Enhancing the Therapeutic Potential of Mesenchymal Stromal Cell-Based Therapies with an Anti-Fibrotic Agent for the Treatment of Chronic Kidney Disease

Chronic kidney disease (CKD) affects 1 in 10 members of the general population, placing these patients at an increasingly high risk of kidney failure. Despite the significant burden of CKD on various healthcare systems, there are no effective cures that reverse or even halt its progression. In recent years, human bone-marrow-derived mesenchymal stromal cells (BM-MSCs) have been recognised as a novel therapy for CKDs, owing to their well-established immunomodulatory and tissue-reparative properties in preclinical settings, and their promising safety profile that has been demonstrated in patients with CKDs from several clinical trials. However, renal fibrosis (scarring), a hallmark of CKD, has been shown to impair the viability and functionality of BM-MSCs post-transplantation. This has suggested that BM-MSCs might require a pre-treatment or adjunct therapy that can enhance the viability and therapeutic efficacy of these stromal cells in chronic disease settings. To address this, recent studies that have combined BM-MSCs with the anti-fibrotic drug serelaxin (RLX), have demonstrated the enhanced therapeutic potential of this combination therapy in normotensive and hypertensive preclinical models of CKD. In this review, a critical appraisal of the preclinical data available on the anti-fibrotic and renoprotective actions of BM-MSCs or RLX alone and when combined, as a treatment option for normotensive vs. hypertensive CKD, is discussed.     

Potential for identification of wild night-flying moths by remote infrared microscopy

There are hundreds of thousands of moth species with crucial ecological roles that are often obscured by their nocturnal lifestyles. The pigmentation and appearance of moths are dominated by cryptic diffuse shades of brown. In this study, 82 specimens representing 26 moth species were analysed using infrared polarimetric hyperspectral imaging in the range of 0.95–2.5 µm. Contrary to previous studies, we demonstrate that since infrared light does not resolve the surface roughness, wings appear glossy and specular at longer wavelengths. Such properties provide unique reflectance spectra between species. The reflectance of the majority of our species could be explained by comprehensive models, and a complete parametrization of the spectral, polarimetric and angular optical properties was reduced to just 11 parameters with physical units. These parameters are complementary and, compared with the within-species variation, were significantly distinct between species. Counterintuitively to the aperture-limited resolution criterion, we could deduce microscopic features along the surface from their infrared properties. These features were confirmed by electron microscopy. Finally, we show how our findings could greatly enhance opportunities for remote identification of free-flying moth species, and we hypothesize that such flat specular wing targets could be expected to be sensed over considerable distances.     

Structural Analysis of Mitochondrial Dynamics—From Cardiomyocytes to Osteoblasts: A Critical Review

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.     

Persistent excitation condition within the dual control framework

Model Predictive Control framework is currently used in many different fields of expertise. The inherent part and very often also the main bottleneck is the model of a process used for the computation of predictions.Due to many reasons e.g. ageing, from time to time there exists a need to adjust/re-identify (if there was already some kind of a model-based controller) or to construct a brand new model (in other cases). Frequently, the process generating the data is under some kind of control, imposing thus problems when classical open loop identification methods are considered. The need for models identified from the data gathered in a closed-loop fashion and a request for possible re-identification of the model parameters lead to the emerge of dual control where the problems of control and system identification are addressed simultaneously.In this paper, we present a new algorithm based on the persistent excitation condition when the minimal eigenvalue of the information matrix is maximized in order to have sufficiently exciting optimal control signal satisfying the control requirements.     

Pour une réponse multiforme à un problème délicat

Résumé

L'accentuation d'une orientation visant à fonder un enseignement des sciences sur une utilité immédiate introuvable, ne peut en définitive que compliquer le problème au lieu de le résoudre. Si le bon point d'entrée est bien celui de la formulation des besoins sociaux en savoir, ces besoins seraient ceux d'une société, et non pas d'une collection d'individus. On avancerait plus facilement dans cette formulation si l'on ne cherchait pas une réponse selon un axe unique, mais par une combinaison de trois types d'activités: la mise en contact avec des points jugés scientifiquement centraux; la mise en contact avec la science qui se fait ; la possibilité d'expérimenter pour soi et collectivement la nature des modélisations scientifiques. Chemin difficile, mais peut‐être pas impossible.     

Analogical transfer from a simulated physical system.

Previous research has consistently found that spontaneous analogical transfer is strongly tied to concrete and contextual similarities between the cases. However, that work has largely failed to acknowledge that the relevant factor in transfer is the similarity between individuals' mental representations of the situations rather than the overt similarities between the cases themselves. Across several studies, we found that participants were able to transfer strategies learned from a perceptually concrete simulation of a physical system to a task with very dissimilar content and appearance. This transfer was reflected in better performance on the transfer task when its underlying dynamics were consistent rather than inconsistent with the preceding training task. Our data indicate that transfer in these tasks relies on the perceptual and spatial nature of the training task but does not depend on direct interaction with the system, with participants performing equally well after simply observing the concrete simulation. We argue that participants generated a spatial, dynamic, and force-based mental model while interacting with the training simulation and tended to spontaneously interpret the transfer task according to this primed model. Unexpectedly, our data consistently show that transfer was independent of reported recognition of the analogy between tasks: Although such recognition was associated with better overall performance, it was not associated with better transfer (in terms of applying an appropriate strategy). Together, these findings suggest that analogical transfer between overtly dissimilar cases may be much more common—and much more relevant to our cognitive processing—than is generally assumed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Electropulse-induced cementite nanoparticle formation in deformed pearlitic steels

Passing one electric current pulse through deformed pearlitic steel wires at room temperature causes the formation of cementite particles around 30 nm in size. This is found not only in some particular locations but throughout the cementite area, which reveals a different mechanism from traditional spheroidization of cementite plates because the latter leads to the formation of particles with much large size. Transmission electron microscopy images show electropulse-induced strain relief and formation of fine precipitations. Differential scanning calorimetry analysis demonstrates the additional stored free energy by electropulsing treatment. The raised free energy accounts the increased interface area in finer microstructure of materials. The experiment evidences that the passing electric current in metal has alternated the free energy sequence of various microstructures in comparison with that of current-free system.     

Degrader foils for the CARIBU project

The Californium Rare Ion Breeder Upgrade (CARIBU) project was conceived to provide neutron rich beams originating from the 3% fission decay branch of a ²⁵²Cf source to be accelerated by the Argonne Tandem Linear Accelerator System (ATLAS). This 1Ci ²⁵²Cf source will be housed in a movable shielded cask, from which it can be directly transferred into a large helium gas stopper cell. Within the gas stopper, the CARIBU ²⁵²Cf source is positioned behind an aluminum degrader foil where the radioactive recoils of interest lose most of their energy before being stopped in the helium gas. To stop recoils over the full fission mass range effectively, three degraders of increasing thickness are required, one to cover the light fission peak and two for the isotopes in the heavy fission peak.The geometry of the source within the gas cell would ideally require a hemispherically shaped degrader foil for uniform energy loss of the fission products. The fabrication of a thin foil of such a shape proved to be exceedingly difficult and, therefore, a compromise “top hat” arrangement was designed. In addition, the ultra-high vacuum (UHV) environment necessary for the gas cell to function properly prevented the use of any epoxy due to vacuum outgassing. Handling, assembling of the foils and mounting must be done under clean room conditions. Details of early attempts at producing these foils as well as handling and mounting will be discussed.     

Influence of Aging Parameters on the Tensile Properties and Quality Index of Al-9?Pct Si-1.8?Pct Cu-0.5?Pct Mg 354-Type Casting Alloys

The current study was carried out with a view to investigating the influence of age-hardening parameters, aging temperature and time, on the tensile properties and quality indices of a high-strength Al-9 pct Si casting alloy, namely, 354-Al-9 pct Si-1.8 pct Cu-0.5 pct Mg. Quality charts were used as an evaluation tool for selecting the optimum conditions to be applied, in practice, in order to develop high strength and optimum quality in 354 casting alloy. Aging at a low temperature of 428 K (155 °C) was observed to produce the greatest strength and optimum quality in the 354-type castings compared to aging at higher temperatures. The peak strength observed for 354 alloy may be attained after shorter aging times on the condition that the aging temperature is increased. The aging times required for reaching peak strength in 354 alloys are 72 hours, 40 hours, 8 hours, 1 hour, and 15 minutes at aging temperatures of 428 K, 443 K, 468 K, 493 K, and 518 K (155 °C, 170 °C, 195 °C, 220 °C, and 245 °C), respectively. Aging treatment at higher temperatures is accompanied by a reduction in the tensile properties and quality index values of the castings; however, it also introduces the possibility of a significant economical strategy for minimizing the time and the cost of this same treatment. Aging treatment at a lower temperature of 428 K (155 °C) produces fine and dense precipitates displaying smaller interparticle spacing, while at higher aging temperatures, such as 518 K (245 °C), the precipitates are coarser in size, less dense, and more widely dispersed. The quality charts developed in the course of the current research facilitate the interpretation and evaluation of the tensile properties of the 354 alloy. Such charts provide a logical evaluation tool, from the metallurgical point of view, for an accurate prediction of the influence of aging parameters studied on the properties of the alloys. Depending on the required level of tensile properties and based on the quality charts developed, it is possible to make a rigorous selection as to the most suitable aging parameters to be applied to the 354 alloy so as to obtain the best possible cost-effective compromise between alloy strength and quality.     

Survey questionnaire results of the current level of knowledge on trenchless technologies in China

With a growing population and densely populated urban environments, China is looking at alternative methods of underground pipeline installation and replacement of their aging infrastructure. Conventional open trench activities result in disruption to these urban centers through road closures, traffic delays, traffic detours, loss of access to homes and business, unsightliness, noise and general disruption for everyone. Trenchless technologies are a viable and sustainable solution to China’s buried infrastructure. Numerous challenges are present when promoting trenchless technologies in China including minimal local engineering knowledge, lack of trained contractors, lack of specifications, and system impact concerns raised by government owners. This paper presents the results of a survey questions obtained from a cross-section of 209 Chinese engineers from Shanghai, Beijing, Shengyang, Chongqing, and Guangzhou to gain a snapshot of the current level of knowledge on trenchless construction methods. The results reveal an understanding of trenchless technology in general; however, a lack of understanding of technologies such as lining of pipe, trenchless grouting, auger boring, and pipe bursting. Pipe jacking and horizontal directional drilling are currently by far the most recognized and understood trenchless technologies in China.