Evaluation of bioactive sphingolipids in 4-HPR-resistant leukemia cells

Background -- N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide) is a synthetic retinoid with potent pro-apoptotic activity against several types of cancer, but little is known regarding mechanisms leading to chemoresistance. Ceramide and, more recently, other sphingolipid species (e.g., dihydroceramide and dihydrosphingosine) have been implicated in 4-HPR-mediated tumor cell death. Because sphingolipid metabolism has been reported to be altered in drug-resistant tumor cells, we studied the implication of sphingolipids in acquired resistance to 4-HPR based on an acute lymphoblastic leukemia model. Methods -- CCRF-CEM cell lines resistant to 4-HPR were obtained by gradual selection. Endogenous sphingolipid profiles and in situ enzymatic activities were determined by LC/MS, and resistance to 4-HPR or to alternative treatments was measured using the XTT viability assay and annexin V-FITC/propidium iodide labeling. Results -- No major crossresistance was observed against other antitumoral compounds (i.e. paclitaxel, cisplatin, doxorubicin hydrochloride) or agents (i.e. ultra violet C, hydrogen peroxide) also described as sphingolipid modulators. CCRF-CEM cell lines resistant to 4-HPR exhibited a distinctive endogenous sphingolipid profile that correlated with inhibition of dihydroceramide desaturase. Cells maintained acquired resistance to 4-HPR after the removal of 4-HPR though the sphingolipid profile returned to control levels. On the other hand, combined treatment with sphingosine kinase inhibitors (unnatural (dihydro)sphingosines ((dh)Sph)) and glucosylceramide synthase inhibitor (PPMP) in the presence or absence of 4-HPR increased cellular (dh)Sph (but not ceramide) levels and were highly toxic for both parental and resistant cells. Conclusions -- In the leukemia model, acquired resistance to 4-HPR is selective and persists in the absence of sphingolipid profile alteration. Therapeutically, the data demonstrate that alternative sphingolipid-modulating antitumoral strategies are suitable for both 4-HPR-resistant and sensitive leukemia cells. Thus, whereas sphingolipids may not be critical for maintaining resistance to 4-HPR, manipulation of cytotoxic sphingolipids should be considered a viable approach for overcoming resistance.

A short survey of the environment at the dumping site for Santa Cruz Harbor dredging and A study of seaward dipping internal structures in marine ripple marks at Whaler's Cove, California. Annual report, Part 4, August 1972

(PDF contains 76 pages)

Financing And Cooperation For Sustainable Development In The Mediterranean, Sophia Antipolis, France, 3-4 June 2004: Volume II: Technical Report of the Workshop

(263 page document)

A Drift Card Study in Monterey Bay, California, September 1971 to April 1973: Annual Report, Part 4, 1973

Drift cards were released in Monterey Bay, California, to detect seasonal variations in the California Current system, and seasonal and diurnal wind variations in the immediate vicinity of the bay. About 23% of the cards were recovered, although the recovery rate varied from about 5% in the winter to about 60% in the late summer. Drift card speeds ranged from 1 to 8 km/day, in the winter and summer months respectively. Good agreement was observed between geostrophic current, wind, drogue, and drift card data, although drift cards were observed to be primarily wind driven. A weekend bias in drift card recoveries was observed for the entire period of study; however, it was less pronounced for those cards released during the summer months. Two bogus releases were used to estimate the discovery lag time, reported position accuracy, and longshore drift currents. Diurnal winds were observed during a 24-hour study, and indicated daily variations in the wind field may be as important as seasonal changes in moving surface water. The drift card speed was observed to be about 3% of the wind velocity, and 1 m/sec was estimated as the minimum effective wind. The wind factor, ranging from 2.2% to 4.0%, was used to estimate the actual paths of drift cards and to examine the role of diurnal winds in affecting surface water movement. (PDF contains 79 pages)

Jornal das Trincheiras : órgão da Revolução Constitucionalista. N.4

Jornal publicado durante a Revolução Constitucionalista de 1932. A coleção completa compõe-se de treze números, produzidos pela Liga de Defesa Paulista (LDP), no período de 14 de agosto a 25 de setembro de 1932.

Aquaculture Asia, Vol. 10, No. 4, pp.1-42, October-December 2005

*Table of Contents* Sustainable aquaculture Peter Edwards writes on rural aquaculture: Small-scale pond culture in Bangladesh. People in aquaculture Community based aquaculture - issues and challenges H.K. De and G.S. Saha. Aquaculture as an action programme: An exercise in building confidence and self worth. B. Shanthi, V.S. Chandrasekaran, M. Kailasam, M. Muralidar, T. Ravisankar,.C. Saradad and M. Krishnan The STREAM Column: Transforming policy recommendations into pro-poor service provision Graham Haylor. Research & farming techniques. Grow out of juvenile spotted Babylon to marketable size in earthen ponds II: Polyculture with seabass. S. Kritsanapuntu, N. Chaitanawisuti, W. Santhaweesuk and Y. Natsukari Asia-Pacific Marine Finfish Aquaculture Network. Influence of economic conditions of importing nations and unforeseen global events on grouper markets. Sih Yang Sim. Present status of hatchery technology for cobia in Vietnam. Nhu Van Can. Report on grouper hatchery training course in Indonesia. Nguyen Quoc Thai. Aquatic animal health. Biosecured and improved penaeid shrimp production through organic nursery raceway system in India. Felix. S. and M. Samaya Kannan. Management of monogenean parasites in brackishwater finfish. K.P. Jithendran, M. Natarajan and I.S. Azad. Vembanad Lake: A potential spawner bank of the giant freshwater prawn Macrobrachium rosenbergii on the southwest coast of India. Paramaraj Balamurugan, Pitchaimuthu Mariappan & Chellam Balasundaram.

“神舟4号”飞船搭载微重力流体物理实验获得圆满成功

由中国科学院力学研究所胡文瑞院士和解京昌研究员领导的研究小组承担的“微重力液滴热毛细迁移实验”项目，利用自行研制的“通用流体实验装置”，于2002年12月30日搭载“神舟4号”飞船，圆满完成了各项预定空间实验任务。对飞船下传数据和图像的初步分析表明，实验装置全部工作正常，实验获得了圆满成功，可望得到有价值的学术成果，并在相关理论研究中取得突破。此次空间实验的成功，显示了科学家和工程师的完美结合，标志着力学所在“两弹一箭”后重返空间技术领域，再铸辉煌！

2,4-D and Mycoleptodiscus terrestris for control of Eurasian Watermilfoil

Growth chamber studies were conducted to evaluate the impact of an indigenous fungal pathogen, Mycoleptodiscus terrestris (Gerd.) Ostazeski, and the herbicide 2,4-D applied alone and in combination with one another, on the growth of a nuisance submersed plant, Eurasian watermilfoil ( Myriophyllum spicatum L.)(PDF has 6 pages.)

Implicações da quebra de ética e decoro parlamentar na 4ª e 5ª legislaturas da Câmara Legislativa do Distrito Federal

Aborda as implicações da quebra de ética e decoro parlamentar na 4ª e 5ª Legislaturas da Câmara Legislativa do Distrito Federal, os critérios técnicos e políticos utilizados na condução e julgamento dos processos por quebra de decoro e confirma a tese de que tais processos, de caráter político, passam pela lógica do corporativismo. Para fundamentar a análise, faz uma breve retrospectiva bibliográfica e examina os diversos processos relativos à quebra de decoro parlamentar na 4ª e 5ª Legislaturas, à luz da Resolução n° 110, de 17 de maio de 1996, que instituiu o Código de Ética e Decoro Parlamentar e criou a Comissão de Ética, e suas alterações posteriores. Analisa as posições dos parlamentares nos casos de quebra de princípios éticos e de decoro no âmbito da Comissão de Ética e Decoro e da Corregedoria, ao longo das duas últimas legislaturas concluídas.

Relatório de atividades da 4ª Sessão Legislativa e 7ª Sessão Legislativa Extraordinária da 50ª legislatura

Trata das ações implementadas ao longo do ano de 1998 e início de 1999 que contribuíram para o estabelecimento de condições politicamente favoráveis para a discussão de problemas e o encaminhamento de soluções para as questões de interesse do setor agropecuário brasileiro.