1,988 research outputs found
Biomechanical controls of epithelial morphostasis
Interactions in biological systems are myriad. Attempting to understand them provides valuable insights with broader bearing in biology, bioengineering, and medicine. Notwithstanding this immense realm of applications, biology presents unique characteristics that are not present in other "traditional" physical systems, making Biological Physics an exciting area of research that has the possibility of introducing new physics. This thesis will be guided by the leitmotif of understanding the coordination that allows functional patterns to arise in biological matter. In other words, what is the interplay between mechanics and signaling that underlies tissue shape?
The shape of biological tissue arises during development through the combination of morphogenetic signals and local mechanical interactions of the tissues' minimal units, the cells. Measuring mechanical observables such as stress and stiffness is crucial to understanding the shaping that occurs. Direct experimental manipulation of biological samples allows access to these observables at the cost of altering their natural course of development at best and destroying them irreversibly at worst. This restricts the type of phenomena that can be studied using these techniques, as investigating processes taking place over longer time scales would be challenging.
Computational methods such as Stress Inference can overcome these problems. These methods do not require further interaction with the sample aside from microscopy imaging. Nonetheless, no publicly available methods exist to apply Stress Inference to time-dependent systems. In this thesis, I develop an innovative method to infer physical forces from a time series of microscopy images, which enables me to address shape generation (morphogenesis) and maintenance (morphostasis) in vivo. I introduce a formalism to incorporate dynamic information into the inference pipeline and model the cells as a viscoelastic material. With that assumption, I derive a relationship between the elastic and viscous scales for the first time in this type of model.
I introduce ForSys as a new tool that utilizes dynamic microscopic information. I have made ForSys Open Source to enhance its usability and impact in the field of tissue biophysics. Tissues can be represented as a collection of geometrical entities. Vertex models use this approach to simulate the evolution of tissues by changing the position of vertices, representing tricellular junctions of the cells. I also introduce seapipy as a tool to create in silico ground truths of stress distributions from vertex models. Aided by this tool, I streamline the validation of ForSys in static and dynamic in silico settings before moving to in vivo systems. I test ForSys in three different systems belonging to two model organisms. I first show that ForSys' static predictions correlate with Myosin II fluorescence measurements in the Xenopus mucociliary epithelium. Then, I use it to investigate the formation of protoneuromasts in the zebrafish lateral line in the early hours of its development. I find that weighted inferred pressures are a good predictor of rosette formation prior to neuromast deposition. Finally, with ForSys, I study the stress distributions between homotypical and heterotypical cell-cell boundaries in the mechanosensory neuromasts of the zebrafish lateral line. There, ForSys predictions show asymmetries in the stress distributions between different cell types.
I then turn my attention to the process by which sensory hair cells in the neuromast acquire their pattern, the Planar Cell Inversion process (PCI). Through careful quantitative measurements, I show that PCI can be divided into three phases with distinct features. Moreover, I study the process in two mutant lines with knockouts of the Emx2 transcription factor and the Notch1a gene, which are suspected to be involved in the Planar Cell Polarity pathway in the organ. My results show that the mutants have distinctive characteristics to the wild type. Then, I present a simple two-agent model to simulate PCI. I implement a one-dimensional Monte Carlo model that evolves using Metropolis-Hastings importance sampling, with a simple Hamiltonian that incorporates a soft spheres repulsion and attractive wells for each agent. Using the position of the wells, I propose two model alternatives: a symmetrical and an asymmetrical model. I show that the asymmetrical model qualitatively matches the wild-type observations, while the symmetrical model does so with the mutants. Using ForSys, I also show that the stress in homotypic hair cell tight junctions is lower than in the heterotypic junctions between them and the surrounding cells, hinting at adhesion differences consistent with experimental observations.
I introduce two new software tools to aid in the experimental exploration of the mechanical state of biological matter. I apply them to study the PCI process and shed some light on the underlying biology that drives it. I believe that the formalism and tools I made available will push forward the development of better and more complete means to measure mechanical quantities in biological systems, aiding our understanding of morphogenesis and morphostasis at the mesoscopic scale.Wechselwirkungen in biologischen Systemen sind vielfältig. Der Versuch, sie zu verstehen, liefert wertvolle Erkenntnisse, die in der Biologie, der Biotechnik und der Medizin von weitreichender Bedeutung sind. Ungeachtet dieses immensen Anwendungsbereichs weist Biologie einzigartige Merkmale auf, die in anderen ``traditionellen'' physikalischen Systemen nicht vorhanden sind. Die Biologische Physik ist somit ein spannendes Forschungsgebiet, welches möglicherweise neue Physik bietet. Das Leitmotiv der vorliegenden Arbeit ist das Verständnis der Koordination, die die Entstehung funktioneller Strukturen in biologischem Gewebe ermöglicht. Mit anderen Worten: Wie spielen Mechanik und Signalübertragung zusammen, um die Struktur von Gewebe zu bestimmen?
Die Form von biologischem Gewebe entsteht während seiner Entwicklung durch die Kombination von morphogenetischen Signalen und lokalen mechanischen Wechselwirkungen zwischen den kleinsten Einheiten des Gewebes, den Zellen. Die Messung mechanischer Größen wie Spannung und Steifigkeit ist äußerst wichtig für das Verständnis dieser Formgebung. Direkte experimentelle Manipulation biologischer Proben ermöglicht den Zugang zu diesen Messgrößen, allerdings mit der Gefahr, dass der natürliche Entwicklungsverlauf im besten Fall verändert und im schlimmsten Fall irreversibel zerstört wird. Dies beschränkt die Arten von Phänomenen, die mithilfe dieser Techniken erforscht werden können, da länger andauernde Prozesse mit diesen Techniken nur schwer untersuchbar sind.
Computergestützte Methoden wie die Spannungsinferenz können diese Probleme überwinden. Diese Methoden erfordern neben mikroskopischer Bildgebung keine weitere Interaktion mit der Probe. Dennoch gibt es keine öffentlich zugänglichen Methoden, um Spannungsinferenz auf zeitabhängige Systeme anzuwenden. In dieser Arbeit entwickle ich eine innovative Methode zur Ableitung physikalischer Kräfte aus einer Zeitreihe von Mikroskopiebildern, die es ermöglicht, die Formbildung (Morphogenese) und -erhaltung (Morphostase) in vivo zu untersuchen. Ich führe einen Formalismus ein, um dynamische Informationen in die Inferenzpipeline einzubeziehen und modelliere die Zellen als ein viskoelastisches Material. Aus dieser Annahme leite ich zum ersten Mal in dieser Art von Modell eine Beziehung zwischen der elastischen und der viskosen Skala ab.
Ich stelle mit ForSys ein neues Tool vor, das dynamische mikroskopische Information nutzt. Ich habe ForSys Open Source zur Verfügung gestellt, um seine Anwendbarkeit zu erhöhen und seinen Beitrag zur Gewebebiophysik zu optimieren. Gewebe können als eine Sammlung von geometrischen Einheiten dargestellt werden. Vertex-Modelle nutzen diesen Ansatz, um die Entwicklung von Geweben zu simulieren, indem sie die Position von Vertices, also trizellulären Verbindungen, verändern. Außerdem präsentiere ich seapipy, ein Softwaretool, mit dem sich aus Vertex-Modellen in silico Ground Truths von Spannungsverteilungen erstellen lassen. Mithilfe dieses Tools optimiere ich die Validierung von ForSys in statischen und dynamischen in silico Konfigurationen, bevor ich zu in vivo Systemen übergehe. Ich teste ForSys in drei verschiedenen Systemen aus zwei Modellorganismen. Zunächst zeige ich, dass die statischen Vorhersagen von ForSys mit Myosin-II-Fluoreszenzmessungen im mukoziliären Epithel von Xenopus korrelieren. Anschließend untersuche ich mit ForSys die Bildung von Protoneuromasten im Seitenlinienorgan des Zebrafisches in den ersten Stunden seiner Entwicklung. Ich stelle fest, dass der gewichtete abgeleitete Druck ein guter Prädiktor für die Rosettenbildung vor der Ablagerung von Neuromasten ist. Schließlich nutze ich ForSys, um die Spannungsverteilung zwischen homotypischen und heterotypischen Zell-Zell-Grenzen in den mechanosensorischen Neuromasten des Zebrafisch-Seitenlinienorgans zu untersuchen. Dort zeigen die Vorhersagen von ForSys Asymmetrien in der Spannungsverteilung zwischen verschiedenen Zelltypen.
Danach betrachte ich den Prozess, durch den die Haarsinneszellen im Neuromast ihre Struktur erhalten, die ebene Zellumkehr (PCI, Planar Cell Inversion). Durch sorgfältige quantitative Messungen zeige ich, dass PCI in drei Phasen mit unterschiedlichen Merkmalen unterteilt werden kann. Darüberhinaus untersuche ich den Prozess in zwei Mutantenlinien mit Knockouts des Transkriptionsfaktors Emx2 und des Gens Notch1a, von denen man annimmt, dass sie an der planaren Zellpolarität (planar cell polarity) in diesem Organ beteiligt sind. Meine Ergebnisse zeigen, dass der Prozess in den Mutanten andere Merkmale aufweist als im Wildtyp. Anschließend stelle ich ein einfaches Zwei-Agenten-Modell zur Simulation von PCI vor. Ich implementiere ein eindimensionales Monte-Carlo-Modell, das sich mithilfe des Metropolis-Hastings Importance Sampling anhand einer einfachen Hamilton-Funktion entwickelt. Diese besteht aus einer weiche-Kugeln-Abstoßung und Potentialtöpfen für jeden Agenten. Anhand der Position der Töpfe schlage ich zwei Modellalternativen vor: ein symmetrisches und ein asymmetrisches Modell. Ich zeige, dass das asymmetrische Modell qualitativ mit den Beobachtungen des Wildtyps, und das symmetrische mit denen der Mutanten übereinstimmt. Mit Hilfe von ForSys zeige ich außerdem, dass der Stress in homotypischen Haarzellen-Tight Junctions geringer ist als in heterotypischen Verbindungen zwischen ihnen und den sie umgebenden Zellen, was auf Adhäsionsunterschiede hinweist, die mit experimentellen Beobachtungen übereinstimmen.
Ich stelle zwei neue Software-Tools vor, die bei der experimentellen Erforschung des mechanischen Zustands biologischer Gewebe helfen. Ich wende sie an, um den PCI-Prozess zu untersuchen und die zugrundeliegende Biologie, die ihn antreibt, zu beleuchten. Ich glaube, dass der Formalismus und die Werkzeuge, die ich zur Verfügung gestellt habe, die Entwicklung besserer und umfassenderer Mittel zur Messung mechanischer Größen in biologischen Systemen vorantreiben und unser Verständnis von Morphogenese und Morphostase auf der mesoskopischen Skala unterstützen werden
Traces of Lorentz symmetry breaking in a Hydrogen atom at ground state
Some traces of a specific Lorentz symmetry breaking scenario in the ground
state of the Hydrogen atom are investigated. It is used standard
Rayleigh-Schr\"odinger perturbation theory in order to obtain the corrections
to the the ground state energy and wave function. It is shown that an induced
four-pole moment arises, due to the Lorentz symmetry breaking. The model
considered is the one studied in reference Eur. Phys. J. C {\bf 74}, 2937
(2014), where the Lorentz symmetry is broken in the electromagnetic sector.Comment: 8 Latex pages, 2 figure
Identificação de neomacho de Jundiá Rhamdia quelen (Quoy e Gaimard, 1824) através do teste de progênie
TCC (graduação) - Universidade Federal de Santa Catarina. Centro de Ciências Agrárias. Curso de Engenharia de Aquicultura.O objetivo deste estudo foi identificar neomachos de Rhamdia quelen através de teste de progênie. Esse é um método indireto para a produção de lotes monosexo, que evita a aplicação de hormônio nos peixes destinados ao consumo humano, uma vez que o esperado no cruzamento entre neomachos e fêmeas normais são proles 100% femininas. Para os testes de progênie, machos fenotípicos cultivados por oito meses foram selecionados de um lote submetido à masculinização por ingestão de 17α-metil-testosterona (MT) incorporado na ração na dose de 60mg/kg. Cinco machos foram cruzados com um “pool” de ovos de três fêmeas normais e as proles resultantes de cada cruzamento foram cultivadas por 150 dias para que a sexagem das gônadas pudesse ser realizada através da técnica do imprint. O teste do qui-quadrado evidenciou que um macho originou prole com maior proporção sexual de fêmeas (P<0,05), sendo 75,56%. Apesar de não serem proles 100% femininas, existe um forte indício de que este macho seja neomacho, porque a proporção sexual das demais proles apresentou maior presença de machos ou foi balanceada (1:1)
Organization, Program and Structure: An Analysis of the Chinese Innovation Policy Framework
The paper first identifies the stakeholders involved in the design and implementation of China’s innovation policy and compares them with different government systems in selected Organization for Economic Co-operation and Development (OECD) countries. In order to disclose the relative strength and weaknesses inside China’s innovation policy framework, we proceed to utilize policy practices in the OECD countries as a guideline to examine China's innovation policy in five categories: reform in the public S&T institutions, financial policy, business innovation support structure, human resource policy and legislative actions. Subsequently, several weak components of the Chinese innovation policy framework are identified and two of them are selected for further analysis: education and human resource policy, and protection of Intellectual Property Rights (IPR). Finally, the paper provides some priorities and possible actions for future innovation policy developments in China.
Transición hacia la paternidad en el contexto de la prematuridad : gestación a tres meses após el alta
The present study aimed to investigate the transition to fatherhood in the context of preterm birth from hospitalization in the neonatal intensive care unit (NICU) to the third month after discharge, through a collective case study. Three fathers of preterm female infants participated in the study. All the fathers were living with the babies' mothers. The reports of the participants were examined through qualitative analysis. Reports on the pregnancy and birth revealed intense anxiety, emphasizing feelings of helplessness and concerns with the wife's health, survival and emotional condition. After the delivery, the participants were very dedicated and caring as fathers, especially during the first days of life of their infants, including frequent visits to the baby and providing emotional support to the wife. Three months after discharge, reports of the fathers showed how their daughters, although healthy, were still perceived as very vulnerable babies, triggering a series of care actions and, therefore, having important repercussions in their lives. The need to provide psychological interventions not only for mothers but also for fathers of preterm children should be highlighted.O presente estudo buscou compreender a transição para a paternidade no contexto da prematuridade desde a internação do bebê na UTIN até o 3º mês após a sua alta hospitalar por meio de um estudo de caso coletivo. Participaram três pais de bebês nascidos pré-termo e do sexo feminino. Todos residiam com a mãe do bebê. As entrevistas foram examinadas através de análise de conteúdo qualitativa. Os relatos sobre gestação e parto revelaram impotência e preocupações referentes à saúde, sobrevivência e condição emocional da esposa. Após o parto, os participantes mostraram-se bastante dedicados e atenciosos como pais, especialmente, durante os primeiros dias de vida do bebê, incluindo visitas ao bebê na UTIN e apoio emocional à esposa. Após a alta hospitalar, os relatos paternos evidenciaram o quanto as filhas, embora saudáveis, ainda eram percebidas como bebês bastante vulneráveis, desencadeando uma série de cuidados e importantes repercussões em suas vidas. Destaca-se a necessidade de se oferecer intervenções psicológicas não só às mães, mas também aos pais dos bebês nascidos pré-termo.El estudio buscó comprender la transición hacia la paternidad en el contexto de la prematuridad desde la internación en la UCI Neonatal hasta tres meses después de alta, por medio de un estudio de caso colectivo. Participaran tres padres de bebés nacidos prematuros y femeninos. Todos los padres vivían con la madre del bebé. Las entrevistas fueron analizadas a través del análisis de contenido cualitativo. Los relatos sobre gestación y parto revelaron impotencia y preocupaciones referentes a la salud, supervivencia y condición emocional de la esposa. Después del parto, los participantes se mostraron bastante dedicados y atenciosos, especialmente durante los primeros días de vida del bebé, incluyendo visitas al bebé en la UCI Neonatal y apoyo emocional a la esposa. Después del alta, los relatos paternos evidenciaron cuánto las hijas, aunque sanos, todavía eran percibidas como bebés muy vulnerables, desencadenando una serie de cuidados y importantes repercusiones en sus vidas. Se destaca la necesidad de ofrecer intervenciones psicológicas no sólo para las madres, sino también a los padres de los bebés nacidos prematuros
Is the United Nations a Locus of International Order Imperiality Maintenance? Reflections from the South West Africa Case and Chagos Archipelago Advisory Opinion
The international legal order, seen through third world lenses, is not only embedded with Europe’s colonial past, but also a regime that assimilates the non-European being, its relations and knowledge. Consequently, the possibility of changing such framework is almost an impossible task, being it constantly rejected by hegemonic powers, that is, by a limited number of nations that have been placed in the center of the world order in the turn of modernity and that have not left. Some may argue, yet, that the United Nations presented the international legal order with a different path, breaking with such an imperial system due to the sovereign equality among nations it pledges. And this is exactly what we aim at verifying with this article. We contend that the United Nations presupposes the maintenance of the status quo between hegemonic and subaltern states to perform its activities, basing this assertion in the analysis of the South West Africa decision, delivered by the International Court of Justice – an organ of the U.N. in the 1960s. Nevertheless, taking into consideration the Court’s recent activities on the Chagos Archipelago Opinion of 2019, we note that it tried to break with such a past in a timid manner, particularly by reaffirming both self- determination and the relevance of the U.N. General Assembly. Despite this, we come to the conclusion that it was not enough, being the Organization still a locus of reproduction of imperiality in the international order
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