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Journal articles on the topic 'Identity anchorages'
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1
Guadagno, T. M., and R. K. Assoian. "G1/S control of anchorage-independent growth in the fibroblast cell cycle." Journal of Cell Biology 115, no. 5 (December 1, 1991): 1419–25. http://dx.doi.org/10.1083/jcb.115.5.1419.
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We have developed methodology to identify the block to anchorage-independent growth and position it within the fibroblast cell cycle. Results with NRK fibroblasts show that mitogen stimulation of the G0/G1 transition and G1-associated increases in cell size are minimally affected by loss of cell anchorage. In contrast, the induction of G1/S cell cycle genes and DNA synthesis is markedly inhibited when anchorage is blocked. Moreover, we demonstrate that the anchorage-dependent transition maps to late G1 and shortly before activation of the G1/S p34cdc2-like kinase. The G1/S block was also detectable in NIH-3T3 cells. Our results: (a) distinguish control of cell cycle progression by growth factors and anchorage; (b) indicate that anchorage mediates G1/S control in fibroblasts; and (c) identify a physiologic circumstance in which the phenotype of mammalian cell cycle arrest would closely resemble Saccharomyces cerevisiae START. The close correlation between anchorage independence in vitro and tumorigenicity in vivo emphasizes the key regulatory role for G1/S control in mammalian cells.
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Dolan, Josephine. "Anchorage and Play in 'Frenchman's Creek': Children, Gender, and National Identity." Yearbook of English Studies 32 (2002): 95. http://dx.doi.org/10.2307/3509050.
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Monini, André da Costa, Luiz Gonzaga Gandini Júnior, Ary dos Santos-Pinto, Luiz Guilherme Martins Maia, and Willian Caetano Rodrigues. "Procedures adopted by orthodontists for space closure and anchorage control." Dental Press Journal of Orthodontics 18, no. 6 (December 2013): 86–92. http://dx.doi.org/10.1590/s2176-94512013000600013.
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OBJECTIVE: The aim of this study was to identify the procedures adopted by Brazilian orthodontists in the following situations: extraction space closure, anchorage control in case of necessary anchorage for group A and frequency of skeletal anchorage use, especially in the upper jaw. METHOD: A questionnaire was sent to the e-mail address of all dentists registered in the Brazilian Federal Council of Dentistry. RESULTS: The results showed that most Brazilian orthodontists usually perform extraction space closure by means of sliding mechanics. The use of palatal bar, inclusion of second molars in the archwire and space closure performed in two phases are the most used techniques for anchorage control in the upper jaw. The skeletal anchorage is referenced by 36.5% of specialists as a routine practice for the upper jaw anchorage. CONCLUSIONS: There is a wide variety of procedures adopted by Brazilian orthodontists for orthodontic space closure and anchorage control.
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Di, Weiguo, Mingming Wang, Xiaoyun Sun, Guang Han, and Hui Xing. "Identification of bolt anchorage defects based on Elman neural network optimised by improved chicken swarm optimisation algorithm." Insight - Non-Destructive Testing and Condition Monitoring 62, no. 10 (October 1, 2020): 588–97. http://dx.doi.org/10.1784/insi.2020.62.10.588.
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Rock bolts play an important supporting role in the construction of slopes, deep foundation pits and tunnels. As such, it is especially necessary to assess bolt anchorage quality. This paper proposes an identification model for bolt anchorage defects based on an Elman neural network (ElmanNN) optimised using an improved chicken swarm optimisation (CSO) algorithm and the frequency response function. First, the principal components of the frequency response functions of different anchorage bolts are used as the input within the model. Next, the weights and thresholds of the ElmanNN are optimised using an improved CSO algorithm based on chaotic disturbance and elite opposition-based learning. Finally, the model is used to identify bolt anchorage defects. The experimental results show that the model has a higher identification accuracy and faster convergence rate than other neural network models.
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Polat, Necati. "Identity Politics and the Domestic Context of Turkey's European Union Accession." Government and Opposition 41, no. 4 (2006): 512–33. http://dx.doi.org/10.1111/j.1477-7053.2006.00202.x.
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AbstractThis article observes a transformation in the largely essentializing, decontextualized form of identity politics that long defined political cosmology in Turkey, now in the process of negotiating accession to the European Union (EU). Accordingly, identity politics – not only the bread and butter of both Kurdish nationalism and Islamism, but also a justification for exhortations towards a limited, authoritarian democracy by Kemalists, the major power holders – is receding in favour of a civic, non-divisive political culture enabled by the EU anchorage. In danger of losing the longstanding centre–periphery configuration in an enhanced, participatory democracy and, concomitant with it, the periphery clientelism created by the waning identity politics, Kemalist nationalists, Islamists and Kurdish separatists appear to have stopped squabbling among themselves and joined forces against Turkey's EU bid.
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Vachiramon, Amornpong, Mark Urata, Hee Moon Kyung, Dennis-Duke Yamashita, and Stephen L.-K. Yen. "Clinical Applications of Orthodontic Microimplant Anchorage in Craniofacial Patients." Cleft Palate-Craniofacial Journal 46, no. 2 (March 2009): 136–46. http://dx.doi.org/10.1597/06-219.1.
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Microimplant anchors, also known as temporary anchorage devices, mini- and micro-screws, have been used to enhance orthodontic anchorage for difficult tooth movements. Here, the authors describe how microimplants can be used to help treat craniofacial patients by supporting distraction osteogenesis procedures, maxillary protraction procedures, cleft segment expansion and stabilization, and tooth movement into narrow alveolar cleft sites. While most craniofacial patients are treated without microimplants, it would be worthwhile to identify which cases could benefit from microimplant anchorage. As an adjunct to orthodontic treatment, the microimplant offers a potential method for solving troublesome orthodontic and surgical problems such as guiding distraction procedures with orthodontics when primary teeth are exfoliating, addressing residual maxillary cants after vertical distraction osteogenesis of a ramus, stabilizing an edentulous premaxilla, and moving teeth into atrophic alveolar ridges. These cases are presented to open a dialogue on their possible uses in craniofacial patients.
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Liu, Heng-Jia, Lisa M. Ooms, Nuthasuda Srijakotre, Joey Man, Jessica Vieusseux, JoAnne E. Waters, Yue Feng, et al. "PtdIns(3,4,5)P3-dependent Rac Exchanger 1 (PREX1) Rac-Guanine Nucleotide Exchange Factor (GEF) Activity Promotes Breast Cancer Cell Proliferation and Tumor Growth via Activation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Signaling." Journal of Biological Chemistry 291, no. 33 (June 29, 2016): 17258–70. http://dx.doi.org/10.1074/jbc.m116.743401.
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PtdIns(3,4,5)P3-dependent Rac exchanger 1 (PREX1) is a Rac-guanine nucleotide exchange factor (GEF) overexpressed in a significant proportion of human breast cancers that integrates signals from upstream ErbB2/3 and CXCR4 membrane surface receptors. However, the PREX1 domains that facilitate its oncogenic activity and downstream signaling are not completely understood. We identify that ERK1/2 MAPK acts downstream of PREX1 and contributes to PREX1-mediated anchorage-independent cell growth. PREX1 overexpression increased but its shRNA knockdown decreased ERK1/2 phosphorylation in response to EGF/IGF-1 stimulation, resulting in induction of the cell cycle regulators cyclin D1 and p21WAF1/CIP1. PREX1-mediated ERK1/2 phosphorylation, anchorage-independent cell growth, and cell migration were suppressed by inhibition of MEK1/2/ERK1/2 signaling. PREX1 overexpression reduced staurosporine-induced apoptosis whereas its shRNA knockdown promoted apoptosis in response to staurosporine or the anti-estrogen drug tamoxifen. Expression of wild-type but not GEF-inactive PREX1 increased anchorage-independent cell growth. In addition, mouse xenograft studies revealed that expression of wild-type but not GEF-dead PREX1 resulted in the formation of larger tumors that displayed increased phosphorylation of ERK1/2 but not AKT. The impaired anchorage-independent cell growth, apoptosis, and ERK1/2 signaling observed in stablePREX1knockdown cells was restored by expression of wild-type but not GEF-dead-PREX1. Therefore, PREX1-Rac-GEF activity is critical for PREX1-dependent anchorage-independent cell growth and xenograft tumor growth and may represent a possible therapeutic target for breast cancers that exhibit PREX1 overexpression.
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Serafin, Marco, Cinzia Maspero, Salvatore Bocchieri, Rosamaria Fastuca, and Alberto Caprioglio. "Subperiosteal Anchorage in Orthodontics: A Narrative Review." Applied Sciences 11, no. 18 (September 9, 2021): 8376. http://dx.doi.org/10.3390/app11188376.
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Orthodontic anchorage is a necessity for every treatment and must be carefully evaluated by the orthodontist. It is defined as the resistance to unwanted dental movement of a tooth or a number of teeth by using different techniques. The purpose of the present paper is to highlight the subperiosteal anchorage applied to orthodontics; this technique has been debated in the literature and the purpose here is to summarize the fields of application. During the first check of previous literature 548 results were found, which have been reduced to 19 selected papers after application of the inclusion criteria and the elimination of duplicates. Multiple electronic databases were searched from 1 January 1995 to 31 December 2020 in order to identify papers eligible for current review. The data obtained by this review underlined the versatility of onplants used as absolute anchorage during orthodontic treatments, the advantages and disadvantages, the biomechanical properties and survival rates, and the clinical procedure. Further clinical studies and research are required to explore other kinds of application and to state specific guidelines; however, this study represents an update and a starting point for clinicians who want to use these devices and for further improvement of the technique.
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Maryns, Katrijn. "Procedures without borders: The language-ideological anchorage of legal-administrative procedures in translocal institutional settings." Language in Society 42, no. 1 (January 24, 2013): 71–92. http://dx.doi.org/10.1017/s0047404512000905.
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AbstractTheoretical and applied research in the field of institutional discourse analysis calls for an increasing awareness of the constitutive nature of discourse in the representation and the assessment of social identities (Sarangi & Roberts 1999; Blommaert 2010; Eades 2010). The staunchly textualist accounts surviving institutional practice, however, tend to obscure complex multidiscursive and language ideologically anchored processes that mold procedural outcomes. On the basis of first-hand ethnographic data collected across legal-administrative procedures in Belgium, this article aims at revealing some meaningful contexts that have been erased in the case of an asylum seeker who became a murder victim and whose asylum file was used in the assize trial as a resource to sketch his social identity. The analysis explores the ideological functioning of textuality in the situated details of communicative practice, thereby aiming for a better understanding of the intricacies of multidiscursive identity construction in translocal procedural settings. (Institutional discourse analysis, multidiscursivity, language ideology and identity, sociolinguistic mobility, asylum procedure, assize court procedure)*
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Howell, Britteny M., and Daniel McLinden. "BARRIERS AND OPPORTUNITIES TO HEALTHY AGING IN ANCHORAGE, ALASKA, USING CONCEPT MAPPING." Innovation in Aging 3, Supplement_1 (November 2019): S422—S423. http://dx.doi.org/10.1093/geroni/igz038.1578.
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Abstract Alaska currently has the fastest growing proportion of older adults than any state in the country, and seniors are choosing to age-in-place in Anchorage in record numbers. Research shows that including older adults with community-based professionals (aging advocates, researchers, service providers) in focus group activities can provide a rich and holistic model of aging that demonstrates a robust foundation for supporting aging and addressing health disparities. This paper presents the results of a project conducted with older adults (50+ years), advocates, and other stakeholders in Anchorage using Concept Mapping (CM) methodology, a technique not often used in the gerontology literature. CM is a mixed-method, participatory approach that uses brainstorming and unstructured card-sorting combined with multivariate statistics (multi-dimensional scaling, hierarchical cluster analysis) to create a data-driven visual representation of thoughts or ideas of a community. CM is well suited to integrating perspectives from multiple points of view. Participants were prompted to address the research question: how do we think about aging in Anchorage & what are the barriers and facilitators to aging well? Results indicate services for seniors should include culturally responsive health programming, low-cost opportunities for social engagement, inclusion of older adults with intellectual/developmental disabilities, transportation considerations, navigators to locate services in Anchorage, and more. CM allowed the researchers to identify how residents view healthy aging in this urban subarctic location and brainstorm practical solutions with stakeholders and local policy-makers. This presentation will also share lessons-learned regarding the use of this participatory approach with older adults.
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Sun, Bing, Xu Tao Zheng, and Sheng Zeng. "Signal Feature Analysis of Excited Stress Waves in Bolts Embed in Different Anchor Medium." Advanced Materials Research 671-674 (March 2013): 393–96. http://dx.doi.org/10.4028/www.scientific.net/amr.671-674.393.
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Based on the one-dimensional wave theory, nondestructive testing with stress wave reflection method bolts is a kind of quick and effective detection method; the method was used to estimates the anchorage quality according to some parameters such as waveform, phase, amplitude, frequency as well as arrival time of both the incident wave and the reflected wave; stress wave velocity is the basic parameter for quality assessment, the velocity is depended on signal identification of the integrity bolts, especially the reflected ones from the bottom. This paper, through the transient dynamic response experiment of anchor in different anchor medium, analyzes the dynamic measurement signal waveform characteristics. The results show that, fixed end reflection signal is very strong , but bottom end reflection signal is very weak, even it is difficult to identify; the compactness of surrounding rock and anchorage medium have certain effect in dynamic measuring signal waveform characteristics, if surrounding rock and anchorage medium is uniform and dense, the wave type of anchor dynamic measuring signal is regular and steady, instead, signal clutter and irregular; model size and boundary conditions also have certain effect on the change characteristics of the signal, so this effect should be considered in laboratory experiment.
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Zhang, X., J. A. Knappett, A. K. Leung, M. O. Ciantia, T. Liang, and F. Danjon. "Small-scale modelling of root-soil interaction of trees under lateral loads." Plant and Soil 456, no. 1-2 (September 18, 2020): 289–305. http://dx.doi.org/10.1007/s11104-020-04636-8.
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Abstract Aim (1) To understand the tree root-soil interaction under lateral and moment loading using a physical modelling technique; (2) To detect the possible factors (e.g. root architecture, water condition, and stress level) influencing a tree’s push-over behaviour; (3) To identify suitable scaling laws to use in physical modelling. Methods Two 1:20 scaled root models with different architectures (namely, deep and narrow, and shallow and wide) were reconstructed and 3D printed based on the field-surveyed root architecture data. Push-over tests were performed both in elevated-gravity (centrifuge 20-g) and normal-gravity (1-g) conditions. Results The shallow and wide model showed higher anchorage strength than the deep and narrow model. Regardless of the root architecture, the root anchorage strength measured from dry soil was higher than that from saturated soil. However, once the effective stress was the same, regardless of water conditions, the root anchorage strength would be the same. Conclusions The presence of water decreasing the soil effective stress and key lateral roots extending along the wind direction play a significant role on a tree’s push-over resistance. Centrifuge tests showed comparable results to the field pull-over measurements while 1-g model tests overestimated the root-soil interaction, which could be corrected for soil strength by using modified scaling laws.
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Abouhussien, Ahmed A., and Assem AA Hassan. "Application of acoustic emission monitoring for assessment of bond performance of corroded reinforced concrete beams." Structural Health Monitoring 16, no. 6 (November 30, 2016): 732–44. http://dx.doi.org/10.1177/1475921716681460.
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This article presents the results of an experimental investigation on the application of acoustic emission monitoring for the evaluation of bond behaviour of deteriorated reinforced concrete beams. Five reinforced concrete beam–anchorage specimens designed to undergo bond failure were exposed to corrosion at one of the anchorage zones by accelerated corrosion. Two additional beams without exposure to corrosion were included as reference specimens. The corroded beams were subjected to four variable periods of corrosion, leading to four levels of steel mass loss (5%, 10%, 20% and 30%). After these corrosion periods, all seven beams were tested to assess their bond performance using a four-point load setup. The beams were continuously monitored by attached acoustic emission sensors throughout the four-point load test until bond failure. The analysis of acquired acoustic emission signals from bond testing was performed to detect early stages of bond damage. Further analysis was executed on signal strength of acoustic emission signals, which used cumulative signal strength, historic index ( H( t)) and severity ( Sr) to characterize the bond degradation in all beams. This analysis allowed early identification of three stages of damage, namely, first crack, initial slip and anchorage cracking, before their visual observation, irrespective of corrosion level or sensor location. Higher corrosion levels yielded significant reduction in both bond strength and corresponding acoustic emission parameters. The results of acoustic emission parameters ( H( t) and Sr) enabled the development of a damage classification chart to identify different stages of bond deterioration.
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Jost, Monika, Teresa M. Huggett, Csaba Kari, and Ulrich Rodeck. "Matrix-independent Survival of Human Keratinocytes through an EGF Receptor/MAPK-Kinase-dependent Pathway." Molecular Biology of the Cell 12, no. 5 (May 2001): 1519–27. http://dx.doi.org/10.1091/mbc.12.5.1519.
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Normal epithelial cells undergo apoptosis when they are denied contact with the extracellular matrix, in a process termed “anoikis.” Conversely, malignant epithelial cells typically acquire anchorage independence, i.e., the capacity to survive and grow in the absence of matrix interaction. Here we asked the question whether anoikis is affected by signaling through the EGF receptor (EGFR). We focused on the EGFR because EGFR signaling is frequently deregulated in malignant epithelial cells. We demonstrate that EGFR activation markedly alleviated the requirement of matrix engagement for survival of primary and immortalized human keratinocytes in suspension culture. Protection of epithelial cells through EGFR activation against anoikis was associated with and required sustained MAPK phosphorylation during the early phase of suspension culture. Interestingly, high levels of MAPK phosphorylation were not only required for EGFR-mediated protection against anoikis but also occurred as a consequence of caspase activation at later stages of suspension culture. These results demonstrate that EGFR activation contributes to anchorage-independent epithelial cell survival and identify MAPK activation as an important mechanism in this process.
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McMahon, M., R. C. Schatzman, and J. M. Bishop. "The amino-terminal 14 amino acids of v-src can functionally replace the extracellular and transmembrane domains of v-erbB." Molecular and Cellular Biology 11, no. 9 (September 1991): 4760–70. http://dx.doi.org/10.1128/mcb.11.9.4760.
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The retroviral oncogene v-erbB encodes a truncated form of the receptor for epidermal growth factor, an integral membrane protein-tyrosine kinase. By contrast, the oncogene v-src encodes a protein-tyrosine kinase that is a peripheral membrane protein. The morphologies and spectra of cells transformed by these two oncogenes differ. In an effort to identify the functional determinant(s) of these differences, we constructed and tested first deletion mutants of v-erbB and then chimeras between v-src and v-erbB. As reported previously, the absence of any membrane anchorage eliminated transformation by v-erbB. Anchorage of the cytoplasmic kinase domain of v-erbB to membranes with amino-terminal portions of the v-src protein permitted transformation. The phenotype and spectrum of transformation were those expected for v-erbB rather than for v-src. The transforming chimeras lost their biological activity if the signal for myristylation at the amino terminus of v-src was compromised by mutation. Biochemical fractionations revealed a correlation between transforming activity and the association of chimeric gene products with the membrane fraction of the cell. For reasons not yet apparent, the combined presence of membrane anchorage domains of v-src, and the transmembrane domain of v-erbB in the same chimera typically (but not inevitably) impeded transformation. Our results suggest that the specificity of transformation by v-erbB resides in the selection of substrates by the cytoplasmic domain of the gene product. The protein retains access to those substrates even when anchored to the membrane in the manner of a peripheral rather than a transmembrane protein.
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McMahon, M., R. C. Schatzman, and J. M. Bishop. "The amino-terminal 14 amino acids of v-src can functionally replace the extracellular and transmembrane domains of v-erbB." Molecular and Cellular Biology 11, no. 9 (September 1991): 4760–70. http://dx.doi.org/10.1128/mcb.11.9.4760-4770.1991.
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The retroviral oncogene v-erbB encodes a truncated form of the receptor for epidermal growth factor, an integral membrane protein-tyrosine kinase. By contrast, the oncogene v-src encodes a protein-tyrosine kinase that is a peripheral membrane protein. The morphologies and spectra of cells transformed by these two oncogenes differ. In an effort to identify the functional determinant(s) of these differences, we constructed and tested first deletion mutants of v-erbB and then chimeras between v-src and v-erbB. As reported previously, the absence of any membrane anchorage eliminated transformation by v-erbB. Anchorage of the cytoplasmic kinase domain of v-erbB to membranes with amino-terminal portions of the v-src protein permitted transformation. The phenotype and spectrum of transformation were those expected for v-erbB rather than for v-src. The transforming chimeras lost their biological activity if the signal for myristylation at the amino terminus of v-src was compromised by mutation. Biochemical fractionations revealed a correlation between transforming activity and the association of chimeric gene products with the membrane fraction of the cell. For reasons not yet apparent, the combined presence of membrane anchorage domains of v-src, and the transmembrane domain of v-erbB in the same chimera typically (but not inevitably) impeded transformation. Our results suggest that the specificity of transformation by v-erbB resides in the selection of substrates by the cytoplasmic domain of the gene product. The protein retains access to those substrates even when anchored to the membrane in the manner of a peripheral rather than a transmembrane protein.
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Mathur, Anirudh K., Vinaya S. Pai, S. Nandini, and Anirban Sarmah. "Finite Element Analysis of Dental Implant as Orthodontic Anchorage." Journal of Contemporary Dental Practice 12, no. 4 (2011): 259–64. http://dx.doi.org/10.5005/jp-journals-10024-1044.
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ABSTRACT Aim The purpose of this three-dimensional (3D) finite element study was to investigate orthodontic loading simulation on a single endosseous implant and its surrounding osseous structure, to analyze the resultant stresses and to identify the changes in the bone adjacent to the implant following orthodontic loading. Materials and methods Two models were constructed using finite element method consisting of endosseous dental implant and the surrounding bone. In the first model, the contact between the implant and the bone was simulated showing no osseointegration, while the second model showed 100% osseointegration. Simulated horizontal loads of 20 N, at 90° from the long axis, were applied to the top of the implant. The study simulated loads in a horizontal direction, similar to a distalmesial orthodontic movement. Results In the first model, the stress was mainly concentrated at the neck of the implant and at the closest surrounding bone. In the second model, the stress was chiefly concentrated at the neck of the implant at the level of the cortical superficial bone. The stresses decreased in the cancellous bone area. On the implant, the highest stress concentration was at the first cervical thread decreasing uniformly to the apex. The stress distribution on the mesial and distal sides showed that the maximum compressive stress was localized mesially and the maximum tensile stress distally. If both models are compared, it can be observed that the stresses were less and more evenly distributed in model 1 (initial stability) than in model 2 when osseointegration was assumed. Conclusion A lack of bony support for the implant represents an unfavorable situation from biomechanical point of view that should be considered and solved. As clinical problems mostly occur at the marginal bone region (bacterial plaque accumulation, overcontoured abutments, infections, osseous defects), attention should be focused on this region. Clinical significance When osseointegrated implants are primarily used as anchorage for orthodontic purposes and then as fixed prosthesis, the functional and structural union of titanium to bone should be preserved. How to cite this article Sarmah A, Mathur AK, Gupta V, Pai VS, Nandini S. Finite Element Analysis of Dental Implant as Orthodontic Anchorage. J Contemp Dent Pract 2011;12(4):259-264.
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Chen, Qin, Rong Deng, Xian Zhao, Haihua Yuan, Hailong Zhang, Jinzhuo Dou, Ran Chen, et al. "Sumoylation of EphB1 Suppresses Neuroblastoma Tumorigenesis via Inhibiting PKCγ Activation." Cellular Physiology and Biochemistry 45, no. 6 (2018): 2283–92. http://dx.doi.org/10.1159/000488174.
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Background/Aims: An increasing number of studies have linked <unterline>e</unterline>rythropoietin-<unterline>p</unterline>roducing <unterline>h</unterline>epatocellular carcinoma (Eph) family receptor tyrosine kinases to cancer progression. However, little knowledge is available about the regulation of their functions in cancer. Methods: SUMOylation was analyzed by performing Ni2+-NTA pull-down assay and immunoprecipitation. Cell proliferation, anchorage-independent growth, and tumorigenesis in vivo were examined by cell counting kit-8, soft agar colony formation assay, and a xenograft tumor mouse model, respectively. Results: We found that EphB1 was post-translationally modified by the small ubiquitin-like modifier (SUMO) protein at lysine residue 785. Analysis of wild-type EphB1 and SUMOylation-deficient EphB1 K785R mutant revealed that SUMOylation of EphB1 suppressed cell proliferation, anchorage-independent cell growth, and xenograft tumor growth. Mechanistic study showed that SUMOylation of EphB1 repressed activation of its downstream signaling molecule PKCγ, and consequently inhibited tumorigenesis. A reciprocal regulatory loop between PKCγ and SUMOylation of EphB1 was also characterized. Conclusion: Our findings identify SUMO1 as a novel key regulator of EphB1-mediated tumorigenesis.
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Blake, Devon R., Angelina V. Vaseva, Richard G. Hodge, McKenzie P. Kline, Thomas S. K. Gilbert, Vikas Tyagi, Daowei Huang, et al. "Application of a MYC degradation screen identifies sensitivity to CDK9 inhibitors in KRAS-mutant pancreatic cancer." Science Signaling 12, no. 590 (July 16, 2019): eaav7259. http://dx.doi.org/10.1126/scisignal.aav7259.
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Stabilization of the MYC oncoprotein by KRAS signaling critically promotes the growth of pancreatic ductal adenocarcinoma (PDAC). Thus, understanding how MYC protein stability is regulated may lead to effective therapies. Here, we used a previously developed, flow cytometry–based assay that screened a library of >800 protein kinase inhibitors and identified compounds that promoted either the stability or degradation of MYC in a KRAS-mutant PDAC cell line. We validated compounds that stabilized or destabilized MYC and then focused on one compound, UNC10112785, that induced the substantial loss of MYC protein in both two-dimensional (2D) and 3D cell cultures. We determined that this compound is a potent CDK9 inhibitor with a previously uncharacterized scaffold, caused MYC loss through both transcriptional and posttranslational mechanisms, and suppresses PDAC anchorage-dependent and anchorage-independent growth. We discovered that CDK9 enhanced MYC protein stability through a previously unknown, KRAS-independent mechanism involving direct phosphorylation of MYC at Ser62. Our study thus not only identifies a potential therapeutic target for patients with KRAS-mutant PDAC but also presents the application of a screening strategy that can be more broadly adapted to identify regulators of protein stability.
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Pedeliento, Giuseppe, and Mihalis Kavaratzis. "Bridging the gap between culture, identity and image: a structurationist conceptualization of place brands and place branding." Journal of Product & Brand Management 28, no. 3 (May 13, 2019): 348–63. http://dx.doi.org/10.1108/jpbm-01-2018-1735.
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Purpose Although place branding is increasingly popular in research as well as in local, regional and national political agendas, the theoretical foundations of the place branding discipline are still underdeveloped. By embracing the stream of identity-based studies, this paper aims to attempt to demonstrate that place brands can be usefully approached through an emphasis of their cultural traits and the practical connection between culture, identity and image. Design/methodology/approach In constructing its theoretical arguments, the paper challenges the place branding model propounded by Kavaratzis and Hatch (2013), and uses practices as units of analysis. The paper conducts a brief review of the principal tenets of practice theory(IES) and uses structuration theory as a theoretical device to demonstrate how this theory can provide a (still lacking) theoretical anchorage for the place branding process. Findings The usefulness of structuration theory for understanding the place branding process is analysed at both the strategic and tactical levels by means of two illustrative examples. Structuration theory proves to be a solid theory which links the constitutive elements of the place branding process, i.e. culture, identity and image, and to inspire further theoretical elaborations and empirical efforts grounded on this theory. Originality/value This is the first paper which uses practice theory(ies) in general and structuration theory in particular to explain the place branding process. The theoretical arguments advanced provide valuable guidance for further theoretical elaborations and empirical applications.
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Yamada, H., T. Omata-Yamada, N. Wakabayashi-Ito, S. G. Carter, and P. Lengyel. "Isolation of recessive (mediator-) revertants from NIH 3T3 cells transformed with a c-H-ras oncogene." Molecular and Cellular Biology 10, no. 4 (April 1990): 1822–27. http://dx.doi.org/10.1128/mcb.10.4.1822.
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We have generated two serum- and anchorage-dependent revertants from NIH 3T3 cells transformed with multiple copies of the human c-H-ras oncogene. In both revertants, the c-H-ras oncogene was fully expressed. Fusion of either revertant with untransformed cells or of the two revertants with one another resulted in transformed progeny. These results indicated that the two revertants were recessive and in different complementation groups. We believe that in our two revertants some of the genes mediating the transforming activity of the c-H-ras oncogene are defective; we are attempting to identify these mediator genes.
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Yamada, H., T. Omata-Yamada, N. Wakabayashi-Ito, S. G. Carter, and P. Lengyel. "Isolation of recessive (mediator-) revertants from NIH 3T3 cells transformed with a c-H-ras oncogene." Molecular and Cellular Biology 10, no. 4 (April 1990): 1822–27. http://dx.doi.org/10.1128/mcb.10.4.1822-1827.1990.
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We have generated two serum- and anchorage-dependent revertants from NIH 3T3 cells transformed with multiple copies of the human c-H-ras oncogene. In both revertants, the c-H-ras oncogene was fully expressed. Fusion of either revertant with untransformed cells or of the two revertants with one another resulted in transformed progeny. These results indicated that the two revertants were recessive and in different complementation groups. We believe that in our two revertants some of the genes mediating the transforming activity of the c-H-ras oncogene are defective; we are attempting to identify these mediator genes.
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Hu, Jun Qiang, Yong Xing Zhang, and Jian Gong Chen. "Identification for Bolt-Surrounding Rock System Based on Wavelet Neural Network." Applied Mechanics and Materials 204-208 (October 2012): 738–42. http://dx.doi.org/10.4028/www.scientific.net/amm.204-208.738.
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The dynamic testing is widely used in undestructive testings of bolt’s anchoring quality. But it’s difficult to estimate bolt’s anchoring quality according to the dynamic response of bolt. The bolt’s anchorage quality depends mainly on bolt-surrounding rock structural system which features must be identified. A new analytical method used in identification for bolt-surrounding rock structural system is put forward, which combine with advantages of wavelet analysis and artificial neural network. The results indicate that this wavelet neural network after training can best identify the bolt’s side rigidity factors and can be a useable intelligentized mean to assess the quality of bolt’s anchoring system.
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Anderson, Steven N., Danli L. Towne, David J. Burns, and Usha Warrior. "A High-Throughput Soft Agar Assay for Identification of Anticancer Compound." Journal of Biomolecular Screening 12, no. 7 (October 2007): 938–45. http://dx.doi.org/10.1177/1087057107306130.
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A 384-well soft agar assay was developed to identify potential novel anticancer compounds. Normally used to detect cell transformation, the assay is used here to quantitate cell proliferation in a 3-dimensional (3-D) anchorage-independent format. HCC827 cells, which are highly sensitive to epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors, were used to develop the method and a set of 9600 compounds used to validate the assay. Results were compared to a monolayer assay using the same compound set. The assay provides a robust method to discover compounds that could be missed using traditional monolayer formats. ( Journal of Biomolecular Screening 2007:938-945)
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Nguyen, Thanh Hung, Adela Ralbovska, and Jan-Michael Kugler. "RhoBTB Proteins Regulate the Hippo Pathway by Antagonizing Ubiquitination of LKB1." G3: Genes|Genomes|Genetics 10, no. 4 (February 28, 2020): 1319–25. http://dx.doi.org/10.1534/g3.120.401038.
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The Hippo pathway regulates growth and apoptosis. We identify RhoBTB proteins as novel regulators of Hippo signaling. RhoBTB depletion in the Drosophila wing disc epithelium cooperated with Yki to drive hyperplasia into neoplasia. Depletion of RhoBTB2 caused elevated YAP activity in human cells. RhoBTB2 deficiency resulted in increased colony formation in assays for anchorage-independent growth. We provide evidence that RhoBTBs acts on Hippo signaling through regulation of the kinase LKB1. LKB1 protein levels were reduced upon RhoBTB2 depletion, which correlated with increased LKB1 ubiquitination. Restoring LKB1 levels rescued loss of RhoBTB in Drosophila. Our results suggest that RhoBTB-dependent LKB1 regulation may contribute to its tumor-suppressive function.
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Ruiz Jiménez, Antonia María, Nieves Aquino Llinares, and Elena Ferri Fuentevilla. "National Identities in Troubled Times: Germany and Southern European Countries after the Great Recession." Genealogy 5, no. 2 (April 16, 2021): 40. http://dx.doi.org/10.3390/genealogy5020040.
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This article aims to elucidate the effects of the Great Recession and the retrenchment of welfare on national identity in several European countries. While different authors have observed that good economic performance, redistribution, and the growth of welfare strengthen countries as political communities of solidarity, there is much less empirical evidence regarding the consequences of an economic crisis for national identity. To investigate these consequences, we focus on a set of countries where the 2008 Great Recession resulted in different impacts, namely, Germany and four countries in Southern Europe (Italy, Spain, Portugal, and Greece). We use secondary quantitative data from Eurobarometer surveys to test aggregated and individual hypotheses relating to both the size and direction of the Great Recession’s effects on national identity. Our results suggest that the roles and impacts of economic variables may be different depending on the relative economic performance of a country within its own context. It seems easier to confirm that good economic performance, in relative terms, might strengthen national identity than proving that poor economic performance will weaken national identity. Even if no definitive empirical evidence can be given at this point, our data suggest a rationalization or compensation mechanism such that citizens look for where to anchor their strong national identities after they have decided on them. If an economy is performing well, then it would become a good anchorage for holding a strong national identity; however, if an economy is not performing well, then economic factors will cease to be a fundamental element for national identity holders.
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Almeida, Eduardo A. C., Duško Ilić, Qin Han, Christof R. Hauck, Fang Jin, Hisaaki Kawakatsu, David D. Schlaepfer, and Caroline H. Damsky. "Matrix Survival Signaling." Journal of Cell Biology 149, no. 3 (May 1, 2000): 741–54. http://dx.doi.org/10.1083/jcb.149.3.741.
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Most transformed cells have lost anchorage and serum dependence for growth and survival. Previously, we established that when serum is absent, fibronectin survival signals transduced by focal adhesion kinase (FAK), suppress p53-regulated apoptosis in primary fibroblasts and endothelial cells (Ilić et al. 1998. J. Cell Biol. 143:547–560). The present goals are to identify survival sequences in FAK and signaling molecules downstream of FAK required for anchorage-dependent survival of primary fibroblasts. We report that binding of the SH3 domain of p130Cas to proline-rich region 1 of FAK is required to support survival of fibroblasts on fibronectin when serum is withdrawn. The FAK–p130Cas complex activates c-Jun NH2-terminal kinase (JNK) via a Ras/Rac1/Pak1/MAPK kinase 4 (MKK4) pathway. Activated (phospho-) JNK colocalizes with FAK in focal adhesions of fibroblasts cultured on fibronectin, which supports their survival, but not in fibroblasts cultured on collagen, which does not. Cells often survive in the absence of extracellular matrix if serum factors are provided. In that case, we confirm work of others that survival signals are transduced by FAK, phosphatidylinositol 3′-kinase (PI3-kinase), and Akt/protein kinase B (PKB). However, when serum is absent, PI3-kinase and Akt/PKB are not involved in the fibronectin-FAK-JNK survival pathway documented herein. Thus, survival signals from extracellular matrix and serum are transduced by FAK via two distinct pathways.
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Chróścielewski, J., M. Miśkiewicz, Ł. Pyrzowski, and B. Sobczyk. "Damage Analysis of Tensioning Cable Anchorage Zone of a Bridge Superstructure, Using CDP Abaqus Material Model." Archives of Civil Engineering 63, no. 3 (September 26, 2017): 3–18. http://dx.doi.org/10.1515/ace-2017-0025.
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AbstractNumerical analysis of the tensioning cables anchorage zone of a bridge superstructure is presented in this paper. It aims to identify why severe concrete cracking occurs during the tensioning process in the vicinity of anchor heads. In order to simulate the tensioning, among others, a so-called local numerical model of a section of the bridge superstructure was created in the Abaqus Finite Element Method (FEM) environment. The model contains all the important elements of the analyzed section of the concrete bridge superstructure, namely concrete, reinforcement and the anchoring system. FEM analyses are performed with the inclusion of both material and geometric nonlinearities. Concrete Damage Plasticity (CDP) constitutive relation from Abaqus is used to describe nonlinear concrete behaviour, which enables analysis of concrete damage and crack propagation. These numerical FEM results are then compared with actual crack patterns, which have been spotted and inventoried at the bridge construction site.
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Mongiardini, Mario, Ronald K. Faller, John D. Reid, and Dean L. Sicking. "Dynamic Evaluation and Implementation Guidelines for a Nonproprietary W-Beam Guardrail Trailing-End Terminal." Transportation Research Record: Journal of the Transportation Research Board 2377, no. 1 (January 2013): 61–73. http://dx.doi.org/10.3141/2377-07.
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Most state departments of transportation use simple adaptations of crashworthy guardrail end terminals, which typically include breakaway posts and an anchor cable, for downstream anchorage systems. The guardrail safety performance for vehicular impacts occurring in close proximity to these simplified, downstream anchorage systems is not well known. Further, the length of need (LON) for the downstream end of these systems has yet to be adequately determined. This research project assessed the safety performance of the Midwest Guardrail System (MGS) for impacts occurring in close proximity to a nonproprietary, trailing-end guardrail terminal under the Test Level 3 conditions of the Manual for Assessing Safety Hardware. The two research objectives were to (a) determine the end of the LON for impacts with light pickup trucks and (b) investigate potential risks for a small passenger car to become unstable when striking the downstream end of the MGS anchored by the nonproprietary, trailing-end terminal. Numerical simulations were carried out to identify the most critical impact location for the 1100C small car and the end of the LON for the 2270P pickup truck. In full-scale crash tests, considerable snag of the 1100C vehicle occurred; however, occupant risk values and vehicle stability were within acceptable limits. The crash test with the 2270P pickup indicated that the end of the LON was located at the sixth post from the downstream-end post. Guidelines were proposed for installing the MGS to shield hazards in close proximity to the tested nonproprietary, trailing-end terminal.
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Karthik, Madhu M., Tevfik Terzioglu, Casey Jones, Stefan Hurlebaus, and Mary Beth D. Hueste. "Nondestructive Evaluation of Non-Strand Defects in Stay Cable Specimens." Transportation Research Record: Journal of the Transportation Research Board 2672, no. 41 (August 10, 2018): 101–12. http://dx.doi.org/10.1177/0361198118790640.
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Stay cable systems are used extensively for the construction of long-span bridges owing to their inherent advantages. In most cable-stayed bridges the steel strands within the main tension elements (MTEs) are grouted to provide a corrosion protection system. However, there could be segregated grout, voids, and water accumulation/infiltration within these voids in the ducts due to poor quality of the grouting material and grouting techniques. These locations may act as initiators for the corrosion of steel strands within the ducts, which can have serious implications on the load carrying capacity and safety of cable-stayed bridges. In this investigation, several nondestructive evaluation (NDE) techniques are evaluated to determine their ability to detect grout defects within the anchorage regions, end caps, and MTEs of the stay cable system. Four stay cable specimen mock-ups with known grout defects and voids were fabricated. NDE methods that were part of this investigation included ground penetrating radar, infrared thermography, electrical capacitance tomography, impact echo, sounding, ultrasonic tomography, ultrasonic pulse velocity, low frequency ultrasound, visual testing, and borescope. While a few NDE methods could identify voids and water infiltration defects within the high-density polyethylene (HDPE) MTEs, it is evident that there is still a need for a method that is effective in detecting grout defects within the metal ducts embedded in the anchorage region and metal MTEs. Although visual testing and borescope methods are effective in identifying the defects, prior information about the location of the defects is generally required.
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Scull, Catherine E., Yinfeng Zhang, Nichole Tower, Lynn Rasmussen, Indira Padmalayam, Robert Hunter, Ling Zhai, Robert Bostwick, and David A. Schneider. "Discovery of novel inhibitors of ribosome biogenesis by innovative high throughput screening strategies." Biochemical Journal 476, no. 15 (August 9, 2019): 2209–19. http://dx.doi.org/10.1042/bcj20190207.
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Abstract Over the past two decades, ribosome biogenesis has emerged as an attractive target for cancer treatment. In this study, two high-throughput screens were used to identify ribosome biogenesis inhibitors. Our primary screen made use of the HaloTag selective labeling strategy to identify compounds that decreased the abundance of newly synthesized ribosomes in A375 malignant melanoma cells. This screen identified 5786 hit compounds. A subset of those initial hit compounds were tested using a secondary screen that directly measured pre-ribosomal RNA (pre-rRNA) abundance as a reporter of rRNA synthesis rate, using quantitative RT-PCR. From the secondary screen, we identified two structurally related compounds that are potent inhibitors of rRNA synthesis. These two compounds, Ribosome Biogenesis Inhibitors 1 and 2 (RBI1 and RBI2), induce a substantial decrease in the viability of A375 cells, comparable to the previously published ribosome biogenesis inhibitor CX-5461. Anchorage-independent cell growth assays further confirmed that RBI2 inhibits cell growth and proliferation. Thus, the RBI compounds have promising properties for further development as potential cancer chemotherapeutics.
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Peraldo-Neia, Caterina, Annamaria Massa, Francesca Vita, Marco Basiricò, Chiara Raggi, Paola Bernabei, Paola Ostano, et al. "A Novel Multidrug-Resistant Cell Line from an Italian Intrahepatic Cholangiocarcinoma Patient." Cancers 13, no. 9 (April 23, 2021): 2051. http://dx.doi.org/10.3390/cancers13092051.
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Chemotherapy resistance is a relevant clinical issue in tumor treatment, in particular in biliary tract carcinoma (BTC), for which there are no effective therapies, neither in the first nor in the second line. The development of chemoresistant cell lines as experimental models to investigate the mechanisms of resistance and identify alternative druggable pathways is mandatory. In BTC, in which genetics and biological behavior depend on the etiology, ethnicity, and anatomical site of origin, the creation of models that better recapitulate these characteristics is even more crucial. Here we have established and characterized an intrahepatic cholangiocarcinoma (iCCA) cell line derived from an Italian patient, called 82.3. Cells were isolated from a patient-derived xenograft (PDX) and, after establishment, immunophenotypic, biological, genetic, molecular characteristics, and tumorigenicity in vivo in NOD/SCID mice were investigated. 82.3 cells exhibited epithelial morphology and cell markers (EPCAM, CK7, and CK19); they also expressed different cancer stem markers (CD44, CD133, CD49b, CD24, Stro1, PAX6, FOXA2, OCT3/4), α–fetoprotein and under anchorage-independent and serum-free conditions were capable of originating cholangiospheres. The population doubling time was approximately 53 h. In vitro, they demonstrated a poor ability to migrate; in vivo, 82.3 cells retained their tumorigenicity, with a long latency period (16 weeks). Genetic identity using DNA fingerprinting analysis revealed 16 different loci, and the cell line was characterized by a complex hyperdiploid karyotype. Furthermore, 82.3 cells showed cross-resistance to gemcitabine, 5-fluorouracil, carboplatin, and oxaliplatin; in fact, their genetic profile showed that 60% of genes (n = 168), specific for drug resistance and related to the epithelial-mesenchymal transition, were deregulated in 82.3 cells compared to a control iCCA cell line sensitive to chemotherapeutics. RNA sequencing analysis revealed the enrichment for genes associated with epithelial to mesenchymal transition (EMT), vasculature development, and extracellular matrix (ECM) remodeling, underlining an aggressive phenotype. In conclusion, we have created a new iCCA cell line of Caucasian origin: this could be exploited as a preclinical model to study drug resistance mechanisms and to identify alternative therapies to improve the prognosis of this tumor type.
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Kong, Kenneth C. C. "A taxonomy of the discourse relations between words and visuals." Information Design Journal 14, no. 3 (November 22, 2006): 207–30. http://dx.doi.org/10.1075/idj.14.3.04kon.
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A document is mainly composed of words and images, but the complex relationship that binds these two completely different semiotic resources is usually taken for granted as transparent. The simple relations between words and images – ‘anchorage’ and ‘relay’, identified by Barthes almost 30 years ago – are unable to deal with the complexity of their bond, made even more complex by current printing and computer technology. This paper aims to identify the potential relations that bind texts and images together by arguing for a multilevel description of their logico-semantic relationships. The multiple, evaluative and metaphorical functions of the relations will also be discussed. The data generated from the proposed framework can form an empirical corpus for quantitative analysis. Examples from a variety of sources will be used as examples to show how the framework can be operationalized.
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Mattioli, Elisabetta, Marta Columbaro, Mohammed Hakim Jafferali, Elisa Schena, Einar Hallberg, and Giovanna Lattanzi. "Samp1 Mislocalization in Emery-Dreifuss Muscular Dystrophy." Cells 7, no. 10 (October 15, 2018): 170. http://dx.doi.org/10.3390/cells7100170.
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LMNA linked-Emery-Dreifuss muscular dystrophy (EDMD2) is a rare disease characterized by muscle weakness, muscle wasting, and cardiomyopathy with conduction defects. The mutated protein lamin A/C binds several nuclear envelope components including the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex and the inner nuclear membrane protein Samp1 (Spindle Associated Membrane Protein 1). Considering that Samp1 is upregulated during muscle cell differentiation and it is involved in nuclear movement, we hypothesized that it could be part of the protein platform formed by LINC proteins and prelamin A at the myotube nuclear envelope and, as previously demonstrated for those proteins, could be affected in EDMD2. Our results show that Samp1 is uniformly distributed at the nuclear periphery of normal human myotubes and committed myoblasts, but its anchorage at the nuclear poles is related to the presence of farnesylated prelamin A and it is disrupted by the loss of prelamin A farnesylation. Moreover, Samp1 is absent from the nuclear poles in EDMD2 myotubes, which shows that LMNA mutations associated with muscular dystrophy, due to reduced prelamin A levels in muscle cell nuclei, impair Samp1 anchorage. Conversely, SUN1 pathogenetic mutations do not alter Samp1 localization in myotubes, which suggests that Samp1 lies upstream of SUN1 in nuclear envelope protein complexes. The hypothesis that Samp1 is part of the protein platform that regulates microtubule nucleation from the myotube nuclear envelope in concert with pericentrin and LINC components warrants future investigation. As a whole, our data identify Samp1 as a new contributor to EDMD2 pathogenesis and our data are relevant to the understanding of nuclear clustering occurring in laminopathic muscle.
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Samarin, D. G., A. A. Filippovich, and V. L. Ustyuzhanin. "About Errors Engineering and Deviceing Anchor Piles, Performed by Discharge-Pulse Technology." Zhilishchnoe Stroitel'stvo, no. 12 (2020): 13–21. http://dx.doi.org/10.31659/0044-4472-2020-12-13-21.
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The article examines a case from the practice of geotechnical construction, when errors in the calculations of anchor piles performed by discharge-pulse technology (DPT anchor) and deviations from engineering solutions could lead to an emergency. During excavation of the foundation pit, an underground parking lot under construction, the enclosing structure, fixed with DPT anchors, received unacceptable displacements. Calculations established that the bearing capacity of the DPT anchors on the ground was overestimated up to 3 times. In addition, the analysis of the available materials on this object allowed the authors to identify serious violations in the construction of the latter. It is shows that when carrying out work on the preliminary tension of the DPT anchors, in some cases, already with an effort of 10 tons, there is a loss of their bearing capacity along the ground. As a result, it became necessary to redesign the anchorage.
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Ambrose, J. Christian, and Geoffrey O. Wasteneys. "CLASP Modulates Microtubule-Cortex Interaction during Self-Organization of Acentrosomal Microtubules." Molecular Biology of the Cell 19, no. 11 (November 2008): 4730–37. http://dx.doi.org/10.1091/mbc.e08-06-0665.
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CLASP proteins associate with either the plus ends or sidewalls of microtubules depending on the subcellular location and cell type. In plant cells, CLASP's distribution along the full length of microtubules corresponds with the uniform anchorage of microtubules to the cell cortex. Using live cell imaging, we show here that loss of CLASP in Arabidopsis thaliana results in partial detachment of microtubules from the cortex. The detached portions undergo extensive waving, distortion, and changes in orientation, particularly when exposed to the forces of cytoplasmic streaming. These deviations from the normal linear polymerization trajectories increase the likelihood of intermicrotubule encounters that are favorable for subsequent bundle formation. Consistent with this, cortical microtubules in clasp-1 leaf epidermal cells are hyper-parallel. On the basis of these data, we identify a novel mechanism where modulation of CLASP activity governs microtubule-cortex attachment, thereby contributing to self-organization of cortical microtubules.
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Kanki, Keita, Ryota Watanabe, Le Nguyen Thai, Chun-Hao Zhao, and Kyoko Naito. "HDAC9 Is Preferentially Expressed in Dedifferentiated Hepatocellular Carcinoma Cells and Is Involved in an Anchorage-Independent Growth." Cancers 12, no. 10 (September 23, 2020): 2734. http://dx.doi.org/10.3390/cancers12102734.
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Aberrant activation of histone deacetylases (HDACs) is one of the causes of tumor cell transformation in many types of cancer, however, the critical HDAC responsible for the malignant transformation remain unclear. To identify the HDAC related to the dedifferentiation of hepatocellular carcinoma (HCC) cells, we investigated the expression profile of HDACs in differentiated and undifferentiated hepatoma cells. We found that HDAC9, a member of the class II HDAC, is preferentially expressed in undifferentiated HCC cells. Analysis of 373 HCC patients in The Cancer Genome Atlas (TCGA) database revealed that the expression of HDAC9 mRNA positively correlated with the markers of mesenchymal phenotype and stemness, and conversely, negatively correlated with hepatic differentiation markers. HDAC9 was transcriptionally upregulated in epithelial–mesenchymal transition (EMT)-induced HCC cells treated with TGF-β. Genetic and pharmacological inhibition of HDAC9 in undifferentiated HCC cells showed decreased sphere-forming activity, which indicates an ability of anchorage-independent cell growth and self-renewal. We also showed that aldehyde dehydrogenase 1A3 (ALDH1A3) was downregulated in HDAC9-suppressing cells, and ALDH inhibitor disulfiram significantly decreased the sphere formation of undifferentiated HCC cells. Together, our data provide useful information for the development of HDAC9-specific inhibitors for the treatment of HCC progression.
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Kadrmas, Julie L., Mark A. Smith, Kathleen A. Clark, Stephen M. Pronovost, Nemone Muster, John R. Yates, and Mary C. Beckerle. "The integrin effector PINCH regulates JNK activity and epithelial migration in concert with Ras suppressor 1." Journal of Cell Biology 167, no. 6 (December 13, 2004): 1019–24. http://dx.doi.org/10.1083/jcb.200408090.
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Cell adhesion and migration are dynamic processes requiring the coordinated action of multiple signaling pathways, but the mechanisms underlying signal integration have remained elusive. Drosophila embryonic dorsal closure (DC) requires both integrin function and c-Jun amino-terminal kinase (JNK) signaling for opposed epithelial sheets to migrate, meet, and suture. Here, we show that PINCH, a protein required for integrin-dependent cell adhesion and actin–membrane anchorage, is present at the leading edge of these migrating epithelia and is required for DC. By analysis of native protein complexes, we identify RSU-1, a regulator of Ras signaling in mammalian cells, as a novel PINCH binding partner that contributes to PINCH stability. Mutation of the gene encoding RSU-1 results in wing blistering in Drosophila, demonstrating its role in integrin-dependent cell adhesion. Genetic interaction analyses reveal that both PINCH and RSU-1 antagonize JNK signaling during DC. Our results suggest that PINCH and RSU-1 contribute to the integration of JNK and integrin functions during Drosophila development.
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Barreiro, Olga, Moreno Zamai, María Yáñez-Mó, Emilio Tejera, Pedro López-Romero, Peter N. Monk, Enrico Gratton, Valeria R. Caiolfa, and Francisco Sánchez-Madrid. "Endothelial adhesion receptors are recruited to adherent leukocytes by inclusion in preformed tetraspanin nanoplatforms." Journal of Cell Biology 183, no. 3 (October 27, 2008): 527–42. http://dx.doi.org/10.1083/jcb.200805076.
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VCAM-1 and ICAM-1, receptors for leukocyte integrins, are recruited to cell–cell contact sites on the apical membrane of activated endothelial cells. In this study, we show that this recruitment is independent of ligand engagement, actin cytoskeleton anchorage, and heterodimer formation. Instead, VCAM-1 and ICAM-1 are recruited by inclusion within specialized preformed tetraspanin-enriched microdomains, which act as endothelial adhesive platforms (EAPs). Using advanced analytical fluorescence techniques, we have characterized the diffusion properties at the single-molecule level, nanoscale organization, and specific intradomain molecular interactions of EAPs in living primary endothelial cells. This study provides compelling evidence for the existence of EAPs as physical entities at the plasma membrane, distinct from lipid rafts. Scanning electron microscopy of immunogold-labeled samples treated with a specific tetraspanin-blocking peptide identify nanoclustering of VCAM-1 and ICAM-1 within EAPs as a novel mechanism for supramolecular organization that regulates the leukocyte integrin–binding capacity of both endothelial receptors during extravasation.
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Stroud, Matthew J., Wei Feng, Jianlin Zhang, Jennifer Veevers, Xi Fang, Larry Gerace, and Ju Chen. "Nesprin 1α2 is essential for mouse postnatal viability and nuclear positioning in skeletal muscle." Journal of Cell Biology 216, no. 7 (May 22, 2017): 1915–24. http://dx.doi.org/10.1083/jcb.201612128.
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The position of the nucleus in a cell is controlled by interactions between the linker of nucleoskeleton and cytoskeleton (LINC) complex and the cytoskeleton. Defects in nuclear positioning and abnormal aggregation of nuclei occur in many muscle diseases and correlate with muscle dysfunction. Nesprin 1, which includes multiple isoforms, is an integral component of the LINC complex, critical for nuclear positioning and anchorage in skeletal muscle, and is thought to provide an essential link between nuclei and actin. However, previous studies have yet to identify which isoform is responsible. To elucidate this, we generated a series of nesprin 1 mutant mice. We showed that the actin-binding domains of nesprin 1 were dispensable, whereas nesprin 1α2, which lacks actin-binding domains, was crucial for postnatal viability, nuclear positioning, and skeletal muscle function. Furthermore, we revealed that kinesin 1 was displaced in fibers of nesprin 1α2–knockout mice, suggesting that this interaction may play an important role in positioning of myonuclei and functional skeletal muscle.
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Sharif, Iman, Christopher S. Meisl, and Kenneth J. Elwood. "Assessment of ASCE 41 Height-to-Thickness Ratio Limits for URM Walls." Earthquake Spectra 23, no. 4 (November 2007): 893–908. http://dx.doi.org/10.1193/1.2790488.
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Unreinforced masonry (URM) walls with sufficient anchorage to the diaphragms will crack above mid-height when subjected to out-of-plane ground motions. This study investigates the sensitivity of the out-of-plane response to varying height-to-thickness ( h/ t) ratios for URM walls connected to rigid diaphragms. ASCE 41, Seismic Rehabilitation Standard, provides guidelines for permissible h/ t ratios for out-of-plane URM walls. To assess these limits, a rigid-body numerical model, calibrated to full-scale shake table tests, was used. The focus of the analysis was to identify the minimum h/ t ratio that would cause collapse of the wall when subjected to seismic shaking. The analysis was performed for 80 input motions and accounted for variability in the crack location. The results of the study suggest that the probability of collapse is dependent on the site class and that walls with limited overburden and satisfying the h/ t limits in ASCE 41 have a very low probability of collapse.
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Golluscio, Lucía, Christian Lehmann, Felipe Daniel Hasler Sandoval, and Anna Pamies. "A corpus-based analysis of referentiality in Mapudungun." LIAMES: Línguas Indígenas Americanas 21 (August 18, 2021): e021010. http://dx.doi.org/10.20396/liames.v21i00.8658929.
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This report presents the methodological guidelines as well as some partial results of the study of referentiality in Mapudungun, a language isolate spoken in Chile and Argentina with different degrees of vitality. Reference in discourse encompasses two basic operations: the individuation of the referents and their anchorage in the discourse. Our research is part of a wider project which seeks to identify the structural resources used by the languages in referential operations. We investigate a set of structural and semantic parameters of referential expressions as they occur in a corpus of Mapudungun texts belonging to different genres. Some of the findings may represent general patterns of reference in natural texts, while others may be representative of specific Mapudungun genres. At a methodological level, our research shows that it is possible to substantiate hypotheses on reference and on discourse structure related to reference by hard figures, to characterize text genres by measurable semantic and structural properties, and to discover new phenomena which demand an explanation.
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Areni, Alesssndra, Gilda Sensales, and Angela Angelastro. "Le rivolte francesi del novembre 2005 nei titoli di ventuno quotidiani italiani. Ricostruzione dei processi rappresentazionali attraverso un'analisi lessicografica." RICERCHE DI PSICOLOGIA, no. 4 (May 2009): 31–58. http://dx.doi.org/10.3280/rip2008-004002.
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- The tradition of the social representations is the framework of research that is part of a wider project focused on the role of mass media, as part of cultural system, and on processes of anchorage and labelling involved to define the events under observation. We studied the social representations of French riots of November 2005 on headlines of 21 Italian daily newspapers with different cultural and ideological orientation. The aims of research, of comparative character, were the exploration: of consistence of results emerged in previous investigations, and of role played from newspapers and from temporal distance by the events 1) on structural organization of representational field, related to lexicon of headlines, and 2) on differential characterization of the lexicon of headlines 2a) of 21 newspapers and 2b) of two periods, more or less near to the beginning of events. The population, composed by 468 headlines, was collected by October 30 to November 18, 2005. The textual data, related to words of headlines, and the extra-textual data, related to newspapers, to period of publication (I and II week), to signature and sex of journalists, have been processed by different steps of statistical package SPAD-T. According to the scree-test were extracted two factors able to explain 20.40% of total variance. Through the intersection between the two factors we analyzed the factorial plan that, by providing the information more synthetic and exhaustive as possible, highlighted the existence of four areas otherwise characterized by the newspapers, by the two weeks and by the signature and gender of journalists. The differential analysis of lexicographical characterization of each of the 21 newspapers and of two periods, allowed the confirmation and deepening of what emerged in the structural analysis. Overall results showed the non-neutrality of language used by the headlines. It was functional to ideological and cultural profile of source, to its geographical area of reference and to temporal distance from origin of events. Furthermore results showed processes of anchorage and la- beling referable to need to preserve and strengthen specific groupal identity of the source.
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Moschetti, Morgan P., Eric M. Thompson, John Rekoske, Michael G. Hearne, Peter M. Powers, Daniel E. McNamara, and Carl Tape. "Ground‐Motion Amplification in Cook Inlet Region, Alaska, from Intermediate‐Depth Earthquakes, Including the 2018 Mw 7.1 Anchorage Earthquake." Seismological Research Letters 91, no. 1 (November 20, 2019): 142–52. http://dx.doi.org/10.1785/0220190179.
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Abstract We measure pseudospectral and peak ground motions from 44 intermediate‐depth Mw≥4.9 earthquakes in the Cook Inlet region of southern Alaska, including those from the 2018 Mw 7.1 earthquake near Anchorage, to identify regional amplification features (0.1–5 s period). Ground‐motion residuals are computed with respect to an empirical ground‐motion model for intraslab subduction earthquakes, and we compute bias, between‐, and within‐event terms through a linear mixed‐effects regression. Between‐event residuals are analyzed to assess the relative source characteristics of the Cook Inlet earthquakes and suggest a difference in the scaling of the source with depth, relative to global observations. The within‐event residuals are analyzed to investigate regional amplification, and various spatial patterns manifest, including correlations of amplification with depth of the Cook Inlet basin and varying amplifications east and west of the center of the basin. Three earthquake clusters are analyzed separately and indicate spatial amplification patterns that depend on source location and exhibit variations in the depth scaling of long‐period basin amplification. The observations inform future seismic hazard modeling efforts in the Cook Inlet region. More broadly, they suggest a greater complexity of basin and regional amplification than is currently used in seismic hazard analyses.
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Picornell, Mercè. "The back side of the postcard: Subversion of the island tourist gaze in the contemporary Mallorcan imaginary." Island Studies Journal 15, no. 2 (2020): 291–314. http://dx.doi.org/10.24043/isj.109.
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This article analyses the manner in which certain artists and activists in Mallorca have recently generated a counter-image of the traditional postcard, which essentially symbolises the tourist gaze. Taking examples from diverse sources, such as artistic pieces, memes, protest posters and underground comics, I analyse the mechanisms used to subvert the conventional tourist perspective of the island space. More specifically, I identify two strategies associated with the limitation of the space and time portrayed in the postcard. The confines of the space are manifest in the display of the off-camera and the critical anchorage of the image, while the limits of temporality are presented in a dystopic revision of the island map. To support the findings of this study, I have drawn on the ideas, theories and methods of island studies, tourism studies, postcolonial criticism and the rhetoric of images. The conclusions of this article aim to provide an interpretation of the complex emergence of a resistant social agency capable of creating its own portrayals of the island.
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Deneen, Benjamin, Scott M. Welford, Thu Ho, Felicia Hernandez, Irwin Kurland, and Christopher T. Denny. "PIM3 Proto-Oncogene Kinase Is a Common Transcriptional Target of Divergent EWS/ETS Oncoproteins." Molecular and Cellular Biology 23, no. 11 (June 1, 2003): 3897–908. http://dx.doi.org/10.1128/mcb.23.11.3897-3908.2003.
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ABSTRACT Despite significant structural diversity, present evidence suggests that EWS/ETS fusion proteins promote oncogenesis by transcriptionally modulating a common set of target genes. In order to identify these genes, microarray expression analyses were performed on NIH 3T3 polyclonal populations expressing one of three EWS/ETS fusion genes. The majority of these genes can be grouped into seven functional categories, including cellular metabolism and signal transduction. The biologic significance of these target genes was pursued. The effects of modulating genes involved in metabolism were assessed by flux studies and demonstrated shifts in glucose utilization and lactate production as a result of EWS/FLI1 expression. The proto-oncogene coding for serine/threonine kinase PIM3 was found to one of several genes encoding signal transduction proteins that were up-regulated by EWS/ETS fusions. PIM3 was found to be expressed in a panel of human Ewing's family tumor cell lines. Forced expression of PIM3 promoted anchorage-independent growth. Coexpression of a kinase-deficient PIM3 mutant attenuated EWS/FLI1-mediated NIH 3T3 tumorigenesis in immunodeficent mice.
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Fiorillo, Alyson A., Terry R. Medler, Yvonne B. Feeney, Yi Liu, Kalie L. Tommerdahl, and Charles V. Clevenger. "HMGN2 Inducibly Binds a Novel Transactivation Domain in Nuclear PRLr to Coordinate Stat5a-Mediated Transcription." Molecular Endocrinology 25, no. 9 (September 1, 2011): 1550–64. http://dx.doi.org/10.1210/me.2011-0106.
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The direct actions of transmembrane receptors within the nucleus remain enigmatic. In this report, we demonstrate that the prolactin receptor (PRLr) localizes to the nucleus where it functions as a coactivator through its interactions with the latent transcription factor signal transducer and activator of transcription 5a (Stat5a) and the high-mobility group N2 protein (HMGN2). We identify a novel transactivation domain within the PRLr that is activated by ligand-induced phosphorylation, an event coupled to HMGN2 binding. The association of the PRLr with HMGN2 enables Stat5a-responsive promoter binding, thus facilitating transcriptional activation and promoting anchorage-independent growth. We propose that HMGN2 serves as a critical regulatory factor in Stat5a-driven gene expression by facilitating the assembly of PRLr/Stat5a onto chromatin and that these events may serve to promote biological events that contribute to a tumorigenic phenotype. Our data imply that phosphorylation may be the molecular switch that activates a cell surface receptor transactivation domain, enabling it to tether chromatin-modifying factors, such as HMGN2, to target promoter regions in a sequence-specific manner.
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Borbone, Eleonora, Giancarlo Troncone, Angelo Ferraro, Zuzana Jasencakova, Lovorka Stojic, Francesco Esposito, Nadine Hornig, Alfredo Fusco, and Valerio Orlando. "Enhancer of Zeste Homolog 2 Overexpression Has a Role in the Development of Anaplastic Thyroid Carcinomas." Journal of Clinical Endocrinology & Metabolism 96, no. 4 (April 1, 2011): 1029–38. http://dx.doi.org/10.1210/jc.2010-1784.
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Abstract Context: Enhancer of zeste homolog 2 (EZH2) is a histone lysine methyltransferase belonging to the polycomb group protein family. Overexpression of EZH2 has been found in several human malignancies including hematological and solid tumors. Objectives: In this study we investigated the expression levels of EZH2 and its polycomb group protein partners in thyroid carcinoma tissues with different degrees of malignancy to identify potential new therapeutic targets for anaplastic thyroid carcinoma (ATC). Results: We show that high EZH2 expression levels are characteristic of undifferentiated ATC, whereas no significant changes were observed in well-differentiated papillary and follicular thyroid carcinomas as compared with normal thyroid. Knockdown of EZH2 in ATC cell lines results in cell growth inhibition, loss of anchorage-independent growth, migration, and invasion properties. Moreover, we demonstrate that EZH2 directly controls differentiation of ATC cells by silencing the thyroid specific transcription factor paired-box gene 8 (PAX8). Conclusions: EZH2 is specifically overexpressed in ATC, and it directly contributes to transcriptional silencing of PAX8 gene and ATC differentiation.
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Eiden, M. V., L. MacArthur, and H. Okayama. "Suppression of the chemically transformed phenotype of BHK cells by a human cDNA." Molecular and Cellular Biology 11, no. 10 (October 1991): 5321–29. http://dx.doi.org/10.1128/mcb.11.10.5321.
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Transformation of the baby hamster kidney cell line BHK SN-10 by chemical carcinogens such as nitrosylmethylurea (NMU) is mediated by the loss of a gene product critical for the suppression of malignant transformation. Somatic cell hybrids between chemically transformed BHK SN-10 cells and either normal hamster kidney or human fibroblast cells are nontransformed; therefore, a recessive mechanism underlies the malignant transformation of BHK SN-10 cells after chemical carcinogenesis (A. Stoler and N. P. Bouck, Proc. Natl. Acad. Sci. USA 82:570-574, 1985). A human fibroblast cDNA library was constructed and introduced into NMU-transformed BHK SN-10 cells (NMU 34m) in order to identify a human cDNA capable of suppressing cellular transformation. NMU-transformed BHK cells were analyzed for reversion to an anchorage-dependent normal cellular phenotype after transfection with human cDNA. The human cDNA capable of inducing stable reversion of NMU 34m cells encodes the intermediate filament protein vimentin, which is apparently required for maintenance of the normal phenotype in BHK SN-10 cells.
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Eiden, M. V., L. MacArthur, and H. Okayama. "Suppression of the chemically transformed phenotype of BHK cells by a human cDNA." Molecular and Cellular Biology 11, no. 10 (October 1991): 5321–29. http://dx.doi.org/10.1128/mcb.11.10.5321-5329.1991.
Full textAbstract:
Transformation of the baby hamster kidney cell line BHK SN-10 by chemical carcinogens such as nitrosylmethylurea (NMU) is mediated by the loss of a gene product critical for the suppression of malignant transformation. Somatic cell hybrids between chemically transformed BHK SN-10 cells and either normal hamster kidney or human fibroblast cells are nontransformed; therefore, a recessive mechanism underlies the malignant transformation of BHK SN-10 cells after chemical carcinogenesis (A. Stoler and N. P. Bouck, Proc. Natl. Acad. Sci. USA 82:570-574, 1985). A human fibroblast cDNA library was constructed and introduced into NMU-transformed BHK SN-10 cells (NMU 34m) in order to identify a human cDNA capable of suppressing cellular transformation. NMU-transformed BHK cells were analyzed for reversion to an anchorage-dependent normal cellular phenotype after transfection with human cDNA. The human cDNA capable of inducing stable reversion of NMU 34m cells encodes the intermediate filament protein vimentin, which is apparently required for maintenance of the normal phenotype in BHK SN-10 cells.