564 research outputs found
Alterations in expression, binding to ligand and DNA, and transcriptional activity of rearranged and wild-type retinoid receptors in retinoid-resistant acute promyelocytic leukemia cell lines
No full textAll-trans retinoic acid (tRA), a naturally occurring ligand of the nuclear retinoic acid receptors (RARs), induces differentiation of leukemic cells and clinical complete remission in patients with acute promyelocytic leukemia (APL). This differentiation effect can also be seen in vitro in both fresh leukemic cells and in the unique permanent APL cell line, NB4. However, APL cells become resistant to RA-induced differentiation both in vitro and in patients. Although pharmacodynamic mechanisms of resistance have been reported, there is growing evidence that resistance both in patients, as well as in vitro, can be mediated by changes in the sensitivity of leukemic cells to retinoids. To investigate possible mechanisms of retinoid resistance, we established subclones of NB4 that are stably resistant to both tRA and 9-cisRA. Unlike the previously reported NB4.306 retinoid-resistant cells, these subclones expressed PML/RAR-alpha RNA and protein, but demonstrated altered ligand binding patterns of PML/RAR-alpha and differed in retinoid-induced gene expression. They were significantly less able to stimulate transcription of an RARE driven CAT-reporter gene on induction by tRA and showed altered DNA binding activity on a RARE. These data suggest that NB4 cells selected for resistance to retinoids demonstrate abnormal ligand binding to PML/RAR-alpha that lead to altered transcriptional activation by retinoids
The PML/RAR alpha oncoprotein is a direct molecular target of retinoic acid in acute promyelocytic leukemia cells.
No full textAcute promyelocytic leukemia (APL) is characterized by the translocation, t(15;17) and the expression of a PML/RAR alpha fusion protein that is diagnostic of the disease. There is evidence that PML/RAR alpha protein acts as a dominant negative inhibitor of normal retinoid receptor function and myeloid differentiation. We now show that the PML/RAR alpha fusion product is directly downregulated in response to retinoic acid (tRA) treatment in the human APL cell line, NB4. tRA treatment induces loss of PML/RAR alpha at the protein level but not at the level of mRNA, as determined by Northern blots, by Western blots, and by ligand binding assays and in binding to RA-responsive DNA elements. We present evidence that this regulation is posttranslational. This evidence suggests that tRA induces synthesis of a protein that selectively degrades PML/RAR alpha. We further show that this loss of PML/ RAR-alpha is not limited to the unique APL cell line. NB4, because PML/RAR alpha protein is selectively downregulated by tRA when expressed in the transfected myeloid cell line U937. The loss of PML/RAR alpha may be directly linked to tRA-induced differentiation, because in a retinoid-resistant subclone of NB4, tRA does not decrease PML/RAR alpha protein expression. In NB4 cells, the specific downregulation of the fusion protein decreases the ratio of PML/RAR alpha to wild-type RAR alpha. Because the ratio of expression of PML/RAR alpha to wild-type RAR alpha and PML may be important in maintaining the dominant negative block of myelocytic differentiation, these data suggest a molecular mechanism for restoration by tRA normal myeloid differentiation in APL cells
Letter from JV [John Victor] Carson, Dominguez Estate Company to J.S. Yoshinobu, June 3, 1938
No full textLetter making final request for information no Mr. Kuda's lease information. Signed by JV [John Victor] Carson
The internationalization and localization of professional services: The case of executive search firms in Australia
No full textThis is the author accepted manuscript. The final version is available from Routledge / Taylor & Francis via the DOI in this record.William Harvey would like to acknowledge the financial support of the University of Sydney Business School in 201
Human Trafficking
No full textHuman trafficking, defined as the recruitment, transport or receipt of individuals for the purpose of exploitation, is perhaps the most negative phenomenon linked to globalisation. The link between migration and human trafficking is close, although domestic trafficking can and does occur. This chapter looks at human trafficking taking globalisation into account. It examines the questions of the definition and understanding of trafficking, as well as exploring the difficulties of establishing good quantitative measures of the extent of trafficking, and concludes with a look at the interactions between counter-trafficking efforts and border control
The dynamics and genius of Nigeria's indigenous legal order
No full textThis article challenges the colonial delegitimization of Nigeria's customary law. The author describes customary law's fundamental bases, and argues that these bases are what ensured customary law's survival during colonial rule, and also what provide for customary law's contemporary relevance. Globalization, increased international interaction, and the eclipse of tribal insularity necessitate a permanent form of customary law that is decipherable to foreigners and non-Indigenous people of Nigeria. However, the author opines that if rigidification of customary law is to be avoided, then the present practice of proving it as a fact ought to be retained. Factual proof is defended as an incident of the primordial nature and primary source of customary law, rather than any weakness in the comparison of customary law with the received English law. Under Nigerian law, after a rule of customary law is proved to exist, the court must consider whether it is judicially enforceable, or whether it is repugnant to natural justice, equity and good conscience. The author argues that the 'repugnancy doctrine' was routinely employed in a legal 'cleansing' mission, and was the engine for the imposition of hegemonic, foreign culture. The author suggests caution in the uncritical and contemporary use of the repugnancy doctrine and its precedents. Other instances of non-judicial enforcement of customary law are also considered, such as the contractual exclusion of customary law, and the exclusion of customary law based on the uncustomary nature of the subject matter of litigation. Finally, the author addresses the specific question of the constitutionality of customary law. Customary law's patriarchal foundation and general discrimination against women and female children are problematic issues that require sensitive and imaginative judicial use of customary law. The author argues that the Nigerian judiciary should undertake careful constitutional and sociological analysis before striking down any rule of customary law. The court should make reference to South Africa's constitutional experience, which has comparative similarities to Nigeria. The article concludes with a call for an interpretive approach to customary law that ensures its survival and adaptation to the dictates of equality in an egalitarian society
Data analysis of an outdoor a-Si:H PV system: Understanding the performance variation of a-Si:H modules manufactured by HyET Solar Netherlands B.V. when aged outdoor
No full textPhotovoltaic (PV ) technology has seen exciting growth in the field of energy for the past few decades. With strong government programs in China, Japan, Germany, and Netherlands, PV systems have grown to become a dominant source of renewable energy. Thin film silicon based a-Si:H solar cells are 2ndgeneration solar cells. They have the ability to be applied on glass or polymer, free of toxic materials in the manufacturing process, and are extremely flexible. Even though they exhibit a lower efficiency with respect to other proven technologies, a lower temperature coefficient and the unique ability to self-anneal in warmer months make it an attractive option. HyET Solar Netherlands B.V. manufactures thin-film solar cells based on a-Si:H technology. These modules are extremely flexible and relatively cheaper to manufacture, hence are suited for Building Integrated Photovoltaics (BIPV ) setups in the form of soundwalls, curved roofs, and solar blinds among many others. The primary aim of this research is to understand the performance variation of the solar modules when they are not under Standard Test Conditions (STC) but are aged outdoor. To understand this, data was collected from solar modules installed outdoor. The installed PV system consists of 16 arrays, each array comprising of two modules connected in series and each module consisting of 28 cells in series. However, during installation, some of the modules were damaged, and analysis was solely done on the best-performing array. To analyse the system, irradiance, temperature, and operating maximum powerpoints(mpp) were recorded every minute while the JV-curves were measured every fifteen minutes. The modules were analysed on two levels: on the system level and the cell level. Analysing the modules on system level was done by calculating the performance ratio and daily energy yield. It was found that the modules performed significantly better in warmer months than in cooler months. This could be explained by a combination of the annealing effect and relatively lower losses due to higher irradiance in warmer months. Upon analysing the daily energy yields of the modules, it was found that the system suffered degradation of 10.3% in the second year of operation. To analyse the modules on the cell level, JV-curve data were used. To extract the intrinsic parameters of the modules from a JV-curve, an in-house software "DoktorDEP" was utilised. In order to validate the output from the software, two experiments were performed, where JV-curve were measured at different temperature points and irradiance. While the experiments were successful in estimating the intrinsic parameters, certain requirements were not met at the outdoor data, hence the focus was now shifted to explicit JV-curve parameters such as short-circuit current density (Jsc), open-circuit voltage (Voc), fill factor (FF), open-circuit resistance (Roc) and shot-circuit resistance (Rsc). Upon analysis, it was found that there was a Jsc loss of 0.63mA/cm2 and Voc loss of 0.02V/c in the second year of operation. Moreover, the ontained trends of FF and Roc exhibited a definite degradation while the Rsc did not exhibit a degrading trend. Even though data analysis was performed on damaged modules, the obtained trends in this study can be of vital importance in developing strategies for reliability of the modules. The same techniques can be applied to a set of undamaged modules to estimate the performance. Because the JV-parameter Roc was affected drastically as the modules aged, future experiments can be designed to observe and tweak Roc to improve both efficiency and reliability. Lastly, based on the insights about DoktorDEP, future versions can be rolled out with the ability to analyse outdoor JV-curve data to discern the intrinsic parameters and their variation when aged outdoor. This could help in targeting and prioritising the factors affecting module performance and hence resulting in a robust product.Electrical Engineering | Sustainable Energy Technolog
Jules Verne - a new polishing technique related to FJP
No full textA variation on the fluid jet polishing (FJP) technique, arbitrarily named Jules Verne (JV), will be described in this article. Jules Verne is a glass processing technique that removes material due to the fact that the tool and the surface are in close contact, and a slurry moves in between the tool and the surface. This approach has both advantages and disadvantages with respect to the original FJP modus: it enables a feed-controlled machining process, but deeper lying areas are harder to reach. A simulation model will be presented that predicts the flow of the slurry in the Jules Verne setup, which is followed by the computation of the trajectories of the particles in the flow. Furthermore, experimental data will be reported demonstrating the feasibility of the JV idea. A model will also be presented simulating the interaction between the surface and the impinging abrasives at a microscopic level, enabling the prediction of the final surface roughness.Optics Research GroepApplied Science
Fire suppression costs and impacts of the 2008 wildfires in Trinity County, California
No full textThis archived document is maintained by the Oregon State Library as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Title from PDF cover (viewed on March 12, 2014)This research was made possible with support from Joint Fire Sciences Agreement # 09-JV-11242309-069Mode of access: Internet from the Oregon Government Publications Collection
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