pinecone/core-2020-05-10-deduplication huggingface dataset:
Web crippling capacities of rivet fastened rectangular hollow flange channel beams under one flange load cases

A new rivet fastened rectangular hollow flange channel beam (RHFCB) was proposed using an intermittently rivet fastening process as an alternative to welded beams. The rivet fastened RHFCB allows greater section optimisation and flexibility in designing suitable combinations of web and flange widths and thicknesses for many industrial applications. In the industrial applications of rivet fastened RHFCBs as flooring, roofing or modular building systems, their flanges will be fastened to supports, which will provide increased web crippling capacities. However no research has been conducted to investigate the web crippling capacities of RHFCBs with flanges unfastened and fastened to supports under one-flange load cases. Similarly the current design rules for cold-formed steel sections are not suitable for rivet fastened RHFCBs due to their two hollow flanges. Hence an experimental study was conducted to investigate the web crippling behaviour and capacities of rivet fastened RHFCBs based on the new AISI S909 standard test method. It included rivet fastened RHFCBs with flanges unfastened and fastened to supports under End One Flange (EOF) and Interior One Flange (IOF) load cases. Tests with flanges fastened to supports showed that web crippling capacities increased by 39 and 5% for EOF and IOF load cases. Comparisons of experimental web crippling capacity results with predictions using the current AS/NZS 4600 and AISI S100 design standards showed that web crippling design equations are conservative for rivet fastened RHFCBs with flanges unfastened and fastened to supports under EOF and IOF load cases. Hence new equations are proposed to determine the web crippling capacities of rivet fastened RHFCBs. This paper presents the details of this web crippling experimental study of rivet fastened RHFCB sections and the results
Bearing capacity of cold-formed unlipped channels with restrained flanges under EOF and IOF load cases

Bearing failure is a form of localized failure that occurs when thin-walled cold-formed steel sections are subjected to concentrated loads or support reactions. To determine the bearing capacity of cold-formed channel sections, a unified design equation with different bearing coefficients is given in the current North American specification AISI S100 and the Australian/New Zealand standard AS/NZS 4600. However, coefficients are not available for unlipped channel sections that are normally fastened to supports through their flanges. Eurocode 3 Part 1.3 includes bearing capacity equations for different load cases, but does not distinguish between fastened and unfastened support conditions. Therefore, an experimental study was conducted to determine the bearing capacities of these sections as used in floor systems. Twenty-eight web bearing tests on unlipped channel sections with restrained flanges were conducted under End One Flange (EOF) and Interior One Flange (IOF) load cases. Using the results from this study, a new equation was proposed within the AISI S100 and AS/NZS 4600 guidelines to determine the bearing capacities of cold-formed unlipped channels with flanges fastened to supports. A new design rule was also proposed based on the direct strength method
Recent research on composite beams with demountable shear connectors

YesThis paper presents experimental and numerical investigation on an innovative composite floor system with deconstructability. In this system, a composite slab formed with metal profiled decking is connected to a steel beam using demountable shear connectors. A series of push tests was conducted to investigate the behaviour of this form of shear connectors. In addition to the push tests, a full-scale composite beam was tested to failure in the laboratory under a number of cycles of monotonic loading. For direct comparison, a similar composite beam test was conducted using same section size, concrete strength, but using the conventional welded headed stud connectors. Test results showed that the behaviour of the composite beam with demountable shear connectors is comparable with the specimen with welded shear connectors. After the test was terminated, the demountable shear connectors were unfastened and the composite floor can be easily lifted off from the steel beam. Test result showed that these demountable shear connectors possess high ductility in comparison with the equivalent welded shear connectors. Simple design rules currently use in Eurocode 4 for the welded shear connections and Eurocode 3 for bolts are proposed to predict the shear resistance of this form of demountable shear connectors
High-performance water-based barrier coatings for the corrosion protection of structural steel

This article provides an overview of the outcomes of a European-funded project called BarrierPlus. A new type of water-based barrier coating was developed for structural steel applications. The advantages of this coating include enhanced moisture resistance, low volatile organic compounds (VOCs) and one-component self-crosslinking free of isocyanates. To enable this performance, a latex polymer binder was uniquely designed without using soap-like molecules, known as surfactants, to form the dispersion. By minimizing surfactants in the coating, the barrier properties were significantly enhanced. The latex was successfully scaled up to 15 kg quantities by an SME, coating formulations were scaled to pilot quantities and a variety of characterization and coating performance tests were completed. A life cycle assessment found that the BarrierPlus coating has a better environmental profile than an industry benchmark solvent-borne coating and showed promising results relative to commercial waterborne benchmarks
REST Regulates Oncogenic Properties of Glioblastoma Stem Cells.

Glioblastoma multiforme (GBM) tumors are the most common malignant primary brain tumors in adults. Although many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs), the mechanisms that regulate self-renewal and other oncogenic properties of GSCs are only now being unraveled. Here we showed that GSCs derived from GBM patient specimens express varying levels of the transcriptional repressor repressor element 1 silencing transcription factor (REST), suggesting heterogeneity across different GSC lines. Loss- and gain-of-function experiments indicated that REST maintains self-renewal of GSCs. High REST-expressing GSCs (HR-GSCs) produced tumors histopathologically distinct from those generated by low REST-expressing GSCs (LR-GSCs) in orthotopic mouse brain tumor models. Knockdown of REST in HR-GSCs resulted in increased survival in GSC-transplanted mice and produced tumors with higher apoptotic and lower invasive properties. Conversely, forced expression of exogenous REST in LR-GSCs produced decreased survival in mice and produced tumors with lower apoptotic and higher invasive properties, similar to HR-GSCs. Thus, based on our results, we propose that a novel function of REST is to maintain self-renewal and other oncogenic properties of GSCs and that REST can play a major role in mediating tumorigenicity in GBM. STEM CELLS 2012;30:405-414
Induction of osteogenesis in mesenchymal stem cells by activated monocytes/macrophages depends on oncostatin M signaling.

International audienceBone resorption by osteoclasts and bone formation by osteoblasts are tightly coupled processes implicating factors in TNF, bone morphogenetic protein, and Wnt families. In osteoimmunology, macrophages were described as another critical cell population regulating bone formation by osteoblasts but the coupling factors were not identified. Using a high-throughput approach, we identified here Oncostatin M (OSM), a cytokine of the IL-6 family, as a major coupling factor produced by activated circulating CD14+ or bone marrow CD11b+ monocytes/macrophages that induce osteoblast differentiation and matrix mineralization from human mesenchymal stem cells while inhibiting adipogenesis. Upon activation of toll-like receptors (TLRs) by lipopolysaccharide or endogenous ligands, OSM was produced in classically activated inflammatory M1 and not M2 macrophages, through a cyclooxygenase-2 and prostaglandin-E2 regulatory loop. Stimulation of osteogenesis by activated monocytes/macrophages was prevented using neutralizing antibodies or siRNA to OSM, OSM receptor subunits gp130 and OSMR, or to the downstream transcription factor STAT3. The induced osteoblast differentiation program culminated with enhanced expression of CCAAT-enhancer-binding protein δ, Cbfa1, and alkaline phosphatase. Overexpression of OSM in the tibia of mice has led to new bone apposition with no sign of bone resorption. Two other cytokines have also a potent role in bone formation induced by monocytes/macrophages and activation of TLRs: IL-6 and leukemia inhibitory factor. We propose that during bone inflammation, infection, or injury, the IL-6 family signaling network activated by macrophages and TLR ligands stimulates bone formation that is largely uncoupled from bone resorption and is thus an important target for anabolic bone therapies
Stochastic choice of allelic expression in human neural stem cells

Monoallelic gene expression, such as genomic imprinting, is well described. Less well-characterized are genes undergoing stochastic monoallelic expression (MA), where specific clones of cells express just one allele at a given locus. We performed genome-wide allelic expression assessment of human clonal neural stem cells derived from cerebral cortex, striatum, and spinal cord, each with differing genotypes. We assayed three separate clonal lines from each donor, distinguishing stochastic MA from genotypic effects. Roughly 2% of genes showed evidence for autosomal MA, and in about half of these, allelic expression was stochastic between different clones. Many of these loci were known neurodevelopmental genes, such as OTX2 and OLIG2. Monoallelic genes also showed increased levels of DNA methylation compared to hypomethylated biallelic loci. Identified monoallelic gene loci showed altered chromatin signatures in fetal brain, suggesting an in vivo correlate of this phenomenon. We conclude that stochastic allelic expression is prevalent in neural stem cells, providing clonal diversity to developing tissues such as the human brain. © AlphaMed Press
Proliferation state and polo-like kinase1 dependence of tumorigenic colon cancer cells.

Tumor-initiating cells are responsible for tumor maintenance and relapse in solid and hematologic cancers. Although tumor-initiating cells were initially believed to be mainly quiescent, rapidly proliferating tumorigenic cells were found in breast cancer. In colon cancer, the proliferative activity of the tumorigenic population has not been defined, although it represents an essential parameter for the development of more effective therapeutic strategies. Here, we show that tumorigenic colon cancer cells can be found in a rapidly proliferating state in vitro and in vivo, both in human tumors and mouse xenografts. Inhibitors of polo-like kinase1 (Plk1), a mitotic kinase essential for cell proliferation, demonstrated maximal efficiency over other targeted compounds and chemotherapeutic agents in inducing death of colon cancer-initiating cells in vitro. In vivo, Plk1 inhibitors killed CD133(+) colon cancer cells leading to complete growth arrest of colon cancer stem cell-derived xenografts, whereas chemotherapeutic agents only slowed tumor progression. While chemotherapy treatment increased CD133(+) cell proliferation, treatment with Plk1 inhibitors eliminated all proliferating tumor-initiating cells. Quiescent CD133(+) cells that survived the treatment with Plk1 inhibitors could be killed by subsequent Plk1 inhibition when they exited from quiescence. Altogether, these results provide a new insight into the proliferative status of colon tumor-initiating cells both in basal conditions and in response to therapy and indicate Plk1 inhibitors as potentially useful in the treatment of colorectal cancer
Lysophosphatidic Acid Induces Migration of Human Lung‐Resident Mesenchymal Stem Cells Through the β‐Catenin Pathway

Mesenchymal stem cells (MSCs) have been demonstrated to reside in human adult organs. However, mechanisms of migration of these endogenous MSCs within their tissue of origin are not well understood. Here, we investigate migration of human adult lung‐resident (LR) mesenchymal progenitor cells. We demonstrate that bioactive lipid lysophosphatidic acid (LPA) plays a principal role in the migration of human LR‐MSCs through a signaling pathway involving LPA1‐induced β‐catenin activation. LR‐MSCs isolated from human lung allografts and lungs of patients with scleroderma demonstrated a robust migratory response to LPA in vitro. Furthermore, LPA levels correlated with LR‐MSC numbers in bronchoalveolar lavage (BAL), providing demonstration of the in vivo activity of LPA in human adult lungs. Migration of LR‐MSCs was mediated via LPA1 receptor ligation and LPA1 silencing significantly abrogated the migratory response of LR‐MSCs to LPA as well as human BAL. LPA treatment of LR‐MSCs induced protein kinase C‐mediated glycogen synthase kinase‐3β phosphorylation, with resulting cytoplasmic accumulation and nuclear translocation of β‐catenin. TCF/LEF dual luciferase gene reporter assay demonstrated a significant increase in transcriptional activity after LPA treatment. LR‐MSC migration and increase in reporter gene activity in the presence of LPA were abolished by transfection with β‐catenin small interfering RNA demonstrating that β‐catenin is critical in mediating LPA‐induced LR‐MSC migration. These data delineate a novel signaling pathway through which ligation of a G protein‐coupled receptor by a biologically relevant lipid mediator induces migration of human tissue‐resident mesenchymal progenitors. S tem  C ells  2012;30:2010–201
Engineering Vascularized Bone: Osteogenic and Pro-Angiogenic Potential of Murine Periosteal Cells

One of the key challenges in bone tissue engineering is the timely formation of blood vessels that promote the survival of the implanted cells in the construct. Fracture healing largely depends on the presence of an intact periosteum but it is still unknown whether periosteum-derived cells (PDC) are critical for bone repair only by promoting bone formation or also by inducing neo-vascularization. We first established a protocol to specifically isolate murine PDC (mPDC) from long bones of adult mice. Mesenchymal stem cells were abundantly present in this cell population as more than 50% of the mPDC expressed mesenchymal markers (CD73, CD90, CD105, Sca#8208;1) and the cells exhibited trilineage differentiation potential (chondrogenic, osteogenic, adipogenic). When transplanted on a collagen-calcium phosphate scaffold in vivo, mPDC attracted numerous blood vessels and formed mature bone which comprises a hematopoiesis-supportive stroma. We explored the pro-angiogenic properties of mPDC using in vitro culture systems and showed that mPDC promote the survival and proliferation of endothelial cells through the production of vascular endothelial growth factor. Co-implantation with endothelial cells demonstrated that mPDC can enhance vasculogenesis by adapting a pericyte-like phenotype, in addition to their ability to stimulate blood vessel ingrowth from the host. In conclusion, these findings demonstrate that periosteal cells contribute to fracture repair, not only through their strong osteogenic potential, but also their pro-angiogenic features and thus provide an ideal cell source for bone regeneration therapies.status: publishe
Surface Tethered Epidermal Growth Factor Protects Proliferating and Differentiating Multipotential Stromal Cells from FasL-Induced Apoptosis

Multipotential stromal cells or mesenchymal stem cells (MSCs) have been proposed as aids in regenerating bone and adipose tissues, as these cells form osteoblasts and adipocytes. A major obstacle to this use of MSC is the initial loss of cells postimplantation. This cell death in part is due to ubiquitous nonspecific inflammatory cytokines such as FasL generated in the implant site. Our group previously found that soluble epidermal growth factor (sEGF) promotes MSC expansion. Furthermore, tethering EGF (tEGF) onto a two-dimensional surface altered MSC responses, by restricting epidermal growth factor receptor (EGFR) to the cell surface, causing sustained activation of EGFR, and promoting survival from FasL-induced death. sEGF by causing internalization of EGFR does not support MSC survival. However, for tEGF to be useful in bone regeneration, it needs to allow for MSC differentiation into osteoblasts while also protecting emerging osteoblasts from apoptosis. tEGF did not block induced differentiation of MSCs into osteoblasts, or adipocytes, a common default MSC-differentiation pathway. MSC-derived preosteoblasts showed increased Fas levels and became more susceptible to FasL-induced death, which tEGF prevented. Differentiating adipocytes underwent a reduction in Fas expression and became resistant to FasL-induced death, with tEGF having no further survival effect. tEGF protected undifferentiated MSC from combined insults of FasL, serum deprivation, and physiologic hypoxia. Additionally, tEGF was dominant in the face of sEGF to protect MSC from FasL-induced death. Our results suggest that MSCs and differentiating osteoblasts need protective signals to survive in the inflammatory wound milieu and that tEGF can serve this function.National Institute of General Medical Sciences (U.S.) (GM069668)National Institute of Dental and Craniofacial Research (U.S.) (DE019523
Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration.

Marielle Saclier and Houda Yacoub-Youssef : Both should be considered as first authorInternational audienceMacrophages (MPs) exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for adult skeletal muscle repair, notably by acting on myogenic precursor cells. However, these interactions have not been fully characterized. Here, we explored both in vitro and in vivo, in human, the interactions of differentially activated MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal muscle regeneration. We showed in vitro that through the differential secretion of cytokines and growth factors, proinflammatory MPs inhibited MPC fusion while anti-inflammatory MPs strongly promoted MPC differentiation by increasing their commitment into differentiated myocytes and the formation of mature myotubes. Furthermore, the in vivo time course of expression of myogenic and MP markers was studied in regenerating human healthy muscle after damage. We observed that regenerating areas containing proliferating MPCs were preferentially associated with MPs expressing proinflammatory markers. In the same muscle, regenerating areas containing differentiating myogenin-positive MPCs were preferentially coupled to MPs harboring anti-inflammatory markers. These data demonstrate for the first time in human that MPs sequentially orchestrate adult myogenesis during regeneration of damaged skeletal muscle. These results support the emerging concept that inflammation, through MP activation, controls stem cell fate and coordinates tissue repair
Essential role of sox2 for the establishment and maintenance of the germ cell line

Sox2 is a pluripotency-conferring gene expressed in primordial germ cells (PGCs) and postnatal oocytes, but the role it plays during germ cell development and early embryogenesis is unknown. Since Sox2 ablation causes early embryonic lethality shortly after blastocyst implantation, we generated mice bearing Sox2-conditional deletion in germ cells at different stages of their development through the Cre/loxP recombination system. Embryos lacking Sox2 in PGCs show a dramatic decrease of germ cell numbers at the time of their specification. At later stages, we found that Sox2 is strictly required for PGC proliferation. On the contrary, Sox2 deletion in meiotic oocytes does not impair postnatal oogenesis and early embryogenesis, indicating that it is not essential for oocyte maturation or for zygotic development. We also show that Sox2 regulates Kit expression in PGCs and binds to discrete transcriptional regulatory sequences of this gene, which is known to be important for PGCs survival and proliferation. Sox2 also stimulates the expression of Zfp148, which is required for normal development of fetal germ cells, and Rif1, a potential regulator of PGC pluripotency. STEM Cells2013;31:1408-1421
Concise Review: Role of DEK in Stem/Progenitor Cell Biology

Understanding the factors that regulate hematopoiesis opens up the possibility of modifying these factors and their actions for clinical benefit. DEK, a non‐histone nuclear phosphoprotein initially identified as a putative proto‐oncogene, has recently been linked to regulate hematopoiesis. DEK has myelosuppressive activity in vitro on proliferation of human and mouse hematopoietic progenitor cells and enhancing activity on engraftment of long‐term marrow repopulating mouse stem cells, has been linked in coordinate regulation with the transcription factor C/EBPα, for differentiation of myeloid cells, and apparently targets a long‐term repopulating hematopoietic stem cell for leukemic transformation. This review covers the uniqueness of DEK, what is known about how it now functions as a nuclear protein and also as a secreted molecule that can act in paracrine fashion, and how it may be regulated in part by dipeptidylpeptidase 4, an enzyme known to truncate and modify a number of proteins involved in activities on hematopoietic cells. Examples are provided of possible future areas of investigation needed to better understand how DEK may be regulated and function as a regulator of hematopoiesis, information possibly translatable to other normal and diseased immature cell systems. S TEM  C ells  2013;31:1447–145
Osteoblast‐Targeted suppression of PPARγ increases osteogenesis through activation of mTOR signaling

Nuclear receptor peroxisome proliferator‐activated receptor‐γ (PPARγ) is an essential transcription factor for adipocyte differentiation. In mesenchymal stem cells, PPARγ has been assumed to play a negative role in osteoblastic differentiation, by working in an adipogenesis dependent manner, due to the reciprocal relationship between osteoblast and adipocyte differentiation. However, the direct role of PPARγ in osteoblast function is not fully understood, due in part to inadequate model systems. Here, we describe an adenoviral‐mediated PPARγ knockout system in which suppression of PPARγ in mesenchymal stem cells enhanced osteoblast differentiation and inhibited adipogenesis in vitro. Consistent with this in vitro observation, lipoatrophic A‐ZIP/F1 mice, which do not form adipocytes, displayed a phenotype in which both cortical and trabecular bone was significantly increased compared with wild‐type mice. We next developed an inducible osteoblast‐targeted  PPARγ  knockout ( Osx  Cre/flox‐  PPARγ ) mouse to determine the direct role of PPARγ in bone formation. Data from both in vitro cultures of mesenchymal stem cells and in vivo µCT analysis of bones suggest that suppression of PPARγ activity in osteoblasts significantly increased osteoblast differentiation and trabecular number. Endogenous PPARγ in mesenchymal stem cells and osteoblasts strongly inhibited Akt/mammalian target of rapamycin (mTOR)/p70S6k activity and led to decreased osteoblastic differentiation. Therefore, we conclude that PPARγ modulates osteoblast differentiation and bone formation through both direct and indirect mechanisms. The direct mode, as shown here, involves PPARγ regulation of the mTOR pathway, while the indirect pathway is dependent on the regulation of adipogenesis. S tem  C ells   2013;31:2183–219