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Grinding tools can be manufactured from metal, vitrified, and resin bond materials. In combination with superabrasives like diamond grains, metal-bonded tools are used in a wide range of applications. The main advantages of metal over vitrified and resin bonds are high grain retention forces and high thermal conductivity. This paper investigates the influence of the atmosphere and manufacturing parameters such as sintering temperature on the properties of titanium-bonded grinding layers. Titanium is an active bond material, which can increase the retention of diamond grains in metal-bonded grinding layers. This can lead to higher bond stress and, consequently, decreased wear of grinding tools in use when compared to other commonly used bond materials like bronze. The reason for this is the adhesive bond between titanium and diamond due to the formation of carbides in the interface, whereas bronze can only form a mechanical cohesion with diamond grains. However, when using oxygen-affine metals such as titanium, oxidizing effects could limit the strength of the bond due to insufficient adhesion between Ti-powder particles and the prevention of carbide formation. The purpose of this paper is to show the influence of the sintering atmosphere and temperature on the properties of titanium-bonded diamond grinding layers using the mechanical and thermal characterization of specimens. A higher vacuum (Δpatm = − 75 mbar) reduces the oxidation of titanium particles during sintering, which leads to higher critical bond stress (+ 38% @ Ts = 900 °C) and higher thermal conductivity (+ 3.4% @Ts = 1000 °C, Ta = 25 °C). X-ray diffraction measurements could show the formation of carbides in the cross-section of specimens, which also has a positive effect on the critical bond stress due to an adhesive bond between titanium and diamond.

Novel aluminum-copper compound castings devoid of oxide layers at the interface between the joining partners were developed in order to increase the thermal conductivity of the hybrid component. Due to the natural oxide layers of both aluminum and copper, metallurgical bonds between such bi-metal castings cannot be easily achieved in conventional processes. However, in an atmosphere comparable to extreme high vacuum created by using silane-doped inert gas, metallurgical bonds between the active surfaces of both aluminum and copper can be realized without additional coatings or fluxes. An intermetallic was created between aluminum and copper. Thus, very high thermal conductivities could be obtained for these hybrid castings, exceeding those of conventionally joined samples considerably. The intermetallic phase seams emerging between the joining partners were investigated using scanning electron microscopy and X-ray diffraction. The reduction of casting temperatures resulted in narrower intermetallic phase seams and these in turn in a much lower contact resistance between the two joining partners. This effect can be utilized for increasing the heat transfer capabilities of compound casting components employed for cooling heat sources such as high-power light-emitting diodes.

To combine the advantages of two materials, hybrid bulk metal workpieces are attractive for subsequent processes such as metal forming. However, hybrid materials rely on the initial bond strength for the effective transfer of applied loads. Thus, a non-destructive evaluation of the bonding along the production process chain is of high interest. To evaluate to what extent non-destructive testing can be employed to monitor the bonding quality between the joining partners steel and aluminum and to characterize the age hardening condition of the aluminum component, ultrasonic testing and electrical conductivity measurements were applied. It was found that a lateral angular co-extrusion process can create homogeneous bonding although the electrical conductivity of the aluminum is altered during processing. A previous bonding before the subsequent die forging process leads to a sufficient bonding in areas with little deformation and is therefore, advantageous compared to unjoined semi-finished products, which do not form a bonding if the deformation ratio is too small. An influence of the subsequent heat treatment on the bonding is not visible in the ultrasonic testing signals though a homogenized electrical conductivity can be detected, which indicates uniform artificial aging conditions of the aluminum alloy

ZusammenfassungMit dem Digitale-Versorgung-Gesetz (DVG) und der Digitale-Gesundheitsanwendungen-Verordnung (DiGAV) wurden digitale Gesundheitsanwendungen (DiGA) definiert und als Regelleistung der gesetzlichen Krankenversicherung (GKV) eingeführt; mit dem Digitale Versorgung und Pflege – Modernisierungs-Gesetz (DVPMG) wurde der neue Leistungsbereich weiter ausgestaltet. Anwendungen, die ein zügiges dreimonatiges Prüfverfahren („Fast-Track-Verfahren“) beim Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) erfolgreich durchlaufen haben und im DiGA-Verzeichnis des BfArM gelistet sind, können nunmehr von jedem Arzt und Psychotherapeuten zulasten der GKV verordnet werden.Auch eine Aufnahme zur Erprobung mit der Verpflichtung zur Durchführung einer Studie ist möglich. Damit hat der Gesetzgeber die dynamische Entwicklung im Bereich der mobilen Anwendungen aufgenommen und digitale Innovationen für Patienten in der Versorgung verfügbar gemacht. Der gesetzte Rahmen ist dabei so konzipiert, dass DiGA potenziell nicht nur die Therapieanteile beim Patienten unterstützen und Bereiche wie Selbstmanagement, Gesundheitskompetenz und Adhärenz stärken, sondern auch die Versorgungsabläufe zwischen Patienten und Leistungserbringern in vielfacher Weise besser gestalten können.Die umfangreichen Vorgaben zur Interoperabilität mit Hilfsmitteln und Implantaten einerseits und der elektronischen Patientenakte (ePA) andererseits unterstützen diese Entwicklungsperspektive. Insgesamt wird es darauf ankommen, DiGA als Bestandteil nutzerfreundlicher, digital gestützter Prozesse in die Versorgung einzubinden. Dazu wird in den kommenden Jahren das initiale Regelungswerk vor dem Hintergrund der mit den neuen Produkten und dem neuen Prüfverfahren gesammelten Erfahrungen stetig angepasst und weiterentwickelt werden.

Proregenerative responses are required for the restoration of nervous-system functionality in demyelinating diseases such as multiple sclerosis (MS). Yet, the limiting factors responsible for poor CNS repair are only partially understood. Here, we test the impact of a Western diet (WD) on phagocyte function in a mouse model of demyelinating injury that requires microglial innate immune function for a regenerative response to occur. We find that WD feeding triggers an ageing-related, dysfunctional metabolic response that is associated with impaired myelin-debris clearance in microglia, thereby impairing lesion recovery after demyelination. Mechanistically, we detect enhanced transforming growth factor beta (TGFβ) signalling, which suppresses the activation of the liver X receptor (LXR)-regulated genes involved in cholesterol efflux, thereby inhibiting phagocytic clearance of myelin and cholesterol. Blocking TGFβ or promoting triggering receptor expressed on myeloid cells 2 (TREM2) activity restores microglia responsiveness and myelin-debris clearance after demyelinating injury. Thus, we have identified a druggable microglial immune checkpoint mechanism regulating the microglial response to injury that promotes remyelination.

The current study presents a novel Tailored Forming process chain developed for the production of hybrid bearing bushings. In a first step, semi-finished products in the form of locally reinforced hollow profiles were produced using a new co-extrusion process. For this purpose, a modular tool concept was developed in which a steel tube made of a case-hardening steel, either C15 (AISI 1015) or 20MnCr5 (AISI 5120), is fed laterally into the tool. Inside the welding chamber, the steel tube is joined with the extruded aluminum alloy EN AW-6082. In the second step, sections from the compound profiles were formed into hybrid bearing bushings by die forging. In order to set the required forming temperatures for each material—aluminum and steel—simultaneously, a tailored heating strategy was developed, which enabled successful die forging of the hybrid workpiece to the desired bearing bushing geometry. Using either of the case-hardening steels in combination with aluminum, this novel process chain made it possible to produce intact hybrid bearing bushings, which showed both macroscopically and microscopically intimate material contact inside the compound zone.

Metal forming of shape memory alloys (SMA) can be challenging since these are very often brittle due to their intermetallic character. However, formability is often needed not only for realising the desired geometry but also for tailoring the microstructure and the functional properties. To investigate whether the encapsulation in a steel shell can improve the formability of shape memory alloys, Co49Ni21Ga30 and Ni49.5Fe14.5Mn4.0Ga26.0Co6.0 samples were subjected to tensile tests, upsetting, rolling and extrusion. A ferritic steel (1.0503) was used as the shell material. The shell was employed to curtail the formation of tensile stresses in the core, to maintain high temperatures during processing and to prevent oxidation. With this approach, not only forming of the SMA in the steel shell was possible but also an intensive metallurgical bond between the SMA and the steel shell can be achieved during hot rolling or extrusion.

The membrane lipids diacylglycerol (DAG) and phosphatidic acid (PA) are important second messengers that can regulate membrane transport by recruiting proteins to the membrane and by altering biophysical membrane properties. DAG and PA are involved in the transport from the Golgi apparatus to endosomes, and we have here investigated whether changes in these lipids might be important for regulation of transport to the Golgi using the protein toxin ricin. Modulation of DAG and PA levels using DAG kinase (DGK) and phospholipase D (PLD) inhibitors gave a strong increase in retrograde ricin transport, but had little impact on ricin recycling or degradation. Inhibitor treatment strongly affected the endosome morphology, increasing endosomal tubulation and size. Furthermore, ricin was present in these tubular structures together with proteins known to regulate retrograde transport. Using siRNA to knock down different isoforms of PLD and DGK, we found that several isoforms of PLD and DGK are involved in regulating ricin transport to the Golgi. Finally, by performing lipidomic analysis we found that the DGK inhibitor gave a weak, but expected, increase in DAG levels, while the PLD inhibitor gave a strong and unexpected increase in DAG levels, showing that it is important to perform lipidomic analysis when using inhibitors of lipid metabolism. Electronic supplementary material The online version of this article (10.1007/s00018-020-03551-6) contains supplementary material, which is available to authorized users.

If bone defects occur, the body’s own healing mechanism can close them below a critical size; for larger defects, bone autografts are used. These are typically cut from the same person’s hip in a second surgery. Consequently, the risk of complications, such as inflammations, rises. To avoid the risks resulting from the second surgery, absorbable, open-pored implants can be used. In the present study, the suitability of different magnesium alloys as absorbable porous bone substitute material has been investigated. Using the investment casting process with its design flexibility, the implant’s structure can be adapted to the ideal pore geometry with respect to bone ingrowth behavior. Different magnesium alloys (Mg-La2, LAE442, and ZX61) were studied and rated in terms of their degradation rate, bone ingrowth behavior, biocompatibility, and resorbability of the individual alloying elements.

Lipidomics has become an indispensable method for the quantitative assessment of lipid metabolism in basic, clinical, and pharmaceutical research. It allows for the generation of information-dense datasets in a large variety of experimental setups and model organisms. Previous studies, mostly conducted in mice (Mus musculus), have shown a remarkable specificity of the lipid compositions of different cell types, tissues, and organs. However, a systematic analysis of the overall variation of the mouse lipidome is lacking. To fill this gap, in the present study, the effect of diet, sex, and genotype on the lipidomes of mouse tissues, organs, and bodily fluids has been investigated. Baseline quantitative lipidomes consisting of 796 individual lipid molecules belonging to 24 lipid classes are provided for 10 different sample types. Furthermore, the susceptibility of lipidomes to the tested parameters is assessed, providing insights into the organ-specific lipidomic plasticity and flexibility. This dataset provides a valuable resource for basic and pharmaceutical researchers working with murine models and complements existing proteomic and transcriptomic datasets. It will inform experimental design and facilitate interpretation of lipidomic datasets.

The process of cyclic bending was investigated using thin sheets of the magnesium alloy AZ31 and α-titanium. These materials possess an hcp crystal lattice with different c/a ratios. It turned out that the latter have a substantial influence on the sheet deformation behavior. Even for small deformations (up to 2% strain), a large influence on the yield stress was present for both materials. In addition, cyclic bending contributes to the activation of prismatic slip, which is accompanied by twinning and detwinning. The changes in sheet anisotropy following cyclic bending were determined using texture measurements. Specifically, the AZ31 alloy sheets exhibited a considerable change in anisotropy of the mechanical properties with an increasing number of bending cycles. The anisotropy in the yield stress increases from 15% in the initial condition to 40% after three cycles. For the α-titanium sheet, the change in anisotropy was approx. 26% less. In general, the largest changes in properties occurred already in the first bending cycle and a stabilization took place upon further cycling.

Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P, Cardiovascular diseases (CVD) are associated with plasma lipid levels. Here, Tabassum et al. perform genome-wide association studies for lipidomic profiles with 141 (non-standard) lipid species which highlights shared genetic loci with CVD and that traditional lipids have low genetic correlation with other lipids.

Sheet metal forming is an inherent part of todays production industry. A major goal is to increase the forming limits of classical deep-drawing processes. One possibility to achieve that is to combine the conventional quasi-static (QS) forming process with electromagnetic high-speed (HS) post-forming. This work focuses on the finite element analysis of such combined forming processes to demonstrate the improvement which can be achieved. For this purpose, a cooperation of different institutions representing different work fields has been established. The material characterization is based on flow curves and forming limit curves for low and high strain rates obtained by novel testing devices. Further experimental investigations have been performed on the process chain of a cross shaped cup, referring to both purely quasi-static and quasi-static combined with electromagnetic forming. While efficient mathematical optimization algorithms support the new viscoplastic ductile damage modelling to find the optimum parameters based on the results of experimental material characterization, the full process chain is studied by means of an electro-magneto-mechanical finite element analysis. The constitutive equations of the material model are integrated in an explicit manner and implemented as a user material subroutine into the commercial finite element package LS-DYNA.

Shotgun lipidomics is the comprehensive and quantitative analysis of the lipid composition of biological and clinical samples. Here we describe the application and performance of the Lipotype shotgun lipidomics technology in clinical high throughput screening projects for the identification of disease-specific lipid patterns as well as in organ-wide analysis aiming at the systemic understanding of lipid-related physiological processes.

Author(s): Cornish-Bowden, Athel; Cornish-Bowden, Athel; Rasnick, David; Heng, Henry H; Horne, Steven; Abdallah, Batoul; Liu, Guo; Ye, Christine J; Bloomfield, Mathew; Vincent, Mark D; Aldaz, C Marcelo; Karlsson, Jenny; Valind, Anders; Jansson, Caroline; Gisselsson, David; Graves, Jennifer A Marshall; Stepanenko, Aleksei A; Andreieva, Svitlana V; Korets, Kateryna V; Mykytenko, Dmytro O; Huleyuk, Nataliya L; Baklaushev, Vladimir P; Kovaleva, Oksana A; Chekhonin, Vladimir P; Vassetzky, Yegor S; Avdieiev, Stanislav S; Bakker, Bjorn; Taudt, Aaron S; Belderbos, Mirjam E; Porubsky, David; Spierings, Diana CJ; de Jong, Tristan V; Halsema, Nancy; Kazemier, Hinke G; Hoekstra-Wakker, Karina; Bradley, Allan; de Bont, Eveline SJM; van den Berg, Anke; Guryev, Victor; Lansdorp, Peter M; Tatche, Maria Colome; Foijer, Floris; Liehr, Thomas; Baudoin, Nicolaas C; Nicholson, Joshua M; Soto, Kimberly; Quintanilla, Isabel; Camps, Jordi; Cimini, Daniela; Durrbaum, M; Donnelly, N; Passerini, V; Kruse, C; Habermann, B; Storchova, Z; Mandrioli, Daniele; Belpoggi, Fiorella; Silbergeld, Ellen K; Perry, Melissa J; Skotheim, Rolf I; Lovf, Marthe; Johannessen, Bjarne; Hoff, Andreas M; Zhao, Sen; SveeStromme, Jonas M; Sveen, Anita; Lothe, Ragnhild A; Hehlmann, R; Voskanyan, A; Fabarius, A; Bocking, Alfred; Biesterfeld, Stefan; Berynskyy, Leonid; Borgermann, Christof; Engers, Rainer; Dietz, Josef; Fritz, A; Sehgal, N; Vecerova, J; Stojkovicz, B; Ding, H; Page, N; Tye, C; Bhattacharya, S; Xu, J

Magnetic magnesium alloys can be utilized as a load sensitive material, in which the inverse magnetostrictive effect is used in order to measure the actual loads in structural components manufactured from such lightweight sensor alloys. To achieve a material which exhibits magnetic properties, Mg is alloyed with ferromagnetic materials like cobalt or samarium-cobalt. Alloying elements commonly used with Mg are utilized to improve the mechanical properties of these alloys, which however may have a slight negative impact on the magnetic sensitivity. In this work, two separate magnetic Mg alloys are compared, each with properties matched to the opposing requirements: (a) high load sensitivity and (b) satisfactory mechanical properties, respectively. The precipitation behavior of the ferromagnetic constituent Co in Mg together with other alloying elements is shown on the basis of SEM images. In addition, the dissolving behavior of the Co powder during the casting process of a binary Mg–Co alloy is investigated. Cyclic loading tests employing harmonic analyses of eddy current signals are utilized in order to verify the alloys’ sensory properties. The mechanical properties are investigated using tensile tests.

Biodegradable and biocompatible magnesium alloys appear to be very promising not only for temporary clinical application but also for developing deformable and degradable medical implants. This study analyzes the in vivo degradation behavior and the impact on the paranasal sinuses of the highly ductile Mg-2 wt%Nd alloy (MgNd2) in order to provide a basis for a satisfying stent system for the therapy of a chronic sinusitis. Moreover, in vitro tests were carried out on primary porcine nasal epithelial cells (PNEC). For the in vivo tests, cylindrical MgNd2 specimens were implanted into the sinus' mucosa of minipigs. During and after a total period of 180 days the long-term biodegradation and biocompatibility properties after direct contact with the physiological tissue were analyzed. Biodegradation was investigated by measuring the mass and volume losses of the MgNd2 specimens as well as by performing element analyses to obtain information about the degradation layer. The influence on the surrounding tissue of paranasal sinuses was evaluated by endoscopic and histopathological examinations of the mucosa. Here, only a locally unspecific chronic infection was found. The degradation rate showed a maximum after 45 days postsurgery and was determined to decrease subsequently. In vitro experiments using PNEC showed adequate biocompatibility of MgNd2. This study demonstrates a good in vivo biocompatibility for MgNd2 in the system of paranasal sinuses and underlines the promising properties of alloy MgNd2 for biodegradable nasal stent applications.

This paper presents a method for the magnetic data storage on the surface of gentelligent components. One key issue is the possibility to store customers’ data on components dynamically and to read it out later on. The data storage is carried out magnetically and is demonstrated on a high-speed milling head. As such components are mostly made of light materials without magnetic properties; areas for the data storage on the surface must first be defined. Sintered components made of Mg and of hard magnetic particles have the potential to meet these requirements.

A simple technique is described for performing repeat samplings in fine-needle aspirations (FNA) without the need for further needle insertions. This technique is advocated for puncture of deeply situated masses and has proved useful in FNA of 726 lesions in various regions yielding a low rate of inadequate material (7.3%), false-negative results (2.5%), and complications. When compared with standard techniques, this technique has the essential advantage that the aspirated material can be judged visually for adequacy before the biopsy needle is withdrawn.

A new technique was applied to improve safety for large-bore biopsies of subpleural pulmonary lesions. In 27 patients, normal saline solution (20-40 ml) was injected extrapleurally under CT-guidance in the access route to subpleurally situated lung lesions. Thickness of ventilated lung interposed between the target and the parietal pleural was up to 8 mm (mean: 4.1 mm). The injected fluid resulted in an extrapleural bulge that abutted the lesion to be biopsied. Biopsy with the 14-gauge Trucut needle did not result in pneumothorax in all cases. There were no complications associated with this technique. Extrapleural injection of saline may provide a safe access route to selected pulmonary lesions for CT-guided large-bore transthoracic biopsies.