The orienting mouse: An input device with attitude

This paper presents a modified computer mouse, the Orienting Mouse, which delivers orientation as an additional dimension of input; when the mouse is moved on a flat surface it reports, in addition to the conventional x, y translation, angular rotation of the device in the x, y plane. The orienting mouse preserves important properties of the standard mouse; all measurements are relative and movement is tracked only while the mouse is on its flat surface. If the user lets go of the mouse, leaving it on the surface, its position and orientation do not change until it is touched again. Picking the mouse up and putting it down in a different orientation leaves the angle and position unchanged. While the concept of sensing mouse rotation is not new, our work focuses on movement and navigation in 3D, rather than on precision positioning tasks. We describe a number of sample applications developed to test its effectiveness in this context. Specific features exploited and described include (i) an algorithm for calculating the mouse angle which cancels drift between the two sensors, and (ii) the use of angular gearing which avoids unnatural and uncomfortable hand positions when moving through large angles; informal user testing validates this idea

Conception d’un Dispositif pour Interagir avec des Données Multidimensionnelles : Disco

National audienceThis paper presents the design of a new device, DISCO. In addition to the traditionnal mouse capabilities, DISCO offers multiple degrees of freedom suitable for multidimensioannl data manipulation. We present various usage scenarios and explore the handling of this device through two studies. First we observe the user’s hand posture on three versions of Disco with different form factors. Then we study the capabilities and limitations related to physical translations, rotations (yaw) and tilt (pitch, roll) on two versions of Disco according to three hand postures. Based on the results, we propose design guidelines to create interaction techniques that take benefit of the degrees of freedom of the device to interact with multidimensional data.En s’inspirant de travaux fondateurs proposant des souris à multiples degrés de liberté, cet article présente la conception d’un nouveau dispositif d’interaction basé sur le principe du culbuto : Disco. Nous présentons divers scénarii d’usage et explorons la manipulation de ce dispositif au travers de deux études. D’abord nous observons la prise en main de trois versions de Disco avec différents facteurs de forme. Ensuite nous étudions les capacités et limites liées à la translation, rotation (yaw) ou inclinaison (pitch, roll) physique de deux versions de Disco selon trois prises en main différentes. A partir des résultats nous proposons des guides de conception afin de créer des techniques d’interaction qui exploitent au mieux les différents degrés de liberté du dispositif pour interagir avec des données multidimensionnelles

Dynamic system simulation on the web

Computer simulation is the discipline of designing a model of an actual or theoretical physical system, executing the model on digital computer, and analysing the execution output. Of late, simulation has been influenced by an increasingly popular phenomenon - the World Wide Web or WWW. Java is a programming language for the WWW that brings a high level of dynamism to Web applications. Java makes it particularly suitable to represent applications on the Web. It has created an illusion of machine independence and interoperability for many applications. Therefore WWW can be considered as an environment for providing modelling and simulation applications. Research in the area of Web-based simulation is developing rapidly as WWW programming tools develop. Bulk of this research is focused only on discrete event simulation. This dissertation introduces dynamic system simulation on the Web. It presents and demonstrates a Web-based simulation software (SimDynamic), entirely developed in Java, for modelling, simulating, and analysing dynamic systems with 3D animated illustration, wherever applicable. SimDynamic can also be used as a non Web-based application on a PC. In both cases, it supports complete model creation and modification capabilities along with graphical and numerical output. Detail design and functional ability of SimDynamic are provided. Some real world systems have been modeled using SimDynamic and results are presented. Characteristic features of the software are discussed from software engineering point of view. Complete source code and installation instructions are included. Current SimDynamic limitations and potential customization and expansion issues are explored

Nonlinear dynamics and fluctuations in biological systems

The present habilitation thesis in theoretical biological physics addresses two central dynamical processes in cells and organisms: (i) active motility and motility control and (ii) self-organized pattern formation. The unifying theme is the nonlinear dynamics of biological function and its robustness in the presence of strong fluctuations, structural variations, and external perturbations. We theoretically investigate motility control at the cellular scale, using cilia and flagella as ideal model system. Cilia and flagella are highly conserved slender cell appendages that exhibit spontaneous bending waves. This flagellar beat represents a prime example of a chemo-mechanical oscillator, which is driven by the collective dynamics of molecular motors inside the flagellar axoneme. We study the nonlinear dynamics of flagellar swimming, steering, and synchronization, which encompasses shape control of the flagellar beat by chemical signals and mechanical forces. Mechanical forces can synchronize collections of flagella to beat at a common frequency, despite active motor noise that tends to randomize flagellar synchrony. In Chapter 2, we present a new physical mechanism for flagellar synchronization by mechanical self-stabilization that applies to free-swimming flagellated cells. This new mechanism is independent of direct hydrodynamic interactions between flagella. Comparison with experimental data provided by experimental collaboration partners in the laboratory of J. Howard (Yale, New Haven) confirmed our new mechanism in the model organism of the unicellular green alga Chlamydomonas. Further, we characterize the beating flagellum as a noisy oscillator. Using a minimal model of collective motor dynamics, we argue that measured non-equilibrium fluctuations of the flagellar beat result from stochastic motor dynamics at the molecular scale. Noise and mechanical coupling are antagonists for flagellar synchronization. In addition to the control of the flagellar beat by mechanical forces, we study the control of the flagellar beat by chemical signals in the context of sperm chemotaxis. We characterize a fundamental paradigm for navigation in external concentration gradients that relies on active swimming along helical paths. In this helical chemotaxis, the direction of a spatial concentration gradient becomes encoded in the phase of an oscillatory chemical signal. Helical chemotaxis represents a distinct gradient-sensing strategy, which is different from bacterial chemotaxis. Helical chemotaxis is employed, for example, by sperm cells from marine invertebrates with external fertilization. We present a theory of sensorimotor control, which combines hydrodynamic simulations of chiral flagellar swimming with a dynamic regulation of flagellar beat shape in response to chemical signals perceived by the cell. Our theory is compared to three-dimensional tracking experiments of sperm chemotaxis performed by the laboratory of U. B. Kaupp (CAESAR, Bonn). In addition to motility control, we investigate in Chapter 3 self-organized pattern formation in two selected biological systems at the cell and organism scale, respectively. On the cellular scale, we present a minimal physical mechanism for the spontaneous self-assembly of periodic cytoskeletal patterns, as observed in myofibrils in striated muscle cells. This minimal mechanism relies on the interplay of a passive coarsening process of crosslinked actin clusters and active cytoskeletal forces. This mechanism of cytoskeletal pattern formation exemplifies how local interactions can generate large-scale spatial order in active systems. On the organism scale, we present an extension of Turing’s framework for self-organized pattern formation that is capable of a proportionate scaling of steady-state patterns with system size. This new mechanism does not require any pre-pattering clues and can restore proportional patterns in regeneration scenarios. We analytically derive the hierarchy of steady-state patterns and analyze their stability and basins of attraction. We demonstrate that this scaling mechanism is structurally robust. Applications to the growth and regeneration dynamics in flatworms are discussed (experiments by J. Rink, MPI CBG, Dresden).:1 Introduction 10 1.1 Overview of the thesis 10 1.2 What is biological physics? 12 1.3 Nonlinear dynamics and control 14 1.3.1 Mechanisms of cell motility 16 1.3.2 Self-organized pattern formation in cells and tissues 28 1.4 Fluctuations and biological robustness 34 1.4.1 Sources of fluctuations in biological systems 34 1.4.2 Example of stochastic dynamics: synchronization of noisy oscillators 36 1.4.3 Cellular navigation strategies reveal adaptation to noise 39 2 Selected publications: Cell motility and motility control 56 2.1 “Flagellar synchronization independent of hydrodynamic interactions” 56 2.2 “Cell body rocking is a dominant mechanism for flagellar synchronization” 57 2.3 “Active phase and amplitude fluctuations of the flagellar beat” 58 2.4 “Sperm navigation in 3D chemoattractant landscapes” 59 3 Selected publications: Self-organized pattern formation in cells and tissues 60 3.1 “Sarcomeric pattern formation by actin cluster coalescence” 60 3.2 “Scaling and regeneration of self-organized patterns” 61 4 Contribution of the author in collaborative publications 62 5 Eidesstattliche Versicherung 64 6 Appendix: Reprints of publications 66Das Thema der vorliegenden Habilitationsschrift in Theoretischer Biologischer Physik ist die nichtlineare Dynamik funktionaler biologischer Systeme und deren Robustheit gegenüber Fluktuationen und äußeren Störungen. Wir entwickeln hierzu theoretische Beschreibungen für zwei grundlegende biologische Prozesse: (i) die zell-autonome Kontrolle aktiver Bewegung, sowie (ii) selbstorganisierte Musterbildung in Zellen und Organismen. In Kapitel 2, untersuchen wir Bewegungskontrolle auf zellulärer Ebene am Modelsystem von Zilien und Geißeln. Spontane Biegewellen dieser dünnen Zellfortsätze ermöglichen es eukaryotischen Zellen, in einer Flüssigkeit zu schwimmen. Wir beschreiben einen neuen physikalischen Mechanismus für die Synchronisation zweier schlagender Geißeln, unabhängig von direkten hydrodynamischen Wechselwirkungen. Der Vergleich mit experimentellen Daten, zur Verfügung gestellt von unseren experimentellen Kooperationspartnern im Labor von J. Howard (Yale, New Haven), bestätigt diesen neuen Mechanismus im Modellorganismus der einzelligen Grünalge Chlamydomonas. Der Gegenspieler dieser Synchronisation durch mechanische Kopplung sind Fluktuationen. Wir bestimmen erstmals Nichtgleichgewichts-Fluktuationen des Geißel-Schlags direkt, wofür wir eine neue Analyse-Methode der Grenzzykel-Rekonstruktion entwickeln. Die von uns gemessenen Fluktuationen entstehen mutmaßlich durch die stochastische Dynamik molekularen Motoren im Innern der Geißeln, welche auch den Geißelschlag antreiben. Um die statistische Physik dieser Nichtgleichgewichts-Fluktuationen zu verstehen, entwickeln wir eine analytische Theorie der Fluktuationen in einem minimalen Modell kollektiver Motor-Dynamik. Zusätzlich zur Regulation des Geißelschlags durch mechanische Kräfte untersuchen wir dessen Regulation durch chemische Signale am Modell der Chemotaxis von Spermien-Zellen. Dabei charakterisieren wir einen grundlegenden Mechanismus für die Navigation in externen Konzentrationsgradienten. Dieser Mechanismus beruht auf dem aktiven Schwimmen entlang von Spiralbahnen, wodurch ein räumlicher Konzentrationsgradient in der Phase eines oszillierenden chemischen Signals kodiert wird. Dieser Chemotaxis-Mechanismus unterscheidet sich grundlegend vom bekannten Chemotaxis-Mechanismus von Bakterien. Wir entwickeln eine Theorie der senso-motorischen Steuerung des Geißelschlags während der Spermien-Chemotaxis. Vorhersagen dieser Theorie werden durch Experimente der Gruppe von U.B. Kaupp (CAESAR, Bonn) quantitativ bestätigt. In Kapitel 3, untersuchen wir selbstorganisierte Strukturbildung in zwei ausgewählten biologischen Systemen. Auf zellulärer Ebene schlagen wir einen einfachen physikalischen Mechanismus vor für die spontane Selbstorganisation von periodischen Zellskelett-Strukturen, wie sie sich z.B. in den Myofibrillen gestreifter Muskelzellen finden. Dieser Mechanismus zeigt exemplarisch auf, wie allein durch lokale Wechselwirkungen räumliche Ordnung auf größeren Längenskalen in einem Nichtgleichgewichtssystem entstehen kann. Auf der Ebene des Organismus stellen wir eine Erweiterung der Turingschen Theorie für selbstorganisierte Musterbildung vor. Wir beschreiben eine neue Klasse von Musterbildungssystemen, welche selbst-organisierte Muster erzeugt, die mit der Systemgröße skalieren. Dieser neue Mechanismus erfordert weder eine vorgegebene Kompartimentalisierung des Systems noch spezielle Randbedingungen. Insbesondere kann dieser Mechanismus proportionale Muster wiederherstellen, wenn Teile des Systems amputiert werden. Wir bestimmen analytisch die Hierarchie aller stationären Muster und analysieren deren Stabilität und Einzugsgebiete. Damit können wir zeigen, dass dieser Skalierungs-Mechanismus strukturell robust ist bezüglich Variationen von Parametern und sogar funktionalen Beziehungen zwischen dynamischen Variablen. Zusammen mit Kollaborationspartnern im Labor von J. Rink (MPI CBG, Dresden) diskutieren wir Anwendungen auf das Wachstum von Plattwürmern und deren Regeneration in Amputations-Experimenten.:1 Introduction 10 1.1 Overview of the thesis 10 1.2 What is biological physics? 12 1.3 Nonlinear dynamics and control 14 1.3.1 Mechanisms of cell motility 16 1.3.2 Self-organized pattern formation in cells and tissues 28 1.4 Fluctuations and biological robustness 34 1.4.1 Sources of fluctuations in biological systems 34 1.4.2 Example of stochastic dynamics: synchronization of noisy oscillators 36 1.4.3 Cellular navigation strategies reveal adaptation to noise 39 2 Selected publications: Cell motility and motility control 56 2.1 “Flagellar synchronization independent of hydrodynamic interactions” 56 2.2 “Cell body rocking is a dominant mechanism for flagellar synchronization” 57 2.3 “Active phase and amplitude fluctuations of the flagellar beat” 58 2.4 “Sperm navigation in 3D chemoattractant landscapes” 59 3 Selected publications: Self-organized pattern formation in cells and tissues 60 3.1 “Sarcomeric pattern formation by actin cluster coalescence” 60 3.2 “Scaling and regeneration of self-organized patterns” 61 4 Contribution of the author in collaborative publications 62 5 Eidesstattliche Versicherung 64 6 Appendix: Reprints of publications 6

Aeronautical engineering: A continuing bibliography with indexes (supplement 315)

This bibliography lists 217 reports, articles, and other documents introduced into the NASA scientific and technical information system in Mar. 1995. Subject coverage includes: design, construction and testing of aircraft and aircraft engines; aircraft components, equipment, and systems; ground support systems; and theoretical and applied aspects of aerodynamics and general fluid dynamics

Stereology and automated measurement of the human brain

Stereology supplies image sampling rules to estimate geometric quantities such as volume, surface area, feature length and number. The method is well suited to non-invasive image acquisition methods such as Magnetic Resonance Imaging (MRI). Meanwhile, in Magnetic Resonance (MR) images analysis area, automated software packages have been continuously developed and become well-established tools especially in human brainMR images processing. The aims of the thesis are (1) to combine proper rules to sample MR images with automated or semi-automated data acquisition methods, in order to implement four different design unbiased stereological volume estimators in the study of the human brain, and (2) to compare volume estimates with those obtained from automated software packages.In volume estimation of three-dimensional (3D) objects, besides one traditional stereological method (i.e. the CAVALIERI method), in recent years a number of newly design-based unbiased methods have been published, which include three used in this thesis (i.e. the ISOTROPIC CAVALIERI (ICAV), INVARIATOR (INV) and DISCRETIZED NUCLEATOR (DN) methods). The ICAV and INV methods both allow the estimation of surface area too. The ICAV method enables volume estimation to be unbiased and precise in individual objects while the INV and DN methods make it efficient to estimate the mean volume of a big cohort. To make it be practical in estimating the volume of human brain solely from MR images, in the thesis the ICAV, INV and DN methods were given two operating protocols for rotation and measurement on a commercial software (i.e. ANALYZE) and were performed in a fetal brain study. The ICAV, INV and DN methods were also programmed in three scripts for rotation, gridding and measurement purposes respectively using three freely available software packages (i.e. FSL, R and IMAGEJ), which were applied in three adult brain studies.In volume estimation of three-dimensional (3D) objects, besides one traditional stereological method (i.e. the CAVALIERI method), in recent years a number of newly design-based unbiased methods have been published, which include three used in this thesis (i.e. the ISOTROPIC CAVALIERI (ICAV), INVARIATOR (INV) and DISCRETIZED NUCLEATOR (DN) methods). The ICAV and INV methods both allow the estimation of surface area too. The ICAV method enables volume estimation to be unbiased and precise in individual objects while the INV and DN methods make it efficient to estimate the mean volume of a big cohort. To make it be practical in estimating the volume of human brain solely from MR images, in the thesis the ICAV, INV and DN methods were given two operating protocols for rotation and measurement on a commercial software (i.e. ANALYZE) and were performed in a fetal brain study. The ICAV, INV and DN methods were also programmed in three scripts for rotation, gridding and measurement purposes respectively using three freely available software packages (i.e. FSL, R and IMAGEJ), which were applied in three adult brain studies.A fetal brain study was carried out to test the application of the ICAV, INV and DN methods. Ten fetuses from three maternal backgrounds (i.e. five healthy, three maternal psychological stress and two maternal substance misuse) were scanned in MRI at both the second and third trimesters of pregnancy. Then fetal brain images were motion corrected using SLIMMER software. Volumes of brain parenchyma (the functional tissue of the brain which is made of two types of brain cells, namely neurons and glia) including ventricles were estimated by the ICAV method in isotropic (i.e. having no preferred orientation) and uniformly random (i.e. uniformly distance (interval) apart) (IUR) triplet of orthogonal section planes (i.e. the ICAV ortrip method) and by the INV and DN methods in isotropically random (IR) triplet of orthogonal section planes through a fixed pivotal point (i.e. the INV ortrip and DN ortrip methods). Due to observation of artefacts in MR images and manual input in the methods, inter- and intra-rater reliability studies were performed to investigate both point counting for the ICAV method and segment length measurement for the INV and DN methods among three raters on five fetal brains from the second and five from the third trimesters. Surface area was also estimated using the ICAV method for error prediction. High reliability (Pearson’s r > 0:997) was shown in inter- and intra-rater studies. In both the second and third trimesters, there were no significant difference in mean volumes of all ten brains estimated by the three methods (p > 0:1). For individual estimates, The predicted coefficients of error (CEs) for the ICAV method were 1:5% ± 0:1% in the second trimester and 2:1% ± 0:1% in the third trimester. Basing on one IR section plane for each data, empirical CEs for the INV method in both trimesters were 19:4% ± 2:9% and 18:5% ± 11:6%, and were 21:4% ± 4:5% and 24:1% ± 11:7% for the DN method. CEs could be decreased to 8.1%, 5.5% for the INV ortrip method and 10.3%, 9.7% for the DN ortrip method in both trimesters. This study showed the ICAV method performed precisely in individual volume measurements while the INV and DN methods worked efficiently in population mean volume estimation. Clinically, no significant differences (p > 0:05) of fetal brain volumes among three maternal groups were detected due to small sample size although potentially in comparison with normal fetal brain, volume might be bigger in the maternal stress group and might be smaller in the substance abused group.As the CAVALIERI method is a design-unbiased method, the main source of potential bias (i.e. if a biased method is applied the mean of the estimated values deviates significantly from the true value) will come from observers in operation who would be the author in this PhD study. To examine whether there is bias caused by the author’s manual point counting procedure in the CAVALIERI method, a slice-by-slice comparison on one adult brain volume estimation on MR images between the CAVALIERI method and an automatically reconstructing software (i.e. FREESURFER) was performed. One healthy elderly (male, age 71) brain MRI scan with good image quality was selected from a dataset of 40 patients affected by the ALZHEIMER’s disease (AD) and 22 healthy elderly volunteers. FREESURFER was used to perform individual volumetric analysis on the adult brain automatically, which outlined grey matter and white matter in the cerebrum on each MR image slice. The CAVALIERI method was applied to a series of coronal images obtained with random starting position and at 1 cm intervals from the TALAIRACH transformed and intensity normalized 3D MR image (i.e. nu.mgz) displayed with the compartment boundaries identified by the FREESURFER pipeline suppressed. The uniformly random (UR) test system for point counting was superimposed on each image. The CAVALIERI method in combination with point counting strategy was used to estimate the volume of cerebrum excluding ventricles (the sum of the two cerebral hemispheres including blood vessels and meninges) using EASYMEASURE software on the grey scale MR images. Additionally, the author overlay the brain boundary segmented by FREESURFER on these selected test points and reassessed the images to compute two scores, namely (i) the total number of test points which had been counted but which were seen to lie outside the FREESURFER segmentation and (ii) total number of the new test points that now needed to be additionally included as lying within the FREESURFER segmentation.. The cerebral volume was 972 cm3 estimated by FREESURFER and 960 cm3 by the author using the CAVALIERI method with CE of 0.34%. FREESURFER had 1.3% bigger measure than that estimated by the author. FREESURFER aided point counting estimate was between 948 cm3 and 982 cm3 with mean volume of 965 cm3. The ratio of points counted by the author but were outside the pial boundary segmented by FREESURFER to total points number counted was between 2.6% to 4.0%, and the ratio of test points not counted by the author but were inside the pial boundary segmented by FREESURFER to total points number counted was between 2.7% to 4.9%. Therefore the author’s estimate was in the range of FREESURFER aided estimation by the CAVALIERI method and both volume ratios were close to each other. No bias could be found between the author using the CAVALIERI method and FREESURFER, which gives the author confidence in performing following studies.Furthermore, volume difference of cerebrum excluding ventricles between AD patients and healthy people were investigated using four stereological methods (i.e. the CAVALIERI, ICAV, INV and DN methods) and the FREESURFER software. From the same dataset of 40 AD patients and 22 healthy elderly volunteers, brain MR images of 13 patients and 13 volunteers were selected with good image quality. Inter-reliability and intra-repeatability studies were performed by two observers on three AD and three normal ageing brains. Both the inter-reliability and intra-repeatability studies showed good consistency. There was no significant difference of individual measures among the CAVALIERI and ICAV methods and FREESURFER. The average time taken for each cerebral volume estimation was less than 15 mins by each of the CAVALIERI, ICAV, INV and DN methods. Clinically, the cerebral volume was significantly smaller in the AD patients, which were found using both the CAVALIERI (p = 0:01) and ICAV (p < 0:01) methods and FREESURFER (p = 0:01) although the INV and DN methods were not able to detect this difference. In this adult brain group study, the volume estimates from the CAVALIERI and ICAV methods were competitive with those obtained from FREESURFER, while the INV and DN methods might be more useful if being applied with a larger sample size or the INV ortrip and DN ortrip methods were applied.Lastly, a systematic investigation on potential imaging biomarkers for AD was performed by the FREESURFER software, one of the imaging biomarkers (i.e. volume ratio of cerebrum excluding ventricles to intra-cranium (the contents of the skull above the level of the foramen magnum)) was re-examined by the INV method manually. From the same dataset of 40 AD patients and 22 healthy elderly volunteers, the brain MR images of 27 AD patients and 16 healthy elderly controls between the maximal common age scope of 47 to 71 were selected, which were analysed by FREESURFER for each brain region. Furthermore, to see the effect of AD on normal ageing atrophy, the difference of volume ratios of each brain region to whole brain between AD patients and healthy controls was investigated. Volume ratios of many brain parenchymal regions (e.g. hippocampus (left p = 0:002, right p < 0:001), amygdala (left p < 0:001, right p < 0:001), accumbens area (left p = 0:002, right p = 0:001), left putamen (p = 0:037) and corpus callosum (mid anterior p = 0:03, mid posterior p = 0:032)) to whole brain were found smaller in AD patients while volume ratios of ventricles (both sides of lateral, inferior lateral and 3rd ventricles, p < 0:001) to whole brain were bigger in AD patients. Besides, the INV method was able to detect significant difference of volume ratio of cerebral parenchyma to intra-cranium between AD patients and healthy elderly subjects too (p < 0:01). In comparison with normal ageing-related atrophy in healthy subjects, brain atrophy with ageing in AD patients presented in a different pattern in volume ratios (e.g. right (p = 0:029) and total cortex (p = 0:013) to brain, total grey matter to brain (p = 0:01), cerebral white matter to brain (p = 0:003), cerebellar cortex to brain (left p = 0:019, right p = 0:032), 5th ventricle to brain (p = 0:048), left fimbria to left hippocampus (p = 0:015), left hippocampal-amygdaloid transition area (HATA) to left hippocampus and right presubiculum to right hippocampus (p = 0:016)). In this AD study, many volume ratios of brain regions to whole brain or other brain regions were found different in AD patients and especially volume ratio of cerebral parenchyma to intra-cranium showed potentiality as an imaging biomarker for AD. Ageing atrophy pattern was found different in AD patients too.In conclusion, by programming in freely available R, FSL and IMAGEJ software packages, the CAVALIERI, ICAV, INV and DN methods were able to be performed conveniently and efficiently on human brain volume estimation using MRI. We made the first applications on the volume estimation of fetal brains, healthy brains and brains affected by AD using the ICAV, INV and DN methods. The volume estimates were competitive with those obtained from automated programme (i.e. FREESURFER)