1,669 research outputs found
Statistical Classification and Visualization of MALDI-Imaging Data
No full textDeininger S-O, Gerhard M, Schleif F-M. Statistical Classification and Visualization of MALDI-Imaging Data. In: Proc. of CBMS 2007. 2007: 403-405
Strong and deep Atlantic meridional overturning circulation during the last glacial cycle
No full textExtreme, abrupt Northern Hemisphere climate oscillations during the last glacial cycle (140,000 years ago to present) were modulated by changes in ocean circulation and atmospheric forcing1. However, the variability of the Atlantic meridional overturning circulation (AMOC), which has a role in controlling heat transport from low to high latitudes and in ocean CO2 storage, is still poorly constrained beyond the Last Glacial Maximum2, 3, 4. Here we show that a deep and vigorous overturning circulation mode has persisted for most of the last glacial cycle, dominating ocean circulation in the Atlantic, whereas a shallower glacial mode with southern-sourced waters filling the deep western North Atlantic prevailed during glacial maxima3, 5. Our results are based on a reconstruction of both the strength and the direction of the AMOC during the last glacial cycle from a highly resolved marine sedimentary record in the deep western North Atlantic. Parallel measurements of two independent chemical water tracers (the isotope ratios of 231Pa/230Th and 143Nd/144Nd)6, 7, 8, which are not directly affected by changes in the global cycle, reveal consistent responses of the AMOC during the last two glacial terminations. Any significant deviations from this configuration, resulting in slowdowns of the AMOC, were restricted to centennial-scale excursions during catastrophic iceberg discharges of the Heinrich stadials. Severe and multicentennial weakening of North Atlantic Deep Water formation occurred only during Heinrich stadials close to glacial maxima with increased ice coverage, probably as a result of increased fresh-water input. In contrast, the AMOC was relatively insensitive to submillennial meltwater pulses during warmer climate states, and an active AMOC prevailed during Dansgaard–Oeschger interstadials (Greenland warm periods)
Optimizing outcomes for patients with advanced disease in chronic myelogenous leukemia
No full textThe treatment of chronic myelogenous leukemia (CML) has been revolutionized by the development of the small-molecule tyrosine kinase inhibitor imatinib. The primary target for this drug is the oncogenic BCR-ABL kinase. Five-year survival rates for patients in chronic phase CML is now greater than 80%. Patients who have advanced beyond the chronic phase to the accelerated phase or blast crisis, however, have not faired as well. Progression occurs for a variety of reasons, including late diagnosis, slow response to imatinib, and the development of imatinib-resistant clones. Imatinib resistance has, in part, been addressed with the introduction of the new BCR-ABL inhibitors, namely dasatinib and nilotinib. These drugs have shown efficacy in CML patients with wild-type BCR-ABL and some BCR-ABL mutants that are imatinib-resistant. Unfortunately, some BCR-ABL mutations remain resistant to these therapies and will require the development of alternative treatments, and other mechanisms of imatinib resistance besides BCR-ABL mutation exist. In the future, genetic and pharmacologic tests may allow the clinician to predict response to imatinib. More aggressive therapies are being considered for high-risk patients, including increased dosage of the current tyrosine kinase inhibitors, along with combination therapies. Aggressive therapy holds promise, as the data suggest that responses are improved. Unfortunately, toxicities are also increased, and thus a balance must be found to ensure safety and compliance. This is especially important for young CML patients, who hopefully will remain in remission for decades. Polymerase chain reaction analysis has become of primary importance as a means of assessing disease burden, and given the idiosyncrasies of this technique, standards must be established to allow results to be compared across different institutions. Additionally, the nature of advanced disease is being explored. Intriguingly, genetic analysis of transformed blasts from patients in blast crisis has identified numerous members of the Wnt/B-catenin pathway and JunB as being activated. Increased activity of these pathways correlates with poor response and eventual disease progression. In addition to these data, evidence is emerging associating survival of the quiescent blast cell with Wnt activity, leading to the hope that Wnt inhibitors will increase the likelihood of eradicating these cells. Other areas such as microRNA profiling and DNA methylation patterns are likely to provide important information.Francis J. Giles, Daniel J. DeAngelo, Michele Baccarani, Michael Deininger, François Guilhot, Timothy Hughes, Michael Mauro, Jerald Radich, Oliver Ottmann and Jorge Corte
Making negotiated land reform work : initial experience from Brazil, Colombia, and South Africa
No full textThe author describes a new type of negotiated land reform that relies on voluntary land transfers negotiated between buyers and sellers, with the government's role restricted to establishing the necessary framework for negotiation and making a land purchase grant available to eligible beneficiaries. This approach has emerged-following the end of the Cold War and broad macroeconomic adjustment--as many countries face a second generation of reforms to address deep-rooted structural problems and provide a basis for sustainable economic growth and poverty reduction. The author describes initial experiences in Brazil, Colombia, and South Africa. It is too soon to know whether negotiated land reform can rise to the challenges administrative land reform failed to solve but the data so far suggests that: 1) Negotiated land reform can succeed only if measures are taken to make the market for land sales and rentals more fluid transparent. 2) Productive projects are likely to be the key to market-assisted land reform. The potential for project productivity establishes an upper bound on the price to be paid and a basis for financial intermediaries to evaluate the project. It also requires beneficiaries to familiarize themselves with the realities they're likely to confront as independent farmers and the limits to how much land reform can help them achieve their goals. 3) The only way to effectively coordinate the entities involved in the process is through decentralized, demand-driven implementation. 4) The long-run success of land reform depends on getting the private sector involved and using the land purchase grant to"crowd in"private money.Banks&Banking Reform,Environmental Economics&Policies,Agricultural Knowledge&Information Systems,Municipal Housing and Land,Land Use and Policies,Environmental Economics&Policies,Agricultural Knowledge&Information Systems,Municipal Housing and Land,Rural Land Policies for Poverty Reduction,Banks&Banking Reform
Sequential treatment with flavopiridol synergistically enhances pyrrolo-1,5-benzoxazepine-induced apoptosis in human chronic myeloid leukaemia cells including those resistant to imatinib treatment
No full textThe Bcr-Abl kinase inhibitor, imatinib mesylate, is the front line treatment for chronic myeloid leukaemia (CML), but the emergence of imatinib resistance has led to the search for alternative drug treatments and the examination of combination therapies to overcome imatinib resistance. The proapoptotic PBOX compounds are a recently developed novel series of microtubule targeting agents (MTAs) that depolymerise tubulin. Recent data demonstrating enhanced MTA-induced tumour cell apoptosis upon combination with the cyclin dependent kinase (CDK)-1 inhibitor flavopiridol prompted us to examine whether this compound could similarly enhance the effect of the PBOX compounds. We thus characterised the apoptotic and cell cycle events associated with combination therapy of the PBOX compounds and flavopiridol and results showed a sequence dependent, synergistic enhancement of apoptosis in CML cells including those expressing the imatinib-resistant 13151 mutant. Flavopiridol reduced the number of polyploid cells formed in response to PBOX treatment but only to a small extent, suggesting that inhibition of endoreplication was unlikely to play a major role in the mechanism by which flavopiridol synergistically enhanced PBOX-induced apoptosis. The addition of flavopiridol following PBOX-6 treatment did however result in an accelerated exit from the G2/M transition accompanied by an enhanced downregulation and deactivation of the CDK1/cyclin B1 complex and an enhanced degradation of the inhibitor of apoptosis protein (IAP) survivin. In conclusion, results from this study highlight the potential of these novel series of PBOX compounds, alone or in sequential combination with flavopiridol, as an effective therapy against CML. (C) 2010 Elsevier Inc. All rights reserved
First experiences with a high-resolution imagery-based adjudication approach in Ethiopia
No full textGreat progress has been made with rural land certification in Ethiopia. This process, however, has been mainly confined to the first phase certificates – those without a georeference. In 2008, a team conducted a simple field test using high resolution imagery. On-site tests were performed to determine if Quickbird satellite imagery could be used to establish parcel index maps in selected villages. The data collection in the field was performed with the help of land rights holders and local officials. The image quality of the plots at a scale of 1:2000 was sufficiently high to allow the parties to easily understand the images and contribute input, making the process very participatory. Many land rights holders were not able to present their certificates, suggesting updating issues. Even though the test was not well prepared, it yielded useful experiences and data. This limited data set was processed initially with ArcGIS and later with the first prototype of the Social Tenure Domain Model (STDM), which is open-source software. Processing the limited graphical display of the boundaries was relatively easy, but trying to link the data to Global Positioning System (GPS) coordinates (collected, at the same time, with hand-held GPS) was not immediately possible due to offsets caused by a number of reasons. Nevertheless, the approach seems very useful for lower land value areas where coverage is more important than (absolute) accuracy.Geo-information and Land DevelopmentOTB Research Institut
Deininger, Paul M. (Death, 1902-04-30)
No full textAddress: 520 E. 5th St.Age at death: 9 mo.Pg 47/1902/7/M WS/City/Dr. W. Mithoefer/Vitt & Stermer/St. Mary'sOriginal record filed in drawer labeled 'DEAN, J-DELM'
Compound mutations in BCR-ABL1 are not major drivers of primary or secondary resistance to ponatinib in CP-CML patients
No full textBCR-ABL1 kinase domain mutations can confer resistance to first- and second-generation tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). In preclinical studies, clinically achievable concentrations of the third-generation BCR-ABL1 TKI ponatinib inhibit T315I and all other single BCR-ABL1 mutants except T315M, which generates a single amino acid exchange, but requires 2 sequential nucleotide exchanges. In addition, certain compound mutants (containing ≥2 mutations in cis) confer resistance. Initial analyses based largely on conventional Sanger sequencing (SS) have suggested that the preclinical relationship between BCR-ABL1 mutation status and ponatinib efficacy is generally recapitulated in patients receiving therapy. Thus far, however, such analyses have been limited by the inability of SS to definitively identify compound mutations or mutations representing less than ~20% of total alleles (referred to as "low-level mutations"), as well as limited patient follow-up. Here we used next-generation sequencing (NGS) to define the baseline BCR-ABL1 mutation status of 267 heavily pretreated chronic phase (CP)-CML patients from the PACE trial, and used SS to identify clonally dominant mutants that may have developed on ponatinib therapy (30.1 months median follow-up). Durable cytogenetic and molecular responses were observed irrespective of baseline mutation status and included patients with compound mutations. No single or compound mutation was identified that consistently conferred primary and/or secondary resistance to ponatinib in CP-CML patients. Ponatinib is effective in CP-CML irrespective of baseline mutation status.Michael W. Deininger, J. Graeme Hodgson, Neil P. Shah, Jorge E. Cortes, Dong-Wook Kim, Franck E. Nicolini, Moshe Talpaz, Michele Baccarani, Martin C. Müller, Jin Li, Wendy T. Parker, Stephanie Lustgarten, Tim Clackson, Frank G. Haluska, Francois Guilhot, Hagop M. Kantarjian, Simona Soverini, Andreas Hochhaus, Timothy P. Hughes, Victor M. Rivera and Susan Branfor
Why liberalization alone has not improved agricultural productivity in Zambia : the role of asset ownership and working capital constraints
No full textThe authors use a large panel data set from Zambia to examine factors that could explain the relatively lackluster performance of the country's agricultural sector after liberalization. Zambia's liberalization significantly opened the economy but failed to alter the structure of productionor help realize efficiency gains. They reach two main conclusions. First, not owning productive assets (in Zambia, draft animals and implements) limits improvements in agricultural productivity and household welfare. Owning oxen increases income directly, allows farmers to till their fields efficiently when rain is delayed, increases the area cultivated, and improves access to credit and fertilizer markets. Second, the authors reject the hypothesis that the application of fertilizer is unprofitable because of high input prices. Rather, fertilizer use appears to have declined because of constraints on supplies, which government intervention exacerbated instead of alleviating. (Extending the use of fertilizer to the many producers not currently using it would be profitable, but increasing the amount applied by the few producers who now have access to it would not be.) Policies to foster accumulation of the assets needed for agricultural production (including draft animals and implements) and to provide complementary public goods (education, credit, and good agricultural extension services) could greatly help reduce poverty and improve productivity.Economic Theory&Research,Environmental Economics&Policies,Labor Policies,Banks&Banking Reform,Agricultural Knowledge&Information Systems,Environmental Economics&Policies,Economic Theory&Research,Banks&Banking Reform,Agricultural Knowledge&Information Systems,Agricultural Research
- …
