Tumors are thought to be sustained by a reservoir of self-renewing cells, termed tumor-initiating cells or cancer stem cells. Osteosarcomas are high-grade sarcomas derived from osteoblast progenitor ...cells and are the most common pediatric bone malignancy. In this report we show that the stem cell transcription factor Sox2 is highly expressed in human and murine osteosarcoma (mOS) cell lines as well as in the tumor samples. Osteosarcoma cells have increased ability to grow in suspension as osteospheres, that are greatly enriched in expression of Sox2 and the stem cell marker, Sca-1. Depletion of Sox2 by short-hairpin RNAs in independent mOS-derived cells drastically reduces their transformed properties in vitro and their ability to form tumors. Sox2-depleted osteosarcoma cells can no longer form osteospheres and differentiate into mature osteoblasts. Concomitantly, they exhibit decreased Sca-1 expression and upregulation of the Wnt signaling pathway. Thus, despite other mutations, these cells maintain a requirement for Sox2 for tumorigenicity. Our data indicate that Sox2 is required for osteosarcoma cell self renewal, and that Sox2 antagonizes the pro-differentiation Wnt pathway that can in turn reduce Sox2 expression. These studies define Sox2 as a survival factor and a novel biomarker of self renewal in osteosarcomas, and support a tumor suppressive role for the Wnt pathway in tumors of mesenchymal origin. Our findings could provide the basis for novel therapeutic strategies based on inhibiting Sox2 or enhancing Wnt signaling for the treatment of osteosarcomas.
Aneurysmal bone cyst Rapp, Timothy B; Ward, James P; Alaia, Michael J
Journal of the American Academy of Orthopaedic Surgeons
20, Številka:
4
Journal Article
Recenzirano
Aneurysmal bone cysts are rare skeletal tumors that most commonly occur in the first two decades of life. They primarily develop about the knee but may arise in any portion of the axial or ...appendicular skeleton. Pathogenesis of these tumors remains controversial and may be vascular, traumatic, or genetic. Radiographic features include a dilated, radiolucent lesion typically located within the metaphyseal portion of the bone, with fluid-fluid levels visible on MRI. Histologic features include blood-filled lakes interposed between fibrous stromata. Differential diagnosis includes conditions such as telangiectatic osteosarcoma and giant cell tumor. The mainstay of treatment is curettage and bone graft, with or without adjuvant treatment. Other management options include cryotherapy, sclerotherapy, radionuclide ablation, and en bloc resection. The recurrence rate is low after appropriate treatment; however, more than one procedure may be required to completely eradicate the lesion.
During the last decades micro electro mechanical systems (MEMS) have been subject to intensive research. In many cases active components, e.g., for regulating fluid flow or generating movement need ...to be included in the system design to ensure controlled operation. However, conventional actuators can seldom be used because their efficiency dec
reases when their size is minimized. On the other hand miniaturization allows usage of a broad band of actuators that are inefficient in the macroscopic world. A significant amount of these actuators relies on phase change phenomena. The most intriguing fact about these transitions is their reversible nature which is associated to a pure physical transition. Facing an increasing amount of papers concerning phase change triggered micro actuation designers and operators of MEMS devices are often unable to decide which actuation principle is best-suited for their specific application. By summing up the content of more than 400 publications this review intends to provide designers as well as users of MEMS with the knowledge necessary for building efficient phase change driven actuators. For doing so the physical principles underlying each phase change phenomenon, which has been used for setting up MEMS, are introduced, followed by a thorough discussion of suitable materials that undergo the specific phase change. In order to enable the reader to choose the material best-suited for the target application the physical properties of more than 240 phase change materials, including some materials that have never been used in MEMS but are known from other research fields, e.g., energy storage, are listed within the review. With a focus on the physical working principle, the review highlights actuator concepts which have been used as printer heads, valves, pumps, grippers, actuators in drug delivery devices, devices for endoscopic surgery, aerospace engineering, and several other applications. The features of these actuators are compared in comprehensible tables in order to allow operators to quickly decide which actuator they could use for their specific application.
Coiled-coil domains can direct the assembly of protein block copolymers into physically cross-linked, viscoelastic hydrogels. Here, we describe the use of fluorescence recovery after photobleaching ...(FRAP) to probe chain mobility in reversible hydrogels assembled from engineered proteins bearing terminal coiled-coil domains. We show that chain mobility can be related to the underlying dynamics of the coiled-coil domains by application of a three-state “hopping” model of chain migration. We further show that genetic programming allows the effective mobility of network chains to be varied 500-fold through modest changes in protein sequence. Destabilization of the coiled-coil domains by site-directed mutagenesis increases the effective diffusivity of probe chains. Conversely, probe mobility is reduced by expanding the hydrophobic surface area of the coiled-coil domains through introduction of the bulky leucine surrogate homoisoleucine. Predictions from the three-state model imply asymmetric sequential binding of the terminal domains. Brownian Dynamics simulations suggest that binding asymmetry is a general feature of reversible gels, arising from a loss in entropy as chains transition to a conformationally restricted bridged state.
The detection of illicit materials is a critical task in the field of homeland security, as international trade has contributed to the increase of smuggling activities. Nonintrusive on-site ...inspections are crucial in this context, but the current active interrogation methods have limitations. Neutron-induced reactions have been used, but the measurement of gamma spectra is complex due to background noise. Active photon interrogation methods have also been overlooked but they are currently limited to actinides detection using photo-fission reactions. This work presents a novel method for the detection of illicit materials based on active photon interrogation and photo-neutron spectrometry. This approach extends the application of active photon interrogation by including the detection of conventional explosives, narcotics, and chemical weapons based on the use photo-nuclear reactions to determine the content of light elements such as nitrogen, oxygen, and carbon. Monte-Carlo codes are the main tool used to simulate this process for the application need. However, because of the lack in the present literature of measured neutron spectra, the experimental validation of the simulations is not straight forward. At present, benchmarking the Monte-Carlo codes seems to be the sole option for testing their ability to accurately simulate photo-neutron production and spectra for the nuclear reactions of interest. Simultaneously, we designed a test bench based on a linear accelerator to generate photons, induce photonuclear reactions, and acquire photo-neutron spectra. This study on the fundamental aspects of photo-neutron production lays the groundwork for a promising new detection method for illicit materials.
The miniaturization of synthesis, analysis and screening experiments is an important step towards more environmentally friendly chemistry, statistically significant biology and fast and ...cost-effective medicinal assays. The facile generation of arbitrary 3D channel structures in polymers is pivotal to these techniques. Here we present a method for printing microchannels directly into viscous curable polymer matrices by injecting a surfactant into the uncured material via a steel capillary attached to a 3D printer. We demonstrate this technique using polydimethylsiloxane (PDMS) one of the most widely used polymers for the fabrication of, e. g. microfluidic chips. We show that this technique which we term Suspended Liquid Subtractive Lithography (SLSL) is well suited for printing actuators, T-junctions and complex three dimensional structures. The formation of truly arbitrary channels in 3D could revolutionize the fabrication of miniaturized chips and will find broad application in biology, chemistry and medicine.
GenBank Benson, Dennis A.; Boguski, Mark S.; Lipman, David J. ...
Nucleic acids research,
1999, 1999-Jan-01, 1999-01-01, 19990101, Letnik:
27, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The GenBank (Registered Trademark symbol) sequence database incorporates DNA sequences from all available public sources, primarily through the direct submission of sequence data from individual ...laboratories and from large-scale sequencing projects. Most submitters use the Bankit (Web) or Sequin programs to format and send sequence data. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive worldwide coverage. GenBank data is accessible through NCBI's integrated retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome and protein structure information. MEDLINE (Registered Trademark symbol) abstracts from published articles describing the sequences are included as an additional source of biological annotation through the PubMed search system. Sequence similarity searching is offered through the BLAST series of database search programs. In addition to FTP, Email, and server/client versions of Entrez and BLAST, NCBI offers a wide range of World Wide Web retrieval and analysis services based on GenBank data. The GenBank database and related resources are freely accessible via the URL: http://www.ncbi.nlm.nih.gov
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