A PDE model for bleb formation and interaction with linker proteins

The aim of this paper is to further develop mathematical models for bleb formation in cells, including cell-membrane interactions with linker proteins. This leads to nonlinear reaction-diffusion equations on a surface coupled to fluid dynamics in the bulk. We provide a detailed mathematical analysis and investigate some singular limits of the model, connecting it to previous literature. Moreover, we provide numerical simulations in different scenarios, confirming that the model can reproduce experimental results on bleb initation

Development of light-addressable potentiometric sensor systems and their applications in biotechnological environments

The simultaneous analysis of multiple analytes and spatially resolved measurements of concentration distributions with a single sensor chip are an important task in the field of (bio-)chemical sensing. Together with the miniaturisation, this is a promising step forward for applications and processes that profit from (bio-)chemical sensors. In combination with biological recognition elements, like enzymes or cells, these biosensors are becoming an interesting tool for e.g., biotechnological, medical and pharmaceutical applications. One promising sensor principle is the light-addressable potentiometric sensor (LAPS). A LAPS is a semiconductor-based potentiometric sensor that allows determining analyte concentrations of aqueous solutions in a spatially resolved manner. Therefore, it is using a focused light source to address the area of interest. The light that illuminates the local area of the LAPS chip generates a photocurrent that correlates with the local analyte concentration on the sensor surface. Based on the "state of the art", further developments of LAPS set-ups were carried out within this PhD thesis. Furthermore, by utilising enzymes and whole cells, the benefits of these LAPS set-ups for biotechnological, medical and pharmaceutical applications are demonstrated. During the present thesis, three different LAPS set-ups were developed: The first LAPS set-up makes use of a field-programmable gate array (FPGA) to drive a 4x4 light-emitting diode (LED) array that defines 16 measurement spots on the sensor-chip surface. With the help of the FPGA, the driving parameters, like light brightness, modulation amplitude and frequency can be selected individually and all LEDs can be driven concurrently. Thus, a simultaneous readout of all measurement spots is possible and chemical images of the whole sensor surface can be achieved within 200 ms. The FPGA-based LAPS set-up is used to observe the frequency behaviour of LAPS chips. In a second LAPS set-up, a commercially available organic-LED (OLED) display is used as light source. The OLED panel consists of 96x64 pixels with a pixel size of 200x200 µm and thus, an over 16 times higher lateral resolution compared to the IR-LED array. It was demonstrated that chemical images of the whole sensor surface can be obtained in 2.5 min. Since the lateral resolution of LAPS is not only specified by the light source, but also by the LAPS chip itself, the lateral resolution of the LAPS structures is characterised. Therefore, the third LAPS set-up has been developed, which utilises a single laser diode that can be moved by an XY-stage. By scanning a specially patterned LAPS chip, a lateral resolution of the LAPS structures in the range of the pixel size of the OLED display is demonstrated. Label-free imaging of biological phenomena is investigated with the FPGA-based LAPS. With the help of an enzymatic layer with the enzyme acetylcholine esterase (AChE) the detection of the neuronal transmitter acetylcholine (ACh) is demonstrated. The dynamic and static response as well as the long-term stability is characterised and compared with another semiconductor-based chemical imaging sensor based on charge-coupled devices (CCD) using the same enzymatic layer. The usage of the FPGA-based LAPS as whole-cell-based biosensor is studied with the model organism Escherichia coli. Here, the metabolic activity of the E. coli cells is investigated by determining the extracellular acidification. An immobilisation technique for embedding the microorganisms in polyacrylamide gel on the sensor surface has been developed. The immobilisation is realised in an on-chip differential arrangement by making use of the addressability of LAPS. This way, external influences such as sensor drift, temperature changes and external pH changes can be compensated. In a comparative study of the extracellular acidification rate between immobilised E. coli and E. coli that are in suspension, acidification rates in the same order were determined, demonstrating that the immobilisation does not have any influence on the metabolic activity. Further measurements with this cell-based LAPS system underline the sensitivity towards different nutrient concentrations, namely glucose. The ability to observe the extracellular acidification of microorganisms and the sensitively towards nutrient concentrations enables to detect high-order effects, like toxicity or pharmacological activity in complex analytes

Flow-cytometric quantification of microbial cells on sand from water biofilters

Rapid quantification of absolute microbial cell abundances is important for a comprehensive interpretation of microbiome surveys and crucial to support theoretical modelling and the design of engineered systems. In this paper, we propose a protocol specifically optimised for the quantification of microbial abundances in water biofilters using flow cytometry (FCM). We optimised cell detachment from sand biofilter particles for FCM quantification through the evaluation of five chemical dispersants (NaCl, Triton-X100, CaCl2, sodium pyrophosphate (PP), Tween 80 combined with PP), different mechanical pre-treatments (low and high energy sonication and shaking) and two fixation methods (glutaraldehyde and ethanol). The developed protocol was cross-compared using other established and commonly employed methods for biomass quantification in water filter samples (adenosine triphosphate (ATP) quantification, real-time quantitative PCR (qPCR) and volatile solids (VS)). The highest microbial count was obtained by detaching the biofilm from biofilter grains and dispersing clusters into singles cells using Tween 80 and sodium pyrophosphate combined with four steps of high energy sonication (27W, for 80 s each step); glutaraldehyde was shown to be the best fixative solution. The developed protocol was reliable and highly reproducible and produced results that are comparable to data from alternative quantification methods. Indeed, high correlations were found with trends obtained through ATP and qPCR (ρ = 0.98 and ρ = 0.91) measurements. The VS content was confirmed as an inaccurate method to express biomass in sand samples since it correlated poorly with all the other three methods (ρ = 0.005 with FCM, 0.002 with ATP and 0.177 with qPCR). FCM and ATP showed the strongest agreement between absolute counts with a slope of the correlation equal to 0.7, while qPCR seemed to overestimate cell counts by a factor of ten. The rapidity and reproducibility of the method developed make its application ideal for routine quantification of microbial cell abundances on sand from water biofilters and thus useful in revealing the ecological patterns and quantifying the metabolic kinetics involved in such systems

A PDE model for bleb formation and interaction with linker proteins

The aim of this paper is to further develop mathematical models for bleb formation in cells, including cell membrane interactions with linker proteins. This leads to nonlinear reaction–diffusion equations on a surface coupled to fluid dynamics in the bulk. We provide a detailed mathematical analysis and investigate some singular limits of the model, connecting it to previous literature. Moreover, we provide numerical simulations in different scenarios, confirming that the model can reproduce experimental results on bleb initiation

Suborbital autorotation landing demonstrator on REXUS 29

Current developments in the aerospace industry point towards more frequent interplanetary travel in the future. However, the main focus of developments is on launcher technology, yet the descent of interplanetary probes is of high importance for the success of future missions. Additionally, to the present landing approaches using either a powered descent requiring fuel or a combination of different parachutes, a third method is investigated in this project. The chosen approach is called autorotation and is commonly used in helicopters. When a helicopter suffers a loss of power, it can still land and even choose its landing site without the utilization of an engine. Similar to parachutes, the presented technology can be applied to various atmospheric conditions by modification of rotor and control parameters. Moreover, a rotor in autorotation can provide directional control and thus the choice of a landing site, which is not feasible using a parachute. All these factors make autorotation an interesting option as an entry descent and landing (EDL) technology for interplanetary missions. Our project, Daedalus 2 implements the autorotation landing strategy as part of the REXUS student project campaign under DLR / ESA / SNSA supervision. Since 2018 we are developing the SpaceSeed Mk.2, a technology demonstrator that incorporates a rotor and all necessary technological means to perform an autorotation EDL maneuver from an apogee of 80 km. The mission concept is laid out within the presented paper. This includes the main challenges like miniaturization of the SpaceSeed v2 due to the size constraints of the REXUS rocket or the used sensors for height and position determination. The importance of a technology demonstrator tested on a sounding rocket to prove the feasibility of our presented system is laid out in our publication. Furthermore, the custom development of electrical, mechanical and software sub systems is discussed. Additionally, the planned mission profile will be explained, including flight phases and different activities conducted by the SpaceSeeds during flight. Moreover, the main differences and improvements to Daedalus 1 are being discusse

Electronics and Sensor Subsystem Design for Daedalus 2 on REXUS 29: An Autorotation Probe for Sub-Orbital Re-Entry

The Daedalus 2 mission aboard REXUS 29 is a technology demonstrator for an alternative descent mechanism for very high altitude drops based on auto-rotation. It consists of two probes that are ejected from a sounding rocket at an altitude of about 80 km and decelerate to a soft landing using only a passive rotor with pitch control. This type of autonomous, scientific experiment poses great challenges upon the electronics subsystem, which include mechanical stress, power system reliability, sensor redundancy, subsystem communication, and development procedures. Based on the data gathered in Daedalus 1 multiple new approaches were developed to fulfill these requirements, such as redundant communication links, mechanical decoupling of PCBs and fault-tolerant power source selection.Comment: 8 pages, 10 figure

Making Distribution State Estimation Practical: Challenges and Opportunities

In increasingly digitalized and metered distribution networks, state estimation is generally recognized as a key enabler of advanced network management functionalities. However, despite decades of research, the real-life adoption of state estimation in distribution systems remains sporadic. This systematization of knowledge paper discusses the cause for this while comparing industrial and academic experiences and reviewing well- and less-established research directions. We argue that to make distribution system state estimation more practical and applicable in the field, new perspectives are needed. In particular, research should move away from conventional approaches and embrace generalized problem specifications and more comprehensive workflows. These, in turn, require algorithm advancements and more general mathematical formulations. We discuss lines of work to enable the delivery of tangible research.Comment: 10 page

Early Clinical and Radiological Experience with a Ceramic Bone Graft Substitute in the Treatment of Benign and Borderline Bone Lesions

Abstract Substitutes for bone grafts experience increasing popularity, but the need for defect-filling following simple curettage of benign bone lesions is controversial. In this study, we wish to objectively report the radiological changes following bone defect-filling using a composite ceramic bone graft substitute, as well as the clinical results and complications. We evaluated 35 surgically treated benign bone lesions with subsequent defect-filling using two variants of a composite ceramic bone graft substitute (CERAMENT|BONE VOID FILLER or CERAMENT|G, BONESUPPORT AB, SWEDEN). After one year, a normal cortical thickness surrounding the defect was seen in approximately 80% of patients. Inside the defect-cavity, an almost complete product-resorption was seen after one year. The most common complication was a post-operative inflammatory soft-tissue reaction, seen in 7 patients (20%), which resolved without further treatment, although short-term antibiotic treatment was initiated at a local hospital in 6 patients, due to suspected wound infection. In summary, cortical thickness most commonly normalizes after bone tumor removal and filling of the bone defect using this particular composite ceramic bone graft substitute. The ceramic substitute undergoes resorption, which causes progressive changes in the radiological appearance inside the bone defect

Beste Landpartie Allgemeinmedizin (BeLA): motivational factors for medical students for rural employment — a qualitative interview-based study

Hintergrund Eine wohnortnahe hausärztliche Versorgung ist durch verschiedene Faktoren gefährdet. In Bayern soll das Programm „Beste Landpartie Allgemeinmedizin“ (BeLA) Studierende für eine (haus)ärztliche Tätigkeit auf dem Land motivieren. Hieraus lassen sich 2 Fragen ableiten: „Mit welchen Motiven bewerben sich Studierende für das BeLA-Programm?“ sowie „Lassen sich übergreifende Faktoren zur ärztlichen Tätigkeit auf dem Land identifizieren und für die Rekrutierung nutzen?“. Methoden Es wurden 18 leitfadengestützte Interviews zur Exploration durchgeführt. Aus den individuellen Motivationen wurden positive Erwartungen und das negative Gegenbild der ärztlichen Tätigkeit auf dem Land individuell entwickelt und ein Idealbild (positiver Gegenhorizont) der angenommenen eigenen ärztlichen Tätigkeit auf dem Land gezeichnet. Ergebnisse Die von den Studierenden im Interview genannten Aspekte des Landlebens lassen sich grob in 4 Kategorien einteilen: das ruhige Landleben, die Nähe zu den Patient:innen, die Familie auf dem Land und die Vergleichbarkeit mit der Stadt. Die Befragten zeichnen ein Idealbild von ärztlicher Tätigkeit auf dem Land. Die Motivation ist dabei bereits so stark ausgeprägt, dass die individuellen positiven Gegenhorizonte negative Aspekte des Idealbilds schwach gewichten. Das Land selbst wird hierbei als natürliche Idylle dargestellt. Diskussion Die Befragten bringen bei Eintritt in das Programm eine hohe Motivation, später Landärzt:in zu werden, mit. Für die Rekrutierung von unentschlossenen Studierenden, die eine ärztliche Tätigkeit auf dem Land in Erwägung ziehen, scheinen in solchen Programmen andere Ansprachen nötig zu sein. Die starke persönliche Verknüpfung der für das Land Motivierten bietet Ansatzpunkte, die Kriterien für den Zugang zum Medizinstudium insbesondere im Hinblick auf Maßnahmen wie die Landarztquote anzupassen

Chlorido{N-[2-(diphenylphosphanyl)- benzyl]-1-(pyridin-2-yl)methanamine-kP} gold(I)

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