Abstract Background aims A clinically applicable tolerance induction regimen that removes the requirement for lifelong immunosuppression would benefit recipients of vascularized composite ...allotransplantation (VCA). We characterized the immunomodulatory properties of syngeneic (derived from the recipient strain) adipocyte-derived stem cells (ADSCs) and investigated their potential to induce VCA tolerance in rats. Methods ADSCs were isolated from Lewis (LEW, RT1Al ) rats; their immunomodulatory properties were evaluated by means of mixed lymphocyte reactions in vitro and VCAs in vivo across a full major histocompatibility complex mismatch with the use of Brown-Norway (BN, RT1An ) donor rats. Two control and four experimental groups were designed to evaluate treatment effects of ADSCs and transient immunosuppressants (anti-lymphocyte globulin, cyclosporine) with or without low-dose (200 cGy) total body irradiation. Flow cytometry was performed to quantify levels of circulating CD4+ CD25+ FoxP3+ regulatory T cells (Tregs). Results Cultured syngeneic ADSCs exhibited CD90.1+ CD29+ CD73+ CD45− CD79a− CD11b/c− phenotype and the plasticity to differentiate to adipocytes and osteocytes. ADSCs dramatically suppressed proliferation of LEW splenocytes against BN antigen and mitogen, respectively, in a dose-dependent fashion, culminating in abrogation of allo- and mitogen-stimulated proliferation at the highest concentration tested. Accordingly, one infusion of syngeneic ADSCs markedly prolonged VCA survival in LEW recipients treated with transient immunosuppression; of these, 66% developed tolerance. Total body irradiation provided no additional VCA survival benefit. An important role for Tregs in tolerance induction/maintenance was suggested in vivo and in vitro. Conclusions Treatment comprising syngeneic ADSCs and transient immunosuppression (i) increased levels of circulating Tregs and (ii) induced tolerance in 66% of recipients of major histocompatibility complex–mismatched VCAs.
Purpose
The purpose of this paper is to propose and demonstrate a new additive manufacturing approach that breaks the layer-based point scanning limitations to increase fabrication speed, obtain ...better surface finish, achieve material flexibility and reduce equipment costs.
Design/methodology/approach
The freeform additive manufacturing approach conceptually views a 3D article as an assembly of freeform elements distributed spatially following a flexible 3D assembly structure, which conforms to the surface of the article and physically builds the article by sequentially forming the freeform elements by a vari-directional vari-dimensional capable material deposition mechanism. Vari-directional building along tangential directions of part surface gives surface smoothness. Vari-dimensional deposition maximizes material output to increase build rate wherever allowed and minimizes deposition sizes for resolution whenever needed.
Findings
Process steps based on geometric and data processing considerations were described. Dispensing and forming of basic vari-directional and vari-dimensional freeform elements and basic operations of joining them were developed using thermoplastics. Forming of 3D articles at build rates of 2-5 times the fused deposition modeling (FDM) rate was demonstrated and improvement over ten times was shown to be feasible. FDM compatible operations using 0.7 mm wire depositions from a variable exit-dispensing unit were demonstrated. Preliminary tests of a surface finishing process showed a result of 0.8-1.9 um Ra. Initial results of dispensing wax, tin alloy and steel were also shown.
Originality/value
This is the first time that both vari-directional and vari-dimensional material depositions are combined in a new freeform building method, which has potential impact on the FDM and other additive manufacturing methods.
Although regional differences in cerebral volume have been revealed in developing human brains, little is known regarding the regionalization of cortical shape. This study documented the regional and ...quantitative shape difference of cortical surfaces for in utero normal fetal brains over a time period essential for the formation of primary cortical folding (22–33 weeks). Each brain surface with complete three‐dimensional morphology was manually extracted from the reconstructed image, which combined surface information from three orthogonal magnetic resonance images in utero. An innovative parcellation was used to dissect the fetal brains into frontal, parietal, temporal and occipital lobes, and to avoid the determination of non‐existent and immature sulci for young fetuses. Distinct cortical shapes were encoded by the shape index automatically. The results of this study show faster shape changes in the occipital lobe than in other regions. Both regional and global shape patterns show that the gyral surface smoothens, whereas the sulcal surface becomes more angular, with gestational age. In addition, the smoothing of gyri is related mainly to the changes in shape of gyral crowns. This study presents the regional differences in early gyrification from the novel aspect of shape. The results of shape pattern analysis for normal fetuses may act as a reference in assessments of prenatal brain pathology and in extensive comparisons between various life stages.
Visceral fat is considered important in the pathogenesis of metabolic syndrome (MS). Here, we developed a novel method for determining visceral fat by measuring liver–kidney space (LKS) on abdominal ...sonography and expanded its utilization in the elderly to predict MS.
To assess the correlation between the LKS and MS, 317 consecutive outpatients scheduled for health evaluation were retrospective analyzed. Anthropometric measurements, blood pressure, fasting blood glucose levels, and lipid profiles were obtained following standard protocols. On sonography, the thickness of visceral fat between the liver and right kidney was measured. We also compared its accuracy to predict MS with sonographic fatty liver changes. A total of 72 elderly patients older than 65 years were evaluated (mean age: 66.02 65–83).
In the current study, LKS = 4 mm enabled a better prediction of MS. The area under the receiver operating characteristic curve was 0.626. The sensitivity and specificity for the presence of visceral fat to predict MS in the elderly were 0.58 and 0.73, respectively. The accuracy to predict MS was 68.1% for the measurement of visceral fat compared with 59.6% for sonographic fatty liver change in the elderly.
Measuring LKS by sonography may be a practical method for evaluating visceral fat in the elderly and for predicting MS better than sonographic fatty liver changes. LKS was more associated with abdominal girth and BMI in the elderly from the study supporting the observation that LKS are well correlated with general adiposity.
Regional differences in human brain development during infancy have been studied for many years, but little is known about how regionalization of the brain proceeds during intrauterine life. We ...investigated the regionalization of cerebral volume and cortical convolutions based on the volumetric magnetic resonance images (MRIs) of 43 fetuses, ranging from 21 to 37 weeks of gestation. Two plausible parcellations of MRI are proposed, and curvature index together with gyrification index are used to quantify the regional cortical convolutions. Our results elucidate that the cortical foldings among different brain regions develop at comparable rates, suggesting a similar uniformity of changes in size of the cortical sheet in these regions over time. On the contrary, the growth of the cerebral volume presents regional difference, with the frontal and parieto‐temporal regions growing significantly faster than other regions due to the contribution from expansion of basal ganglia. This quantitative regional information suggests that cerebral volume is not a relevant parameter to measure in relation to gyrification, and that the size of the cortical sheet is more likely to be directly related to cortical folding. The availability of quantitative regional information on normal fetal brains in utero will allow clinical application of this information when probing neurodevelopmental disorders in the future.
Musculoskeletal fibromatosis remains a disease of unknown etiology. Surgical excision is the standard of care, but the recurrence rate remains high. Superficial fibromatosis typically presents as ...subcutaneous nodules caused by rapid myofibroblast proliferation followed by slow involution to dense acellular fibrosis. In this study, we demonstrate that fibromatosis stem cells (FSCs) can be isolated from palmar nodules but not from cord or normal palm tissues. We found that FSCs express surface markers such as CD29, CD44, CD73, CD90, CD105, and CD166 but do not express CD34, CD45, or CD133. We also found that FSCs are capable of expanding up to 20 passages, that these cells include myofibroblasts, osteoblasts, adipocytes, chondrocytes, hepatocytes, and neural cells, and that these cells possess multipotentiality to develop into the three germ layer cells. When implanted beneath the dorsal skin of nude mice, FSCs recapitulated human fibromatosis nodules. Two weeks after implantation, the cells expressed immunodiagnostic markers for myofibroblasts such as α-smooth muscle actin and type III collagen. Two months after implantation, there were fewer myofibroblasts and type I collagen became evident. Treatment with the antifibrogenic compound Trichostatin A (TSA) inhibited the proliferation and differentiation of FSCs in vitro. Treatment with TSA before or after implantation blocked formation of fibromatosis nodules. These results suggest that FSCs are the cellular origin of fibromatosis and that these cells may provide a promising model for developing new therapeutic interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Different capping layers were deposited on 2.5 nm Co72Fe8B20 to investigate their effects on damping constants and critical current density (JC0) for spin-torque-transfer switching. The damping ...constant of CoFeB is affected by the interfacial conditions and the spin-pumping effects. The Cu capping layer significantly suppresses intermixing and possesses the lowest damping constant of 0.009. The micromagnetic simulations reveal that the low damping constant of CoFeB may result in the nucleation of domains at lower current density, and thus reduces JC0. A reduction of 27% in JC0 can be achieved by replacing the conventional Ta capping layer with a Cu layer.
► We isolated stem cells from human palmar fibromatosis and compared it with bone marrow stem cells. ► Fibromatosis stem cells possessed better fibrogenic differentiation potential. ► Fibromatosis ...stem cells could recapitulate murine model of fibromatosis nodule. ► Bone marrow stem cells have a limited role in the progression of palmar fibromatosis. ► This murine model of fibromatosis model can be used as a platform for preclinical trial.
Palmar fibromatosis is a benign fibroproliferative tumor of unknown etiology, with a high rate of recurrence after excision. The offending cells of palmar fibromatosis are myofibroblasts and the cellular origin of other myofibroblasts has previously been reported to be the bone marrow. However, further clarification of the relationship between bone marrow precursors and palmar fibromatosis is required. Stem cells (SCs) are known to exist in various tissues, but whether SCs can be isolated from fibromatosis tissue is still unclear. The purpose of this study was to isolate and identify stem cells from human palmar fibromatosis, and to evaluate the differences in the differentiation and fibrogenic capacities of bone marrow stem cells (BMSCs) and fibromatosis-derived stem cells (FSCs). We found that FSCs had better fibrogenic differentiation potential than BMSCs, whereas BMSCs had better adipogenic and chondrogenic differentiation capacities. Treatment with transforming growth factor-β1 increased the expression of α-smooth muscle actin, and types III and I collagen significantly more in FSCs than in BMSCs. An in vivo study further confirmed the results of fibrogenesis and suggested that FSCs can recapitulate the fibromatosis nodule. In summary, their myofibroblastic differentiation both in vivo and in vitro makes FSCs a potential cell source for future applications in murine models of fibromatosis or fibrogenesis.
Commercial as-hp (hot pressing) treated Cr–Si targets are used throughout this study, with three different compositions: Cr20–Si80, Cr35–Si65 and Cr50–Si50. To evaluate the effects of microstructure ...and properties of as-hp treated Cr–Si targets by hot isostatic pressing (HIP) SEM, XRD and porosity inspections were performed. The experimental results showed that the 1373
K, 1750
MPa, 4
h HIP treated with three different Cr–Si targets had suppressed porosities successfully. The most efficient was Cr50–Si50 target subjected to HIP treatment. Porosity decreased about 60% after HIP treatment, and both the nitrogen and oxygen concentrations of the targets were slightly increased after HIP treatment. This was especially true for the single silicon in Cr–Si targets such as Cr20–Si80 and Cr35–Si65. The aim of this paper is to discuss these methods and finding suitable temperatures for the HIP for Cr–Si targets.
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