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Search Results: 1 - 10 of 211190 matches for " Stephen P Hunger "
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Current Concepts in Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Kathrin M. Bernt,Stephen P. Hunger
Frontiers in Oncology , 2014, DOI: 10.3389/fonc.2014.00054
Abstract: The t(9;22)(q34;q11) or Philadelphia chromosome creates a BCR–ABL1 fusion gene encoding for a chimeric BCR–ABL1 protein. It is present in 3–4% of pediatric acute lymphoblastic leukemia (Ph+ ALL), and about 25% of adult ALL cases. Prior to the advent of tyrosine kinase inhibitors (TKI), Ph+ ALL was associated with a very poor prognosis despite the use of intensive chemotherapy and frequently hematopoietic stem-cell transplantation (HSCT) in first remission. The development of TKIs revolutionized the therapy of Ph+ ALL. Addition of the first generation ABL1 class TKI imatinib to intensive chemotherapy dramatically increased the survival for children with Ph+ ALL and established that many patients can be cured without HSCT. In parallel, the mechanistic understanding of Ph+ ALL expanded exponentially through careful mapping of pathways downstream of BCR–ABL1, the discovery of mutations in master regulators of B-cell development such as IKZF1 (Ikaros), PAX5, and early B-cell factor (EBF), the recognition of the complex clonal architecture of Ph+ ALL, and the delineation of genomic, epigenetic, and signaling abnormalities contributing to relapse and resistance. Still, many important basic and clinical questions remain unanswered. Current clinical trials are testing second generation TKIs in patients with newly diagnosed Ph+ ALL. Neither the optimal duration of therapy nor the optimal chemotherapy backbone are currently defined. The role of HSCT in first remission and post-transplant TKI therapy also require further study. In addition, it will be crucial to continue to dig deeper into understanding Ph+ ALL at a mechanistic level, and translate findings into complementary targeted approaches. Expanding targeted therapies hold great promise to decrease toxicity and improve survival in this high-risk disease, which provides a paradigm for how targeted therapies can be incorporated into treatment of other high-risk leukemias.
Low-Molecular-Weight Heparin Use in a Case of Noncardiogenic Multifocal Perinatal Thromboembolic Stroke
Matthew A. Saxonhouse,Dan Tarquinio,Paul R. Carney,Jeff Bennett,Amy Smith,Stephen P. Hunger,James D. Geyer
Advances in Hematology , 2009, DOI: 10.1155/2009/153643
Abstract: A full-term neonate suffered multifocal cerebral infarctions due to multiple large vessel thrombi. Thrombophilia and cardiovascular assessments were negative, but due to the severity of the lesions and the concern for expansion of the thrombi or future embolic events, treatment with low-molecular-weight heparin (LMWH) was initiated. No complications from treatment were experienced. We present this severe case in order to highlight difficult management decisions for newborns with multifocal perinatal thromboembolic stroke and to stress the need for further practice guidelines and research in this area.
Gene-based outcome prediction in multiple cohorts of pediatric T-cell acute lymphoblastic leukemia: a Children's Oncology Group study
Amanda L Cleaver, Alex H Beesley, Martin J Firth, Nina C Sturges, Rebecca A O'Leary, Stephen P Hunger, David L Baker, Ursula R Kees
Molecular Cancer , 2010, DOI: 10.1186/1476-4598-9-105
Abstract: Using HG-U133Plus2 microarrays we modeled a five-gene classifier (5-GC) that accurately predicted clinical outcome in a cohort of 50 T-ALL patients. The 5-GC was further tested against three independent cohorts of T-ALL patients, using either qRT-PCR or microarray gene expression, and could predict patients with significantly adverse clinical outcome in each. The 5-GC featured the interleukin-7 receptor (IL-7R), low-expression of which was independently predictive of relapse in T-ALL patients. In T-ALL cell lines, low IL-7R expression was correlated with diminished growth response to IL-7 and enhanced glucocorticoid resistance. Analysis of biological pathways identified the NF-κB and Wnt pathways, and the cell adhesion receptor family (particularly integrins) as being predictive of relapse. Outcome modeling using genes from these pathways identified patients with significantly worse relapse-free survival in each T-ALL cohort.We have used two different approaches to identify, for the first time, robust gene signatures that can successfully discriminate relapse and CCR patients at the time of diagnosis across multiple patient cohorts and platforms. Such genes and pathways represent markers for improved patient risk stratification and potential targets for novel T-ALL therapies.T-cell acute lymphoblastic leukemia (T-ALL) affects approximately 15% of newly diagnosed pediatric ALL patients. Continuous complete clinical remission (CCR) in T-ALL patients is now approaching 80% due to the implementation of aggressive chemotherapy protocols [1-6]. However, patients that relapse (R) have poor prognosis and aggressive therapy can lead to long-term side effects in those that achieve CCR [7]. In the clinical setting, age and white blood cell count (WBC) at diagnosis are used to stratify B-lineage ALL patients as either standard or high risk, significantly impacting on the type and intensity of post-induction therapy used. However these NCI-defined criteria have been shown to hav
Value of river discharge data for global-scale hydrological modeling
M. Hunger ,P. D ll
Hydrology and Earth System Sciences (HESS) & Discussions (HESSD) , 2008,
Abstract: This paper investigates the value of observed river discharge data for global-scale hydrological modeling of a number of flow characteristics that are e.g. required for assessing water resources, flood risk and habitat alteration of aquatic ecosystems. An improved version of the WaterGAP Global Hydrology Model (WGHM) was tuned against measured discharge using either the 724-station dataset (V1) against which former model versions were tuned or an extended dataset (V2) of 1235 stations. WGHM is tuned by adjusting one model parameter (γ) that affects runoff generation from land areas in order to fit simulated and observed long-term average discharge at tuning stations. In basins where γ does not suffice to tune the model, two correction factors are applied successively: the areal correction factor corrects local runoff in a basin and the station correction factor adjusts discharge directly the gauge. Using station correction is unfavorable, as it makes discharge discontinuous at the gauge and inconsistent with runoff in the upstream basin. The study results are as follows. (1) Comparing V2 to V1, the global land area covered by tuning basins increases by 5% and the area where the model can be tuned by only adjusting γ increases by 8%. However, the area where a station correction factor (and not only an areal correction factor) has to be applied more than doubles. (2) The value of additional discharge information for representing the spatial distribution of long-term average discharge (and thus renewable water resources) with WGHM is high, particularly for river basins outside of the V1 tuning area and in regions where the refined dataset provides a significant subdivision of formerly extended tuning basins (average V2 basin size less than half the V1 basin size). If the additional discharge information were not used for tuning, simulated long-term average discharge would differ from the observed one by a factor of, on average, 1.8 in the formerly untuned basins and 1.3 in the subdivided basins. The benefits tend to be higher in semi-arid and snow-dominated regions where the model is less reliable than in humid areas and refined tuning compensates for uncertainties with regard to climate input data and for specific processes of the water cycle that cannot be represented yet by WGHM. Regarding other flow characteristics like low flow, inter-annual variability and seasonality, the deviation between simulated and observed values also decreases significantly, which, however, is mainly due to the better representation of average discharge but not of variability. (3) The choice of the optimal sub-basin size for tuning depends on the modeling purpose. While basins over 60 000 km2 are performing best, improvements in V2 model performance are strongest in small basins between 9000 and 20 000 km2, which is primarily related to a low level of V1 performance. Increasing the density of tuning stations provides a better spatial representation of discharge, but it
Value of river discharge data for global-scale hydrological modeling
M. Hunger,P. D?ll
Hydrology and Earth System Sciences Discussions , 2007,
Abstract: This paper investigates the value of observed river discharge data for global-scale hydrological modeling of a number of flow characteristics that are required for assessing water resources, flood risk and habitat alteration of aqueous ecosystems. An improved version of WGHM (WaterGAP Global Hydrology Model) was tuned in a way that simulated and observed long-term average river discharges at each station become equal, using either the 724-station dataset (V1) against which former model versions were tuned or a new dataset (V2) of 1235 stations and often longer time series. WGHM is tuned by adjusting one model parameter (γ) that affects runoff generation from land areas, and, where necessary, by applying one or two correction factors, which correct the total runoff in a sub-basin (areal correction factor) or the discharge at the station (station correction factor). The study results are as follows. (1) Comparing V2 to V1, the global land area covered by tuning basins increases by 5%, while the area where the model can be tuned by only adjusting γ increases by 8% (546 vs. 384 stations). However, the area where a station correction factor (and not only an areal correction factor) has to be applied more than doubles (389 vs. 93 basins), which is a strong drawback as use of a station correction factor makes discharge discontinuous at the gauge and inconsistent with runoff in the basin. (2) The value of additional discharge information for representing the spatial distribution of long-term average discharge (and thus renewable water resources) with WGHM is high, particularly for river basins outside of the V1 tuning area and for basins where the average sub-basin area has decreased by at least 50% in V2 as compared to V1. For these basins, simulated long-term average discharge would differ from the observed one by a factor of, on average, 1.8 and 1.3, respectively, if the additional discharge information were not used for tuning. The value tends to be higher in semi-arid and snow-dominated regions where hydrological models are less reliable than in humid areas. The deviation of the other simulated flow characteristics (e.g. low flow, inter-annual variability and seasonality) from the observed values also decreases significantly, but this is mainly due to the better representation of average discharge but not of variability. (3) The optimal sub-basin size for tuning depends on the modeling purpose. On the one hand, small basins between 9000 and 20 000 km2 show a much stronger improvement in model performance due to tuning than the larger basins, which is relat
Simulating river flow velocity on global scale
K. Schulze, M. Hunger,P. D ll
Advances in Geosciences (ADGEO) , 2005,
Abstract: Flow velocity in rivers has a major impact on residence time of water and thus on high and low water as well as on water quality. For global scale hydrological modeling only very limited information is available for simulating flow velocity. Based on the Manning-Strickler equation, a simple algorithm to model temporally and spatially variable flow velocity was developed with the objective of improving flow routing in the global hydrological model of WaterGAP. An extensive data set of flow velocity measurements in US rivers was used to test and to validate the algorithm before integrating it into WaterGAP. In this test, flow velocity was calculated based on measured discharge and compared to measured velocity. Results show that flow velocity can be modeled satisfactorily at selected river cross sections. It turned out that it is quite sensitive to river roughness, and the results can be optimized by tuning this parameter. After the validation of the approach, the tested flow velocity algorithm has been implemented into the WaterGAP model. A final validation of its effects on the model results is currently performed.
Intense Long-Lived Fluorescence of 1,6-Diphenyl-1,3,5-Hexatriene: Emission from the S1-State Competes with Formation of O2 Contact Charge Transfer Complex  [PDF]
Katharina Hunger, Karl Kleinermanns
Open Journal of Physical Chemistry (OJPC) , 2013, DOI: 10.4236/ojpc.2013.31008
Abstract:

The fluorescence kinetics of 1,6-diphenyl-1,3,5-hexatriene (DPH) dissolved in cyclohexane was investigated as a function of temperature, concentration and 355 nm excitation pulse energy. At concentrations above 2.5 μM and excitation energies above 1 mJ a long-lived, very intense emission, which appears within less than 5 ns and lasts up to 70 ns, is observed. During the first 50 ns the decay does not follow an exponential but rather a linear behaviour. In oxygen saturated solutions the long-lived emission is suppressed and solely short-lived fluorescence with τ < 5 ns can be detected. A kinetic simulation was performed, based on a model whereupon the long-lived emission originates from the S1-state and competes with the formation of DPH-O2 contact charge-transfer complexes and intersystem crossing which both quench the fluorescence. Our investigations show that even the small amount of oxygen dissolved in nitrogen saturated solutions has a distinct influence on the fluorescence kinetics of DPH.

Spurensuche einer Rezeptionsgeschichte Alexander von Humboldt und Johann Gottfried Herder
Bernhard Hunger
HiN. Alexander von Humboldt im Netz , 2009,
Abstract: Article in German, Abstracts in English, German and Spanish.Alexander von Humboldt's work displays traces of Johann Gottfried Herder which are as multifaceted as the references to the latter are scarce. In light of this aspect, the present essay focuses on Humboldt's Physiognomy of Plants (1806), in which he explicitly mentions Herder for the first time in a publication. Two years later, the text is incorporated within Aspects of Nature (1808 ff.). In the third edition of Aspects (1849), Herder's name is curiously omitted. This omission is incomprehensible both in form and content. The historical context characterising the years between 1805 and 1808 suggests that Humboldt's references to Herder must have been made very deliberately. Humboldt's correspondence with the historian Johannes von M ller and other sources shows that Humboldt carefully studied Herder's writings. As the publisher of Herder's complete works, Johannes von M ller, who was Humboldtís friend and neighbour at the time, even considered Humboldt to be a direct descendant of the Herder school.
Psarros, Nikos: "Die Chemie und ihre Methoden. Eine philosophische Betrachtung" (Weinheim 1999) (book review)
Johannes Hunger
Hyle : International Journal for Philosophy of Chemistry , 2001,
Abstract: book review of Psarros, Nikos: "Die Chemie und ihre Methoden. Eine philosophische Betrachtung" (Weinheim 1999)
The Heavenly Writing: Divination, Horoscopy, and Astronomy in Mesopotamian Culture by Francesca Rochberg
Hermann Hunger
Aestimatio : Critical Reviews in the History of Science , 2004,
Abstract:
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