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Purpose: Impaired paravascular drainage of β-Amyloid (Aβ) has been proposed as a contributing cause for sporadic Alzheimer’s disease (AD), as decreased cerebral blood vessel pulsatility and subsequently reduced propulsion in this pathway could lead to the accumulation and deposition of Aβ in the brain. Therefore, we hypothesized that there is an increased impairment in pulsatility across AD spectrum.
Patients and Methods: Using transcranial color-coded duplex sonography (TCCS) the resistance and pulsatility index (RI; PI) of the middle cerebral artery (MCA) in healthy controls (HC, n=14) and patients with AD dementia (ADD, n=12) were measured. In a second step, we extended the sample by adding patients with mild cognitive impairment (MCI) stratified by the presence (MCI-AD, n=8) or absence of biomarkers (MCI-nonAD, n=8) indicative for underlying AD pathology, and compared RI and PI across the groups. To control for atherosclerosis as a confounder, we measured the arteriolar-venular-ratio of retinal vessels.
Results: Left and right RI (p=0.020; p=0.027) and left PI (p=0.034) differed between HC and ADD controlled for atherosclerosis with AUCs of 0.776, 0.763, and 0.718, respectively. The RI and PI of MCI-AD tended towards ADD, of MCI-nonAD towards HC, respectively. RIs and PIs were associated with disease severity (p=0.010, p=0.023).
Conclusion: Our results strengthen the hypothesis that impaired pulsatility could cause impaired amyloid clearance from the brain and thereby might contribute to the development of AD. However, further studies considering other factors possibly influencing amyloid clearance as well as larger sample sizes are needed.
Transgenic plants have the potential to produce recombinant proteins on an agricultural scale, with yields of several tons per year. The cost-effectiveness of transgenic plants increases if simple cultivation facilities such as greenhouses can be used for production. In such a setting, we expressed a novel affinity ligand based on the fluorescent protein DsRed, which we used as a carrier for the linear epitope ELDKWA from the HIV-neutralizing antibody 2F5. The DsRed-2F5-epitope (DFE) fusion protein was produced in 12 consecutive batches of transgenic tobacco (Nicotiana tabacum) plants over the course of 2 years and was purified using a combination of blanching and immobilized metal-ion affinity chromatography (IMAC). The average purity after IMAC was 57 ± 26% (n = 24) in terms of total soluble protein, but the average yield of pure DFE (12 mg kg−1) showed substantial variation (± 97 mg kg−1, n = 24) which correlated with seasonal changes. Specifically, we found that temperature peaks (>28°C) and intense illuminance (>45 klx h−1) were associated with lower DFE yields after purification, reflecting the loss of the epitope-containing C-terminus in up to 90% of the product. Whereas the weather factors were of limited use to predict product yields of individual harvests conducted for each batch (spaced by 1 week), the average batch yields were well approximated by simple linear regression models using two independent variables for prediction (illuminance and plant age). Interestingly, accumulation levels determined by fluorescence analysis were not affected by weather conditions but positively correlated with plant age, suggesting that the product was still expressed at high levels, but the extreme conditions affected its stability, albeit still preserving the fluorophore function. The efficient production of intact recombinant proteins in plants may therefore require adequate climate control and shading in greenhouses or even cultivation in fully controlled indoor farms.
Training-induced increase in Achilles tendon stiffness affects tendon strain pattern during running
(2019)
Background
During the stance phase of running, the elasticity of the Achilles tendon enables the utilisation of elastic energy and allows beneficial contractile conditions for the triceps surae muscles. However, the effect of changes in tendon mechanical properties induced by chronic loading is still poorly understood. We tested the hypothesis that a training-induced increase in Achilles tendon stiffness would result in reduced tendon strain during the stance phase of running, which would reduce fascicle strains in the triceps surae muscles, particularly in the mono-articular soleus.
Methods
Eleven subjects were assigned to a training group performing isometric singleleg plantarflexion contractions three times per week for ten weeks, and another ten subjects formed a control group. Before and after the training period, Achilles tendon stiffness was estimated, and muscle-tendon mechanics were assessed during running at preferred speed using ultrasonography, kinematics and kinetics.
Results
Achilles tendon stiffness increased by 18% (P <0:01) in the training group, but the associated reduction in strain seen during isometric contractions was not statistically significant. Tendon elongation during the stance phase of running was similar after training, but tendon recoil was reduced by 30% (P <0:01), while estimated tendon force remained unchanged. Neither gastrocnemius medialis nor soleus fascicle shortening during stance was affected by training.
Discussion
These results show that a training-induced increase in Achilles tendon
stiffness altered tendon behaviour during running. Despite training-induced changes in tendon mechanical properties and recoil behaviour, the data suggest that fascicle shortening patterns were preserved for the running speed that we examined. The asymmetrical changes in tendon strain patterns supports the notion that simple inseries models do not fully explain the mechanical output of the muscle-tendon unit during a complex task like running.
Neuromuscular strength training of the leg extensor muscles plays an important role in the rehabilitation and prevention of age and wealth related diseases. In this paper, we focus on the design and implementation of a Cartesian admittance control scheme for isotonic training, i.e. leg extension and flexion against a predefined weight. For preliminary testing and validation of the designed algorithm an experimental research and development platform consisting of an
industrial robot and a force plate mounted at its end-effector has been used. Linear, diagonal and arbitrary two-dimensional motion trajectories with different weights for the leg extension and flexion part are applied. The proposed algorithm is easily adaptable to trajectories consisting of arbitrary six-dimensional poses and allows the implementation of individualized trajectories.
The movement of magnetic beads due to a magnetic field gradient is of great interest in different application fields. In this report we present a technique based on a magnetic tweezers setup to measure the velocity factor of magnetically actuated individual superparamagnetic beads in a fluidic environment. Several beads can be tracked simultaneously in order to gain and improve statistics. Furthermore we show our results for different beads with hydrodynamic diameters between 200 and 1000 nm from diverse manufacturers. These measurement data can, for example, be used to determine design parameters for a magnetic separation system, like maximum flow rate and minimum separation time, or to select suitable beads for fixed experimental requirements.
For performing point-of-care molecular diagnostics, magnetic immunoassays constitute a promising alternative to established enzyme-linked immunosorbent assays (ELISA) because they are fast, robust and sensitive. Simultaneous detection of multiple biomolecular targets from one body fluid sample is desired. The aim of this work is to show that multiplex magnetic immunodetection based on magnetic frequency mixing by means of modular immunofiltration columns prepared for different targets is feasible. By calculations of the magnetic response signal, the required spacing between the modules was determined. Immunofiltration columns were manufactured by 3D printing and antibody immobilization was performed in a batch approach. It was shown experimentally that two different target molecules in a sample solution could be individually detected in a single assaying step with magnetic measurements of the corresponding immobilization filters. The arrangement order of the filters and of a negative control did not influence the results. Thus, a simple and reliable approach to multi-target magnetic immunodetection was demonstrated.
In modern bioanalytical methods, it is often desired to detect several targets in one sample within one measurement. Immunological methods including those that use superparamagnetic beads are an important group of techniques for these applications. The goal of this work is to investigate the feasibility of simultaneously detecting different superparamagnetic beads acting as markers using the magnetic frequency mixing technique. The frequency of the magnetic excitation field is scanned while the lower driving frequency is kept constant. Due to the particles’ nonlinear magnetization, mixing frequencies are generated. To record their amplitude and phase information, a direct digitization of the pickup-coil’s signal with subsequent Fast Fourier Transformation is performed. By synchronizing both magnetic beads using frequency scanning in magnetic frequency mixing technique magnetic fields, a stable phase information is gained. In this research, it is shown that the amplitude of the dominant mixing component is proportional to the amount of superparamagnetic beads inside a sample. Additionally, it is shown that the phase does not show this behaviour. Excitation frequency scans of different bead types were performed, showing different phases, without correlation to their diverse amplitudes. Two commercially available beads were selected and a determination of their amount in a mixture is performed as a demonstration for multiplex measurements.
Sensitive and rapid detection of cholera toxin subunit B using magnetic frequency mixing detection
(2019)
Cholera is a life-threatening disease caused by the cholera toxin (CT) as produced by some Vibrio cholerae serogroups. In this research we present a method which directly detects the toxin’s B subunit (CTB) in drinking water. For this purpose we performed a magnetic sandwich immunoassay inside a 3D immunofiltration column. We used two different commercially available antibodies to capture CTB and for binding to superparamagnetic beads. ELISA experiments were performed to select the antibody combination. The beads act as labels for the magnetic frequency mixing detection technique. We show that the limit of detection depends on the type of magnetic beads. A nonlinear Hill curve was fitted to the calibration measurements by means of a custom-written python software. We achieved a sensitive and rapid detection of CTB within a broad concentration range from 0.2 ng/ml to more
than 700 ng/ml.
The paper deals with an asymptotic relative efficiency concept for confidence regions of multidimensional parameters that is based on the expected volumes of the confidence regions. Under standard conditions the asymptotic relative efficiencies of confidence regions are seen to be certain powers of the ratio of the limits of the expected volumes. These limits are explicitly derived for confidence regions associated with certain plugin estimators, likelihood ratio tests and Wald tests. Under regularity conditions, the asymptotic relative efficiency of each of these procedures with respect to each one of its competitors is equal to 1. The results are applied to multivariate normal distributions and multinomial distributions in a fairly general setting.
Suppose we have k samples X₁,₁,…,X₁,ₙ₁,…,Xₖ,₁,…,Xₖ,ₙₖ with different sample sizes ₙ₁,…,ₙₖ and unknown underlying distribution functions F₁,…,Fₖ as observations plus k families of distribution functions {G₁(⋅,ϑ);ϑ∈Θ},…,{Gₖ(⋅,ϑ);ϑ∈Θ}, each indexed by elements ϑ from the same parameter set Θ, we consider the new goodness-of-fit problem whether or not (F₁,…,Fₖ) belongs to the parametric family {(G₁(⋅,ϑ),…,Gₖ(⋅,ϑ));ϑ∈Θ}. New test statistics are presented and a parametric bootstrap procedure for the approximation of the unknown null distributions is discussed. Under regularity assumptions, it is proved that the approximation works asymptotically, and the limiting distributions of the test statistics in the null hypothesis case are determined. Simulation studies investigate the quality of the new approach for small and moderate sample sizes. Applications to real-data sets illustrate how the idea can be used for verifying model assumptions.
Im Rahmen der Digitalisierung ist die zunehmende Automatisierung von bisher manuellen Prozessschritten ein Aspekt, der massive Auswirkungen auf die zukünftige Arbeitswelt haben wird. In diesem Kontext werden an den Einsatz von Softwarerobotern zur Prozessautomatisierung hohe Erwartungen geknüpft. Bei den Implementierungsansätzen wird die Diskussion aktuell insbesondere durch Robotic Process Automation (RPA) und Chatbots geprägt. Beide Ansätze verfolgen das gemeinsame Ziel einer 1:1-Automatisierung von menschlichen Handlungen und dadurch ein direktes Ersetzen von Mitarbeitern durch Maschinen. Bei RPA werden Prozesse durch Softwareroboter erlernt und automatisiert ausgeführt. Dabei emulieren RPA-Roboter die Eingaben auf der bestehenden Präsentationsschicht, so dass keine Änderungen an vorhandenen Anwendungssystemen notwendig sind. Am Markt werden bereits unterschiedliche RPA-Lösungen als Softwareprodukte angeboten. Durch Chatbots werden Ein- und Ausgaben von Anwendungssystemen über natürliche Sprache realisiert. Dadurch ist die Automatisierung von unternehmensexterner Kommunikation (z. B. mit Kunden) aber auch von unternehmensinternen Assistenztätigkeiten möglich. Der Beitrag diskutiert die Auswirkungen von Softwarerobotern auf die Arbeitswelt anhand von Anwendungsbeispielen und erläutert die unternehmensindividuelle Entscheidung über den Einsatz von Softwarerobotern anhand von Effektivitäts- und Effizienzzielen.
Kein Urteil zum Datenschutzrecht sorgte im vergangenen Jahr für mehr panische Reaktionen als die Entscheidung des EuGH in der Rechtssache “Wirtschaftsakademie Schleswig-Holstein”(C-210/16). Das Urteil warf in datenschutzrechtlicher Literatur und Öffentlichkeit zahlreiche Fragen auf: Ist jetzt jeder “gemeinsam” Verantwortlicher? Was sind die Kriterien? Der EuGH hat kürzlich in einem – dem allgemeinen Vernehmen nach aufsehenerregenden, de facto aber kaum überraschenden – Urteil für Klarheit gesorgt. Dabei hat das Gericht jedoch einige Fragen offengelassen und neue Fragen aufgeworfen. Ein Blick auf alte und neue Herausforderungen in Kooperationsszenarien.
Kurz vor der parlamentarischen Sommerpause hat der Bundestag am 28.6.2019 das 2. Datenschutz-Anpassungs- und Umsetzungsgesetz EU (2. DSAnpUG-EU) beschlossen, der Bundesrat hat diesem Gesetz am 20.9.2019 zugestimmt. Das Artikelgesetz, welches im sog. Omnibusverfahren zahlreiche Gesetze auf Bundesebene ändert, soll zur Vereinheitlichung und Anpassung des Bundesrechts an die seit Mai 2018 geltende Datenschutz-Grundverordnung (DSGVO) beitragen.
Wie sieht das unbemannte Flugzeug von Übermorgen aus? Dieser Frage stellen sich Forscher an der Fachhochschule Aachen. Die weltweit rasant fortschreitende Entwicklung des Marktes für unbemannte Fluggeräte (UAVs - „Unmanned Aerial Vehicles“) bietet großes Potenzial für Wachstum und Wertschöpfung. Unbemannte fliegende Systeme können – für bestimmte Anwendungsgebiete – wesentlich günstiger, kleiner und effizienter ausgelegt werden als bemannte Lösungen. Dabei sind sich viele Unternehmen über das mögliche Potential dieser Technologie noch gar nicht bewusst.
The optical performance of a 2-axis solar concentrator was simulated with the COMSOL Multiphysics® software. The concentrator consists of a mirror array, which was created using the application builder. The mirror facets are preconfigured to form a focal point. During tracking all mirrors are moved simultaneously in a coupled mode by 2 motors in two axes, in order to keep the system in focus with the moving sun. Optical errors on each reflecting surface were implemented in combination with the solar angular cone of ± 4.65 mrad. As a result, the intercept factor of solar radiation that is available to the receiver was calculated as a function of the transversal and longitudinal angles of incidence. In addition, the intensity distribution on the receiver plane was calculated as a function of the incidence angles.
The 2012 Emilia-Romagna earthquake, that mainly struck the homonymous Italian region provoking 28 casualties and damage to thousands of structures and infrastructures, is an exceptional source of information to question, investigate, and challenge the validity of seismic fragility functions and loss curves from an empirical standpoint. Among the most recent seismic events taking place in Europe, that of Emilia-Romagna is quite likely one of the best documented, not only in terms of experienced damages, but also for what concerns occurred losses and necessary reconstruction costs. In fact, in order to manage the compensations in a fair way both to citizens and business owners, soon after the seismic sequence, the regional administrative authority started (1) collecting damage and consequence-related data, (2) evaluating information sources and (3) taking care of the cross-checking of various reports. A specific database—so-called Sistema Informativo Gestione Europa (SFINGE)—was devoted to damaged business activities. As a result, 7 years after the seismic events, scientists can rely on a one-of-a-kind, vast and consistent database, containing information about (among other things): (1) buildings’ location and dimensions, (2) occurred structural damages, (3) experienced direct economic losses and (4) related reconstruction costs. The present work is focused on a specific data subset of SFINGE, whose elements are Long-Span-Beam buildings (mostly precast) deployed for business activities in industry, trade or agriculture. With the available set of data, empirical fragility functions, cost and loss ratio curves are elaborated, that may be included within existing Performance Based Earthquake Engineering assessment toolkits.
Heating efficiency of magnetic nanoparticles decreases with gradual immobilization in hydrogels
(2019)
Bacterial cell appendix formation supports cell-cell interaction, cell adhesion and cell movement. Additionally, in bioelectrochemical systems (BES), cell appendages have been shown to participate in extracellular electron transfer. In this work, the cell appendix formation of Clostridium acetobutylicum in biofilms of a BES are imaged and compared with conventional biofilms. Under all observed conditions, the cells possess filamentous appendages with a higher number and density in the BES. Differences in the amount of extracellular polymeric substance in the biofilms of the electrodes lead to the conclusion that the cathode can be used as electron donor and the anode as electron acceptor by C. acetobutylicum. When using conductive atomic force microscopy, a current response of about 15 nA is found for the cell appendages from the BES. This is the first report of conductivity for clostridial cell appendices and represents the basis for further studies on their role for biofilm formation and electron transfer.