247 research outputs found
26.5 ps Time Resolution Using 50 {\mu}m Low Gain Avalanche Detectors Fabricated by Micron Semiconductor Ltd
Low Gain Avalanche Detectors (LGADs) are silicon semiconductor sensors with
an implanted thin p-doped multiplication layer that is designed to provide low
gain. Most importantly, LGADs are specifically engineered to provide excellent
spatial and temporal resolution simultaneously. The technology shows promising
prospects of fulfilling the 4D tracking requirements of future high energy
physics experiments. Micron Semiconductor Ltd. has fabricated LGADs with an
active thickness of 50 m. The electrical and timing performance has been
measured and compared with devices fabricated at IMB-CNM for reference. 50
m thin LGADs by Micron Semiconductor Ltd. were measured to have a timing
resolution in the region of 30 ps using a dedicated setup involving minimum
ionising particles produced by Sr-90. Specifically, the best timing resolution
of 26.5 ps was measured at a bias voltage of 200 V at -30{\deg}C
Cells under pressure – the relationship between hydrostatic pressure and mesenchymal stem cell chondrogenesis
Early osteoarthritis (OA), characterised by cartilage defects, is a degenerative disease that greatly affects the adult population. Cell-based tissue engineering methods are being explored as a solution for the treatment of these chondral defects. Chondrocytes are already in clinical use but other cell types with chondrogenic properties, such as mesenchymal stem cells (MSCs), are being researched. However, present methods for differentiating these cells into stable articular-cartilage chondrocytes that contribute to joint regeneration are not effective, despite extensive investigation. Environmental stimuli, such as mechanical forces, influence chondrogenic response and are beneficial with respect to matrix formation. In vivo, the cartilage is subjected to multiaxial loading involving compressive, tensile, shear and fluid flow and cellular response. Tissue formation mechanobiology is being intensively studied in the cartilage tissue-engineering research field. The study of the effects of hydrostatic pressure on cartilage formation belongs to the large area of mechanobiology. During cartilage loading, interstitial fluid is pressurised and the surrounding matrix delays pressure loss by reducing fluid flow rate from pressurised regions. This fluid pressurisation is known as hydrostatic pressure, where a uniform stress around the cell occurs without cellular deformation. In vitro studies, examining chondrocytes under hydrostatic pressure, have described its anabolic effect and similar studies have evaluated the effect of hydrostatic pressure on MSC chondrogenesis. The present review summarises the results of these studies and discusses the mechanisms through which hydrostatic pressure exerts its effects
Integrins α2β1 and α11β1 regulate the survival of mesenchymal stem cells on collagen I
Although mesenchymal stem cells (MSCs) are the natural source for bone regeneration, the exact mechanisms governing MSC crosstalk with collagen I have not yet been uncovered. Cell adhesion to collagen I is mostly mediated by three integrin receptors – α1β1, α2β1 and α11β1. Using human MSC (hMSC), we show that α11 subunit exhibited the highest basal expression levels but on osteogenic stimulation, both α2 and α11 integrins were significantly upregulated. To elucidate the possible roles of collagen-binding integrins, we applied short hairpin RNA (shRNA)-mediated knockdown in hMSC and found that α2 or α11 deficiency, but not α1, results in a tremendous reduction of hMSC numbers owing to mitochondrial leakage accompanied by Bcl-2-associated X protein upregulation. In order to clarify the signaling conveyed by the collagen-binding integrins in hMSC, we analyzed the activation of focal adhesion kinase, extracellular signal-regulated protein kinase and serine/threonine protein kinase B (PKB/Akt) kinases and detected significantly reduced Akt phosphorylation only in α2- and α11-shRNA hMSC. Finally, experiments with hMSC from osteoporotic patients revealed a significant downregulation of α2 integrin concomitant with an augmented mitochondrial permeability. In conclusion, our study describes for the first time that disturbance of α2β1- or α11β1-mediated interactions to collagen I results in the cell death of MSCs and urges for further investigations examining the impact of MSCs in bone conditions with abnormal collagen I
Interactions of Human Endothelial and Multipotent Mesenchymal Stem Cells in Cocultures
Current strategies for tissue engineering of bone rely on the implantation of scaffolds, colonized with human mesenchymal stem cells (hMSC), into a recipient. A major limitation is the lack of blood vessels. One approach to enhance the scaffold vascularisation is to supply the scaffolds with endothelial cells (EC)
Different culture conditions affect the growth of human tendon stem/progenitor cells (TSPCs) within a mixed tendon cells (TCs) population
Gene expression markers of tendon fibroblasts in normal and diseased tissue compared to monolayer and three dimensional culture systems
<p>Abstract</p> <p>Background</p> <p>There is a paucity of data regarding molecular markers that identify the phenotype of the tendon cell. This study aims to quantify gene expression markers that distinguish between tendon fibroblasts and other mesenchymal cells which may be used to investigate tenogenesis.</p> <p>Methods</p> <p>Expression levels for 12 genes representative of musculoskeletal tissues, including the proposed tendon progenitor marker scleraxis, relative to validated reference genes, were evaluated in matched samples of equine tendon (harvested from the superficial digital flexor tendon), cartilage and bone using quantitative PCR (qPCR). Expression levels of genes associated with tendon phenotype were then evaluated in healthy, including developmental, and diseased equine tendon tissue and in tendon fibroblasts maintained in both monolayer culture and in three dimensional (3D) collagen gels.</p> <p>Results</p> <p>Significantly increased expression of scleraxis was found in tendon compared with bone (P = 0.002) but not compared to cartilage. High levels of COL1A2 and scleraxis and low levels of tenascin-C were found to be most representative of adult tensional tendon phenotype. While, relative expression of scleraxis in developing mid-gestational tendon or in acute or chronically diseased tendon did not differ significantly from normal adult tendon, tenascin-C message was significantly upregulated in acutely injured equine tendon (P = 0.001). Relative scleraxis gene expression levels in tendon cell monolayer and 3D cultures were significantly lower than in normal adult tendon (P = 0.002, P = 0.02 respectively).</p> <p>Conclusion</p> <p>The findings of this study indicate that high expression of both COL1A2 and scleraxis, and low expression of tenascin-C is representative of a tensional tendon phenotype. The <it>in vitro </it>culture methods used in these experiments however, may not recapitulate the phenotype of normal tensional tendon fibroblasts in tissues as evidenced by gene expression.</p
In situ guided tissue regeneration in musculoskeletal diseases and aging: Implementing pathology into tailored tissue engineering strategies
In situ guided tissue regeneration, also addressed as in situ tissue engineering or endogenous regeneration, has a great potential for population-wide “minimal invasive” applications. During the last two decades, tissue engineering has been developed with remarkable in vitro and preclinical success but still the number of applications in clinical routine is extremely small. Moreover, the vision of population-wide applications of ex vivo tissue engineered constructs based on cells, growth and differentiation factors and scaffolds, must probably be deemed unrealistic for economic and regulation-related issues. Hence, the progress made in this respect will be mostly applicable to a fraction of post-traumatic or post-surgery situations such as big tissue defects due to tumor manifestation. Minimally invasive procedures would probably qualify for a broader application and ideally would only require off the shelf standardized products without cells. Such products should mimic the microenvironment of regenerating tissues and make use of the endogenous tissue regeneration capacities. Functionally, the chemotaxis of regenerative cells, their amplification as a transient amplifying pool and their concerted differentiation and remodeling should be addressed. This is especially important because the main target populations for such applications are the elderly and diseased. The quality of regenerative cells is impaired in such organisms and high levels of inhibitors also interfere with regeneration and healing. In metabolic bone diseases like osteoporosis, it is already known that antagonists for inhibitors such as activin and sclerostin enhance bone formation. Implementing such strategies into applications for in situ guided tissue regeneration should greatly enhance the efficacy of tailored procedures in the future
Mechanical characteristics of mesenchymal stem cells under impact of silica-based nanoparticles
Multiscale multifactorial approaches for engineering tendon substitutes
The physiology of tendons and the continuous strains experienced daily make tendons very prone to injury. Excessive and prolonged loading forces and aging also contribute to the onset and progression of tendon injuries, and conventional treatments have limited efficacy in restoring tendon biomechanics. Tissue engineering and regenerative medicine (TERM) approaches hold the promise to provide therapeutic solutions for injured or damaged tendons despite the challenging cues of tendon niche and the lack of tendon-specific factors to guide cellular responses and tackle regeneration. The roots of engineering tendon substitutes lay in multifactorial approaches from adequate stem cells sources and environmental stimuli to the construction of multiscale 3D scaffolding systems.
To achieve such advanced tendon substitutes, incremental strategies have been pursued to more closely recreate the native tendon requirements providing structural as well as physical and chemical cues combined with biochemical and mechanical stimuli to instruct cell behavior in 3D architectures, pursuing mechanically competent constructs with adequate maturation before implantation.Authors acknowledge the project “Accelerating tissue engineering and personalized medicine discoveries by the integration of key enabling nanotechnologies, marinederived biomaterials and stem cells,” supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European
Regional Development Fund (ERDF).
Authors acknowledge the H2020 Achilles Twinning Project No. 810850, and also the European
Research Council CoG MagTendon No. 772817, and the FCT Project MagTT PTDC/CTM-CTM/
29930/2017 (POCI-01-0145-FEDER-29930
Studies of and production in and Pb collisions
The production of and mesons is studied in proton-proton and
proton-lead collisions collected with the LHCb detector. Proton-proton
collisions are studied at center-of-mass energies of and ,
and proton-lead collisions are studied at a center-of-mass energy per nucleon
of . The studies are performed in center-of-mass rapidity
regions (forward rapidity) and
(backward rapidity) defined relative to the proton beam direction. The
and production cross sections are measured differentially as a function
of transverse momentum for and , respectively. The differential cross sections are used to
calculate nuclear modification factors. The nuclear modification factors for
and mesons agree at both forward and backward rapidity, showing
no significant evidence of mass dependence. The differential cross sections of
mesons are also used to calculate cross section ratios,
which show evidence of a deviation from the world average. These studies offer
new constraints on mass-dependent nuclear effects in heavy-ion collisions, as
well as and meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb
public pages
- …