy research: an integrative view encompassing psychodynamic and neuroscience theoretical frameworks
Interpersonal autonomic physiology is an interdisciplinary research field, assessing the relational interdependence of two (or more) interacting individual both at the behavioral and psychophysiological levels. Despite its quite long tradition, only eight studies since 1955 have focused on the interaction of psychotherapy dyads, and none of them have focused on the shared processual level, assessing dynamic phenomena such as dissociation. We longitudinally observed two brief psychodynamic psychotherapies, entirely audio and video-recorded (16 sessions, weekly frequency, 45 min.). Autonomic nervous system measures were continuously collected during each session. Personality, empathy, dissociative features and clinical progress measures were collected prior and post therapy, and after each clinical session. Two-independent judges, trained psychotherapist, codified the interactions\u2019 micro-processes. Time-series based analyses were performed to assess interpersonal synchronization and de-synchronization in patient\u2019s and therapist\u2019s physiological activity. Psychophysiological synchrony revealed a clear association with empathic attunement, while desynchronization phases (range of length 30-150 sec.) showed a linkage with dissociative processes, usually associated to the patient\u2019s narrative core relational trauma. Our findings are discussed under the perspective of psychodynamic models of Stern (\u201cpresent moment\u201d), Sander, Beebe and Lachmann (dyad system model of interaction), Lanius (Trauma model), and the neuroscientific frameworks proposed by Thayer (neurovisceral integration model), and Porges (polyvagal theory). The collected data allows to attempt an integration of these theoretical approaches under the light of Complex Dynamic Systems. The rich theoretical work and the encouraging clinical results might represents a new fascinating frontier of research in psychotherapy
Sustainable Prosperity in the New Economy?: Business Organization and High-Tech Employment in the United States
Lazonick explores the origins of the new era of employment insecurity and income inequality, and considers what governments, businesses, and individuals can do about it. He also asks whether the United States can refashion its high-tech business model to generate stable and equitable economic growth.https://research.upjohn.org/up_press/1029/thumbnail.jp
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Inferring structures, free energy differences, and kinetic rates of biological macromolecular assemblies by integrative modeling
Biological macromolecular assemblies play crucial roles in most cellular processes. The determination of their structures, thermodynamics, and kinetics is essential to understand their function, evolution, modulation, and design. Determining such models, however, remains challenging. One particularly powerful approach to constructing models in general is integrative modeling. Integrative modeling aims to maximize the accuracy, precision, and completeness of models, by simultaneously utilizing all available information, including experimental data, physical principles, statistical analyses, and other prior models. The goal of this thesis is to expand the scope of integrative modeling to the inference of spatial, thermodynamic, and kinetic aspects of macromolecular assemblies. In Chapter I, I introduce the integrative modeling framework for spatiotemporal modeling of biological macromolecular assemblies. In Chapter II, I demonstrate how the synergy between multi-chemistry cross-linking mass spectrometry and integrative modeling can map the structural dynamics of macromolecular assemblies, by application to the human Cop9 signalosome complex. In Chapter III, I present a method for determining structures, free energy differences, and kinetic rates of macromolecular assemblies along their functional cycle, mainly from negative stain electron microscopy (EM). We apply the method to the yeast Hsp90 to estimate the free energy differences and kinetic parameters along its nucleotide hydrolysis cycle, which includes open and closed states of Hsp90. In Chapter IV, I describe a validation of stochastic sampling in integrative modeling. The remaining chapters describe applications of integrative modeling to assemblies of various sizes and scales, using various sources of information, thus illustrating the flexibility of the integrative modeling approach. Specifically, I apply integrative modeling to the human ECM29-Proteasome assembly under oxidative stress (Chapter V), the yeast nuclear pore complex (NPC) cytoplasmic mRNA export platform (Chapter VI), the major membrane ring component of the yeast NPC (Chapter VII), the entire yeast NPC (Chapter VIII), and the reconstruction of 3D structures of MET antibodies (Chapter IX)
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Live Cell Interferometry: A Novel Quantitative Phase Imaging Technique for Rapid Characterizations of Tumor Heterogeneity, Drug Resistance, Cell Fates and Biophysical Properties
Cell mass is an important biophysical property that provides a crucial link between external physical measurements and internal cellular processes such as cell cycle progression, division, differentiation and cell death. Advancements in quantitative phase imaging (QPI) techniques have enabled many in-depth studies of cell mass in the context of basic and translational research. This thesis describes the development and implementation of live cell interferometry (LCI) as a novel QPI technique that is high speed, high throughput, precise and label-free. It was validated as a powerful tool in dissecting tumor heterogeneity and drug resistance in patient derived melanoma cell lines. LCI analysis of cell fate in response to mitotic inhibitors provided valuable insights in cancer drug development and dose selection. Furthermore, it was utilized to characterize many other biophysical responses in fundamental research such as cardiomyocyte hypertrophy in cardiac wound healing responses. These studies showcased the unique capabilities and advantages of LCI in applications from bench to bedside
Library buildings around the world
"Library Buildings around the World" is a survey based on researches of several years. The objective was to gather library buildings on an international level starting with 1990
Electrical Communication and its Physiological Relevance in Retinal Pigment Epithelium
Verkkokalvon pigmenttiepiteeli (eng. retinal pigment epithelium, RPE) tekee tiivistä yhteistyötä verkkokalvon kanssa turvatakseen näköaistin toiminnan. Useita RPE:n tärkeimpiä tehtäviä, kuten valoa aistivien näköaistinsolujen uusiutumista, säädellään ionikanavien avulla. Näiden kanavien toimintaa ja RPE:n kykyä säädellä kalvopotentiaaliaan ei kuitenkaan vielä täysin ymmärretä. Tässä väitöskirjatyössä tutkittiin jänniteherkkien ionikanavien toimintaa sekä RPE:n sähköistä kytkeytyvyyttä käyttäen mallina ihmisen alkion kantasoluista erilaistettuja RPE-soluja sekä hiiren RPE-kudosta.
Jänniteherkät natriumkanavat (NaV) tunnetaan parhaiten osallisuudestaan aktiopotentiaalin synnyssä hermosoluissa, mutta näiden kanavien tiedetään esiintyvän myös useissa muissa solutyypeissä, kuten makrofageissa ja astrosyyteissä, joissa aktiopotentiaaleja ei lähtökohtaisesti muodostu. NaV kanavien ei kuitenkaan uskottu esiintyvän RPE-kudoksessa huolimatta siitä, että niitä on toisinaan havaittu RPE-soluviljelmissä. Tämä väitöskirjatyö osoitti, että sekä kantasoluista erilaistetuissa RPE-soluissa että hiiren RPE-soluissa ilmentyy useita NaV- kanavaperheen alatyyppejä. Samalla havaittiin, että aikaisempi virheellinen johtopäätös aiheutui tutkimusten suorittamisesta yksittäisillä soluilla toiminnallisen kudoksen sijaan. Tässä työssä osoitettiin myös löydettyjen Nav-kanavatyyppien toiminnallisuus sähköfysiologisilla mittauksilla. Merkittävimpien kanavatyyppien (NaV1.4–NaV1.6 sekä NaV1.8) havaittiin sijoittuvan solu-soluliitoksiin tai RPE:n apikaaliselle solukalvolle.
RPE-solujen sähköfysiogisia mittauksia on tyypillisesti tehty yksittäisistä eristetyistä soluista. Tästä johtuen RPE-solujen sähköistä kytkeytyvyyttä ei ole selvitetty nisäkkäillä, vaikka tiedetään, että aukkoliitoksilla on tärkeitä tehtäviä silmän kehityksessä. Tämä väitöskirjatyö osoitti, että solujen merkittävin aukkoliitosproteiini (engl. Connexin, Cx) on Cx43, jonka havaittiin muodostavan sekä aukkoliitoksia että puolikkaita hemikanavia solujen apikaalisella pinnalla. Sähköfysiologiset mittaukset osoittivat, että RPE:n laajasta aukkoliitosten verkostosta huolimatta RPE-solujen välinen kytkeytyvyys on suhteellisen alhainen. Kytkeytyvyyttä voitiin kuitenkin säädellä aukkoliitosten farmakologisilla estäjillä, tai estämällä tietyn Cdk5 (engl. cyclin-dependent kinase 5) kinaasi-entsyymin toimintaa.
NaV-kanavien ja aukkoliitosten merkitystä RPE:n fysiologiassa tutkittiin keskittymällä näköaistinsolujen kalvojen uusiutumiseen, jossa RPE:n solusyönti eli fagosytoosi on merkittävässä roolissa. Tulokset osoittivat, että fagosytoosin aikana NaV-alatyypit NaV1.4 ja NaV1.8 esiintyvät lähellä näköaistinsolujen kalvopartikkeleita. NaV-kanavien toiminnan estäminen farmakologisesti tai geneettisesti (engl. short hairpin RNA, shRNA) vähensi merkittävästi fagosytoosin tehokkuutta. Lisäksi näiden kanavien havaittiin paikantuvan sekä apikaalipinnalle muodostuviin fagosytoosi-kuppeihin, että jo sisään otettuihin fagosomeihin yhdessä endosomien markkeriproteiinien (engl. rat sarcoma virus-related protein, Rab7) kanssa. Nämä tulokset antavat viitteitä siitä, että NaV-kanavilla olisi monipuolisia tehtäviä fagosytoosin aikana.
NaV-kanavien lisäksi myös Cx43:n havaittiin esiintyvän näköaistinsolujen kalvopartikkelien kanssa fagosytoosissa ja tulokset antavat viitteitä siitä, että aukkoliitoksia otetaan solujen sisälle prosessin aikana. Fosforylaation havaittiin säätelevän tätä aukkoliitosten siirtymää ja erityisesti Cdk5-, ja proteiinikinaasi C- entsyymeillä oli merkittävä rooli tässä säätelyssä. Tämän työn tulokset osoittivat, että Cx43 liittyy fagosytoosikuppien muodostukseen sekä solujen aktiini-tukirangan uudelleen järjestymiseen. Fagosytoosin säätelyn tiedetään perustuvan vuorokausirytmiin ja mielenkiintoista on, että Cdk5-kinaasin on osoitettu vaikuttavan tähän rytmiin. On siis mahdollista, että Cdk5 auttaa myös fagosytoosin ajoituksen säätelyssä.
Kokonaisuutena työni osoittaa RPE:n fysiologian ja sen ionikanavakoneiston säätelyn monimutkaisuuden. Nav-kanavien roolin on havaittu olevan huomattavasti monipuolisempi kuin aktiopotentiaalien muodostus hermosoluissa ja tuloksemme vahvistavat tätä käsitystä. Yksi työni yllättävimmistä ja merkittävimmistä tuloksista oli, että RPE voi säädellä kalvojännitettään ja epiteelikudoksen solujen välistä viestintäänsä nopeasti. Tarkemmat tiedot tämän ionisignaloinnin roolista fagosytoosissa lisäävät ymmärrystämme prosessista, joka on merkittävä näkökyvyllemme. Yhteenvetona tämä työ osoittaa, että RPE:n rooli yhteistyössä verkkokalvon kanssa on paljon aktiivisempi kuin on aikaisemmin luultu.Retinal pigment epithelium (RPE) is a tissue that preserves the health and functionality of its closely associated neural tissue, the retina. Many of the essential functions of RPE, including the renewal of light-sensing retinal photoreceptors, are regulated by ion channels. Yet, the involved ionic mechanisms, the extent of membrane potential dynamics, and the intercellular communication are not entirely understood. In this thesis, I studied the voltage-gated ion channels and electrical coupling of RPE in both human embryonic stem cell-derived and mouse RPE.
Voltage-gated sodium channels (NaV), while best known for their role in action potential generation, are expressed in several non-excitable cell types such as macrophages and astrocytes. Yet, these channels had not been considered to exist in native RPE, although they had occasionally been detected in cell culture. This thesis demonstrates that stem cell-derived and mouse RPE exhibit several subtypes of NaV channels and that their earlier dismissal was due to cell isolation procedures. Our electrophysiological recordings showed that these identified NaV channels are functional. The main channel subtypes NaV1.4–NaV1.6 and NaV1.8 were found to localize in the cell-cell junctions or apical membrane in RPE.
As the conventional method to carry out electrophysiological recordings in RPE is to use single cells, the electrical connectivity had not been characterized in mammalian RPE, despite the importance of gap junctions in ocular development. In this thesis, we showed that the major connexin (Cx) isoform was Cx43 which was found to form both gap junctions and apical hemichannels. The electrophysiological recordings demonstrated that the electrical connectivity was relatively low despite the extensive network of gap junctions in RPE. Yet, it was modifiable by gap junction blockers or by inhibiting a specific kinase known as cyclin-dependent kinase 5 (Cdk5).
The significance of NaV channels and gap junctions to RPE physiology was investigated by focusing on the renewal of photoreceptor outer segments, where phagocytosis by RPE plays a key role. The results demonstrated that NaV subtypes NaV1.4 and NaV1.8 localize with the outer segments during phagocytosis. Moreover, inhibiting the activity of NaV channels with pharmacological modulators or short hairpin RNA (shRNA) significantly impaired phagocytosis efficiency.
Furthermore, Nav channels were found to localize to the forming phagocytic cups in the apical membrane and the ingested phagosomes together with an endosomal marker Rab7. The results obtained in this thesis imply that NaV channels have versatile roles in phagocytosis.
In addition to NaV channels, Cx43 localized adjacent to outer segments during phagocytosis, and the results indicate that gap junctions are internalized during the process. This translocation of gap junctions was shown to be regulated by phosphorylation, particularly by kinases such as Cdk5 and protein kinase C. The results obtained in this thesis imply that Cx43 is involved in the formation of phagocytic cups. As phagocytosis is known to be under circadian control, and Cdk5 has previously been shown to regulate this cycle, it is plausible that Cdk5 helps to control the rhythm of photoreceptor renewal.
Our results highlight the complexity of RPE physiology and its ion channel machinery. The findings add to the growing body of evidence demonstrating that NaV channels' role is much more diverse than action potential generation. The results show that RPE can generate fast changes in voltage and rapidly modify its cell-cell connectivity across the epithelium. Gaining a deeper understanding of the involvement of ionic mechanisms in phagocytosis could help us to understand the phagocytosis pathway both in the healthy and diseased eye. Ultimately, this work highlights that RPE's role in its interaction with the neural retina is far more active than was previously thought
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