Geometry linking the art of building and the Universe: Geometric patterns on shells and grid shells

Geometry links the art of building and the physics of space-time. Mathematical breakthroughs in geometry have led to new ways of designing our structures and our ability to visualise and describe the world, phenomena in nature and the universe. However, in contemporary architecture and structural engineering, a more profound understanding of geometry has been forgotten. This thesis aims to resurrect geometry in architecture and engineering in connection with the rapid development of new digital tools for design and production—particularly the connection between the structural action related to the design of the geometrical patterns on shells structures are treated. A brief historical overview of geometry is conducted, and with an emphasis on its applications in architecture in terms of structural design and economic production. Furthermore, the connection to a sustainable building culture from the standpoint of the Davos declaration 2018, calling for a high-quality Baukultur is investigated. The concept of Baukultur (building culture in English) defined in the Davos declaration is related to architectural quality but has a broader meaning as it concerns the final product and the associated processes and its effect in society. Moreover, the concept of craftsmanship and workshop culture is examined, and how it is already present in computer code development and contemporary innovative research cultures combining architectural design and technology. Taking departure from the 18th-century experimental scientist Joseph Plateau and the contemporary artist Andy Goldsworthy, the connection between scientific and artistic research is investigated.Four articles are included; all connected to various ways of architectural applications of geometry in the design process. The first article describes a way to interpret empirically derived brick patterns, specifically the bed joints, using differential geometry. Two methods to apply this in the design processes of new brick vaults are presented. The first is purely geometrical and can be applied on an arbitrary shape with the possibility to apply several patterns; the second is an iterative method of generating a funicular shape and its pattern simultaneously. The second and third paper describes the design and construction process of two different wooden structures built of straight planar laths. Both studies examine the possibilities of using geometry as a link between various parameters in a design process using digital tools to achieve complex forms using simple elements and production methods. The fourth paper examines an appropriate form for a shell, that can balance aesthetics, structural performance and build-ability, with a proposal for the use of surfaces with constant solid angle. In this paper, the surface was generated with a Delaunay triangulation. Thus, future studies would include incorporation of other types of patterns facilitating buildability

Investigations of a compartmental model for leucine kinetics using nonlinear mixed effects models with ordinary and stochastic differential equations

Nonlinear mixed effects models represent a powerful tool to simultaneously analyze data from several individuals. In this study a compartmental model of leucine kinetics is examined and extended with a stochastic differential equation to model non-steady state concentrations of free leucine in the plasma. Data obtained from tracer/tracee experiments for a group of healthy control individuals and a group of individuals suffering from diabetes mellitus type 2 are analyzed. We find that the interindividual variation of the model parameters is much smaller for the nonlinear mixed effects models, compared to traditional estimates obtained from each individual separately. Using the mixed effects approach, the population parameters are estimated well also when only half of the data are used for each individual. For a typical individual the amount of free leucine is predicted to vary with a standard deviation of 8.9% around a mean value during the experiment. Moreover, leucine degradation and protein uptake of leucine is smaller, proteolysis larger, and the amount of free leucine in the body is much larger for the diabetic individuals than the control individuals. In conclusion nonlinear mixed effects models offers improved estimates for model parameters in complex models based on tracer/tracee data and may be a suitable tool to reduce data sampling in clinical studies

Inhibition of MAPK Hog1 Results in Increased Hsp104 Aggregate Formation Probably through Elevated Arsenite Influx into the Cells, an Approach with Numerous Potential Applications

Arsenic is a highly toxic and carcinogenic metalloid widely dispersed in the environment, contaminating water and soil and accumulating in crops. Paradoxically, arsenic is also part of modern therapy and employed in treating numerous ailments and diseases. Hence, inventing strategies to tune cellular arsenic uptake based on purpose is striking. Here, we describe an approach in which the arsenite uptake can be increased using a MAPK inhibitor. Employing microfluidic flow chambers in combination with optical tweezers and fluorescent microscopy, we elevated the influx of arsenite into the yeast Saccharomyces cerevisiae cells following short-term treatment with a Hog1 kinase inhibitor. The increase in arsenite uptake was followed on arsenite triggered redistribution of a reporter protein, Hsp104-GFP, which was imaged over time. The effect was even more pronounced when the yeast mother and daughter cells were analyzed disjointedly, an opportunity provided owing to single-cell analysis. Our data firstly provide a strategy to increase arsenite uptake and secondly show that arsenite triggered aggregates, previously shown to be sites of damaged proteins, are distributed asymmetrically and less accumulated in daughter cells. Inventing approaches to tune arsenite uptake has a great value for its use in environmental as well as medical applications

BMI and mortality in patients with new-onset type 2 diabetes: a comparison with age- and sex-matched control subjects from the general population

Objective: Type 2 diabetes is strongly associated with obesity, but the mortality risk related to elevated body weight in people with type 2 diabetes compared with people without diabetes has not been established. Research Design and Methods: We prospectively assessed short- and long-term mortality in people with type 2 diabetes with a recorded diabetes duration ≤5 years identified from the Swedish National Diabetes Registry between 1998 and 2012 and five age- and sex-matched control subjects per study participant from the general population. Results: Over a median follow-up of 5.5 years, there were 17,546 deaths among 149,345 patients with type 2 diabetes (mean age 59.6 years [40% women]) and 68,429 deaths among 743,907 matched control subjects. Short-term all-cause mortality risk (≤5 years) displayed a U-shaped relationship with BMI, with hazard ratios (HRs) ranging from 0.81 (95% CI 0.75-0.88) among patients with diabetes and BMI 30 to <35 kg/m2 to 1.37 (95% CI 1.11-1.71) with BMI ≥40 kg/m2 compared with control subjects after multiple adjustments. Long-term, all weight categories showed increased mortality, with a nadir at BMI 25 to <30 kg/m2 and a stepwise increase up to HR 2.00 (95% CI 1.58-2.54) among patients with BMI ≥40 kg/m2, that was more pronounced in patients <65 years old. Conclusions: Our findings suggest that the apparent paradoxical findings in other studies in this area may have been affected by reverse causality. Long-term, overweight (BMI 25 to <30 kg/m2) patients with type 2 diabetes had low excess mortality risk compared with control subjects, whereas risk in those with BMI ≥40 kg/m2 was substantially increased

The architectural application of shells whose boundaries subtend a constant solid angle

Surface geometry plays a central role in the design of bridges, vaults and shells, using various techniques for generating a geometry which aims to balance structural, spatial, aesthetic and construction requirements. In this paper we propose the use of surfaces defined such that given closed curves subtend a constant solid angle at all points on the surface and form its boundary. Constant solid angle surfaces enable one to control the boundary slope and hence achieve an approximately constant span-to-height ratio as the span varies, making them structurally viable for shell structures. In addition, when the entire surface boundary is in the same plane, the slope of the surface around the boundary is constant and thus follows a principal curvature direction. Such surfaces are suitable for surface grids where planar quadrilaterals meet the surface boundaries. They can also be used as the Airy stress function in the form finding of shells having forces concentrated at the corners. Our technique employs the Gauss-Bonnet theorem to calculate the solid angle of a point in space and Newton's method to move the point onto the constant solid angle surface. We use the Biot-Savart law to find the gradient of the solid angle. The technique can be applied in parallel to each surface point without an initial mesh, opening up for future studies and other applications when boundary curves are known but the initial topology is unknown. We show the geometrical properties, possibilities and limitations of surfaces of constant solid angle using examples in three dimensions

Design and evaluation of a microfluidic system for inhibition studies of yeast cell signaling

In cell signaling, different perturbations lead to different responses and using traditional biological techniques that result in averaged data may obscure important cell-to-cell variations. The aim of this study was to develop and evaluate a four-inlet microfluidic system that enables single-cell analysis by investigating the effect on Hog1 localization post a selective Hog1 inhibitor treatment during osmotic stress. Optical tweezers was used to position yeast cells in an array of desired size and density inside the microfluidic system. By changing the flow rates through the inlet channels, controlled and rapid introduction of two different perturbations over the cell array was enabled. The placement of the cells was determined by diffusion rates flow simulations. The system was evaluated by monitoring the subcellular localization of a fluorescently tagged kinase of the yeast "High Osmolarity Glycerol" (HOG) pathway, Hog1-GFP. By sequential treatment of the yeast cells with a selective Hog1 kinase inhibitor and sorbitol, the subcellular localization of Hog1-GFP was analysed on a single-cell level. The results showed impaired Hog1-GFP nuclear localization, providing evidence of a congenial design. The setup made it possible to remove and add an agent within 2 seconds, which is valuable for investigating the dynamic signal transduction pathways and cannot be done using traditional methods. We are confident that the features of the four-inlet microfluidic system will be a valuable tool and hence contribute significantly to unravel the mechanisms of the HOG pathway and similar dynamic signal transduction pathways

The yeast osmostress response is carbon source dependent

Adaptation to altered osmotic conditions is a fundamental property of living cells and has been studied in detail in the yeast Saccharomyces cerevisiae. Yeast cells accumulate glycerol as compatible solute, controlled at different levels by the High Osmolarity Glycerol (HOG) response pathway. Up to now, essentially all osmostress studies in yeast have been performed with glucose as carbon and energy source, which is metabolised by glycolysis with glycerol as a by-product. Here we investigated the response of yeast to osmotic stress when yeast is respiring ethanol as carbon and energy source. Remarkably, yeast cells do not accumulate glycerol under these conditions and it appears that trehalose may partly take over the role as compatible solute. The HOG pathway is activated in very much the same way as during growth on glucose and is also required for osmotic adaptation. Slower volume recovery was observed in ethanol-grown cells as compared to glucose-grown cells. Dependence on key regulators as well as the global gene expression profile were similar in many ways to those previously observed in glucose-grown cells. However, there are indications that cells re-arrange redox-metabolism when respiration is hampered under osmostress, a feature that could not be observed in glucose-grown cells

Fast and Accurate Nanoparticle Characterization Using Deep-Learning-Enhanced Off-Axis Holography

Characterization of suspended nanoparticles in their native environment plays a central role in a wide range of fields, from medical diagnostics and nanoparticleenhanced drug delivery to nanosafety and environmental nanopollution assessment. Standard optical approaches for nanoparticle sizing assess the size via the diffusion constant and, as a consequence, require long trajectories and that the medium has a known and uniform viscosity. However, in most biological applications, only short trajectories are available, while simultaneously, the medium viscosity is unknown and tends to display spatiotemporal variations. In this work, we demonstrate a label-free method to quantify not only size but also refractive index of individual subwavelength particles using 2 orders of magnitude shorter trajectories than required by standard methods and without prior knowledge about the physicochemical properties of the medium. We achieved this by developing a weighted average convolutional neural network to analyze holographic images of single particles, which was successfully applied to distinguish and quantify both size and refractive index of subwavelength silica andpolystyrene particles without prior knowledge of solute viscosity or refractive index. We further demonstrate how these features make it possible to temporally resolve aggregation dynamics of 31 nm polystyrene nanoparticles, revealing previously unobserved time-resolved dynamics of the monomer number and fractal dimension of individual subwavelength aggregates