ER Stress in ERp57 Knockout Knee Joint Chondrocytes Induces Osteoarthritic Cartilage Degradation and Osteophyte Formation

Ageing or obesity are risk factors for protein aggregation in the endoplasmic reticulum (ER) of chondrocytes. This condition is called ER stress and leads to induction of the unfolded protein response (UPR), which, depending on the stress level, restores normal cell function or initiates apoptotic cell death. Here the role of ER stress in knee osteoarthritis (OA) was evaluated. It was first tested in vitro and in vivo whether a knockout (KO) of the protein disulfide isomerase ERp57 in chondrocytes induces sufficient ER stress for such analyses. ER stress in ERp57 KO chondrocytes was confirmed by immunofluorescence, immunohistochemistry, and transmission electron microscopy. Knee joints of wildtype (WT) and cartilage-specific ERp57 KO mice (ERp57 cKO) were analyzed by indentation-type atomic force microscopy (IT-AFM), toluidine blue, and immunofluorescence/-histochemical staining. Apoptotic cell death was investigated by a TUNEL assay. Additionally, OA was induced via forced exercise on a treadmill. ER stress in chondrocytes resulted in a reduced compressive stiffness of knee cartilage. With ER stress, 18-month-old mice developed osteoarthritic cartilage degeneration with osteophyte formation in knee joints. These degenerative changes were preceded by apoptotic death in articular chondrocytes. Young mice were not susceptible to OA, even when subjected to forced exercise. This study demonstrates that ER stress induces the development of age-related knee osteoarthritis owing to a decreased protective function of the UPR in chondrocytes with increasing age, while apoptosis increases. Therefore, inhibition of ER stress appears to be an attractive therapeutic target for OA.     

Multicriteria optimization as enabler for Sustainable Ceramic Matrix Composites

Over the past 40 years, development of Ceramic Matrix Composites (CMCs) has focused mainly on the improvement of material performance and optimization of cost-efficient production routes. Recently, more fields of application have opened up for CMCs, in which environmental impacts are relevant. These impacts have barely been investigated so far but receive growing interest due to increasing awareness of the environmental consequences. Our innovative approach frames material properties in relation to environmental impacts (e.g., global warming potential in CO₂ emission) by varying process parameters to balance optimum performance against environmental considerations. First, the process of wet filament winding has been investigated up to the Carbon Fiber Reinforced Plastic (CFRP) state by changing both the curing and tempering temperatures. During the production of CFRP plates, mass and energy flows were tracked in each step. Three point-bending and interlaminar shear tests have been performed on the resulting samples to identify basic mechanical properties. The environmental impacts are determined by a cradle-to-gate Life Cycle Assessment (LCA), using the software SimaPro. The resulting tradeoffs between mechanical properties and environmental impacts show nonlinear behavior, thus revealing optimum points above which improved mechanical properties are associated with significantly higher CO₂ emissions.     

Short fiber-reinforced oxide fiber composites

This paper presents a novel fiber spraying process for the manufacturing of short fiber bundle-reinforced Nextel™ 610/Al₂O₃-ZrO₂ oxide fiber composites (SF-OFC) and its characterization. First, the influence of varying fiber lengths (7, 14, and 28 mm, continuous fibers) and fiber orientations (unidirectional 0°, quasi-isotropic, ±45°) was investigated using hand-laid SF-OFC. Due to the weak matrix, the hand-laid material exhibited a strongly fiber-dominated material behavior, that is, variations in fiber length and orientation had a strong influence on the material properties. Second, the automated sprayed SF-OFC, however, exhibited a random orientation of the fiber bundles, which resulted in in-plane isotropic material properties. Average bending strengths of up to 177 MPa, strains of .39%, and a quasi-ductile fracture behavior were achieved. The strain was, therefore, in the range of fabric-reinforced OFC. While the bending strength of the SF-OFC was somewhat lower than that of fabric-reinforced OFC with the fiber orientation parallel to the loading direction, it was more than two times higher than the strength in 45° direction relative to the fabric reinforcement. Combined with good drapability and lower material costs compared to fabric-reinforced OFC, SF-OFC is, therefore, a promising material for industrial applications.     

Enhancing Post-Stroke Rehabilitation and Preventing Exo-Focal Dopaminergic Degeneration in Rats—A Role for Substance P

Dopaminergic signaling is a prerequisite for motor learning. Delayed degeneration of dopaminergic neurons after stroke is linked to motor learning deficits impairing motor rehabilitation. This study investigates safety and efficacy of substance P (SP) treatment on post-stroke rehabilitation, as this neuropeptide combines neuroprotective and plasticity-promoting properties. Male Sprague Dawley rats received a photothrombotic stroke within the primary motor cortex (M1) after which a previously acquired skilled reaching task was rehabilitated. Rats were treated with intraperitoneal saline (control group, n = 7) or SP-injections (250 µg/kg) 30 min before (SP-pre; n = 7) or 16 h (SP-post; n = 6) after rehabilitation training. Dopaminergic neurodegeneration, microglial activation and substance P-immunoreactivity (IR) were analyzed immunohistochemically. Systemic SP significantly facilitated motor rehabilitation. This effect was more pronounced in SP-pre compared to SP-post animals. SP prevented dopaminergic cell loss after stroke, particularly in the SP-pre condition. Despite its proinflammatory propensity, SP administration did not increase stroke volumes, post-stroke deficits or activation of microglia in the midbrain. Finally, SP administration prevented ipsilesional hypertrophy of striatal SPergic innervation, particularly in the SP-post condition. Mechanistically, SP-pre likely involved plasticity-promoting effects in the early phase of rehabilitation, whereas preservation of dopaminergic signaling may have ameliorated rehabilitative success in both SP groups during later stages of training. Our results demonstrate the facilitating effect of SP treatment on motor rehabilitation after stroke, especially if administered prior to training. SP furthermore prevented delayed dopaminergic degeneration and preserved physiological endogenous SPergic innervation.     

Control of the Preferred Orientation in MFI Films Synthesized by Seeding

Single crystal silicon and quartz wafers were seeded with colloidal TPA-silicalite-1 crystals. Hydrothermal treatment of the seeded substrates was used to grow dense MFI films. The preferred orientation of the crystals constituting the films as a function of the amount and size of seeds, film thickness and hydrothermal treatment conditions was investigated. In thin films, most of the crystalline material was found to be oriented with the b-axes close to perpendicular to the substrate surface. In thick films, the a- or c-axes were close to perpendicular to the substrate surface depending on the conditions used for hydrothermal treatment. The seed size and amount was found to affect the rate of change in preferred orientation as a function of film thickness. A film growth mechanism which is able to explain the experimental results is proposed.     

Indentation Damage and Residual Stress Field in Alumina-Y2O3-Stabilized Zirconia Composites

Fracture features, residual stresses, and zirconia transformation are studied in indentation strength specimens of alumina-Y₂O₃-stabilized zirconia (3% mol of Y₂O₃, 3YTZP) ceramics in order to analyze the extension of the indentation damage in the bulk of the specimens. Two compositions, 5 vol% 3YTZP (A5) and 40 vol% 3YTZP (A40), have been prepared by stacking tape-casted tapes and sintering. After indentation with loads ranging from 50 to 300 N, samples were fractured in four-point bending and the fracture surfaces were characterized by scanning electron microscopy. Raman and piezospectroscopic techniques were used to determine the monoclinic zirconia fraction and the residual stresses through the fracture surfaces. In the A5 composition, the indentation damage morphology was clearly half-penny, whereas the A40 composition presented Palmqvist crack formation. Zirconia transformation was only observed in the plastically deformed zones underneath the imprints whereas there were significant residual compressive stresses outside the plastic zones due to the indentation damage. The intensity of this residual compressive field was dependent on the level of zirconia transformation due to indentation damage because zirconia transformation induced tensile stress fields superimposed on the compressive stresses.     

Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing

The sodium-activated potassium channel Slack (K_Na1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (I_KNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated I_KNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated I_KNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.     

Droplet Entrainment Analysis in a Flash Evaporator with an Image-Based Measurement Technique

Local droplet sizes and volumes of entrained liquid are captured with an image-based measurement technique for comparison with a conventional, integral method for entrainment analysis. Experiments in a forced circulation flash evaporation were performed for different operating conditions and with two different chemical systems. Droplet size and frequency rise with an increase in thermal energy input. The local readings confirm the trends found by the integral measurement method. The modification of the image-based probe enables the detection of small (≈ 10 µm) and at the same time fast droplets under challenging operating conditions, such as vacuum and superheated feed similar to industrial process conditions.     

The dynamic transformation of deformed austenite at temperatures above the Ae3

Recent observations regarding the dynamic transformation of deformed austenite at temperatures above the Ae₃ are reviewed. Experimental results obtained on four different steels over the temperature range from 743 to 917 °C and at strains up to ε = 5 are described. It is shown that there is a critical strain for the formation of superequilibrium ferrite and that the volume fraction of transformed ferrite increases with the strain. The structures observed are Widmanstätten in form and appear to have nucleated displacively. The effect of deformation on the Gibbs energy of austenite is estimated by assuming that the austenite continues to work-harden after initiation of the transformation and that its flow stress and dislocation density can be derived from the experimental flow curve by making suitable assumptions about two-phase flow. By further taking into account the inhomogeneity of the dislocation density, Gibbs energy contributions (driving forces) are derived that are sufficient to promote transformation as much as 100 °C above the Ae₃. The C diffusion times required for the dynamic formation of the cementite particles observed are estimated. These range from ～25 to 100 μs and are therefore consistent with the times available during rolling. The Gibbs energy calculations suggest that growth of the Widmanstätten ferrite is followed by C diffusion at the lower carbon contents, while it is accompanied by C diffusion at the higher carbon levels.     

Life cycle cost analysis of a car,a city bus and an intercity bus powertrain for year 2005 and 2020

The international economy, in the beginning of the 20th century, is characterized by uncertainty about the supply and the price of oil. Together with the fast decrease of electrical propulsion component prices, it becomes more and more cost effective to develop vehicles with alternative powertrains. This paper focuses on two questions: Are alternative powertrains especially cost effective for specific applications?; How does an increased fossil fuel price influences the choose of powertrain? To assess these questions, a computer tool named THEPS, developed in a Ph.D. project, is used. Three applications and three scenarios are analysed. The applications, a car, a city bus and an intercity bus, are vehicles all assumed to operate in Sweden. One scenario represents year 2005, the other two year 2020. The two future scenarios are characterized by different fossil fuel prices. The study, presented in the paper, indicates that alternative powertrains can be competitive from a cost perspective, in some applications, already in year 2005. It is for example cost effective to equip a city bus, running in countries with a high fuel price, with a hybrid powertrain. The study also indicates that pure electric, hybrid and/or fuel cell cars will probably be a more cost effective choice than conventional cars in year 2020. Another indication is that it will not be clear which powertrain concept to choose. The reason is that many cost effective powertrain concepts will be offered. The best choice will depend on the application.