187 resultados para CSC
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Wars continue to ravage in Syria, Iraq and Yemen. Refugees are wandering around aimlessly in the Middle East with many fleeing to Europe. Saudi Arabia and Iran are adding fuel to the flames. They are vying for supremacy while remaining highly suspicious of each other. A Conference for Security and Cooperation could help to ease existing tensions. Many years ago the CSCE was a resounding success. It could thus serve as a blueprint with the nuclear agreement with Iran as a starting point of such a venture.
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Emerging evidence supports that prostate cancer originates from a rare sub-population of cells, namely prostate cancer stem cells (CSCs). Conventional therapies for prostate cancer are believed to mainly target the majority of differentiated tumor cells but spare CSCs, which may account for the subsequent disease relapse after treatment. Therefore, successful elimination of CSCs may be an effective strategy to achieve complete remission from this disease. Gamma-tocotrienols (-T3) is one of the vitamin-E constituents which have been shown to have anticancer effects against a wide-range of human cancers. Recently, we have reported that -T3 treatment not only inhibits prostate cancer cell invasion but also sensitizes the cells to docetaxel-induced apoptosis, suggesting that -T3 may be an effective therapeutic agent against advanced stage prostate cancer. Here, we demonstrate for the first time that -T3 can down-regulate the expression of prostate CSC markers (CD133/CD44) in androgen independent (AI) prostate cancer cell lines (PC-3 & DU145), as evident from western blotting analysis. Meanwhile, the spheroid formation ability of the prostate cancer cells was significantly hampered by -T3 treatment. In addition, pre-treatment of PC-3 cells with -T3 was found to suppress tumor initiation ability of the cells. More importantly, while CD133-enriched PC-3 cells were highly resistant to docetaxel treatment, these cells were as sensitive to -T3 treatment as the CD133-depleted population. Our data suggest that -T3 may be an effective agent in targeting prostate CSCs, which may account for its anticancer and chemosensitizing effects reported in previous studies.
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My research investigates why nouns are learned disproportionately more frequently than other kinds of words during early language acquisition (Gentner, 1982; Gleitman, et al., 2004). This question must be considered in the context of cognitive development in general. Infants have two major streams of environmental information to make meaningful: perceptual and linguistic. Perceptual information flows in from the senses and is processed into symbolic representations by the primitive language of thought (Fodor, 1975). These symbolic representations are then linked to linguistic input to enable language comprehension and ultimately production. Yet, how exactly does perceptual information become conceptualized? Although this question is difficult, there has been progress. One way that children might have an easier job is if they have structures that simplify the data. Thus, if particular sorts of perceptual information could be separated from the mass of input, then it would be easier for children to refer to those specific things when learning words (Spelke, 1990; Pylyshyn, 2003). It would be easier still, if linguistic input was segmented in predictable ways (Gentner, 1982; Gleitman, et al., 2004) Unfortunately the frequency of patterns in lexical or grammatical input cannot explain the cross-cultural and cross-linguistic tendency to favor nouns over verbs and predicates. There are three examples of this failure: 1) a wide variety of nouns are uttered less frequently than a smaller number of verbs and yet are learnt far more easily (Gentner, 1982); 2) word order and morphological transparency offer no insight when you contrast the sentence structures and word inflections of different languages (Slobin, 1973) and 3) particular language teaching behaviors (e.g. pointing at objects and repeating names for them) have little impact on children's tendency to prefer concrete nouns in their first fifty words (Newport, et al., 1977). Although the linguistic solution appears problematic, there has been increasing evidence that the early visual system does indeed segment perceptual information in specific ways before the conscious mind begins to intervene (Pylyshyn, 2003). I argue that nouns are easier to learn because their referents directly connect with innate features of the perceptual faculty. This hypothesis stems from work done on visual indexes by Zenon Pylyshyn (2001, 2003). Pylyshyn argues that the early visual system (the architecture of the "vision module") segments perceptual data into pre-conceptual proto-objects called FINSTs. FINSTs typically correspond to physical things such as Spelke objects (Spelke, 1990). Hence, before conceptualization, visual objects are picked out by the perceptual system demonstratively, like a finger pointing indicating ‘this’ or ‘that’. I suggest that this primitive system of demonstration elaborates on Gareth Evan's (1982) theory of nonconceptual content. Nouns are learnt first because their referents attract demonstrative visual indexes. This theory also explains why infants less often name stationary objects such as plate or table, but do name things that attract the focal attention of the early visual system, i.e., small objects that move, such as ‘dog’ or ‘ball’. This view leaves open the question how blind children learn words for visible objects and why children learn category nouns (e.g. 'dog'), rather than proper nouns (e.g. 'Fido') or higher taxonomic distinctions (e.g. 'animal').
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Design teams are confronted with the quandary of choosing apposite building control systems to suit the needs of particular intelligent building projects, due to the availability of innumerable ‘intelligent’ building products and a dearth of inclusive evaluation tools. This paper is organised to develop a model for facilitating the selection evaluation for intelligent HVAC control systems for commercial intelligent buildings. To achieve these objectives, systematic research activities have been conducted to first develop, test and refine the general conceptual model using consecutive surveys; then, to convert the developed conceptual framework into a practical model; and, finally, to evaluate the effectiveness of the model by means of expert validation. The results of the surveys are that ‘total energy use’ is perceived as the top selection criterion, followed by the‘system reliability and stability’, ‘operating and maintenance costs’, and ‘control of indoor humidity and temperature’. This research not only presents a systematic and structured approach to evaluate candidate intelligent HVAC control system against the critical selection criteria (CSC), but it also suggests a benchmark for the selection of one control system candidate against another.
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Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.
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The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. Through the use of xenotransplantation assays, putative CSCs have been identified in many cancers, often identified by markers usually expressed in normal stem cells. This is also the case in lung cancer, and the accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are beginning to clarify the true phenotype of the lung cancer stem cell. Furthermore, it is now clear that many of the pathways of normal stem cells, which guide cellular proliferation, differentiation, and apoptosis are also prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being notable examples. The CSC hypothesis suggests that there is a small reservoir of cells within the tumor, which are resistant to many standard therapies, and can give rise to new tumors in the form of metastases or relapses after apparent tumor regression. Therapeutic interventions that target CSC pathways are still in their infancy and clinical data of their efficacy remain limited. However Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt antagonists, and CBP/β-catenin inhibitors have all shown promising anticancer effects in early studies. The evidence to support the emerging picture of a lung cancer CSC phenotype and the development of novel therapeutic strategies to target CSCs are described in this review.
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Resistance to chemotherapy and metastases are the major causes of breast cancer-related mortality. Moreover, cancer stem cells (CSC) play critical roles in cancer progression and treatment resistance. Previously, it was found that CSC-like cells can be generated by aberrant activation of epithelial–mesenchymal transition (EMT), thereby making anti-EMT strategies a novel therapeutic option for treatment of aggressive breast cancers. Here, we report that the transcription factor FOXC2 induced in response to multiple EMT signaling pathways as well as elevated in stem cell-enriched factions is a critical determinant of mesenchymal and stem cell properties, in cells induced to undergo EMT- and CSC-enriched breast cancer cell lines. More specifically, attenuation of FOXC2 expression using lentiviral short hairpin RNA led to inhibition of the mesenchymal phenotype and associated invasive and stem cell properties, which included reduced mammosphere-forming ability and tumor initiation. Whereas, overexpression of FOXC2 was sufficient to induce CSC properties and spontaneous metastasis in transformed human mammary epithelial cells. Furthermore, a FOXC2-induced gene expression signature was enriched in the claudin-low/basal B breast tumor subtype that contains EMT and CSC features. Having identified PDGFR-β to be regulated by FOXC2, we show that the U.S. Food and Drug Administration-approved PDGFR inhibitor, sunitinib, targets FOXC2-expressing tumor cells leading to reduced CSC and metastatic properties. Thus, FOXC2 or its associated gene expression program may provide an effective target for anti-EMT-based therapies for the treatment of claudin-low/basal B breast tumors or other EMT-/CSC-enriched tumors.
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Linking Karumba: Creating Sustainable Connections This exhibition showcases the work of 3rd -4th year undergraduate landscape architecture, architecture, Industrial Design, Environmental Engineering, Civil Engineering students in response to issues of sustainability in the Gulf of Carpentaria town of Karumba. It presented the work to the Karumba and Carpentaria Shire community. 16 students and four staff set off on a 2488km journey to undertake the first half of the Carpentaria Project: a fortnight-long strategic planning project entitled Linking Karumba to encourage social, economic, environmental and cultural linkages across the town. Karumba, along with the nearby town of Normanton, is one of Queensland’s most remote settlements. Its economy is based on fishing, tourism, and mining. It has two centres, 2.5km apart by river, or 9km by road. This physical disconnect was identified by Carpentaria Shire Council (CSC) and the Karumba Progress Association (KPA) as a source of socio-cultural disconnection, which formed the basis of our project brief. Student designs were highly responsive to the character of Karumba’s culture and environment, indicating remarkable levels of immersion, and attracting $830 000 in Qld. state government funding for implementation. The Exhibition Four groups of four students produced four strategic planning and design options toward this future: Make the Switch: Alice Anonuevo, Michael Marriott, Carla Priestley & Grant Harvey Realigning the Systems: Claudia Bergs, Rebecca Stephens, Anna Coulson & Lois Kerrigan Diversification of Experience: Rebecca North, Kyle Bush, Debra Sullivan & Jenna Green The River is the Main Street: Ashley Nicholson, Monica Kuiken, Dean Bowen & Bill Schild
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QUT Linking Karumba Project This exhibition showcases the work of 3rd -4th year undergraduate landscape architecture, architecture, Industrial Design, Environmental Engineering, Civil Engineering students in response to issues of sustainability in the Gulf of Carpentaria town of Karumba. It presented the final, polished set of work to the Karumba and Carpentaria Shire community, following revisions in line with feedback from the 2008 exhibition. 16 students and four staff set off on a 2488km journey to undertake the first half of the Carpentaria Project: a fortnight-long strategic planning project entitled Linking Karumba to encourage social, economic, environmental and cultural linkages across the town. Karumba, along with the nearby town of Normanton, is one of Queensland’s most remote settlements. Its economy is based on fishing, tourism, and mining. It has two centres, 2.5km apart by river, or 9km by road. This physical disconnect was identified by Carpentaria Shire Council (CSC) and the Karumba Progress Association (KPA) as a source of socio-cultural disconnection, which formed the basis of our project brief. Student designs were highly responsive to the character of Karumba’s culture and environment, indicating remarkable levels of immersion, and attracting $830 000 in Qld. state government funding for implementation. The Exhibition Four groups of four students produced four strategic planning and design options toward this future: Make the Switch: Alice Anonuevo, Michael Marriott, Carla Priestley & Grant Harvey Realigning the Systems: Claudia Bergs, Rebecca Stephens, Anna Coulson & Lois Kerrigan Diversification of Experience: Rebecca North, Kyle Bush, Debra Sullivan & Jenna Green The River is the Main Street: Ashley Nicholson, Monica Kuiken, Dean Bowen & Bill Schild
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This paper presents the blast response, damage mechanism and evaluation of residual load capacity of a concrete–steel composite (CSC) column using dynamic computer simulation techniques. This study is an integral part of a comprehensive research program which investigated the vulnerability of structural framing systems to catastrophic and progressive collapse under blast loading and is intended to provide design information on blast mitigation and safety evaluation of load bearing vulnerable columns that are key elements in a building. The performance of the CSC column is compared with that of a reinforced concrete (RC) column with the same dimensions and steel ratio. Results demonstrate the superior performance of the CSC column, compared to the RC column in terms of residual load carrying capacity, and its potential for use as a key element in structural systems. The procedure and results presented herein can be used in the design and safety evaluation of key elements of multi-storey buildings for mitigating the impact of blast loads.