Educating Future Robotics Engineers In Multidisciplinary Approaches In Robot Software Design

In 2020, a new two-year MSc programme in robotics was launched. Unlike most existing robotics programmes, which approach robotics from a specific discipline, this programme aims to train multi-deployable robot generalists using a cognitive approach (no hardware creation). The field of robotics is multidisciplinary by nature and educating students on how to approach projects with a multidisciplinary mindset is at the forefront of the programme. Hence, at the end of the first year, students are thrust into experiencing the true multi-disciplinarity of the robotics field in a synthesizing, multidisciplinary project-based course. In this 5 EC course, students work together in groups of 5 on an industry-based assignment making a translation of societal issues from different perspectives (human, sustainability, safety, ethics, economic, etc.) into intelligent robot solutions. Each team develops and tests a complete, integrated software package for a complex robot system in a simulated environment and implements it in a real robot at the end of the course. Various robots are used, each related to a different case study which is taken on by multiple teams. Students are supported in their project with workshops and minilectures on transferable skills, systems engineering and the Robot Operating System (ROS). This paper describes the development, implementation, and results of the course over its first three years of running. It will present lessons learned from the perspectives of all parties involved: lecturers, technical staff, industry, and students as well as future plans and recommendations for others looking at creating similar courses

Teaching molecular genetics: chapter 4—positional cloning of genetic disorders

Positional cloning is the approach of choice for the identification of genetic mutations underlying the pathological development of diseases with simple Mendelian inheritance. It consists of different consecutive steps, starting with recruitment of patients and DNA collection, that are critical to the overall process. A genetic analysis of the enrolled patients and their families is performed, based on genetic recombination frequencies generated by meiotic cross-overs and on genome-wide molecular studies, to define a critical DNA region of interest. This analysis culminates in a statistical estimate of the probability that disease features may segregate in the families independently or in association with specific molecular markers located in known regions. In this latter case, a marker can be defined as being linked to the disease manifestations. The genetic markers define an interval that is a function of their recombination frequencies with the disease, in which the disease gene is localised. The identification and characterisation of chromosome abnormalities as translocations, deletions and duplications by classical cytogenetic methods or by the newly developed microarray-based comparative genomic hybridisation (array CGH) technique may define extensions and borders of the genomic regions involved. The step following the definition of a critical genomic region is the identification of candidate genes that is based on the analysis of available databases from genome browsers. Positional cloning culminates in the identification of the causative gene mutation, and the definition of its functional role in the pathogenesis of the disorder, by the use of cell-based or animal-based experiments. More often, positional cloning ends with the generation of mice with homologous mutations reproducing the human clinical phenotype. Altogether, positional cloning has represented a fundamental step in the research on genetic renal disorders, leading to the definition of several disease mechanisms and allowing a proper diagnostic approach to many conditions

Alkylation damage causes MMR-dependent chromosomal instability in vertebrate embryos

SN1-type alkylating agents, like N-methyl-N-nitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU), are potent mutagens. Exposure to alkylating agents gives rise to O6-alkylguanine, a modified base that is recognized by DNA mismatch repair (MMR) proteins but is not repairable, resulting in replication fork stalling and cell death. We used a somatic mutation detection assay to study the in vivo effects of alkylation damage on lethality and mutation frequency in developing zebrafish embryos. Consistent with the damage-sensing role of the MMR system, mutant embryos lacking the MMR enzyme MSH6 displayed lower lethality than wild-type embryos after exposure to ENU and MNU. In line with this, alkylation-induced somatic mutation frequencies were found to be higher in wild-type embryos than in the msh6 loss-of-function mutants. These mutations were found to be chromosomal aberrations that may be caused by chromosomal breaks that arise from stalled replication forks. As these chromosomal breaks arise at replication, they are not expected to be repaired by non-homologous end joining. Indeed, Ku70 loss-of-function mutants were found to be equally sensitive to ENU as wild-type embryos. Taken together, our results suggest that in vivo alkylation damage results in chromosomal instability and cell death due to aberrantly processed MMR-induced stalled replication forks

Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas

Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity

Systematic generation of in vivo G protein-coupled receptor mutants in the rat

G-protein-coupled receptors (GPCRs) constitute a large family of cell surface receptors that are involved in a wide range of physiological and pathological processes, and are targets for many therapeutic interventions. However, genetic models in the rat, one of the most widely used model organisms in physiological and pharmacological research, are largely lacking. Here, we applied N-ethyl-N-nitrosourea (ENU)-driven target-selected mutagenesis to generate an in vivo GPCR mutant collection in the rat. A pre-selected panel of 250 human GPCR homologs was screened for mutations in 813 rats, resulting in the identification of 131 non-synonymous mutations. From these, seven novel potential rat gene knockouts were established as well as 45 lines carrying missense mutations in various genes associated with or involved in human diseases. We provide extensive in silico modeling results of the missense mutations and show experimental data, suggesting loss-of-function phenotypes for several models, including Mc4r and Lpar1. Taken together, the approach used resulted not only in a set of novel gene knockouts, but also in allelic series of more subtle amino acid variants, similar as commonly observed in human disease. The mutants presented here may greatly benefit studies to understand specific GPCR function and support the development of novel therapeutic strategies

COVER: Een programma dat dekkingspatronen van radioplaatsbepalingssystemen tekent

Er is door mij een software pakket ontwikkeld, dat dekkingspatronen van radioplaatsbepalingssystemen tekent. Deze patronen zijn in feite lijnen waarop met gelijke standaardafwijking de positie bepaald kan worden. Een logische eis hierbij is, dat de zenders ontvangen moeten kunnen worden. De dekkingspatronen zijn dan ook een combinatie van lijnen van gelijke precisie en lijnen, die de maximale reikwijdte van de zenders markeren.Civil Engineering and Geoscience

Fleet Design for Last-Mile OnDemand Logistics

The simultaneous rapidly increasing demand for home delivery of goods and on-demand expectancy of customers over the past years leaves a tough challenge for the logistical branch. They have to keep up with this increasing demand and simultaneously they are obliged to satisfy consumer service level demands to preserve their customers. On the other hand, as economic goals drive these businesses, they are prompted to operate cost-effectively. As a result, the fleet, deployed to execute the last-mile delivery, should meet both the requirement of cost-efficiency as well as the requirement for meeting consumer service level demands. This raises the question of how to efficiently design a fleet for last-mile on-demand logistics. For a fleet to be able to operate cost-efficiently, the fleet design decisions are required to take both fixed and variable costs into account. As such, the fleet design decisions need to include the consideration of the size of the fleet as well as the distance the vehicles travel on daily basis. Therefore, the goal of this thesis is to develop a novel method for fleet design for last-mile on-demand logistics. This work contributes by being the first to investigate methods for doing fleet design specifically for last-mile on-demand logistics considering multiple depots and variable pick-up locations. The purpose of the method is to determine the operational plans of the individual vehicles, the number of vehicles needed throughout a certain time period, the pick-up locations for all orders and the total distance travelled by the full fleet of vehicles. The proposed method builds upon established fleet design methods for ride-sharing taxi problems. The optimization method is adapted for last-mile on-demand logistics, yielding the required number of vehicles and their individual operational plans. The input of the system is a set of trips, which represent a path of a single vehicle to deliver one or multiple orders from a depot. Connecting two trips, which is called chaining, has the benefit of reducing the number of vehicles used, as chained trips are served by a single vehicle. Additionally, from multiple available depots where orders can be picked up, the method determines the best depot per order. This part of the method is called depot re-assignment. Furthermore, the fleet design problem is modelled as a multi-objective optimisation problem to find the trade-off between fleet size and the total distance the vehicles travel. Three different modelled datasets, each containing 10.000 order requests in the city centre of Amsterdam, are used to prove the value of the given method. A comparison between the method with and without depot re-assignment is made, to prove the value of the given addition of depot re-assignment. It is proven that depot re-assignment is valuable as it decreases or retains the fleet size for all test cases. The experiments conducted show that a significant decrease of the required fleet size can be established by a minor increase in total travelled distance. Furthermore, the optimal trade-off between the fleet size and the total distance travelled can be determined for a specific operation with the knowledge of operational costs for that operation.Mechanical Engineering | Vehicle Engineering | Cognitive Robotic

Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model

OBJECTIVE - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multi-system disorder characterized by progressive cyst formation in the kidneys. Serious complications of ADPKD are intracranial and aortic aneurysms. The condition is mainly caused by mutations in the PKD1 or PKD2 gene. We have carefully analyzed vascular remodeling in hypomorphic Pkd1 mouse model with dissecting aneurysms in the aorta. METHODS AND RESULTS - Quantitative real-time polymerase chain reaction revealed that in the aorta the expression of normal Pkd1 is reduced to approximately 26%. Using (immuno)histochemistry we have characterized the pathogenetic sequence for dissecting aneurysm formation. The aorta shows regions with accumulation of matrix components between the elastin lamellae. This is followed by increased numbers of smooth muscle cells and locally weakening of the media. In the intima, accumulation of matrix components and detachment of endothelial cells from the elastin lamellae results in a tear. The combination of weak media and a tear in the intima leads to rupture of the vessel wall resulting in intramural bleeding. CONCLUSIONS - The Pkd1 mouse reveals that polycystin1 is implicated in maintenance of the vessel wall structural integrity, and it is a useful model for dissecting aneurysm formation studies. © 2007 American Heart Association, Inc. Chemicals / CAS: calcium, 7440-70-2; collagen, 9007-34-5; elastin, 9007-58-3; fibronectin, 86088-83-7; gelatinase A, 146480-35-5; gelatinase B, 146480-36-6; osteopontin, 106441-73-0; perlecan, 143972-95-6; versican, 126968-45-4; polycystic kidney disease 1 protein; RNA, Messenger; TRPP Cation Channel