Using nodal coordinates as variables for the dimensional synthesis of mechanisms

The method of the lower deformation energy has been successfully used for the synthesis of mechanisms for quite a while. It has shown to be a versatile, yet powerful method for assisting in the design of mechanisms. Until now, most of the implementations of this method used the dimensions of the mechanism as the synthesis variables, which has some advantages and some drawbacks. For example, the assembly configuration is not taken into account in the optimization process, and this means that the same initial configuration is used when computing the deformed positions in each synthesis point. This translates into a reduction of the total search space. A possible solution to this problem is the use of a set of initial coordinates as variables for the synthesis, which has been successfully applied to other methods. This also has some additional advantages, such as the fact that any generated mechanism can be assembled. Another advantage is that the fixed joint locations are also included in the optimization at no additional cost. But the change from dimensions to initial coordinates means a reformulation of the optimization problem when using derivatives if one wants them to be analytically derived. This paper tackles this reformulation, along with a proper comparison of the use of both alternatives using sequential quadratic programming methods. In order to do so, some examples are developed and studied.The authors wish to thank the Spanish Ministry of Economy and Competitiveness for its support through Grant DPI2013-46329-P and DPI2016-80372-R. Additionally the authors wish to thank the Education Department of the Basque Government for ist support through grant IT947-16

Optimization of Planar Mechanisms by using a Minimum Distance Function

The paper examines the application of a general minimum distance error function to the dimensional kinematic synthesis of bidimensional mechanisms. The minimum distance ap- proach makes it possible to solve the problem maintaining the same generality as that of the minimum deformation energy method while solving the problems that occasionally appear in the former method involving low stiffness mechanisms. It is a general method that can deal both with unprescribed and prescribed timing problems, and is applicable for path generation problems, function generation, solid guidance, and any combination of the aforementioned requirements as introduced in the usual precision point scheme. The method exhibits good convergence and computational efficiency. The minimum distance error function is solved with a sequential quadratic programming (SQP) approach. In the study, the synthesis problem is also optimized by using SQP, and the function can be easily adapted to other methods such as genetic algorithms. In the study, the minimum distance approach is initially presented. Subsequently, an efficient SQP method is developed by using analytic derivatives for solving. The next point addresses the application of the concept for the synthesis of mechanisms by using an SQP approach with approximate derivatives. This delivers a situation where the optimization is performed on an error function that itself consists of an inner optimization function. A few examples are presented and are also compared with the minimum deformation energy method. Finally, a few conclusions and future studies are discussedThe authors acknowledge direct or indirect economic support provided by the Investigation Groups recognized by the Basque Government under section IT 947-16 , and the Spanish Ministry of Economy and Competitiveness through the project DPI2016-80372-R (AEI/FEDER. UE

Studies of Single-Molecule Dynamics in Microorganisms

Fluorescence microscopy is one of the most extensively used techniques in the life sciences. Considering the non-invasive sample preparation, enabling live-cell compliant imaging, and the specific fluorescence labeling, allowing for a specific visualization of virtually any cellular compound, it is possible to localize even a single molecule in living cells. This makes modern fluorescence microscopy a powerful toolbox. In the recent decades, the development of new, "super-resolution" fluorescence microscopy techniques, which surpass the diffraction limit, revolutionized the field. Single-Molecule Localization Microscopy (SMLM) is a class of super-resolution microscopy methods and it enables resolution of down to tens of nanometers. SMLM methods like Photoactivated Localization Microscopy (PALM), (direct) Stochastic Optical Reconstruction Microscopy ((d)STORM), Ground-State Depletion followed by Individual Molecule Return (GSDIM) and Point Accumulation for Imaging in Nanoscale Topography (PAINT) have allowed to investigate both, the intracellular spatial organization of proteins and to observe their real-time dynamics at the single-molecule level in live cells. The focus of this thesis was the development of novel tools and strategies for live-cell SingleParticle Tracking PALM (sptPALM) imaging and implementing them for biological research. In the first part of this thesis, I describe the development of new Photoconvertible Fluorescent Proteins (pcFPs) which are optimized for sptPALM lowering the phototoxic damage caused by the imaging procedure. Furthermore, we show that we can utilize them together with Photoactivatable Fluorescent Proteins (paFPs) to enable multi-target labeling and read-out in a single color channel, which significantly simplifies the sample preparation and imaging routines as well as data analysis of multi-color PALM imaging of live cells. In parallel to developing new fluorescent proteins, I developed a high throughput data analysis pipeline. I have implemented this pipeline in my second project, described in the second part of this thesis, where I have investigated the protein organization and dynamics of the CRISPR-Cas antiviral defense mechanism of bacteria in vivo at a high spatiotemporal level with the sptPALM approach. I was successful to show the differences in the target search dynamics of the CRISPR effector complexes as well as of single Cas proteins for different target complementarities. I have also first data describing longer-lasting bound-times between effector complex and their potential targets in vivo, for which only in vitro data has been available till today. In summary, this thesis is a significant contribution for both, the advances of current sptPALM imaging methods, as well as for the understanding of the native behavior of CRISPR-Cas systems in vivo

Swarm-Organized Topographic Mapping

Topographieerhaltende Abbildungen versuchen, hochdimensionale oder komplexe Datenbestände auf einen niederdimensionalen Ausgaberaum abzubilden, wobei die Topographie der Daten hinreichend gut wiedergegeben werden soll. Die Qualität solcher Abbildung hängt gewöhnlich vom eingesetzten Nachbarschaftskonzept des konstruierenden Algorithmus ab. Die Schwarm-Organisierte Projektion ermöglicht eine Lösung dieses Parametrisierungsproblems durch die Verwendung von Techniken der Schwarmintelligenz. Die praktische Verwendbarkeit dieser Methodik wurde durch zwei Anwendungen auf dem Feld der Molekularbiologie sowie der Finanzanalytik demonstriert

KINE[SIS]TEM'17 From Nature to Architectural Matter

Kine[SiS]tem – From Kinesis + System. Kinesis is a non-linear movement or activity of an organism in response to a stimulus. A system is a set of interacting and interdependent agents forming a complex whole, delineated by its spatial and temporal boundaries, influenced by its environment. How can architectural systems moderate the external environment to enhance comfort conditions in a simple, sustainable and smart way? This is the starting question for the Kine[SiS]tem’17 – From Nature to Architectural Matter International Conference. For decades, architectural design was developed despite (and not with) the climate, based on mechanical heating and cooling. Today, the argument for net zero energy buildings needs very effective strategies to reduce energy requirements. The challenge ahead requires design processes that are built upon consolidated knowledge, make use of advanced technologies and are inspired by nature. These design processes should lead to responsive smart systems that deliver the best performance in each specific design scenario. To control solar radiation is one key factor in low-energy thermal comfort. Computational-controlled sensor-based kinetic surfaces are one of the possible answers to control solar energy in an effective way, within the scope of contradictory objectives throughout the year.FC

Advances in Robotics, Automation and Control

The book presents an excellent overview of the recent developments in the different areas of Robotics, Automation and Control. Through its 24 chapters, this book presents topics related to control and robot design; it also introduces new mathematical tools and techniques devoted to improve the system modeling and control. An important point is the use of rational agents and heuristic techniques to cope with the computational complexity required for controlling complex systems. Through this book, we also find navigation and vision algorithms, automatic handwritten comprehension and speech recognition systems that will be included in the next generation of productive systems developed by man

Research and Technology Objectives and Plans Summary (RTOPS)

This publication represents the NASA research and technology program for FY 1985. It is a compilation of the Summary portions of each of the RTOPs (Research and Technology Objectives and Plans) used for management review and control of research currently in progress throughout NASA. The RTOP summary is designed to facilitate communication and coordination among concerned technical personnel in government, in industry, and in universities. The first section containing citations and abstracts of the RTOPs is followed by four indexes: Subject, Technical Monitor, Responsible NASA Organization, and RTOP number

Sox10 regulates enteric neural crest cell migration in the developing gut

Concurrent Sessions 1: 1.3 - Organs to organisms: Models of Human Diseases: abstract no. 1417th ISDB 2013 cum 72nd Annual Meeting of the Society for Developmental Biology, VII Latin American Society of Developmental Biology Meeting and XI Congreso de la Sociedad Mexicana de Biologia del Desarrollo. The Conference's web site is located at http://www.inb.unam.mx/isdb/Sox10 is a HMG-domain containing transcription factor which plays important roles in neural crest cell survival and differentiation. Mutations of Sox10 have been identified in patients with Waardenburg-Hirschsprung syndrome, who suffer from deafness, pigmentation defects and intestinal aganglionosis. Enteric neural crest cells (ENCCs) with Sox10 mutation undergo premature differentiation and fail to colonize the distal hindgut. It is unclear, however, whether Sox10 plays a role in the migration of ENCCs. To visualize the migration behaviour of mutant ENCCs, we generated a Sox10NGFP mouse model where EGFP is fused to the N-terminal domain of Sox10. Using time-lapse imaging, we found that ENCCs in Sox10NGFP/+ mutants displays lower migration speed and altered trajectories compared to normal controls. This behaviour was cell-autonomous, as shown by organotypic grafting of Sox10NGFP/+ gut segments onto control guts and vice versa. ENCCs encounter different extracellular matrix (ECM) molecules along the developing gut. We performed gut explant culture on various ECM and found that Sox10NGFP/+ ENCCs tend to form aggregates, particularly on fibronectin. Time-lapse imaging of single cells in gut explant culture indicated that the tightly-packed Sox10 mutant cells failed to exhibit contact inhibition of locomotion. We determined the expression of adhesion molecule families by qPCR analysis, and found integrin expression unaffected while L1-cam and selected cadherins were altered, suggesting that Sox10 mutation affects cell adhesion properties of ENCCs. Our findings identify a de novo role of Sox10 in regulating the migration behaviour of ENCCs, which has important implications for the treatment of Hirschsprung disease.postprin

Analysis of craniofacial defects in Six1/Eya1-associated Branchio-Oto-Renal Syndrome

Poster Session I - Morphogenesis: 205/B10117th ISDB 2013 cum 72nd Annual Meeting of the Society for Developmental Biology, 7th Latin American Society of Developmental Biology Meeting and 11th Congreso de la Sociedad Mexicana de Biologia del Desarrollo.Branchio-Oto-Renal (BOR) syndrome patients exhibit craniofacial and renal anomalies as well as deafness. BOR syndrome is caused by mutations in Six1 or Eya1, both of which regulate cell proliferation and differentiation. The molecular mechanism underlying the craniofacial and branchial arch (BA) defects in BOR syndrome is unclear. We have found that Hoxb3 is up-regulated in the second branchial arch (BA2) of Six1-/- mutants. Moreover, Hoxb3 over-expression in transgenic mice leads to BA abnormalities which are similar to the BA defects in Six1-/- or Eya1-/- mutants, suggesting a regulatory relationship among Six1, Eya1 and Hoxb3 genes. The aim of this study is to investigate the molecular mechanism underlying abnormal BA development in BOR syndrome using Six1 and Eya1 mutant mice. Two potential Six1 binding sites were identified on the Hoxb3 gene. In vitro and in vivo Chromatin IP assays showed that Six1 could directly bind to one of the sites specifically. Furthermore, using a chick in ovo luciferase assay we showed that Six1 could suppress gene expression through one of the specific binding sites. On the other hand, in Six1-/- mutants, we found that the Notch ligand Jag1 was up-regulated in BA2. Similarly, in Hoxb3 transgenic mice, ectopic expression of Jag1 could be also detected in BA2. To investigate the activation of Notch signaling pathway, we found that Notch intracellular domain (NICD), a direct indicator of Notch pathway activation, was up-regulated in BAs of Six1-/-; Eya1-/- double mutants. Our results indicate that Hoxb3 and Notch signaling pathway are involved in mediating the craniofacial defects of Six1/Eya1-associated Branchio-Oto-Renal Syndrome.postprin