Sample records for aml mds und

  1. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation; Myeloablative Radioimmuntherapien zur Konditionierung bei Patienten mit AML, MDS und multiplem Myelom vor Stammzelltransplantation

    Buchmann, I. [Abt. fuer Nuklearmedizin, Universitaetsklinik Heidelberg (Germany)


    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. {sup 90}Y, {sup 188}Re and {sup 131}I are the most frequently used {beta}{sup -}-particles. Of these, {sup 90}Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate {sup 90}Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The {sup 90}Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow < 25%. The specific doses (Gy/GBq) are 10.2 {+-} 1.8 (bone marrow), 2.7 {+-} 2 (liver) and < 1 (kidneys). In contrast, radiolabeled anti-CD33- and anti-CD45-antibodies bind to both, most of white blood cells and

  2. How I treat MDS and AML in Fanconi anemia.

    Peffault de Latour, Régis; Soulier, Jean


    Fanconi anemia (FA) is the most frequent inherited cause of bone marrow failure (BMF). Most FA patients experience hematopoietic stem cell attrition and cytopenia during childhood, which along with intrinsic chromosomal instability, favor clonal evolution and the frequent emergence in their teens or young adulthood of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). To early identify and further predict bone marrow (BM) clonal progression and enable timely treatment, the follow-up of FA patients includes regular BM morphological and cytogenetic examinations. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment of FA patients with MDS or AML. Although questions remain concerning HSCT itself (including the need for pretransplant chemotherapy, the best conditioning regimen, and the optimal long-term follow-up of such patients especially regarding secondary malignancies), clonal evolution in the absence of significant BM dysplasia and blast cells can be difficult to address in FA patients, for whom the concept of preemptive HSCT is discussed. Illustrated by 3 representative clinical vignettes showing specific features of MDS and AML in FA patients, this paper summarizes our practical approach from diagnosis through treatment in this particular situation. PMID:27020090

  3. Point mutations in the AML1/RUNX1 gene associated with myelodysplastic syndrome (MDS)

    Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells characterized by ineffective and inadequate hematopoiesis. MDS in a subset of patients arise after previous chemotherapy or radiation exposure for other malignancies. As MDS is a heterogeneous disorder, specific gene abnormalities playing a role in the myelodysplastic process have been difficult to identify. In this study, we analyzed the somatic mutations in the AML1/RUNX1 gene, which is a critical regulator of definitive hematopoiesis and the most frequent targets for translocation of acute myeloid leukemia (AML), in patients with MDS. We detected AML1 point mutations in 26 of 110 (23.6%) patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEBt) and AML following MDS (defined these categories as MDS/AML). Among 22 patients with radiation-related (including 14 atomic bomb survivors) and/or therapy-related MDS/AML, 11 (50%) patients had the AML1 mutations mostly in N-terminal region. In contrast, 15 of 88 (17%) patients with sporadic MDS/AML showed the AML1 mutations equally in both N-terminal and C-terminal region. The MDS/AML patients with AML1 mutations had a significantly worse prognosis than those without AML1 mutations. Most of AML1 mutants lost trans-activation potential, regardless of their DNA binding potential. These data suggested that AML1 point mutation is one of the major driving forces of MDS/AML, and these mutations may represent a distinct clinicopathologic-genetic entity. (author)

  4. Mechanisms of MDS/AML molecular pathogenesis in population exposed to radiation

    MDS (myelodysplastic syndrome) is a currently increasing hematological abnormality in A-bomb survivors (about 60 years after exposure), and is considered to be a pre-leukemic state since the disease progresses to AML (acute myeloid leukemia). This paper describes the outline of AML1 gene, its genetic alteration in the radiation-exposed population and the mechanism of progression from MDS to AML in AML1 mutants. AML1 (RUNX1) codes an essential transcriptional factor for hemopoiesis. Recently, the point mutation of AML1 has been implicated as a major molecular pathogenesis of MDS/AML as seen by its high frequency in the patients exposed in Hiroshima (36% vs 17% in non-exposed), in a population of Chernobyl nuclear accident, in the patients in Semipalatinsk nuclear test site (39%), and also in patients treated with radio-/chemo-therapy of malignancies like lymphoma. The mutation in MDS/AML patients can roughly classified in 4 types, resulting in proteins with different functions, all of which lack the transcription activating function. In the 4 types, the clinical feature of patients with Ni type (N-terminal, inframe, missense mutation) is known to be marrow hypoplastic MDS/AML, whereas Ct type (C-terminal, truncation, deletion), hyperplastic. Studies in mice and in human cells with transformed muted AML1 genes have shown that pathogenic expression of Ni type AML requires another genetic alteration to promote cell proliferation, and further, that, in Ni and Ct types, progression to AML is dependent on different mechanisms of BMI-1 overexpression for hemopoietic stem cells to proliferate, and of suppression of differentiation of blast cells, respectively. Thus molecular pathogenesis of MDS/AML, refractory hitherto, is being close to elucidation for aiming at its treatment. (K.T)

  5. The chimeric genes AML1/MDS1 and AML1/EAP inhibit AML1B activation at the CSF1R promoter, but only AML1/MDS1 has tumor-promoter properties.

    Zent, C S; Mathieu, C.; Claxton, D F; Zhang, D E; Tenen, D.G.; Rowley, J D; Nucifora, G


    The (3;21)(q26;q22) translocation associated with treatment-related myelodysplastic syndrome, treatment-related acute myeloid leukemia, and blast crisis of chronic myeloid leukemia results in the expression of the chimeric genes AML1/EAP, AML1/MDS1, and AML1/EVI1. AML1 (CBFA2), which codes for the alpha subunit of the heterodimeric transcription factor CBF, is also involved in the t(8;21), and the gene coding for the beta subunit (CBFB) is involved in the inv(16). These are two of the most co...

  6. Therapy-related AML/MDS after treatment of low-grade B-cell lymphoma

    Described is the therapy-related AML (acute myelogenetic leukemia)/MDS (myelo-dysplasia syndrome), which is manifested after various treatments of low-grade B-cell lymphoma and has strongly attracted attention because of the markedly improved prognosis due to recent advantages of the therapy for the disease. AML/MDS occurs several years after chemotherapy and/or radiation therapy which cause DNA damage in hematopoietic cells, and the AML/MDS risk is known increased in patients undergone especially with autologous transplantation of those cells. AML/MDS has the feature similar to that caused either by alkylating agent or by topoisomerase-2 inhibitor, and the disease by radiation belong to the former. Yet unclear is the problem whether malignant cells causing the disease after therapy are derived from the remaining cells in the graft or in the body. Although irradiations of total body and total lymphaden as well as chemotherapy are said to be related to AML/MDS and local irradiation does not contribute to its risk, the most important factor for the disease is considered to be the autotransplantation as the recurrence occurs in 50% after it. Thus the treatment history should be taken into consideration for suppressing AML/MDS, for which follow up with consideration for the disease is required particularly after autotransplantation. (R.T.)

  7. Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation.

    Radivoyevitch, T; Sachs, R K; Gale, R P; Molenaar, R J; Brenner, D J; Hill, B T; Kalaycio, M E; Carraway, H E; Mukherjee, S; Sekeres, M A; Maciejewski, J P


    Risks of acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) are known to increase after cancer treatments. Their rise-and-fall dynamics and their associations with radiation have, however, not been fully characterized. To improve risk definition we developed SEERaBomb R software for Surveillance, Epidemiology and End Results second cancer analyses. Resulting high-resolution relative risk (RR) time courses were compared, where possible, to results of A-bomb survivor analyses. We found: (1) persons with prostate cancer receiving radiation therapy have increased RR of AML and MDS that peak in 1.5-2.5 years; (2) persons with non-Hodgkin lymphoma (NHL), lung and breast first cancers have the highest RR for AML and MDS over the next 1-12 years. These increased RR are radiation specific for lung and breast cancer but not for NHL; (3) AML latencies were brief compared to those of A-bomb survivors; and (4) there was a marked excess risk of acute promyelocytic leukemia in persons receiving radiation therapy. Knowing the type of first cancer, if it was treated with radiation, the interval from first cancer diagnosis to developing AML or MDS, and the type of AML, can improve estimates of whether AML or MDS cases developing in this setting are due to background versus other processes. PMID:26460209

  8. Gene expression profiling in MDS and AML: potential and future avenues

    Theilgaard-Mönch, K; Boultwood, J; Ferrari, S; Giannopoulos, K; Hernandez-Rivas, J M; Kohlmann, A; Morgan, M; Porse, Bo T; Tagliafico, E; Zwaan, C M; Wainscoat, J; Van den Heuvel-Eibrink, M M; Mills, K; Bullinger, L


    AML with regard to diagnosis, prediction of clinical outcome, discovery of novel subclasses and identification of novel therapeutic targets and novel drugs. As many challenges remain ahead, we discuss the pitfalls of this technology and its potential including future integrative studies with other......, and even within some cytogenetically well-defined subclasses there is considerable clinical heterogeneity. Recent advances in genomics technologies such as gene expression profiling (GEP) provide powerful tools to further characterize myeloid malignancies at the molecular level, with the goal to...... genomics technologies, which will continue to improve our understanding of malignant transformation in myeloid malignancies and thereby contribute to individualized risk-adapted treatment strategies for MDS and AML patients....

  9. Paclitaxel Induced MDS and AML: A Case Report and Literature Review

    Bhatnagar, Udit Bhaskar; Singh, Daulath; Glazyrin, Alexy; Moormeier, Jill


    Therapy related acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) have been classically linked to alkylating agents and topoisomerase inhibitors. They constitute about 1% of all AMLs. There is less evidence on association of taxanes (paclitaxel and docetaxel) with these myeloid neoplasms. We present a case of paclitaxel therapy related acute myelogenous leukemia after treatment of endometrial cancer with a regimen containing paclitaxel and carboplatin. A 63-year-old female underwent surgery followed by a total of 6 cycles of chemotherapy with carboplatin and paclitaxel. Six months after last cycle of chemotherapy, she was diagnosed with myelodysplastic syndrome with refractory anemia and excess blasts. Six weeks later, she had worsening anemia and thrombocytopenia which prompted a bone marrow biopsy which revealed acute myelomonocytic leukemia. A thorough literature review revealed 12 other case reports where taxanes have been implicated in the development of therapy related myeloid neoplasm. Based on the timeline of events in our patient, paclitaxel is the likely culprit in the pathogenesis of this myeloid neoplasm. This rare but significantly grave adverse effect should be kept in consideration when deciding on treatment options for gynecological malignancies. PMID:27057370

  10. Paclitaxel Induced MDS and AML: A Case Report and Literature Review

    Udit Bhaskar Bhatnagar


    Full Text Available Therapy related acute myelogenous leukemia (AML and myelodysplastic syndromes (MDS have been classically linked to alkylating agents and topoisomerase inhibitors. They constitute about 1% of all AMLs. There is less evidence on association of taxanes (paclitaxel and docetaxel with these myeloid neoplasms. We present a case of paclitaxel therapy related acute myelogenous leukemia after treatment of endometrial cancer with a regimen containing paclitaxel and carboplatin. A 63-year-old female underwent surgery followed by a total of 6 cycles of chemotherapy with carboplatin and paclitaxel. Six months after last cycle of chemotherapy, she was diagnosed with myelodysplastic syndrome with refractory anemia and excess blasts. Six weeks later, she had worsening anemia and thrombocytopenia which prompted a bone marrow biopsy which revealed acute myelomonocytic leukemia. A thorough literature review revealed 12 other case reports where taxanes have been implicated in the development of therapy related myeloid neoplasm. Based on the timeline of events in our patient, paclitaxel is the likely culprit in the pathogenesis of this myeloid neoplasm. This rare but significantly grave adverse effect should be kept in consideration when deciding on treatment options for gynecological malignancies.

  11. Invasive fungal infections in AML/MDS patients treated with azacitidine: a risk worth considering antifungal prophylaxis?

    Pomares, Helena; Arnan, Montserrat; Sánchez-Ortega, Isabel; Sureda, Anna; Duarte, Rafael F


    The aim of this study is to analyse the risk of invasive fungal infection (IFI) and the need for antifungal prophylaxis in patients with acute myeloid leukaemia and myelodysplastic syndromes (AML/MDS) treated with azacitidine. We retrospectively analysed the incidence of IFI according to EORTC-MSG criteria in 121 consecutive AML/MDS patients receiving 948 azacitidine courses (median 5, range 1-43) between June 2007 and June 2015. Four cases of IFI (two possible, one probable aspergillosis and one proven candidemia) occurred in this series. The incidence rate of proven/probable IFI was 0.21% per treatment cycle and 1.6% per patient treated for the whole series, and 0.73% per treatment cycle and 4.1% per patient treated in those with severe neutropenia. Two patients died from IFI, leading to an IFI-attributable mortality rate of 1.65% per patient and 0.21% per treatment cycle. The numbers needed to treat with prophylaxis to prevent one case of IFI are 238 azacitidine cycles or 30 patients throughout their whole treatment course, and 137 azacitidine cycles or 24 patients among those with severe neutropenia. AML/MDS patients treated with azacitidine, including those with severe prolonged neutropenia, have a very low risk of IFI which does not justify the use of antifungal prophylaxis. PMID:27027972

  12. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation

    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. 90Y, 188Re and 131I are the most frequently used β--particles. Of these, 90Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate 90Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The 90Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow 90Y-anti-CD45-mAb YAML568 are 6.4 ± 1.2 (bone marrow), 3.9 ± 1.4 (liver) and 1.1 ± 0.4 (kidneys). CD45 is expressed also on the extramedullar clonogenic myeloma progenitor cell that circulates in the peripheral blood. Thus, the conditioning of patients with

  13. Downregulation but lack of promoter hypermethylation or somatic mutations of the potential tumor suppressor CXXC5 in MDS and AML with deletion 5q

    Treppendahl, Marianne Bach; Möllgård, L; Hellström-Lindberg, E;


    During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells...

  14. Treatment-related MDS/AML in a patient after treatment for large-cell neuroendocrine lung cancer.

    Ansari, Junaid; Ravipati, Hari P; Munker, Reinhold; Cotelingam, James D; Shackelford, Rodney E; Prouty, Leonard A


    Secondary leukemia is a common late complication after exposure to cancer therapies such as chemotherapy and radiotherapy. With the increase in the overall survival of cancer patients over the past 3 decades, treatment-related malignant neoplasms have increased in incidence. Secondary leukemias due to breast cancer and Hodgkin lymphoma have been studied in detail, but to our knowledge only a few case studies have reported secondary leukemias with previous lung cancer.¹⁻⁴ Lung cancer is the leading cause of cancer death in the United States.⁵ Since the overall survival (OS) as well as the progression-free survival (PFS) of lung cancer has improved, secondary malignancies, which are usually aggressive and have a poor prognosis, have become a common occurrence among survivors. The use of concurrent chemo-radiotherapy could increase the risk for secondary cancers. Here we report the case of a patient who developed treatment-related acute myelogenous leukemia (t-AML) with a likely prior myelodysplasia (t-MDS) after receiving combined chemo-radiotherapy for lung cancer. PMID:26863022

  15. Reduced Intensity Hematopoietic-cell Transplantation in Older Patients with AML/MDS: Umbilical Cord Blood is a Feasible Option for Patients without HLA-matched Sibling Donors

    Majhail, Navneet S; Brunstein, Claudio G.; Shanley, Ryan; Sandhu, Karamjeet; McClune, Brian; Oran, Betul; Erica D Warlick; Wagner, John E.; Weisdorf, Daniel J.


    Umbilical cord blood (UCB) has increased access to hematopoietic-cell transplantation (HCT) for patients without HLA-matched sibling donors (MSD). We compared outcomes of HCT using MSD (N=38) or UCB (N=60) among older patients (age ≥55 years) with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). All patients received a reduced intensity regimen consisting of cyclophosphamide, fludarabine and 200 cGy total body irradiation. Median age at HCT was 63 years for MSD and 61 years fo...

  16. NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS).

    Schneider, Friederike; Hoster, Eva; Unterhalt, Michael; Schneider, Stephanie; Dufour, Annika; Benthaus, Tobias; Mellert, Gudrun; Zellmeier, Evelin; Bohlander, Stefan K; Feuring-Buske, Michaela; Buske, Christian; Braess, Jan; Fritsch, Susanne; Heinecke, Achim; Sauerland, Maria C; Berdel, Wolfgang E; Buechner, Thomas; Woermann, Bernhard J; Hiddemann, Wolfgang; Spiekermann, Karsten


    Mutations in the NPM1 gene represent the most frequent genetic alterations in patients with acute myeloid leukemia (AML) and are associated with a favorable outcome. In 690 normal karyotype (NK) AML patients the complete remission rates (CRs) and the percentage of patients with adequate in vivo blast cell reduction 1 week after the end of the first induction cycle were significantly higher in NPM1(+) (75% and 80%, respectively) than in NPM1(-) (57% and 57%, respectively) patients, but were unaffected by the FLT3-ITD status. Multivariate analyses revealed the presence of a NPM1 mutation as an independent positive prognostic factor for the achievement of an adequate day-16 blast clearance and a CR. In conclusion, NPM1(+) blast cells show a high in vivo sensitivity toward induction chemotherapy irrespective of the FLT3-ITD mutation status. These findings provide insight into the pathophysiology and help to understand the favorable clinical outcome of patients with NPM1(+) AML. PMID:19279329

  17. TEL-AML1 - Spleißvarianten und sequentielle Untersuchung zum Therapieansprechen von TEL-AML1 positiven ALL-Rezidiven im Kindesalter

    Elbers, Sandra


    The translocation t(12;21) which fuses the TEL-gene on chromosome 12 to the AML1-gene on chromosome 21 is the most common genetic anomaly in childhood ALL. TEL-AML1 positive patients are a heterogeneous group with different rates of relapse and the impact of TEL-AML1 on long-term prognosis is still discussed controversially. Two TEL-AML1 transcripts are known which result from different breakpoints in the AML1-gene and from alternative mRNA splicing. In this study, we investigated whether the...

  18. High frequency of AML1/RUNX1 point mutations in radiation-associated myelodysplastic syndrome around Semipalatinsk Nuclear Test Site

    It is known that bone marrow is a sensitive organ to ionizing radiation, and many patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) have been diagnosed in radiation-treated cases and atomic bomb survivors in Hiroshima and Nagasaki. The AML1/RUNX1 gene has been known to be frequently mutated in MDS/AML patients among atomic bomb survivors and radiation therapy-related MDS/AML patients. In this study, we investigated the AML1 mutations in radiation-exposed patients with MDS/AML among the residents near the Semipalatinsk Nuclear Test Site (SNTS), where the risk of solid cancers and leukemias was increased due to the radiation effects. AML1 mutations were identified in 7 (39%) of 18 radiation-exposed MDS/AML patients. In contrast, no AML1 mutation was found in 13 unexposed MDS/AML cases. The frequency of AML1 mutations in radiation-exposed patients with MDS/AML was significantly higher compared with unexposed patients (p<0.05).We also found a significant correlation between individual estimated doses and AML1 mutations (p<0.05). Considering these results, AML1 point mutations might be a useful biomarker that differentiates radio-induced MDS/AML from spontaneous MDS/AML. (author)

  19. AML1/RUNX1 point mutations in radiation-associated myelodysplastic syndrome around Semipalatinsk Nuclear Test Site

    It is known that bone marrow is a sensitive organ to ionizing radiation, and many patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) have been diagnosed in radiation-treated cases and atomic bomb survivors in Hiroshima and Nagasaki. The AML1/RUNX1 gene has been known to be frequently mutated in MDS/AML patients among atomic bomb survivors and radiation therapy-related MDS/AML patients. In this study, the analyze of gene mutations in the patients with hematological malignancies, living near the Semipalatinsk Nuclear Test Site (SNTS), where the risk of solid cancers and leukemias were increased. The majority of AML1 mutations identified in these MDS/AML were localized in the amino (N)-terminal region. By contrast, AML1 mutations in sporadic MDS/AML were distributed throughout the gene. AML1 mutations were identified in 9 (38%) of 24 radiation-exposed MDS/AML patients. In contrast, no AML1 mutation was found in unexposed MDS/AML cases. All mutations were in (N)-terminal region, but not in (C)-terminal region. The frequency of AML1 mutations in radiation-exposed patients with MDS/AML was significantly higher compared with unexposed patients. These results suggested that radiation might contribute to the development of MDS/AML through AML1 mutations among the residents near the SNTS, as well as among A-bomb survivors.

  20. AML Handboek

    Wiechen CMAG van; CIM


    Het AML handboek is ontstaan uit een behoefte aan standaardisering binnen het Rijksinstituut voor Volksgezondheid en Milieu. Het biedt AML-programmeurs de algemene standaard waaraan RIVM-brede applicaties, geschreven in de Arc Macro Language, moeten voldoen. Bepaalde elementen van een AML bleken goed te standaardiseren, zoals de lay-out en de opbouw van het bestand. Ook zaken als taalgebruik, tekst, gebruik van directieven, functies en variabelen komen aan de orde, voor zowel AML's als M...

  1. Myelodysplastic changes mimicking MDS following treatment for osteosarcoma

    Løhmann, Ditte

    -MDS/AML) is a feared long-term complication of paediatric cancer including osteosarcoma. Few develop t-MDS/AML, but it is not known how many have significant haematological changes after finishing treatment for osteosarcoma. In this study we reviewed biochemistry from a consecutive series of children for up....... In one case MDS (refractory anaemia with excess blasts) with monosomy 7 was found and a hematopoietic stem cell transplant was performed. In the other case MDS without excess of blasts was found and a spontaneous normalization of the biochemistry occurred. In conclusion in our study most patients......Myelodysplastic changes mimicking MDS following treatment for osteosarcoma Ditte Juel Adolfsen Løhmann, Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark Authors: Ditte Juel Adolfsen Løhmann and Henrik Hasle. Therapy-related myelodysplastic syndrome/acute myeloid leukaemia (t...

  2. AML1 gene rearrangements and mutations in radiation-associated acute myeloid leukemia and myelodysplastic syndromes

    Several studies suggested a causal link between AML1 gene rearrangements and both radiation-induced acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Fifty-three AML samples were analyzed for the presence of AML1 abnormalities using fluorescent in-situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR). Of these patients, 24 had experienced radiation exposure due to the Chernobyl accident, and 29 were non-irradiated spontaneous AML cases and served as controls. AML1/ETO translocations were found in 9 of 29 spontaneous AML but only in 1 of 24 radiation-associated AML cases. This difference between translocation frequencies is statistically significant in the age-unstratified cohorts (p=0.015). Following age stratification, the difference becomes less pronounced but remains on borderline significance (p=0.053). AML1 mutation status was assessed in 5 clean-up workers at Chemobyl NPP with MDS, or AML following MDS, by direct sequencing of genomic DNA from the coding region (exon 3 through 8). In one patient who developed MDS following an acute radiation syndrome, a hexanucleotide duplication of CGGCAT in exon 8 was found, inserted after base position 1502. Our results suggest that AML1 gene translocations are infrequent in radiation-induced leukemogenesis but are consistent with the idea that radiation may contribute to the development of MDS through AML1 gene mutation. (author)

  3. The applicability of the WHO classification in paediatric AML. A NOPHO-AML study

    Sandahl, Julie D; Kjeldsen, Eigil; Abrahamsson, Jonas; Ha, Shau-Yin; Heldrup, Jesper; Jahnukainen, Kirsi; Jónsson, Ólafur G; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Forestier, Erik; Hasle, Henrik


    population-based paediatric acute myeloid leukaemia (AML) cohort. We included children diagnosed with de novo AML, 0-18 years of age from the Nordic countries and Hong Kong from 1993 to 2012. Data were retrieved from the Nordic Society for Paediatric Haematology and Oncology AML database and patients...... classified according to the WHO 2008 classification. A successful karyotype was available in 97% of the cases. AML with recurrent genetic abnormalities were present in 262 (41%) and 94 (15%) were classified as AML with myelodysplasia-related changes (AML-MDS). WHO classifies patients with monosomy 7 and del......(7q) into one group. We found that -7 (n = 14) had significantly poorer outcome than del(7q) (n = 11); 5-year event-free survival 26% vs. 67%, (P = 0·02), and 5-year overall survival 51% vs. 90%, (P = 0·04). The largest group was the highly heterogeneous AML not otherwise specified (NOS) (n = 280...

  4. Atmospheric Measurements Laboratory (AML)

    Federal Laboratory Consortium — The Atmospheric Measurements Laboratory (AML) is one of the nation's leading research facilities for understanding aerosols, clouds, and their interactions. The AML...

  5. Cytogenetic findings in adult secondary acute myeloid leukemia (AML): frequency of favorable and adverse chromosomal aberrations do not differ from adult de novo AML

    Preiss, Birgitte S; Bergman, Olav J; Friis, Lone S; Sørensen, Anne; Frederiksen, Michael; Gadeberg, Ole V; Mourits-Andersen, Torben; Østergaard, Birthe; Kerndrup, Gitte B


    by treatment with chemotherapy and/or irradiation (t-AML). Cytogenetic analysis was carried out in 93%, of which 61% had clonal chromosome aberrations. MDS-AML correlated to a normal karyotype (P <0.001). t-AML correlated to abnormal clones with numerical and structural aberrations (P = 0.03), five...... or more unrelated aberrations (P = 0.03), marker chromosomes (P = 0.006), abnormal mitoses only (P = 0.01), female sex (P <0.001), and -7 (P = 0.006). Centromeric breakage correlated to a complex karyotype (P = 0.01). The frequencies of aberrations in s-AML patients were compared with an age......-matched group of de novo AML patients diagnosed in the same area and period. In this comparison, s-AML only correlated to -7 (P = 0.02). In 42 patients, we found that MDS patients with an abnormal karyotype were more likely to show cytogenetic evolution during progression to AML than MDS patients with a normal...

  6. Aplastic Anemia & MDS International Foundation

    ... Netherlands Antilles New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Northern Mariana Islands North Korea ... Gifts Corporate Sponsorship Invest in Research Diseases Aplastic Anemia Causes Symptoms Diagnosis Types Treatments Myelodysplastic Syndromes (MDS) ...

  7. RUNX1/AML1 point mutations take part in the pathogenesis of radiation-and therapy-related myeloid neoplasms

    High frequency of myelodysplastic syndrome (MDS) has been reported in Hiroshima A-bomb exposed survivors, in resident around Semipalatinsk Nuclear Laboratory and in exposed people by Chernobyl Nuclear Power Station Accident. MDS/acute myeloid leukemia (AML) is thought to be caused by mutation of runt-related transcription factor 1 (RUNX1) gene after a long time post exposure to relatively low dose radiation. In this study, participation of RUNX1/AML1 point mutations was examined in pathogenesis of the title neoplasms experienced in authors' facility. Subjects were 18/417 cases in whom myeloproliferative neoplasms (MPN) had switched to MDS or AML in the follow-up period of 1-25 years, and 11/124 cases in whom t-MN (therapy-related myeloid neoplasms) had developed during the remission of acute promyelocytic leukemia (APL) in the 1-9.7 years follow up. Point mutations were analyzed by PCR-single strand conformation polymorphism (PCR-SSCP) followed by base sequencing. In the former cases above, RUNX1 point mutation was found in 5/18 cases and in the latter, 4/11. When patients with persistent decrease of blood cells post therapy of APL were followed up for mutation, their RUNX1 point mutation was detected before they were diagnosed to be morbid of MDS/AML. The point mutation was thus a biomarker of myelo-hematogenic cancer, and was thought useful for early diagnosis of MDS and AML. (T.T.)

  8. The NAE inhibitor pevonedistat interacts with the HDAC inhibitor belinostat to target AML cells by disrupting the DDR.

    Zhou, Liang; Chen, Shuang; Zhang, Yu; Kmieciak, Maciej; Leng, Yun; Li, Lihong; Lin, Hui; Rizzo, Kathryn A; Dumur, Catherine I; Ferreira-Gonzalez, Andrea; Rahmani, Mohamed; Povirk, Lawrence; Chalasani, Sri; Berger, Allison J; Dai, Yun; Grant, Steven


    Two classes of novel agents, NEDD8-activating enzyme (NAE) and histone deacetylase (HDAC) inhibitors, have shown single-agent activity in acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS). Here we examined mechanisms underlying interactions between the NAE inhibitor pevonedistat (MLN4924) and the approved HDAC inhibitor belinostat in AML/MDS cells. MLN4924/belinostat coadministration synergistically induced AML cell apoptosis with or without p53 deficiency or FLT3-internal tandem duplication (ITD), whereas p53 short hairpin RNA (shRNA) knockdown or enforced FLT3-ITD expression significantly sensitized cells to the regimen. MLN4924 blocked belinostat-induced antiapoptotic gene expression through nuclear factor-κB inactivation. Each agent upregulated Bim, and Bim knockdown significantly attenuated apoptosis. Microarrays revealed distinct DNA damage response (DDR) genetic profiles between individual vs combined MLN4924/belinostat exposure. Whereas belinostat abrogated the MLN4924-activated intra-S checkpoint through Chk1 and Wee1 inhibition/downregulation, cotreatment downregulated multiple homologous recombination and nonhomologous end-joining repair proteins, triggering robust double-stranded breaks, chromatin pulverization, and apoptosis. Consistently, Chk1 or Wee1 shRNA knockdown significantly sensitized AML cells to MLN4924. MLN4924/belinostat displayed activity against primary AML or MDS cells, including those carrying next-generation sequencing-defined poor-prognostic cancer hotspot mutations, and CD34(+)/CD38(-)/CD123(+) populations, but not normal CD34(+) progenitors. Finally, combined treatment markedly reduced tumor burden and significantly prolonged animal survival (P < .0001) in AML xenograft models with negligible toxicity, accompanied by pharmacodynamic effects observed in vitro. Collectively, these findings argue that MLN4924 and belinostat interact synergistically by reciprocally disabling the DDR in AML/MDS cells. This strategy

  9. Access/AML

    Department of Transportation — The AccessAML is a web-based internet single application designed to reduce the vulnerability associated with several accounts assinged to a single users. This is a...

  10. MDS 3.0 Frequency Report

    U.S. Department of Health & Human Services — The MDS 3.0 Frequency Report summarizes information for active residents currently in nursing homes. The source of these counts is the residents MDS assessment...

  11. Reasons for treating secondary AML as de novo AML

    Ostgård, Lene Sofie Granfeldt; Kjeldsen, Eigil; Holm, Mette Skov;


    77 cases (49%), CMPD (chronic myeloproliferative disorder) in 43 cases (27%) and was therapy-related AML (t-AML) in 37 cases (24%). Median age at diagnosis of AML was 69 yr in secondary cases when compared to 66 yr in de novo cases (P = 0.006). In univariate analyses, secondary AML was associated...... with an inferior complete remission (CR) rate (P = 0.008) and poorer overall survival (OS, P = 0.003) whereas in complete remitters, disease-free survival (DFS) of secondary cases was equal to that of de novo cases. Interestingly, in all further analyses of CR-rates, OS and DFS, when correcting for the...

  12. Acute myelogenous leukemia (AML) - children

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  13. Clofarabine±Fludarabine with Once Daily IV Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and MDS

    Andersson, Borje S.; Valdez, Benigno C.; Lima, Marcos; Wang, Xuemei; Thall, Peter F.; Worth, Laura L.; Popat, Uday; Madden, Timothy; Hosing, Chitra; Alousi, Amin; Rondon, Gabriela; Kebriaei, Partow; Elizabeth J. Shpall; Jones, Roy B.; Champlin, Richard E.


    While a combination of IV busulfan (Bu) and fludarabine (Flu) is a safe, reduced-toxicity conditioning program for AML/MDS, recurrent leukemia post transplantation remains a problem. To enhance the conditioning regimen’s antileukemic effect we decided to supplant Flu with clofarabine (Clo), and assayed the interactions of these nucleoside analogs alone and in combination with Busulfan (Bu) in Bu-resistant human cell lines in vitro. We found pronounced synergy between each nucleoside and the a...

  14. Long Term Care Minimum Data Set (MDS)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  15. The CloudMdsQL Multistore System

    Kolev, Boyan; Bondiombouy, Carlyna; Valduriez, Patrick; Jiménez-Peris, Ricardo; Pau, Raquel; Pereira, José


    The blooming of different cloud data management infrastructures has turned multistore systems to a major topic in the nowadays cloud landscape. In this demonstration, we present a Cloud Multidatastore Query Language (CloudMdsQL), and its query engine. CloudMdsQL is a functional SQL-like language, capable of querying multiple heterogeneous data stores (relational and NoSQL) within a single query that may contain embedded invocations to each data store's native query interface. The major innova...

  16. Herunterregulation des Proto-Onkogens c-Jun durch das CCAAT/Enhancer bindende Protein alpha in der Myelopoese und in der akuten myeloischen Leukämie (AML)

    Treiber, Nicolai


    Verschiedene Transkriptionsfaktoren spielen eine Rolle in der Entwicklung myeloischer Zellen. c-Jun gehört zur Familie der AP-1 Transkriptionsfaktoren und ist ein Koaktivator des Transkriptionsfaktors PU.1, der für die Differenzierung zu Monozyten wichtig ist. C/EBPa ist ein an den CCAAT-Enhancer bindender Transkriptionsfaktor. Wird C/EBPa exprimiert, differenzieren sich bipotente myeloische Zellen zu neutrophilen Granulozyten. Die durch den Induktor TPA hervorgerufene Differenzierung zu Mono...

  17. Lessons from the atomic bomb about secondary MDS.

    Hata, Tomoko; Imanishi, Daisuke; Miyazaki, Yasushi


    Myelodysplastic syndromes (MDSs) is a hematological neoplasm defined by ineffective hematopoiesis, dysplasia of hematopoietic cells, and risk of progression to acute leukemia. MDS occurs as de novo or secondary, and chemoradiotherapy for cancers is thought to increase the risk of MDS among patients. Recently, an epidemiological study for MDS among A-bomb survivors was performed, and it clearly demonstrated that the exposure to external radiation significantly increased the risk of MDS. Precise epidemiological data among survivors have revealed important clinical factors related to the risk of leukemias. In this review, by comparing data for secondary MDS and leukemia/MDS among survivors, several factors which would affect the risk of MDS, especially secondary MDS, are discussed. PMID:25240475

  18. Nearly MDS expander codes with reduced alphabet size

    Armand, Marc A.; Zhang, Jianwen


    Recently, Roth and Skachek proposed two methods for constructing nearly maximum-distance separable (MDS) expander codes. We show that through the simple modification of using mixed-alphabet codes derived from MDS codes as constituent codes in their code designs, one can obtain nearly MDS codes of significantly smaller alphabet size, albeit at the expense of a (very slight) reduction in code rate.

  19. Chronic GVHD induced GVL effect after unmanipulated haploidentical hematopoietic SCT for AML and myelodysplastic syndrome.

    Mo, X-D; Xu, L-P; Zhang, X-H; Liu, D-H; Wang, Y; Chen, H; Yan, C-H; Chen, Y-H; Han, W; Wang, F-R; Wang, J-Z; Liu, K-Y; Huang, X-J


    The aim of this study was to investigate the impact of occurrence of chronic GVHD (cGVHD) and its severity on transplantation outcomes in a consecutive cohort of AML and myelodysplastic syndrome (MDS) patients who received unmanipulated haploidentical hematopoietic SCT (haplo-HSCT; n=324). The cumulative incidence of relapse was significantly decreased in patients with cGVHD compared with the non-cGVHD group (1 year: 3.2% vs 11.9%, P=0.002; 3 years: 6.0% vs 16.3%, P=0.002), particularly in those with mild cGVHD. The cumulative incidence of non-relapse mortality was comparable between patients with and without cGVHD. The probabilities of disease-free survival (DFS) were significantly better in patients with cGVHD than in those in the non-cGVHD group (1 year: 90.5% vs 78.5%, P=0.002; 3 years: 86.5% vs 71.5%, PGVL effect in patients with AML and MDS receiving unmanipulated haplo-HSCT; however, only mild or moderate cGVHD was associated with a lower risk of relapse translating into improved DFS. PMID:25387095

  20. On the Upper Bounds of MDS Codes

    Yang, Jiansheng; Zhang, Yunying


    Let $M_{q}(k)$ be the maximum length of MDS codes with parameters $q,k$. In this paper, the properties of $M_{q}(k)$ are studied, and some new upper bounds of $M_{q}(k)$ are obtained. Especially we obtain that $M_{q}(q-1)\\leq q+2(q\\equiv4(mod 6)), M_{q}(q-2)\\leq q+1(q\\equiv4(mod 6)), M_{q}(k)\\leq q+k-3 (q=36(5s+1), s\\in N$ and $ k=6,7).

  1. Patients with Fanconi Anemia and AML have Different Cytogenetic Clones than de novo Cases of AML

    Rochowski, Andrzej; Olson, Susan B; Alonzo, Todd A; Gerbing, Robert B.; Lange, Beverly J.; Alter, Blanche P.


    Specific cytogenetic clones might distinguish patients with unrecognized Fanconi anemia (FA) who present with acute myeloid leukemia (AML) from those with sporadic AML. Cytogenetic reports in literature cases of FA and AML were compared with de novo cases enrolled on CCG-2961. Gain of 1q, gain of 3q, monosomy 7, deleted 7q, gain of 13q, and deleted 20q were more frequent in FA AML; t(8;21), trisomy 8, t(9;11), t(6;9) and inversion 16 were exclusive to de novo AML cases. Observation of the FA ...

  2. How to treat MDS without stem cell transplantation.

    Gattermann, Norbert


    Although allogeneic hematopoietic cell transplantation (HCT) is the only proven curative treatment for myelodysplastic syndromes (MDS), it is only used to treat a minority of MDS patients. The majority of patients are too old or suffer from comorbidities rendering allogeneic HCT too risky. Alternative treatment strategies for patients with higher risk MDS try to alter the natural course of disease by preventing or delaying leukemic transformation. In patients with lower risk MDS, treatment is mainly focused on maintaining or improving the quality of life. PMID:19857591

  3. AML1/ETO oncoprotein is directed to AML1 binding regions and co-Localizes with AML1 and HEB on its targets

    Gardini, A.; M. Cesaroni; Luzi, L.; A.J. Okumura; J.R. Biggs; S.P.Minardi; E. Venturini; Zhang, D E; Pelicci, P G; Alcalay, M


    A reciprocal translocation involving chromosomes 8 and 21 generates the AML1/ETO oncogenic transcription factor that initiates acute myeloid leukemia by recruiting co-repressor complexes to DNA. AML1/ETO interferes with the function of its wild-type counterpart, AML1, by directly targeting AML1 binding sites. However, transcriptional regulation determined by AML1/ETO probably relies on a more complex network, since the fusion protein has been shown to interact with a number of other transcrip...

  4. The drift-flux correlation package MDS

    Based on the SONNENBURG drift-flux correlation, developed at GRS/Garching (Germany), a comprehensive drift-flux correlation package (MDS) has been established. Its aim is to support thermal-hydraulic mixture-fluid models, models being used for the simulation of the steady state and transient behaviour of characteristic thermal-hydraulic parameters of single- or two-phase fluids flowing along coolant channels of different types (being, e.g., parts of NPP-s, steam generators etc.). The characteristic properties of this package with respect to the behaviour at co- and counter-current flow, its inverse solutions needed for steady state simulations, its behaviour when approaching the lower or upper boundary of a two-phase region, its verification and behaviour with respect to other correlations will be discussed. An adequate driver code, MDSDRI, has been established too, allowing to test the package very thoroughly out of the complex thermal-hydraulic codes. (author)

  5. AML Guide: Information for Patients and Caregivers

    ... to have children later on) {{ Bone problems {{ Heart problems {{ Learning problems. Adults who are treated for AML may have {{ Fertility problems {{ Thyroid problems {{ Problems ... child’s learning skills should be checked. Want more information? You ...

  6. A case of Ph1 positive AML

    An 83-year-old woman with AML was exposed to A-bomb at 1,700 m from the hypocenter in Hiroshima at the age of 44 years. In this patient, the lack of splenomegaly and basophilia, which are characteristic of Ph1 positive AML, were observed. She died one month after the occurrence of the disease. The relevant literature was reviewed. (Namekawa, K.)

  7. Iron overload in MDS-pathophysiology, diagnosis, and complications.

    Gattermann, Norbert; Rachmilewitz, Eliezer A


    Many patients with myelodysplastic syndromes (MDS) become dependent on blood transfusions and develop transfusional iron overload, which is exacerbated by increased absorption of dietary iron in response to ineffective erythropoiesis. However, it is uncertain whether there is an association among iron accumulation, clinical complications, and decreased likelihood of survival in MDS patients. Here, we discuss our current understanding of the effects of transfusion dependency and iron overload in MDS, indicate our knowledge gaps, and suggest that particular emphasis should be placed on further characterizing the role of redox-active forms of labile iron, which may be as important as the total iron burden. PMID:20938663

  8. AML engraftment in the NOD/SCID assay reflects the outcome of AML: implications for our understanding of the heterogeneity of AML

    Pearce, Daniel J.; Taussig, David; Zibara, Kazem; Smith, Lan-Lan; Ridler, Christopher M.; Preudhomme, Claude; Young, Bryan D.; Rohatiner, Ama Z; Lister, T. Andrew; Bonnet, Dominique


    The nonobese diabetic/severe combined immunodeficient (NOD/SCID) assay is the current model for assessment of human normal and leukemic stem cells. We explored why 51% of 59 acute myeloid leukemia (AML) patients were unable to initiate leukemia in NOD/SCID mice. Increasing the cell dose, using more permissive recipients, and alternative tissue sources did not cause AML engraftment in most previously nonengrafting AML samples. Homing of AML cells to the marrow was the same between engrafters a...

  9. MDS 2.0 Public Quality Indicator and Resident Reports

    U.S. Department of Health & Human Services — The Minimum Data Set (MDS) is part of the federally mandated process for clinical assessment of all residents in Medicare or Medicaid certified nursing homes. This...

  10. Resident Assessment Instrument/Minimum Data Set (RAI/MDS)

    Department of Veterans Affairs — The Resident Assessment Instrument/Minimum Data Set (RAI/MDS) is a comprehensive assessment and care planning process used by the nursing home industry since 1990...

  11. Impact on survival of different treatments for myelodysplastic syndromes (MDS).

    Nachtkamp, Kathrin; Kündgen, Andrea; Strupp, Corinna; Giagounidis, Aristoteles; Kobbe, Guido; Gattermann, Norbert; Haas, Rainer; Germing, Ulrich


    Therapies for myelodysplastic syndromes (MDS) often achieve hematological responses but their impact on overall survival has generally not been evaluated. The Duesseldorf MDS Registry allowed us to perform matched-pair analyses to assess a possible survival benefit of treatment with thalidomide, valproic acid, low-dose Ara-C, antithymocyte globulin (ATG), induction chemotherapy, or allogeneic stem cell transplantation (allo-SCT). For all treatment modalities, lengthening of survival was restricted to certain subgroups of patients. With the exception of allo-SCT, MDS treatment was generally palliative. Recently, epigenetic treatment with demethylating agents proved to be the first therapy that can significantly prolong survival in patients with higher-risk MDS. PMID:19185917

  12. An improved resource management model based on MDS

    Yuan, Man; Sun, Changying; Li, Pengfei; Sun, Yongdong; He, Rui


    GRID technology provides a kind of convenient method for managing GRID resources. This service is so-called monitoring, discovering service. This method is proposed by Globus Alliance, in this GRID environment, all kinds of resources, such as computational resources, storage resources and other resources can be organized by MDS specifications. However, this MDS is a theory framework, particularly, in a small world intranet, in the case of limit of resources, the MDS has its own limitation. Based on MDS, an improved light method for managing corporation computational resources and storage resources is proposed in intranet(IMDS). Firstly, in MDS, all kinds of resource description information is stored in LDAP, it is well known although LDAP is a light directory access protocol, in practice, programmers rarely master how to access and store resource information into LDAP store, in such way, it limits MDS to be used. So, in intranet, these resources' description information can be stored in RDBMS, programmers and users can access this information by standard SQL. Secondly, in MDS, how to monitor all kinds of resources in GRID is not transparent for programmers and users. In such way, it limits its application scope, in general, resource monitoring method base on SNMP is widely employed in intranet, therefore, a kind of resource monitoring method based on SNMP is integrated into MDS. Finally, all kinds of resources in the intranet can be described by XML, and all kinds of resources' description information is stored in RDBMS, such as MySql, and retrieved by standard SQL, dynamic information for all kinds of resources can be sent to resource storage by SNMP, A prototype resource description, monitoring is designed and implemented in intranet.

  13. Iron overload in MDS?pathophysiology, diagnosis, and complications

    Gattermann, Norbert; Rachmilewitz, Eliezer A


    Abstract Many patients with myelodysplastic syndromes (MDS) become dependent on blood transfusions and develop transfusional iron overload, which is exacerbated by increased absorption of dietary iron in response to ineffective erythropoiesis. However, it is uncertain whether there is an association among iron accumulation, clinical complications, and decreased likelihood of survival in MDS patients. Here, we discuss our current understanding of the effects of transfusion dependenc...

  14. Rational Combinations of Targeted Agents in AML

    Prithviraj Bose


    Full Text Available Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing to both aggressive disease biology and the high toxicity of current chemotherapeutic regimens. It has become increasingly apparent in recent years that coordinated interruption of cooperative survival signaling pathways in malignant cells is necessary for optimal therapeutic results. The modest efficacy of monotherapy with both cytotoxic and targeted agents in AML testifies to this. As the complex biology of AML continues to be elucidated, many “synthetic lethal” strategies involving rational combinations of targeted agents have been developed. Unfortunately, relatively few of these have been tested clinically, although there is growing interest in this area. In this article, the preclinical and, where available, clinical data on some of the most promising rational combinations of targeted agents in AML are summarized. While new molecules should continue to be combined with conventional genotoxic drugs of proven efficacy, there is perhaps a need to rethink traditional philosophies of clinical trial development and regulatory approval with a focus on mechanism-based, synergistic strategies.

  15. Prevalence, clinical characteristics and prognosis of GATA2-related myelodysplastic syndromes (MDS) in children and adolescents

    Wlodarski, Marcin W; Hirabayashi, Shinsuke; Pastor, Victor; Starý, Jan; Hasle, Henrik; Masetti, Riccardo; Dworzak, Michael; Schmugge, Markus; van den Heuvel-Eibrink, Marry; Ussowicz, Marek; De Moerloose, Barbara; Catala, Albert; Smith, Owen P; Sedlacek, Petr; Lankester, Arjan C; Zecca, Marco; Bordon, Victoria; Matthes-Martin, Susanne; Abrahamsson, Jonas; Kühl, Jörn Sven; Sykora, Karl-Walter; Albert, Michael H; Przychodzien, Bartlomiej; Maciejewski, Jaroslaw; Schwarz, Stephan; Göhring, Gudrun; Schlegelberger, Brigitte; Cseh, Annámaria; Noellke, Peter; Yoshimi, Ayami; Locatelli, Franco; Baumann, Irith; Strahm, Brigitte; Niemeyer, Charlotte M


    MDS in Childhood (EWOG-MDS) conducted in Germany over a period of 15 years. Germline GATA2 mutations accounted for 15% of advanced and 7% of all primary MDS cases, but were absent in children with MDS secondary to therapy or acquired aplastic anemia. Mutation carriers were older at diagnosis and more...

  16. Hypomethylation and up-regulation of PD-1 in T cells by azacytidine in MDS/AML patients

    Ørskov, A. D.; Treppendahl, M. B.; Skovbo, A.;


    receptor PD-1 is regulated by DNA methylation. In 12 of 27 patients (44%) PD-1 promoter demethylation was observed in sorted peripheral blood T cells isolated over consecutive cycles of treatment with 5-azacytidine (5-aza). The PD-1 promoter demethylation correlated with an increase in PD-1 expression...

  17. From Stata to aML


    This presentation explains how to exploit Stata to run multilevel multiprocess regressions with aML (software downloadable for free from I show how a single do-file can prepare the dataset, write the control files, input the starting values, and run the regressions without the need to manually open the aML’s Command Prompt window. In this sense, Stata helps to avoid the difficulties of running complicated regressions with aML by automatically generating the necessary files,...

  18. Prognostic Factors in Childhood Leukemia (ALL or AML)

    ... leukemias Prognostic factors in childhood leukemia (ALL or AML) Certain factors that can affect a child’s outlook ( ... more intensive chemotherapy. Prognostic factors for children with AML Prognostic factors are not quite as important in ...

  19. Acute Myeloid Leukemia (AML) with Erythroid Predominance Exhibits Clinical and Molecular Characteristics that Differ from Other Types of AML

    Zuo, Zhuang; Medeiros, L. Jeffrey; Chen, Zhao; Liu, Dingsheng; Bueso-Ramos, Carlos E.; Luthra, Rajyalakshmi; A.Wang, Sa


    The clinical importance of erythroid predominance in bone marrow of patients with acute myeloid leukemia (AML) is controversial. These cases represent a heterogeneous group of diseases that historically have been classified into different categories. We studied 313 AML patients and specifically compared the clinical, cytogenetic, and molecular features of cases of AML with erythroid predominance, arbitrarily defined as ≥50% erythroid precursors, to AML cases without erythroid predominance. We...

  20. Update on MDS therapy: from famine to feast.

    Chaudhary, Preeti; Shah, Chirag


    Myelodysplastic syndromes (MDS) are acquired hematopoietic stem cell disorders characterized by ineffective hematopoiesis, cellular dysfunction and increased risks of transformation into acute myeloid leukemia. The natural history of the disease remains variable and depend upon multiple prognostic factors at the time of initial diagnosis. The current prognostic models are helpful to determine the outcome of individual patients but they remain imperfect. Earlier, the most frequent treatment given for patients with MDS was supportive with transfusion of blood products and administration of erythropoietic stimulating agents and iron chelation therapy. Now, there is an arsenal of therapies available and the landscape for the treatment of MDS is rapidly evolving. There are several FDA approved therapies available for this disorder that makes this review particularly timely and relevant. PMID:20712577

  1. Monitoring the grid with the Globus Toolkit MDS4

    The Globus Toolkit Monitoring and Discovery System (MDS4) defines and implements mechanisms for service and resource discovery and monitoring in distributed environments. MDS4 is distinguished from previous similar systems by its extensive use of interfaces and behaviors defined in the WS-Resource Framework and WS-Notification specifications, and by its deep integration into essentially every component of the Globus Toolkit. We describe the MDS4 architecture and the Web service interfaces and behaviors that allow users to discover resources and services, monitor resource and service states, receive updates on current status, and visualize monitoring results. We present two current deployments to provide insights into the functionality that can be achieved via the use of these mechanisms

  2. Pathophysiological and clinical aspects of iron chelation therapy in MDS.

    Gattermann, Norbert


    The majority of patients with myelodysplastic syndromes (MDS) become transfusion-dependent during the course of disease and may thus develop transfusional iron overload. As a further contributor to iron overload there is increased absorption of dietary iron from the gut, as a consequence of ineffective erythropoiesis. Compared with thalassemia, it is less clear how frequent patients with MDS develop clinical complications of iron overload, and whether the accumulation of iron shortens their survival. This review aims to summarize our current knowledge of the detrimental effects of transfusional iron overload in MDS, point out the risks associated with iron-induced oxidative stress, describe the tools available for diagnosing iron overload, indicate the treatment options with currently available iron chelators, and discuss the measurement of labile plasma iron (LPI) as a tool to monitor the efficacy of iron chelation therapy. PMID:22571702

  3. Hyperdiploidy in Childhood AML Associated with Low Age and AML-M7. A NOPHO-AML Study and Literature Review

    Sandahl, Julie Damgaard; Abrahamson, Jonas; Heldrup, Jesper; Jahnukainen, Kirsi; Ólafur, G; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Forestier, Erik; Kjeldsen, Eigil; Hasle, Henrik

    (AML), however, is a rare cytogenetic finding. It is most often categorized as a complex karyotype, which is considered associated with an unfavorable outcome. The group of complex karyotypes is heterogeneous and the significance of multiple additional chromosomes with or without structural...... abnormalities among the pediatric hyperdiploid AML patients is relatively unknown. Current knowledge in this field is based on small adult series or case reports. In this descriptive study we describe the clinical - and cytogenetic features in childhood hyperdiploid AML with a modal chromosome number at 50 or...... more. We report a series of 29 children from the Nordic Countries diagnosed with high hyperdiploid (50+) AML along with 105 cases identified from the literature. Material and Method: Children age 0–18 years diagnosed with AML and treated according to the NOPHO –AML-93 or 2004 protocols from 1993 to...

  4. Mouse models of human AML accurately predict chemotherapy response

    Zuber, Johannes; Radtke, Ina; Pardee, Timothy S.; Zhao, Zhen; Rappaport, Amy R.; Luo, Weijun; McCurrach, Mila E.; Yang, Miao-Miao; Dolan, M. Eileen; Kogan, Scott C.; Downing, James R.; Lowe, Scott W.


    The genetic heterogeneity of cancer influences the trajectory of tumor progression and may underlie clinical variation in therapy response. To model such heterogeneity, we produced genetically and pathologically accurate mouse models of common forms of human acute myeloid leukemia (AML) and developed methods to mimic standard induction chemotherapy and efficiently monitor therapy response. We see that murine AMLs harboring two common human AML genotypes show remarkably diverse responses to co...

  5. Identification of AML1-ETO modulators by chemical genomics

    Corsello, Steven M.; Roti, Giovanni; Ross, Kenneth N.; Chow, Kwan T.; Galinsky, Ilene; DeAngelo, Daniel J.; Stone, Richard M.; Kung, Andrew L.; Golub, Todd R.; Stegmaier, Kimberly


    Somatic rearrangements of transcription factors are common abnormalities in the acute leukemias. With rare exception, however, the resultant protein products have remained largely intractable as pharmacologic targets. One example is AML1-ETO, the most common translocation reported in acute myeloid leukemia (AML). To identify AML1-ETO modulators, we screened a small molecule library using a chemical genomic approach. Gene expression signatures were used as surrogates for the expression versus ...

  6. Ibrutinib inhibits SDF1/CXCR4 mediated migration in AML

    Zaitseva, Lyubov; Murray, Megan Y; Shafat, Manar S.; Lawes, Matthew J.; MacEwan, David J.; Bowles, Kristian M.; Rushworth, Stuart A.


    Pharmacological targeting of BTK using ibrutinib has recently shown encouraging clinical activity in a range of lymphoid malignancies. Recently we reported that ibrutinib inhibits human acute myeloid leukemia (AML) blast proliferation and leukemic cell adhesion to the surrounding bone marrow stroma cells. Here we report that in human AML ibrutinib, in addition, functions to inhibit SDF1/CXCR4-mediated AML migration at concentrations achievable in vivo. It has previously been shown that SDF1/C...

  7. Interaction Mediated by the Putative Tip Regions of MdsA and MdsC in the Formation of a Salmonella-Specific Tripartite Efflux Pump

    Song, Saemee; Hwang, Soonhye; Lee, SeungHwa; Ha, Nam-Chul; Lee, Kangseok


    To survive in the presence of a wide range of toxic compounds, gram-negative bacteria expel such compounds via tripartite efflux pumps that span both the inner and outer membranes. The Salmonella-specific MdsAB pump consists of MdsB, a resistance-nodulation-division (RND)-type inner membrane transporter (IMT) that requires the membrane fusion protein (MFP) MdsA, and an outer membrane protein (OMP; MdsC or TolC) to form a tripartite efflux complex. In this study, we investigated the role of th...

  8. Cellular origin of prognostic chromosomal aberrations in AML patients

    Mora-Jensen, H.; Jendholm, J.; Rapin, N.;


    these aberrations occur in normal hematopoietic stem and progenitor cells (HSCs/HPCs) before definitive leukemic transformation through additional acquisition of a few (that is, mostly 1 or 2) leukemia-promoting driver aberrations. NGS studies on sorted bone marrow (BM) populations of AML patients with...... molecular aberrations that were present in the fully transformed committed HPCs together with the prognostic driver aberration. Adding to this vast heterogeneity and complexity of AML genomes and their clonal evolution, a recent study of a murine AML model demonstrated that t(9;11) AML originating from HSCs...

  9. New study reveals relatively few mutations in AML genomes - TCGA

    Investigators for The Cancer Genome Atlas (TCGA) Research Network have detailed and broadly classified the genomic alterations that frequently underlie the development of acute myeloid leukemia (AML).

  10. Aberrant splicing and drug resistance in AML.

    de Necochea-Campion, Rosalia; Shouse, Geoffrey P; Zhou, Qi; Mirshahidi, Saied; Chen, Chien-Shing


    The advent of next-generation sequencing technologies has unveiled a new window into the heterogeneity of acute myeloid leukemia (AML). In particular, recurrent mutations in spliceosome machinery and genome-wide aberrant splicing events have been recognized as a prominent component of this disease. This review will focus on how these factors influence drug resistance through altered splicing of tumor suppressor and oncogenes and dysregulation of the apoptotic signaling network. A better understanding of these factors in disease progression is necessary to design appropriate therapeutic strategies recognizing specific alternatively spliced or mutated oncogenic targets. PMID:27613060

  11. A Non-MDS Erasure Code Scheme For Storage Applications

    Kiani, Abbas


    This paper investigates the use of redundancy and self repairing against node failures in distributed storage systems, using various strategies. In replication method, access to one replication node is sufficient to reconstruct a lost node, while in MDS erasure coded systems which are optimal in terms of redundancy-reliability tradeoff, a single node failure is repaired after recovering the entire stored data. Moreover, regenerating codes yield a tradeoff curve between storage capacity and repair bandwidth. The current paper aims at investigating a new storage code. Specifically, we propose a non-MDS (2k, k) code that tolerates any three node failures and more importantly, it is shown using our code a single node failure can be repaired through access to only three nodes.

  12. A Construction of Systematic MDS Codes with Minimum Repair Bandwidth

    Wu, Yunnan


    In a distributed storage system based on erasure coding, an important problem is the \\emph{repair problem}: If a node storing a coded piece fails, in order to maintain the same level of reliability, we need to create a new encoded piece and store it at a new node. This paper presents a construction of systematic $(n,k)$-MDS codes for $2k\\le n$ that achieves the minimum repair bandwidth when repairing from $k+1$ nodes.

  13. MDS Nordion - a Canadian Radioisotope success story Science advancing health

    At MDS Nordion we use nuclear science and technology to advance human life and health through a wide range of applications. We could not do this without the strong partnerships we have formed with the Canadian nuclear power industry. Together, we have developed and applied radioisotope technology in ways that have saved millions of lives around the world. This is a success story of which we all can be proud. It is a success story that we should share with others. As an industry, we are often challenged by activists , who fear and attack anything nuclear and who do not care to understand how vital nuclear energy and nuclear science are to an environmentally sound, economically healthy future. MDS Nordion has not escaped this kind of public scrutiny, but much of this criticism is muted by the tremendous contributions we have made to medicine and health care generally. That is why it is so important for you to see MDS Nordion's story as a success story that everyone in the industry has contributed to, in the support they have provided, and in the products or services they supply

  14. Temporal MDS Plots for Analysis of Multivariate Data.

    Jäckle, Dominik; Fischer, Fabian; Schreck, Tobias; Keim, Daniel A


    Multivariate time series data can be found in many application domains. Examples include data from computer networks, healthcare, social networks, or financial markets. Often, patterns in such data evolve over time among multiple dimensions and are hard to detect. Dimensionality reduction methods such as PCA and MDS allow analysis and visualization of multivariate data, but per se do not provide means to explore multivariate patterns over time. We propose Temporal Multidimensional Scaling (TMDS), a novel visualization technique that computes temporal one-dimensional MDS plots for multivariate data which evolve over time. Using a sliding window approach, MDS is computed for each data window separately, and the results are plotted sequentially along the time axis, taking care of plot alignment. Our TMDS plots enable visual identification of patterns based on multidimensional similarity of the data evolving over time. We demonstrate the usefulness of our approach in the field of network security and show in two case studies how users can iteratively explore the data to identify previously unknown, temporally evolving patterns. PMID:26529694

  15. Advanced Manned Launch System (AMLS) study

    Ehrlich, Carl F., Jr.; Potts, Jack; Brown, Jerry; Schell, Ken; Manley, Mary; Chen, Irving; Earhart, Richard; Urrutia, Chuck; Randolph, Ray; Morris, Jim


    To assure national leadership in space operations and exploration in the future, NASA must be able to provide cost effective and operationally efficient space transportation. Several NASA studies and the joint NASA/DoD Space Transportation Architecture Studies (STAS) have shown the need for a multi-vehicle space transportation system with designs driven by enhanced operations and low costs. NASA is currently studying an advanced manned launch system (AMLS) approach to transport crew and cargo to the Space Station Freedom. Several single and multiple stage systems from air-breathing to all-rocket concepts are being examined in a series of studies potential replacements for the Space Shuttle launch system in the 2000-2010 time frame. Rockwell International Corporation, under contract to the NASA Langley Research Center, has analyzed a two-stage all-rocket concept to determine whether this class of vehicles is appropriate for the AMLS function. The results of the pre-phase A study are discussed.

  16. RUNX1/AML1 DNA-binding domain and ETO/MTG8 NHR2-dimerization domain are critical to AML1-ETO9a leukemogenesis

    Yan, Ming; Ahn, Eun-Young; Hiebert, Scott W.; Zhang, Dong-Er


    The 8;21 translocation, which involves the gene encoding the RUNX family DNA-binding transcription factor AML1 (RUNX1) on chromosome 21 and the ETO (MTG8) gene on chromosome 8, generates AML1-ETO fusion proteins. Previous analyses have demonstrated that full-length AML1-ETO blocks AML1 function and requires additional mutagenic events to promote leukemia. More recently, we have identified an alternatively spliced form of AML1-ETO, AML1-ETO9a, from t(8;21) acute myeloid leukemia (AML) patient ...

  17. CNS Involvement in AML Patient Treated with 5-Azacytidine

    Diamantina Vasilatou; Sotirios Papageorgiou; Efthymia Bazani; Athina Prasouli; Christina Economopoulou; Christoforos Roumpakis; Petros Karakitsos; George Dimitriadis; Vasiliki Pappa


    Central nervous system (CNS) involvement in acute myeloid leukemia (AML) is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.

  18. CNS Involvement in AML Patient Treated with 5-Azacytidine.

    Vasilatou, Diamantina; Papageorgiou, Sotirios; Bazani, Efthymia; Prasouli, Athina; Economopoulou, Christina; Roumpakis, Christoforos; Karakitsos, Petros; Dimitriadis, George; Pappa, Vasiliki


    Central nervous system (CNS) involvement in acute myeloid leukemia (AML) is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status. PMID:25197583

  19. CNS Involvement in AML Patient Treated with 5-Azacytidine

    Vasilatou, Diamantina; Papageorgiou, Sotirios; Bazani, Efthymia; Prasouli, Athina; Economopoulou, Christina; Roumpakis, Christoforos; Karakitsos, Petros; Dimitriadis, George; Pappa, Vasiliki


    Central nervous system (CNS) involvement in acute myeloid leukemia (AML) is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status. PMID:25197583

  20. Nassi-Schneiderman Diagram in HTML Based on AML

    Menyhárt, László


    In an earlier work I defined an extension of XML called Algorithm Markup Language (AML) for easy and understandable coding in an IDE which supports XML editing (e.g. NetBeans). The AML extension contains annotations and native language (English or Hungarian) tag names used when coding our algorithm. This paper presents a drawing tool with which…

  1. Stem cell expression of the AML1/ETO fusion protein induces a myeloproliferative disorder in mice

    Fenske, Timothy S; Pengue, Gina; Mathews, Vikram; Hanson, Piia T.; Hamm, Sarah E.; Riaz, Noor; Graubert, Timothy A


    The t(8;21)(q22;q22) translocation, present in 10-15% of acute myeloid leukemia (AML) cases, generates the AML1/ETO fusion protein. To study the role of AML1/ETO in the pathogenesis of AML, we used the Ly6A locus that encodes the well characterized hematopoietic stem cell marker, Sca1, to target expression of AML1/ETO to the hematopoietic stem cell compartment in mice. Whereas germ-line expression of AML1/ETO from the AML1 promoter results in embryonic lethality, heterozygous Sca1+/AML1-ETO i...

  2. The Mice Drawer System Tissue Sharing Program (MDS-TSP)

    Biticchi, Roberta; Cancedda, Ranieri; Cilli, Michele; Cotronei, Vittorio; Costa, Delfina; Liu, Yi; Piccardi, Federica; Pignataro, Salvatore; Ruggiu, Alessandra; Tasso, Roberta; Tavella, Sara

    Several organs and apparatus are affected by weightless conditions and in particular by the weightless experienced during space flights. Therefore space missions are good opportunities to investigate in a whole organism the controlling cellular and molecular mechanisms. For this type of studies mice represent an excellent animal model for several reasons: reduced body size, relatively short time needed to reach adulthood, availability of strains with different genetic background and of different transgenic lines, etc. In line with the International Space Station (ISS) development, the Italian Space Agency (ASI) contracted Thales Alenia Space Italia, the largest Italian aerospace industry, to design and build a spaceflight payload for rodent research on ISS, the Mouse Drawer System (MDS -see abstract P. Cipparelli et al.). This payload meets NIH guideline for several physical parameters to maintain 6 animals in good health conditions in a space environment. Given the interest of our laboratory in the microgravity induced skeleton alterations, we focused our attention on transgenic mice over-expressing pleiotrophin (PTN) under the control of the human bone specific osteocalcin promoter. This protein is a heparin-binding cytokine with different functions. PTN is expressed by the cells in an early differentiation stage and is upregulated in tissue injury and wound repair. PTN is specifically involved in bone formation, neurite outgrowth and angiogenesis. As PTN-transgenic mice show an increased bone mass and mineralization, we decided to use this mouse model in the flight experiment and to study its potential role in counteracting bone loss in microgravity. Not all mouse strains are equally suitable for flight. After preliminary tests in the MDS breadboard at our animal facility on the behavior of different mouse strains, PTN-transgenic mice originally obtained in the BDF strain were backcrossed in the C57Bl/J10 strain before being used in this study. In order to

  3. Hematopoietic organ tumors post exposure and AML1 transcription factor

    This review describes the functions of AML1 transcription factor (tf) in hemopoiesis and the mechanism of hematopoietic organ tumorigenesis related with the product of chimaeric AML1 gene caused by chromosomal translocation and with AML1 mutation. Abnormality of AML1 (RUNX1) tf, an important factor for development and maintenance of hemopoiesis, is a representative cause of leukemia and is shown to be frequently observed in hematopoietic organ tumors of A-bomb survivors and radiation- and anticancer agent-treated patients. The dimmer via β-subunit (CDFβ) of AML1 product binds to DNA and functions at the budding of adult-type hematopoietic stem cells from aortic endothelial cells. Point mutations of AML1 are recognized in 46% A-bomb survivors with marrow dysplastic syndrome. Their distance from the explosion site is mostly 1.5-2.7 km and their exposure dose is low. Since histone acetylation is a key for hematopoietic cell tumorigenesis and differentiation by chimaeric AML/ETO tf, agent to control its activity is a target strategy for a new treatment. For this, analysis is important in such models as conditional knock-in mice. (K.H.)

  4. Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells.

    Geyh, S; Oz, S; Cadeddu, R-P; Fröbel, J; Brückner, B; Kündgen, A; Fenk, R; Bruns, I; Zilkens, C; Hermsen, D; Gattermann, N; Kobbe, G; Germing, U; Lyko, F; Haas, R; Schroeder, T


    Ineffective hematopoiesis is a major characteristic of myelodysplastic syndromes (MDS) causing relevant morbidity and mortality. Mesenchymal stromal cells (MSC) have been shown to physiologically support hematopoiesis, but their contribution to the pathogenesis of MDS remains elusive. We show that MSC from patients across all MDS subtypes (n=106) exhibit significantly reduced growth and proliferative capacities accompanied by premature replicative senescence. Osteogenic differentiation was significantly reduced in MDS-derived MSC, indicated by cytochemical stainings and reduced expressions of Osterix and Osteocalcin. This was associated with specific methylation patterns that clearly separated MDS-MSC from healthy controls and showed a strong enrichment for biological processes associated with cellular phenotypes and transcriptional regulation. Furthermore, in MDS-MSC, we detected altered expression of key molecules involved in the interaction with hematopoietic stem and progenitor cells (HSPC), in particular Osteopontin, Jagged1, Kit-ligand and Angiopoietin as well as several chemokines. Functionally, this translated into a significantly diminished ability of MDS-derived MSC to support CD34+ HSPC in long-term culture-initiating cell assays associated with a reduced cell cycle activity. Taken together, our comprehensive analysis shows that MSC from all MDS subtypes are structurally, epigenetically and functionally altered, which leads to impaired stromal support and seems to contribute to deficient hematopoiesis in MDS. PMID:23797473

  5. Safety Study of AG-120 or AG-221 in Combination With Induction and Consolidation Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia With an IDH1 and/or IDH2 Mutation


    Newly Diagnosed Acute Myeloid Leukemia (AML); Untreated AML; AML Arising From Myelodysplastic Syndrome (MDS); AML Arising From Antecedent Hematologic Disorder (AHD); AML Arising After Exposure to Genotoxic Injury

  6. Trisomy 8 in Pediatric Acute Myeloid Leukemia. A NOPHO-AML Study

    Laursen, Anne Cathrine Lund; Sandahl, Julie Damgaard; Kjeldsen, Eigil;


    Trisomy 8 (+8) is a common cytogenetic aberration in acute myeloid leukemia (AML); however, the impact of +8 in pediatric AML is largely unknown. We retrospectively investigated 609 patients from the NOPHO-AML database to determine the clinical and cytogenetic characteristics of +8 in pediatric AML...

  7. Measuring depression in nursing home residents with the MDS and GDS: an observational psychometric study

    Fries Brant E


    Full Text Available Abstract Background The objective of this study was to examine the Minimum Data Set (MDS and Geriatric Depression Scale (GDS as measures of depression among nursing home residents. Methods The data for this study were baseline, pre-intervention assessment data from a research study involving nine nursing homes and 704 residents in Massachusetts. Trained research nurses assessed residents using the MDS and the GDS 15-item version. Demographic, psychiatric, and cognitive data were obtained using the MDS. Level of depression was operationalized as: (1 a sum of the MDS Depression items; (2 the MDS Depression Rating Scale; (3 the 15-item GDS; and (4 the five-item GDS. We compared missing data, floor effects, means, internal consistency reliability, scale score correlation, and ability to identify residents with conspicuous depression (chart diagnosis or use of antidepressant across cognitive impairment strata. Results The GDS and MDS Depression scales were uncorrelated. Nevertheless, both MDS and GDS measures demonstrated adequate internal consistency reliability. The MDS suggested greater depression among those with cognitive impairment, whereas the GDS suggested a more severe depression among those with better cognitive functioning. The GDS was limited by missing data; the DRS by a larger floor effect. The DRS was more strongly correlated with conspicuous depression, but only among those with cognitive impairment. Conclusions The MDS Depression items and GDS identify different elements of depression. This may be due to differences in the manifest symptom content and/or the self-report nature of the GDS versus the observer-rated MDS. Our findings suggest that the GDS and the MDS are not interchangeable measures of depression.

  8. Genomic, immunophenotypic, and NPM1/FLT3 mutational studies on 17 patients with normal karyotype acute myeloid leukemia (AML) followed by aberrant karyotype AML at relapse.

    Wang, Eunice S; Sait, Sheila N J; Gold, David; Mashtare, Terry; Starostik, Petr; Ford, Laurie Ann; Wetzler, Meir; Nowak, Norma J; Deeb, George


    Normal karyotype (NK) is the most common cytogenetic group in acute myeloid leukemia (AML) diagnosis; however, up to 50% of these patients at relapse will have aberrant karyotype (AK) AML. To determine the etiology of relapsed AK AML cells, we evaluated cytogenetic, immunophenotypic, and molecular results of 17 patients with diagnostic NK AML and relapsed AK AML at our institute. AK AML karyotype was diverse, involving no favorable and largely (8 of 17) complex cytogenetics. Despite clear cytogenetic differences, immunophenotype and NPM1/FLT3 gene mutation status did not change between presentation and relapse in 83% (10 of 12) and 94% (15 of 16) cases, respectively. High-resolution array-based comparative genomic hybridization (aCGH) performed via paired aCGH on NK AML and AK AML samples from the same patient confirmed cytogenetic aberrations only in the relapse sample. Analysis of 16 additional diagnostic NK AML samples revealed no evidence of submicroscopic aberrations undetected by conventional cytogenetics in any case. These results favor evolution of NK AML leukemia cells with acquisition of novel genetic changes as the most common etiology of AK AML relapse as opposed to secondary leukemogenesis. Additional studies are needed to confirm whether AK AML cells represent selection of rare preexisting clones below aCGH detection and to further characterize the molecular lesions found at time of AK AML relapse. PMID:20875872

  9. CNS Involvement in AML Patient Treated with 5-Azacytidine

    Diamantina Vasilatou


    Full Text Available Central nervous system (CNS involvement in acute myeloid leukemia (AML is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.

  10. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed;


    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction ......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  11. New q-ary quantum MDS codes with distances bigger than q/2

    He, Xianmang; Xu, Liqing; Chen, Hao


    The construction of quantum MDS codes has been studied by many authors. We refer to the table in page 1482 of (IEEE Trans Inf Theory 61(3):1474-1484, 2015) for known constructions. However, there have been constructed only a few q-ary quantum MDS [[n,n-2d+2,d

  12. New q-ary quantum MDS codes with distances bigger than q/2

    He, Xianmang; Xu, Liqing; Chen, Hao


    The construction of quantum MDS codes has been studied by many authors. We refer to the table in page 1482 of (IEEE Trans Inf Theory 61(3):1474-1484, 2015) for known constructions. However, there have been constructed only a few q-ary quantum MDS [[n,n-2d+2,d

  13. Measurement of Radiation Belt Partcles by MDS-1 Onboard SEDA

    Matsumoto, H.; Koshiishi, H.; Goka, T.

    The Space Environment Data Acquisition Equipment (SEDA) is on board the Mission Demonstration Test Satellite-1 (MDS-1) to measure the radiation environment, which was launched into geo-stationary transfer orbit (GTO) on February 4, 2002 with an apogee of about 35,700km, a perigee of about 500 km and an inclination of about 28.5 degrees. SEDA consists of the four instruments. Standard Dose Monitor monitors the electron and proton flux. Dosimeter measures the integrated radiation dose at fifty-six points of the satellite. Heavy Ion Telescope monitors the flux of heavy ions from He to Fe. Magnetometer measures the magnetic field in the magnetosphere. In this paper are described first results and comparison with the ISO standard model for the space environment

  14. Incidence and prevalence of myelodysplastic syndromes: data from the Düsseldorf MDS-registry.

    Neukirchen, Judith; Schoonen, Wilma M; Strupp, Corinna; Gattermann, Norbert; Aul, Carlo; Haas, Rainer; Germing, Ulrich


    Population-based data on patients with MDS are scarce. Here we report the incidence and prevalence of MDS based on data from the Düsseldorf MDS Registry. Cases in the city of Düsseldorf in the study period were identified from the MDS Registry. We calculated crude, calendar-year, age- and sex-specific and European Standard Population age-standardized incidence rates as well as point prevalences per 100,000 The crude incidence rate was 4.15/100,000/year and the point prevalence per 100,000 persons of 7. We found that the incidence and prevalence of MDS was higher in men than women and increased sharply with increasing age. PMID:21708407

  15. Spatial Clustering of MDS in the Seattle-Puget Sound Region

    Ross, Michelle E; Wakefield, Jon; Davis, Scott; De Roos, Anneclaire J


    OBJECTIVES Incidence of myelodysplastic syndromes (MDS) has been described in the United States since its inclusion in the Surveillance, Epidemiology, and End Results program in 2001, and the Seattle-Puget Sound region of Washington State has among the highest rates of the registries. In this investigation, we described small-scale incidence patterns of MDS within the Seattle-Puget Sound region from 2002 to 2006 and identified potential spatial clusters to inform planning of future studies of MDS etiology. METHODS We used a spatial disease mapping model to estimate smoothed relative risks for each census tract and to describe the spatial component of variability in the incidence rates. We also used two methods to describe the location of potential MDS clusters: the approach of Besag and Newell and the Kulldorff spatial scan statistic. RESULTS Our findings from all three approaches indicated the most likely areas of increased MDS incidence were located on Whidbey Island in Island County. CONCLUSION Interpretation is limited because our data are based on the residential location of the MDS case only at the time of diagnosis. Nevertheless, inclusion of identified cluster regions in future population-based research and investigation of individual-level exposures could shed light on environmental risk factors for MDS. PMID:20101455

  16. The AML1/ETO fusion protein activates transcription of BCL-2

    Klampfer, Lidija; Zhang, Jin; Zelenetz, Andrew O.; Uchida, Hideo; Nimer, Stephen D.


    The AML1 gene, located on chromosome 21, is involved in several distinct chromosomal translocations in human leukemia. In t(8;21) acute myelogenous leukemia (AML), the AML1 gene is juxtaposed to the ETO gene located on chromosome 8, generating an AML1/ETO fusion protein. Both AML1/ETO and the AML1 proteins recognize the same consensus DNA-binding motif (TGT/CGGT), which is found in the promoters of several genes involved in hematopoiesis. We found that two myeloid ...

  17. Osteolytic Bone Lesions – A Rare Presentation of AML M6

    N. Geetha; Sreelesh, K.P.; Priya, M. J.; Lali, V.S.; N. Rekha


    Acute myeloid leukemia (AML) M6 is a rare form of AML accounting for < 5 % of all AML. Extramedullary involvement is very rarely seen in this entity. Skeletal lesion has not been described in AML M6 before. We discuss the case of a 17 year old boy with AML M6, who presented with osteolytic lesion of right humerus. He was treated with induction and consolidation chemotherapy. The present case is the first report in literature of AML M6 presenting with skeletal lesions.


    Francesco D'Alò


    Full Text Available Acute myeloid leukemia (AML is a clonal disorder of the hematopoietic stem cell, typical of the elderly, with a median age of over 60 years at diagnosis. In AML, older age is one of the strongest independent adverse prognostic factor, associated with decreased complete response rate, worse disease-free and overall survival, with highest rates of treatment related mortality, resistant disease and relapse, compared to younger patients. While clinical risk factors do not significantly differ between older and younger patients, outcomes are compromised in elderly patients not only by increased comorbidities and susceptibility to toxicity from therapy, but it is now recognized that elderly AML represents a biologically distinct disease, that is itself more aggressive and less responsive to therapy. In elderly individuals prolonged exposure to environmental carcinogens may be the basis for the aggressive biology of the disease. This may also be the basis for similarities between elderly AML and therapy-related myeloid malignancies, mimicking toxic effects of previous cytotoxic treatments on hematopoietic stem cells. Age is itself a risk factor for t-MN, which are more frequent in elderly patients, where also a shorter latency between treatment of primary tumor and t-MN has been reported. Similarities between therapy-related malignancies and elderly AML include morphological aspects, as the presence of multilineage dysplasia preceding and/or concomitant to the development of leukemia, and adverse cytogenetics, including poor karyotype and chromosome 5 and/or 7 abnormalities. Looking at molecular prognosticators in elderly AML, similar to t-MN,  reduced frequency of favorable factors, as reduced number of NPM1 and CEBPA mutated cases has been observed, together with increased incidence of negative factors, as increased MDR1 expression, accelerated telomere shortening  and frequency of methylation changes. Given the unfavorable prognosis of elderly and

  19. Ten uncommon and unusual variants of renal angiomyolipoma (AML): radiologic–pathologic correlation

    Classic (triphasic) renal angiomyolipoma (AML) is currently classified as a neoplasm of perivascular epithelioid cells. For diagnosis of AML, the use of thin-section non-contrast enhanced CT (NECT) improves diagnostic accuracy; however, identifying gross fat within a very small AML is challenging and often better performed with chemical-shift MRI. Although the presence of gross intra-tumoural fat is essentially diagnostic of AML; co-existing intra-tumoural fat and calcification may represent renal cell carcinoma (RCC). Differentiating AML from retroperitoneal sarcoma can be difficult when AML is large; the feeding vessel and claw signs are suggestive imaging findings. AML can haemorrhage, with intra-tumoural aneurysm size >5 mm a more specific predictor of future haemorrhage than tumor size >4 cm. Diagnosis of AML in the setting of acute haemorrhage is complex; comparison studies or follow-up imaging may be required. Not all AML contain gross fat and imaging features of AML without visible fat overlap with RCC; however, homogeneity, hyperdensity at NECT, low T2-weighted signal intensity and, microscopic fat are suggestive features. Patients with tuberous sclerosis often demonstrate a combination of classic and minimal fat AML, but are also at a slightly increased risk for RCC and should be imaged cautiously. Several rare pathological variants of AML exist including AML with epithelial cysts and epithelioid AML, which have distinct imaging characteristics. Classic AML, although benign, can be locally invasive and the rare epithelioid AML can be frankly malignant. The purpose of this review is to highlight the imaging manifestations of 10 uncommon and unusual variants of AML using pathological correlation

  20. I-123 based development program at MDS Nordion

    Ultra-pure iodine-123 (>99.8% radionuclide purity) has been produced by the irradiation of enriched xenon-124 (99.8%) on external beam lines of CP-42 and TR-30 cyclotrons. Typically, an incident proton energy of 24-30 MeV has resulted in a yield of 6.6 mCi/μAh at the end of processing (end of bombardment + 9h). The largest quantity of iodine-123 produced on a single run has been 12 Ci. The availability of large quantities of ultra-pure I-123 and reliable production four to five times per week has led to a vibrant radiopharmaceutical programme based on I-123. Currently, a number of pharmaceuticals have been licensed in Canada or are undergoing clinical trials in the United States. MDS Nordion has state of the art facilities such as Class 100 Isolators in Class 10,000 Clean Rooms for aseptic filling operations and has developed expertise in Ci scale labelling operations. (author)


    Mazyar Shadman


    Full Text Available The incidence of myeloid malignancies, including myelodysplastic syndromes (MDS increases with age. While several therapeutic modalities have been developed, for most of these patients the only treatment with curative potential is allogeneic hematopoietic cell transplantation (HCT. The development of reduced/low intensity transplant conditioning regimens allows to successfully transplant patients in their ‘60s and even ‘70s, although comorbidities may determine who does come to transplantation and who does not. Also, as many as half of the patients will develop graft versus host disease (GVHD, even with HLA matched  donors, requiring therapy for extended periods of time,  and GVHD and treatment  with glucocorticoids is likely to impact the quality  of life. Nevertheless, dependent upon disease stage at HCT, the presence of comorbidities and the regimen used, 30% to 50% of patients  60 years of age or older, may survive long-term cured of their disease. Future studies should focus on the incorporation of non-transplant modalities into the overall transplant approach, the prevention of GVHD, and the utilization of immunotherapy to reduce the incidence of relapse and GVHD and further improve overall transplant success.

  2. MDS-Multifunctional Dynamometer for Application in Space

    Adamcik, G.; Barta, N.; Talla, R.; Angeli, T.; Kozlovskaya, I. B.; Grigoriev, A. I.; Tschan, H.; Bachl, N.


    The project MDS (Multifunctional Dynamometer for Application in Space) is an international collaboration of the University of Vienna (Faculty of Sport Science, Department of Sport and Exercise Physiology), the Russian Academy of Sciences (Institute of Biomedical Problems) and the Technical University of Vienna (Institute for Engineering Design and Logistics Engineering) with the aim to develop a training and diagnostic device that counteracts the muscle and bone loss during long term space flights. Due to the scientific results of the last years research in space medicine, it is well known, that the muscles and bones of the lower extremities and the trunk are most affected by the atrophy. Based on this knowledge a various number of resistance exercises can be done in order to train the muscles of these parts of the body and to increase the efficiency of the training by intra- and intermuscular coordination. The resisting power for the training is provided by an electric motor, thereby force, position and speed of the training can be well-regulated for different training modes.

  3. MDS 3.0 for Nursing Homes and Swing Bed Providers

    U.S. Department of Health & Human Services — The MDS is a powerful tool for implementing standardized assessment and for facilitating care management in nursing homes (NHs) and non-critical access hospital...

  4. Energetic particle cross-field diffusion: Interaction with Magnetic Decreases (MDs

    B. T. Tsurutani


    Full Text Available Magnetic field Decreases (MDs are detected in the heliospheric polar regions. The MDs have minimum spatial scales sizes of 25 proton thermal gyroradii, and are typically bounded by tangential or rotational discontinuities. The distribution of the magnitudes of the decreases within AIDs is a continuum, with the smallest decreases being most frequent in occurrence. The largest decreases can be 80% of the ambient field. The thickness distribution is also a continuum, and is shown to be independent of the field magnitude decrease. Charged particle interactions with the MDs lead to particle guiding center displacements and hence particle cross-held diffusion. We develop a diffusion model to apply to energetic ion interactions with MDs using the MD properties described in this paper. One specific day of data is used to illustrate that the particle cross-field diffusion will be extremely rapid due to such interactions.

  5. 分布式操作系统MDS/DOS的设计与实现%Design and Implementation of the Distributed Operating System MDS/DOS

    何炎祥; 刘蓬



  6. [Treatment outcome for myelodysplastic syndromes (MDS) obtained by the Polish Children's Leukemia/Lymphoma Study Group].

    Chybicka, A; Kołecki, P; Pietras, W; Bogusławska-Jaworska, J; Wójcik, D; Armata, J; Eliasińska, A; Kowalczyk, J; Jackowska, T; Klus, K; Matysiak, M; Krauze, A; Stefańska, K; Rokicka-Milewska, R; Wiśniewska-Slusarz, H


    Fourty children with MDS treated in seven centres of The Polish Children's Leukemia Lymphoma Study Group in period 1975-1998y were included to the study. In 16 children RAEB-T, in 2 CMML in 10 RA and in 12 RAEB were diagnosed. Our and literature data showed that BMT is the best therapy for children with MDS. For children, who don't have a donor for BMT. Roacutan therapy seems to be the most effective. PMID:9686518

  7. Schattenwirtschaft und Arbeitsplatzbeschaffung

    Merz, Joachim


    Ziel dieser Studie ist die empirisch fundierte Auseinandersetzung mit dem Thema Schattenwirtschaft und Arbeitsplatzschaffung. Die hier aufgefächerte Diskussion des Themas in Wirtschaft, Sozialpolitik und Gesellschaft, der weitere Diskurs und die empirische Fundierung erfordern eine klare und dann folgende begriffliche Abgrenzung der Schattenwirtschaft. Argumente der Diskussion zu Ursachen und positiven und negativen Wirkungen der Schattenwirtschaft auf die Arbeitsplatzbeschaffung werden im An...

  8. AML cells are differentially sensitive to chemotherapy treatment in a human xenograft model

    Wunderlich, Mark; Mizukawa, Benjamin; Chou, Fu-Sheng; Sexton, Christina; Shrestha, Mahesh; Saunthararajah, Yogen; Mulloy, James C.


    A relevant xenograft chemotherapy model was developed by using standard AML induction therapy drugs and primary human AML patient samples.Human AML cells show significantly increased sensitivity to in vivo chemotherapy treatment compared with murine LSK and total bone marrow cells.

  9. AML1/RUNX1 Phosphorylation by Cyclin-Dependent Kinases Regulates the Degradation of AML1/RUNX1 by the Anaphase-Promoting Complex‡

    Biggs, Joseph R.; Peterson, Luke F.; Zhang, Youhong; Kraft, Andrew S.; Zhang, Dong-Er


    AML1 (RUNX1) regulates hematopoiesis, angiogenesis, muscle function, and neurogenesis. Previous studies have shown that phosphorylation of AML1, particularly at serines 276 and 303, affects its transcriptional activation. Here, we report that phosphorylation of AML1 serines 276 and 303 can be blocked in vivo by inhibitors of the cyclin-dependent kinases (CDKs) Cdk1 and Cdk2. Furthermore, these residues can be phosphorylated in vitro by purified Cdk1/cyclin B and Cdk2/cyclin A. Mutant AML1 pro...

  10. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy

    Bruedigam, Claudia; Bagger, Frederik Otzen; Heidel, Florian H.;


    priority. Here, we show that targeting telomerase activity eradicates AML LSCs. Genetic deletion of the telomerase subunit Terc in a retroviral mouse AML model induces cell-cycle arrest and apoptosis of LSCs, and depletion of telomerase-deficient LSCs is partially rescued by p53 knockdown. Murine Terc......(-/-) LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia...... progression, and delays relapse following chemotherapy. Altogether, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs....

  11. Osteolytic bone lesions – A rare presentation of AML M6.

    Geetha N.


    Full Text Available Acute myeloid leukemia (AML M6 is a rare form of AML  accounting  for < 5 % of all AML.  Extramedullary involvement  is very rarely seen in this entity.  Skeletal lesion has not been described in AML M6 before. We discuss the case of  a 17 year old boy with AML M6 who presented with  osteolytic lesion of right humerus.  He was treated with  induction and consolidation chemotherapy. The present case is the first report in literature of AML M6 presenting with skeletal lesions.

  12. Cell Type Dependent Regulation of Multidrug Resistance-1 Gene Expression by AML1-ETO

    Hines, Robert; Boyapati, Anita; Zhang, Dong-Er


    The AML1-ETO fusion protein is generated from the 8;21 chromosome translocation that is commonly identified in acute myeloid leukemia. AML1-ETO is a DNA binding transcription factor and has been demonstrated to play a critical role in promoting leukemogenesis. Therefore, it is important to define the molecular mechanism of AML1-ETO in the regulation of gene expression. Here, we report that the effect of AML1-ETO on the promoter of multidrug resistance-1 (MDR1) gene, a known AML1-ETO target, i...

  13. Osteolytic bone lesions – A rare presentation of AML M6.

    Geetha N; Sreelesh KP; Priya Mary Jacob; Lali VS; Rekha A Nair


    Acute myeloid leukemia (AML) M6 is a rare form of AML  accounting  for < 5 % of all AML.  Extramedullary involvement  is very rarely seen in this entity.  Skeletal lesion has not been described in AML M6 before. We discuss the case of  a 17 year old boy with AML M6 who presented with  osteolytic lesion of right humerus.  He was treated with  induction and consolidation chemotherapy. The present case is the first report in literature of AML M6 presenting with skeletal lesions.

  14. In vivo consequences of AML1-ETO fusion protein expression for hematopoiesis

    Cabezas Wallscheid, Nina


    The t(8;21) (q22;q22) translocation fusing the ETO (also known as MTG8) gene on human chromosome 8 with the AML1 (also called Runx1 or CBFα) gene on chromosome 21 is one of the most common genetic aberrations found in acute myeloid leukemia (AML). This chromosomal translocation occurs in 12 % of de novo AML cases and in up to 40 % of the AML-M2 subtype of the French-American-British classification. To date, the in vivo function of aberrant AML1-ETO fusion protein expression has been investig...

  15. Dichotomy of AML1-ETO Functions: Growth Arrest versus Block of Differentiation†

    Burel, Sebastien A.; Harakawa, Nari; Zhou, Liming; Pabst, Thomas; Tenen, Daniel G.; Zhang, Dong-Er


    The fusion gene AML1-ETO is the product of t(8;21)(q22;q22), one of the most common chromosomal translocations associated with acute myeloid leukemia. To investigate the impact of AML1-ETO on hematopoiesis, tetracycline-inducible AML1-ETO-expressing cell lines were generated using myeloid cells. AML1-ETO is tightly and strongly induced upon tetracycline withdrawal. The proliferation of AML1-ETO+ cells was markedly reduced, and most of the cells eventually underwent apoptosis. RNase protection...

  16. The t(8;21) fusion protein interferes with AML-1B-dependent transcriptional activation.

    Meyers, S; Lenny, N; Hiebert, S W


    The AML-1/CBF beta transcription factor complex is targeted by both the t(8;21) and the inv(16) chromosomal alterations, which are frequently observed in acute myelogenous leukemia. AML-1 is a site-specific DNA-binding protein that recognizes the enhancer core motif TGTGGT. The t(8;21) translocation fuses the first 177 amino acids of AML-1 to MTG8 (also known as ETO), generating a chimeric protein that retains the DNA-binding domain of AML-1. Analysis of endogenous AML-1 DNA-binding complexes...

  17. [Results of the treatment of myelodysplastic syndrome (MDS)obtained by the Polish Paediatric Leukaemia /Lymphoma Study Group].

    Chybicka, A; Wójcik, D; Pietras, W; Bogusławska-Jaworska, J; Kolecki, P; Balcerska, A; Balwierz, W; Bubała, H; Eliasinska, A; Kowalczyk, J; Jackowska, T; Klus, K; Krenke, K; Kurylak, A; Malinowska, I; Matysiak, M; Stefańska, K; Stefaniak, M J; Rokicka-Milewska, R; Wiśniewska-Slusarz, H; Sońta-Jakimczyk, D; Wysocki, M


    Sixty children with MDS treated in six centres of the Polish Paediatric Leukaemia/Lymphoma Study Group in the period 1975-1999 were included in the study. In 20 children RAEB-T, in 13 RA, in 21 RAEB and in 6 CMML were diagnosed. Our own and literature data showed that BMT is the best therapy for children with MDS. We need a new comprehensive protocol for the diagnosis and treatment of children with MDS in Poland. PMID:12021466

  18. Physical properties of Kentucky's AML landslides: Case studies analyzed

    Once an abandoned mined land (AML) landslide occurs and is identified as an emergency, engineers must rapidly implement a slope stabilization design. Correct slope remediation solutions are generally derived from well-executed geotechnical examinations. This paper summarizes a large body of geotechnical data compiled by the US office of Surface Mining Reclamation and Enforcement (OSM) from AML landslides in eastern Kentucky. Special attention is placed on the examination of subsurface failures, phreatic water levels, soil profiles, and soil composition information from numerous borehole exploration programs. Strength properties calculated from laboratory procedures and stability analysis techniques were also reviewed. Laboratory-determined soil shear strength values were found to be higher than those inferred from stability analysis. This suggests that postfailure determinations of the phreatic surface may be largely inappropriate when used in stability analysis or that laboratory-measured shear strengths are ineffective in replicating in situ colluvium/spoil slope properties

  19. Cloning of chicken AML1-EVI-1 fusion protein

    Balková, Simona; Buchtová, Marcela; Matalová, Eva; Míšek, Ivan

    Plzeň, 2009. s. 42-42. [Morphology 2009. 45th International Congress on Anatomy and 46th Lojda symposium on Histochemy. 07.09.2009-09.09.2009, Plzeň] R&D Projects: GA ČR GA304/09/0725 Institutional research plan: CEZ:AV0Z50450515 Keywords : AML-1-EVI-1 * cloning Subject RIV: EG - Zoology

  20. AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations

    Yuan, Youzhong; Zhou, Liming; Miyamoto, Toshihiro; Iwasaki, Hiromi; Harakawa, Nari; Hetherington, Christopher J.; Burel, Sebastien A.; Lagasse, Eric; Weissman, Irving L.; Akashi, Koichi; Zhang, Dong-Er


    The t(8;21) is one of the most frequent chromosomal abnormalities associated with acute myeloid leukemia (AML). The translocation, which involves the AML1 gene on chromosome 21 and the ETO gene on chromosome 8, generates an AML1-ETO fusion transcription factor. To examine the effect of the AML1-ETO fusion protein on leukemogenesis, we made transgenic mice in which expression of AML1-ETO is under the control of the human MRP8 promoter (hMRP8-AML1-ETO). AML1-ETO is specifically expressed in mye...

  1. AML1/RUNX1 Works as a Negative Regulator of c-Mpl in Hematopoietic Stem Cells*

    Satoh, Yusuke; Matsumura, Itaru; Tanaka, Hirokazu; Ezoe, Sachiko; Fukushima, Kentaro; Tokunaga, Masahiro; Yasumi, Masato; Shibayama, Hirohiko; Mizuki, Masao; Era, Takumi; Okuda, Tsukasa; Kanakura, Yuzuru


    In this study, we analyzed the roles for AML1/RUNX1 in the regulation of the c-mpl promoter. Wild-type AML1 activated the c-mpl promoter through the proximal AML-binding site in luciferase assays using 293T and HeLa cells. In accord with this result, electrophoretic mobility shift assay and chromatin immunoprecipitation assays demonstrated that AML1 bound to this site. Next, we analyzed the function of AML1 using a mutant of AML1 lacking the C terminus (AML1dC), which ...

  2. Reduced-intensity conditioned allogeneic SCT in adults with AML.

    Reshef, R; Porter, D L


    AML is currently the most common indication for reduced-intensity conditioned (RIC) allo-SCT. Reduced-intensity regimens allow a potent GVL response to occur with minimized treatment-related toxicity in patients of older age or with comorbidities that preclude the use of myeloablative conditioning. Whether RIC SCT is appropriate for younger and more standard risk patients is not well defined and the field is changing rapidly; a prospective randomized trial of myeloablative vs RIC (BMT-CTN 0901) was recently closed when early results indicated better outcomes for myeloablative regimens. However, detailed results are not available, and all patients in that study were eligible for myeloablative conditioning. RIC transplants will likely remain the standard of care as many patients with AML are not eligible for myeloablative conditioning. Recent publication of mature results from retrospective and prospective cohorts provide contemporary efficacy and toxicity data for these attenuated regimens. In addition, recent studies explore the use of alternative donors, introduce regimens that attempt to reduce toxicity without reducing intensity, and identify predictive factors that pave the way to personalized approaches. These studies paint a picture of the future of RIC transplants. Here we review the current status of RIC allogeneic SCT in AML. PMID:25730186

  3. Point mutation in AML1 disrupts subnuclear targeting, prevents myeloid differentiation, and effects a transformation-like phenotype

    Vradii, Diana; Zaidi, Sayyed K.; Lian, Jane B.; van Wijnen, Andre J; Stein, Janet L.; Stein, Gary S.


    The multifunctional C terminus of the hematopoietic AML1 transcription factor interacts with coregulatory proteins, supports the convergence and integration of physiological signals, and contains the nuclear matrix targeting signal, the protein motif that is necessary and sufficient to target AML1 to subnuclear sites. The (8;21) chromosomal translocation, which replaces the C terminus of AML1 with the ETO protein, modifies subnuclear targeting of AML1 in acute myeloid leukemia (AML) and resul...

  4. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed;


    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction...... with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  5. Improved survival in MDS patients receiving iron chelation therapy - a matched pair analysis of 188 patients from the Düsseldorf MDS registry.

    Neukirchen, Judith; Fox, Frank; Kündgen, Andrea; Nachtkamp, Kathrin; Strupp, Corinna; Haas, Rainer; Germing, Ulrich; Gattermann, Norbert


    MDS patients are prone to develop transfusional iron overload. Iron overload may partly explain why transfusion dependency is associated with a decreased likelihood of survival. Our matched-pair analysis included 94 patients on long-term chelation therapy and 94 matched patients without it. All patients had iron overload, defined as serum ferritin (SF) above 1000 ng/ml or a history of multiple transfusions and SF ≥ 500 ng/ml. Median SF was 1954 ng/ml in chelated and 875 ng/ml in non-chelated patients. The difference in median survival (74 vs. 49 months, respectively; p=0.002) supports the idea that iron chelation therapy is beneficial for MDS patients. PMID:22564985

  6. Transcriptome Profiling of Pediatric Core Binding Factor AML.

    Chih-Hao Hsu

    Full Text Available The t(8;21 and Inv(16 translocations disrupt the normal function of core binding factors alpha (CBFA and beta (CBFB, respectively. These translocations represent two of the most common genomic abnormalities in acute myeloid leukemia (AML patients, occurring in approximately 25% pediatric and 15% of adult with this malignancy. Both translocations are associated with favorable clinical outcomes after intensive chemotherapy, and given the perceived mechanistic similarities, patients with these translocations are frequently referred to as having CBF-AML. It remains uncertain as to whether, collectively, these translocations are mechanistically the same or impact different pathways in subtle ways that have both biological and clinical significance. Therefore, we used transcriptome sequencing (RNA-seq to investigate the similarities and differences in genes and pathways between these subtypes of pediatric AMLs. Diagnostic RNA from patients with t(8;21 (N = 17, Inv(16 (N = 14, and normal karyotype (NK, N = 33 were subjected to RNA-seq. Analyses compared the transcriptomes across these three cytogenetic subtypes, using the NK cohort as the control. A total of 1291 genes in t(8;21 and 474 genes in Inv(16 were differentially expressed relative to the NK controls, with 198 genes differentially expressed in both subtypes. The majority of these genes (175/198; binomial test p-value < 10(-30 are consistent in expression changes among the two subtypes suggesting the expression profiles are more similar between the CBF cohorts than in the NK cohort. Our analysis also revealed alternative splicing events (ASEs differentially expressed across subtypes, with 337 t(8;21-specific and 407 Inv(16-specific ASEs detected, the majority of which were acetylated proteins (p = 1.5 x 10(-51 and p = 1.8 x 10(-54 for the two subsets. In addition to known fusions, we identified and verified 16 de novo fusions in 43 patients, including three fusions involving NUP98 in six

  7. Time-dependent changes in mortality and transformation risk in MDS.

    Pfeilstöcker, Michael; Tuechler, Heinz; Sanz, Guillermo; Schanz, Julie; Garcia-Manero, Guillermo; Solé, Francesc; Bennett, John M; Bowen, David; Fenaux, Pierre; Dreyfus, Francois; Kantarjian, Hagop; Kuendgen, Andrea; Malcovati, Luca; Cazzola, Mario; Cermak, Jaroslav; Fonatsch, Christa; Le Beau, Michelle M; Slovak, Marilyn L; Levis, Alessandro; Luebbert, Michael; Maciejewski, Jaroslaw; Machherndl-Spandl, Sigrid; Magalhaes, Silvia M M; Miyazaki, Yasushi; Sekeres, Mikkael A; Sperr, Wolfgang R; Stauder, Reinhard; Tauro, Sudhir; Valent, Peter; Vallespi, Teresa; van de Loosdrecht, Arjan A; Germing, Ulrich; Haase, Detlef; Greenberg, Peter L


    In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. Hazards regarding mortality and acute myeloid leukemia transformation diminished over time from diagnosis in higher-risk MDS patients, whereas they remained stable in lower-risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and were essentially equivalent after 5 years. This fact led to loss of prognostic power of different scoring systems considered, which was more pronounced for survival. Inclusion of age resulted in increased initial prognostic power for survival and less attenuation in hazards. If needed for practicability in clinical management, the differing development of risks suggested a reasonable division into lower- and higher-risk MDS based on the IPSS-R at a cutoff of 3.5 points. Our data regarding time-dependent performance of prognostic scores reflect the disparate change of risks in MDS subpopulations. Lower-risk patients at diagnosis remain lower risk whereas initially high-risk patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making. PMID:27335276

  8. Valproic acid triggers differentiation and apoptosis in AML1/ETO-positive leukemic cells specifically.

    Zapotocky, Michal; Mejstrikova, Ester; Smetana, Karel; Stary, Jan; Trka, Jan; Starkova, Julia


    Valproic acid (VPA) has extensive effects on leukemic blasts through its inhibition of histone deacetylases. The main goal of this study was to identify the subgroup of patients who may benefit most from VPA treatment. We examined the significance of t(8;21) chromosomal aberration for VPA treatment response among acute myeloid leukemia (AML) patients by direct comparison of AML1/ETO-negative vs. positive leukemic cell-lines as well as bone marrow blasts from AML patients. In t(8;21) AML, leukemogenesis is supposed to be induced via aberrant recruitment of histone deacetylases. AML cell lines of different genotypes (Kasumi-1, Kasumi-6, MV4;11, K562) and diagnostic bone marrow samples from patients were treated with VPA. VPA induced apoptosis in AML1/ETO-positive and MLL-AF4-positive cells in a dose-dependent manner. Differentiation, as indicated by changes in immunophenotype, was observed only in AML1/ETO-positive cells. VPA increased the expression of AML1 target genes - PU.1, C/EBPa, BPI and IGFBP7 only in AML1/ETO-positive cells. This AML1/ETO-specific effect was confirmed also using patient blasts isolated at the time of diagnosis. AML1/ETO-positive leukemia shows specific mechanism of VPA residing from differentiation followed by apoptosis that is accompanied by an increase in the expression of repressed AML1 target genes. Our data suggest that AML1/ETO-positive patients might derive the greatest benefit from VPA treatment. PMID:22261333

  9. Anti-thymocyte Globulin plus Etanercept as Therapy for Myelodysplastic Syndromes (MDS): a Phase II Study

    Scott, Bart L.; Ramakrishnan, Aravind; Fosdal, Mark; Storer, Barry; Becker, Pamela; Petersdorf, Steve; Deeg, H. Joachim


    Immunosuppressive therapies have proven valuable in treating patients with myelodysplastic syndromes (MDS). We evaluated the combination of equine anti-thymocyte globulin (ATGAM®) and the soluble TNF receptor etanercept (Enbrel®) in a phase II trial. Twenty-five patients with MDS (4-RA, 2-RARS, 15-RCMD, 3-RCMD-RS, 1-RAEB-1) in IPSS risk groups low (n=11) or intermediate-1 (n=14) were enrolled. All patients were platelet or red cell transfusion dependent. Nineteen patients completed therapy wi...

  10. Age-dependent frequencies of NPM1 mutations and FLT3-ITD in patients with normal karyotype AML (NK-AML).

    Schneider, Friederike; Hoster, Eva; Schneider, Stephanie; Dufour, Annika; Benthaus, Tobias; Kakadia, Purvi M; Bohlander, Stefan K; Braess, Jan; Heinecke, Achim; Sauerland, Maria C; Berdel, Wolfgang E; Buechner, Thomas; Woermann, Bernhard J; Feuring-Buske, Michaela; Buske, Christian; Creutzig, Ursula; Thiede, Christian; Zwaan, Michel C; van den Heuvel-Eibrink, Marry M; Reinhardt, Dirk; Hiddemann, Wolfgang; Spiekermann, Karsten


    Prognosis of AML in elderly patients is poor due to adverse patient characteristics and comorbidities. In addition, disease-associated parameters reveal differences between older and younger patients with AML. Survival in normal karyotype AML (NK-AML) is influenced by different clinical and molecular markers. The aim of this work was to investigate the frequencies of molecular markers in patients with NK-AML with a focus on NPM1 mutations and FLT3-ITD in different age groups. In the present study, we analyzed the frequencies of mutations of NPM1 and FLT3-ITD in a cohort of 1,321 adult patients and 148 children with AML treated within the AMLCG99, the AML98, and AML04 trials and their distribution in different age groups. Additionally, the frequencies of mutations in CEBPA genes, FLT3-TKD, and MLL-PTD were analyzed in the cohort with NK-AML (n = 729). Our data show that the presence of mutations of NPM1 (from 60% to 40%) and FLT3-ITD (from 50% to 20%) significantly decreased with age in adult AML. Consequently, the proportion of NPM1-/FLT3-ITD- patients increased with age. The decreasing frequency of NPM1 mutations in elderly patients was paralleled by a reduced complete remission (CR) rate in the elderly of 55% compared to 80% in the younger patients. By contrast, the frequencies of other gene mutations, like FLT3-TKD and MLL-PTD, and mutations in CEBPA were not age-dependent. The decreasing frequency of the favorable NPM1 mutations with increasing age may partially explain the worse outcome in the elderly patients. Furthermore, the increasing amount of elderly patients without NPM1 mutations or FLT3-ITD suggests that other molecular and clinical risk factors may influence prognosis in this age group. PMID:21744003

  11. Diskurs und Praxis: Geschlecht und Gewalt

    Angela Koch


    Full Text Available Der Sammelband befasst sich kulturwissenschaftlich mit den Verschränkungen der diskursiven Repräsentationen von Geschlecht und Gewalt, mit deren alltäglichen Erscheinungsformen und juristischen Auslegungen. Im Vordergrund steht die personale Gewalttätigkeit als physisches Mittel des Zwangs, der Dominanz und der Macht. Der Band geht auf die Tagung „Frauen und Gewalt“ zurück, die im Oktober 2001 in Greifswald stattgefunden hat, und versammelt 18 Beiträge, die unterschiedliche Facetten des Themenkomplexes behandeln: Gewalt gegen Frauen wie Inzest, Vergewaltigung, Folter, Anprangerung im Internet, und weibliche Gewalttätigkeit wie Verbrechen, Mord, Kindsmord, physische Gewalt.

  12. Exploiting AML algorithm for multiple acoustic source 2D and 3D DOA estimations


    The approximate maximum likelihood (AML) algorithm shows promises for joint estimations of acoustic source spectrum and direction-of-arrival (DOA). For the multisource case, the AML algorithm remains feasible as one considers an alternating projection procedure based on sequential iterative search on single source parameters. In order to perform multisource beamforming operations, earlier, we used a two-dimensional (2D) sensor array with 2D AML to obtain the DOA estimations for sources in the far field of t...

  13. Prognostic Value of AML1/ETO Fusion Transcripts in Patients with Acute Myelogenous Leukemia

    Cho, Eun Kyung; Bang, Soo Mee; Ahn, Jeong Yeal; Yoo, Seung Min; Park, Pil Whan; Seo, Yieh Hea; Shin, Dong Bok; Lee, Jae Hoon


    Background The t (8;21) (q22;q22), which produces the fusion gene AML1/ETO, is associated with relatively good prognosis and, in particular, with a good response to cytosine arabinoside. Analysis of t (8;21) positive leukemic blasts has shown characteristic morphological and immunological features. We performed this study to investigate the incidence of AML1/ETO rearrangement in adult acute myelogenous leukemia (AML), especially in M2 subtype, to make a comparison of clinical, morphological a...

  14. Novel formulation of cytarabine and daunorubicin: A new hope in AML treatment

    Lalit S Raut


    Acute myeloid leukemia (AML) treatment has always been a challenge to the treating physician. Continuous efforts are being made to improve treatment outcomes in AML. CPX-351 is a pharmacologic advancement in this direction. It is a liposomal fixed drug combination of cytarabine and daunorubicin. Early studies indicate that it will play a big role in AML treatment. This is a short review about this drug.

  15. MgA与MDS-RA细胞形态学的区别

    安娜; 薛少青


    目的 为了提高对骨髓增生异常综合征--难治性贫血(MDS-RA)和巨幼细胞贫血(MgA)诊断与鉴别水平,对其进行细胞形态学比较.方法 对57例MDS-RA与70例MgA患者进行常规骨髓穿刺涂片,进行瑞氏染色光学显微镜下观察比较.结果 MDS-RA以双核红细胞及奇数核红细胞、淋巴样小巨核最有特征.MgA骨髓红系呈明显的"核幼质老"改变;粒系以中幼粒以下各阶段细胞巨型改变,未发现淋巴样小巨核细胞.结论 淋巴样小巨核细胞是MDS-RA主要特征.MgA骨髓细胞呈"核幼质老",并以红系为明显.

  16. A generalization of the MDS method by mixed integer linear and nonlinear mathematical models

    Sadegh Niroomand


    Full Text Available The Multi-Dimensional Scaling (MDS method is used in statistics to detect hidden interrelations among multi-dimensional data and it has a wide range of applications. The method’s input is a matrix that describes the similarity/dissimilarity among objects of unknown dimension. The objects are generally reconstructed as points of a lower dimensional space to reveal the geometric configuration of the objects. The original MDS method uses Euclidean distance, for measuring both the distance of the reconstructed points and the bias of the reconstructed distances from the original similarity values. In this paper, these distances are distinguished, and distances other than Euclidean are also used, generalizing the MDS method. Two different distances may be used for the two different purposes. Therefore the instances of the generalized MDS model are denoted as  model, where the first distance is the type of distance of the reconstructed points and the second one measures the bias of the reconstructed distances and the similarity values. In the case of   and   distances mixed-integer programming models are provided. The computational experiences show that the generalized model can catch the key properties of the original configuration, if any exist. Keywords: Multivariate Analysis; Multi-Dimensional Scaling; Optimization; Mixed Integer Linear Programming; Statistics.

  17. TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia

    Sabaawy, Hatem E.; Azuma, Mizuki; Embree, Lisa J.; Tsai, Huai-Jen; Matthew F Starost; Dennis D Hickstein


    Acute lymphoblastic leukemia (ALL) is a clonal disease that evolves through the accrual of genetic rearrangements and/or mutations within the dominant clone. The TEL-AML1 (ETV6-RUNX1) fusion in precursor-B (pre-B) ALL is the most common genetic rearrangement in childhood cancer; however, the cellular origin and the molecular pathogenesis of TEL-AML1-induced leukemia have not been identified. To study the origin of TEL-AML1-induced ALL, we generated transgenic zebrafish expressing TEL-AML1 eit...

  18. Outcome of poor response Paediatric AML using early SCT

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas;


    treated with SCT. MATERIAL AND METHODS: Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17......) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. RESULTS: Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13...

  19. Response properties of cat AMLS neurons to optic flow stimuli

    LI; Baowang(李宝旺); LI; Bing(李兵); CHEN; Hui(陈辉); XU; Ying(徐颖); DIAO; Yuncheng(刁云程)


    Spiral and translation stimuli were used to investigate the response properties of cat AMLS (anteromedial lateral suprasylvian area) neurons to optic flow. The overwhelming majority of cells could be significantly excited by the two modes of stimuli and most responsive cells displayed obvious direction selectivity. It is the first time to find a visual area in mammalian brain preferring rotation stimuli. Two representative hypotheses are discussed here on the neural mechanism of optic flow analysis in visual cortex, and some new viewpoints are proposed to explain the experimental results.

  20. American experience in the implementation of AML / CFT system

    Larin Dmitry; Popova Ekaterina


    This article presents a research into very specific matters and issues of creating and further improvement of Anti-Money Laundering and Combating the Financing of Terrorism system (abbreviated as AML/CFT) in the USA. In contains a precise analysis of key elements of this system, as well as a deep look into the nature and purposes of financial intelligence “FinCEN”. Strong emphasis is laid on The US Foreign Account Tax Compliance Act (FATCA) for the reason that, according to this Act, any fore...

  1. Valuation of transfusion-free living in MDS: results of health utility interviews with patients

    Lübbert Michael


    Full Text Available Abstract Background This study measured how myelodysplastic syndrome (MDS patients value transfusion independence (TI, reduced transfusions (RT and transfusion-dependence (TD using health utility assessment methodology. Methods 47 MDS patients were interviewed, US (n = 8, France (n = 9, Germany (n = 9 and the UK (n = 21, to elicit the utility value of TI, RT and TD. Health states were developed based on literature; patient forum discussions; and were validated by a hematologist. Face-to-face interviews used the feeling thermometer Visual Analogue Scale (VAS and the Time Trade-Off (TTO method to value the health states on a 0 (dead to 1 (perfect health scale. Socio-demographic, clinical, and quality-of-life (EQ-5D characteristics were surveyed to describe the patient sample. Results and Discussion The mean age was 67 years (range: 29-83; 45% male, 70% retired; 40% had secondary/high school education, or higher (32%, and 79% lived with family, a partner or spouse, or friends. The mean time from MDS diagnosis was 5 years (range:1-23. Most patients (87% received previous transfusions and 49% had received a transfusion in the last 3 months. Mean EQ-5D index score was 0.78; patients reported at least some problem with mobility (45%, usual activities (40%, pain/discomfort (47%, and anxiety/depression (34%. Few patients had difficulty understanding the VAS (n = 3 and TTO (n = 4 exercises. Utility scores for TI were higher than for RT (0.84 vs. 0.77; p Conclusion Patients value TI, suggesting an important role for new treatments aiming to achieve greater TI in MDS. These results can be used in preference-based health economic evaluation of new MDS treatments, such as in future cost-utility studies.

  2. Disruption of the NHR4 domain structure in AML1-ETO abrogates SON binding and promotes leukemogenesis

    Ahn, Eun-Young; Yan, Ming; Malakhova, Oxana A.; Lo, Miao-Chia; Boyapati, Anita; Ommen, Hans Beier; Hines, Robert; Hokland, Peter; Zhang, Dong-Er


    AML1-ETO is generated from t(8;21)(q22;q22), which is a common form of chromosomal translocation associated with development of acute myeloid leukemia (AML). Although full-length AML1-ETO alone fails to promote leukemia because of its detrimental effects on cell proliferation, an alternatively spliced isoform, AML1-ETO9a, without its C-terminal NHR3/NHR4 domains, strongly induces leukemia. However, full-length AML1-ETO is a major form of fusion product in many t(8;21) AML patients, suggesting...

  3. Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1.

    Shinobu Tsuzuki


    Full Text Available BACKGROUND: AML1/RUNX1 is the most frequently mutated gene in leukaemia and is central to the normal biology of hematopoietic stem and progenitor cells. However, the role of different AML1 isoforms within these primitive compartments is unclear. Here we investigate whether altering relative expression of AML1 isoforms impacts the balance between cell self-renewal and differentiation in vitro and in vivo. METHODS AND FINDINGS: The human AML1a isoform encodes a truncated molecule with DNA-binding but no transactivation capacity. We used a retrovirus-based approach to transduce AML1a into primitive haematopoietic cells isolated from the mouse. We observed that enforced AML1a expression increased the competitive engraftment potential of murine long-term reconstituting stem cells with the proportion of AML1a-expressing cells increasing over time in both primary and secondary recipients. Furthermore, AML1a expression dramatically increased primitive and committed progenitor activity in engrafted animals as assessed by long-term culture, cobblestone formation, and colony assays. In contrast, expression of the full-length isoform AML1b abrogated engraftment potential. In vitro, AML1b promoted differentiation while AML1a promoted proliferation of progenitors capable of short-term lymphomyeloid engraftment. Consistent with these findings, the relative abundance of AML1a was highest in the primitive stem/progenitor compartment of human cord blood, and forced expression of AML1a in these cells enhanced maintenance of primitive potential both in vitro and in vivo. CONCLUSIONS: These data demonstrate that the "a" isoform of AML1 has the capacity to potentiate stem and progenitor cell engraftment, both of which are required for successful clinical transplantation. This activity is consistent with its expression pattern in both normal and leukaemic cells. Manipulating the balance of AML1 isoform expression may offer novel therapeutic strategies, exploitable in

  4. Erlebnisanalyse und szenisches Verstehen

    Nagbøl, Søren Peter


    Im Folgenden stelle ich einige Leitgedanken der psychoanalytischen Herme-neutik und Merkmale für die Anwendung des szenischen Verstehens heraus. Ich mache dies u.a. auch in der Absicht, meine Art und Weise, und die kon-zeptuelle vorarbeiten in der ich forsche, sichtbar zu machen und zu positionieren...

  5. Physikdidaktik Theorie und Praxis

    Girwidz, Raimund; Häußler, Peter


    „Physikdidaktik – Theorie und Praxis“ ist ein Sammelband, der dynamisch gewachsen ist. Der Teil I wurde im Jahre 2000 in erster Linie für Studierende des Lehramts Physik konzipiert. Der Teil II zeigt Konkretisierungen und im Unterricht erprobte Beispiele zu neueren didaktischen und methodischen Ansätzen, die aus der Pädagogik und der allgemeinen Didaktik für die Physikdidaktik aufbereitet wurden. Die Physikdidaktik befasst sich natürlich auch mit der Frage, welche Elemente aus der modernen Physik in den Unterricht eingehen können und sollen. Vor der Aufbereitung der Inhalte für den Unterricht, mit Vereinfachungen und angemessenen didaktischen Reduktionen, steht die Sachanalyse und die Zusammenfassung von interessanten Themen aus aktuellen experimentellen und theoretischen Arbeitsgebieten der Physik (Teil III). In der vorliegenden 3. Ausgabe eines Gesamtbandes „Physikdidaktik – Theorie und Praxis“ wurden Astrophysik, Elementar­teilchenphysik und Biophysik als interessante Beispiele aus ...

  6. Frauen und Sucht : Literaturkompendium

    Franke, Alexa; Mohn, Karin; Welbrink, Andrea; Witte, Maibritt; Teuber, Jutta


    Das vorliegende Literaturkompendium stellt die aktuelle wissenschaftliche Literatur zu dem Thema "Frauen und Sucht" systematisch und möglichst umfassend dar. Es beinhaltet Literaturhinweise zu frauenspezifischen Ursachen, Bedingungen, Verläufen und Folgen des Substanzmißbrauchs. Zur besseren Überschaubarkeit und um den Umfang der Recherche einzugrenzen, bezieht sich das Kompendium ausschließlich auf folgende Substanzen: Alkohol, Medikamente und illegale Drogen. Grundlage des Kompendiums ...

  7. Gesundheit, Essen und Nachhaltigkeit

    Reisch, Lucia


    Das vielschichtige Thema Ernährung ist angesichts weltweiter Ernährungskrisen sowie der Bedrohung durch den Klimawandel noch komplexer geworden: Immer deutlicher wird die wissenschaftliche Evidenz der direkten und indirekten Zusammenhänge zwischen Ernährung und Gesundheit, Energie und Klima sowie...... oder überfordern diese; hinzukommen müsse daher eine geschickte „Architektur der Wahl“, die Verhalten deutlich beeinflussen und nachhaltige Ernährungs- und Lebensstile fördern kann....

  8. Diskurs und Praxis: Geschlecht und Gewalt

    Angela Koch


    Der Sammelband befasst sich kulturwissenschaftlich mit den Verschränkungen der diskursiven Repräsentationen von Geschlecht und Gewalt, mit deren alltäglichen Erscheinungsformen und juristischen Auslegungen. Im Vordergrund steht die personale Gewalttätigkeit als physisches Mittel des Zwangs, der Dominanz und der Macht. Der Band geht auf die Tagung „Frauen und Gewalt“ zurück, die im Oktober 2001 in Greifswald stattgefunden hat, und versammelt 18 Beiträge, die unterschiedliche Facetten des Theme...

  9. Spontaneous remission in three cases of AML M5 with NPM1 mutation

    Camus, Vincent; Etancelin, Pascaline; Jardin, Fabrice; Lenain, Pascal; Contentin, Nathalie; Daliphard, Sylvie; Buchonnet, Gérard; Lemasle, Emilie; Lanic, Hélène; Leprêtre, Stéphane; Penther, Dominique; Dubois, Sydney; Tilly, Hervé; Bastard, Christian; Stamatoullas, Aspasia


    Key Clinical Message Patients with NPM1-mutated AML M5 who develop spontaneous remission (SR) after antibiotic therapy at diagnosis seem to form a favorable prognosis and chemo sensitive subtype. We report three cases of AML M5 patients with the same genotype that experienced transient SR and are now leukemia free after standard treatment.

  10. Spontaneous remission in three cases of AML M5 with NPM1 mutation

    Camus, Vincent; Etancelin, Pascaline; Jardin, Fabrice; Lenain, Pascal; Contentin, Nathalie; Daliphard, Sylvie; Buchonnet, Gérard; Lemasle, Emilie; Lanic, Hélène; Leprêtre, Stéphane; Penther, Dominique; Dubois, Sydney; Tilly, Hervé; Bastard, Christian; Stamatoullas, Aspasia


    Key Clinical Message Patients with NPM1-mutated AML M5 who develop spontaneous remission (SR) after antibiotic therapy at diagnosis seem to form a favorable prognosis and chemo sensitive subtype. We report three cases of AML M5 patients with the same genotype that experienced transient SR and are now leukemia free after standard treatment. PMID:26576281

  11. The leukemogenic t(8;21) fusion protein AML1-ETO controls ribosomal RNA genes and associates with nucleolar organizing regions at mitotic chromosomes

    Bakshi, Rachit; Zaidi, Sayyed K.; Pande, Sandhya; Hassan, Mohammad Q.; Young, Daniel W; Lian, Jane B.; van Wijnen, Andre J; Stein, Janet L.; Stein, Gary S.


    RUNX1/AML1 is required for definitive hematopoiesis and is frequently targeted by chromosomal translocation in acute myeloid leukemias (AML). The t(8;21) related AML1-ETO fusion protein blocks differentiation of myeloid progenitors. Here, we show by immunofluorescence microscopy that during interphase, endogenous AML1-ETO localizes to nuclear microenvironments distinct from those containing native RUNX1/AML1 protein. At mitosis, we clearly detect binding of AML1-ETO to nucleolar organizing re...

  12. The HPB-AML-I cell line possesses the properties of mesenchymal stem cells

    Tatsumi Eiji


    Full Text Available Abstract Background In spite of its establishment from the peripheral blood of a case with acute myeloid leukemia (AML-M1, HPB-AML-I shows plastic adherence with spindle-like morphology. In addition, lipid droplets can be induced in HPB-AML-I cells by methylisobutylxanthine, hydrocortisone, and indomethacin. These findings suggest that HPB-AML-I is similar to mesenchymal stem cells (MSCs or mesenchymal stromal cells rather than to hematopoietic cells. Methods To examine this possibility, we characterized HPB-AML-I by performing cytochemical, cytogenetic, and phenotypic analyses, induction of differentiation toward mesenchymal lineage cells, and mixed lymphocyte culture analysis. Results HPB-AML-I proved to be negative for myeloperoxidase, while surface antigen analysis disclosed that it was positive for MSC-related antigens, such as CD29, CD44, CD55, CD59, and CD73, but not for CD14, CD19, CD34, CD45, CD90, CD105, CD117, and HLA-DR. Karyotypic analysis showed the presence of complicated abnormalities, but no reciprocal translocations typically detected in AML cases. Following the induction of differentiation toward adipocytes, chondrocytes, and osteocytes, HPB-AML-I cells showed, in conjunction with extracellular matrix formation, lipid accumulation, proteoglycan synthesis, and alkaline phosphatase expression. Mixed lymphocyte culture demonstrated that CD3+ T-cell proliferation was suppressed in the presence of HPB-AML-I cells. Conclusions We conclude that HPB-AML-I cells appear to be unique neoplastic cells, which may be derived from MSCs, but are not hematopoietic progenitor cells.

  13. Prenatal origin of childhood AML occurs less frequently than in childhood ALL

    While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. We analysed Guthrie cards of 12 ALL patients aged 2–6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1–14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1–3 positive cells were present in the neonatal blood spot. In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases

  14. Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-α transcription factors

    Zeng, Congmei; van Wijnen, André J.; Stein, Janet L.; Meyers, Shari; Sun, Wuhua; Shopland, Lindsay; Lawrence, Jeanne B.; Penman, Sheldon; Lian, Jane B.; Stein, Gary S.; Hiebert, Scott W.


    Transcription factors of the AML (core binding factor-α/polyoma enhancer binding protein 2) class are key transactivators of tissue-specific genes of the hematopoietic and bone lineages. Alternative splicing of the AML-1 gene results in two major AML variants, AML-1 and AML-1B. We show here that the transcriptionally active AML-1B binds to the nuclear matrix, and the inactive AML-1 does not. The association of AML-1B with the nuclear matrix is independent of DNA binding and requires a nuclear...

  15. Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ–CBP fusion protein

    Kitabayashi, Issay; Aikawa, Yukiko; Nguyen, Lan Anh; Yokoyama, Akihiko; Ohki, Misao


    The AML1–CBFβ transcription factor complex is the most frequent target of specific chromosome translocations in human leukemia. The MOZ gene, which encodes a histone acetyltransferase (HAT), is also involved in some leukemia-associated translocations. We report here that MOZ is part of the AML1 complex and strongly stimulates AML1-mediated transcription. The stimulation of AML1-mediated transcription is independent of the inherent HAT activity of MOZ. Rather, a potent transactivation domain w...

  16. Improving diffusion power of AES Rijndael with 8x8 MDS matrix



    Full Text Available AES Rijndael is a block cipher developed by NIST as the Advanced Encryption Standard (AES replacing DES and published as FIPS 197 in November 2001 [5] to address the threatened key size of Data Encryption Standard (DES. AES-Rijndael was developed by Joan Daemen and Vincent Rijmen, Rijndael [4, 5] and was selected from five finalists. Advancement in computation speed every day puts lotsof pressure on AES and AES may not with stand attack for longer time. This work focuses on improving security of an encryption algorithm, beyond AES. Though there are various techniques available to enhance the security, an attempt is made to improve the diffusion strength of an algorithm. For enhancing the diffusion power AES Rijndael in MixColumn operation the branch number of MDS matrix is raised from 5 to 9 using a new 8X8 MDS matrix with trade off of speed [8, 9] and implemented on R8C microcontroller.

  17. American experience in the implementation of AML / CFT system

    Larin Dmitry


    Full Text Available This article presents a research into very specific matters and issues of creating and further improvement of Anti-Money Laundering and Combating the Financing of Terrorism system (abbreviated as AML/CFT in the USA. In contains a precise analysis of key elements of this system, as well as a deep look into the nature and purposes of financial intelligence “FinCEN”. Strong emphasis is laid on The US Foreign Account Tax Compliance Act (FATCA for the reason that, according to this Act, any foreign financial institution is legitimately forced to sign a special agreement with The US Internal Revenue Service (IRS, giving the Service power to maintain control over any American asset within its equity. The latter is understood as a legal right to investigate not only the accounts and property of American taxpayers, but to investigate any account or capital of any foreign institution having American shares or stocks.

  18. Measurement of the Mass Difference m(D_s^+) - m(D^+) at CDF II

    Acosta, D; Ahn, M H; Akimoto, T; Albrow, M G; Alcorn, B; Alexander, C; Allen, D; Allspach, D H; Amaral, P; Ambrose, D; Amendolia, S R; Amidei, D; Amundson, J F; Anastassov, A; Anderson, J; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J F; Arisawa, T; Artikov, A; Asakawa, T; Ashmanskas, W; Attal, A; Avanzini, C; Azfar, F; Azzi-Bacchetta, P; Babik, M; Bacchetta, N; Bachacou, H; Badgett, W F; Bailey, S; Bakken, J; Barbaro-Galtieri, A; Bardi, A; Bari, M; Barker, G; Barnes, V E; Barnett, B A; Baroiant, S; Barone, M; Barsotti, E; Basti, A; Bauer, G; Beckner, D; Bedeschi, F; Behari, S; Belforte, S; Bell, W H; Bellendir, G; Bellettini, Giorgio; Bellinger, J; Benjamin, D; Beretvas, A; Berg, B; Bhatti, A A; Binkley, M; Bisello, D; Bishai, M; Blair, R E; Blocker, C; Bloom, K; Blumenfeld, B; Bocci, A; Bodek, A; Bogdan, M; Bölla, G; Bolshov, A; Booth, P S L; Bortoletto, Daniela; Boudreau, J; Bourov, S; Bowden, M; Box, D; Bromberg, C; Brown, W; Brozovic, M; Brubaker, E; Buckley-Geer, L; Budagov, Yu A; Budd, H S; Burkett, K; Busetto, G; Bussey, P; Byon-Wagner, A; Byrum, K L; Cabrera, S; Calafiura, P; Campanelli, M; Campbell, M; Canal, P; Canepa, A; Carithers, W C; Carlsmith, D; Carosi, R; Carrell, K; Carter, H; Caskey, W; Castro, A; Cauz, D; Cerri, A; Cerri, C; Cerrito, L; Chandler, J T; Chapman, J; Chappa, S; Chen, C; Chen, Y C; Cheng, M T; Chertok, M; Chiarelli, G; Chirikov-Zorin, I E; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chu, M L; Chung, J Y; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Cisko, S; Clark, A G; Coca, M; Coiley, K; Colijn, A P; Colombo, R M; Connolly, A; Convery, M; Conway, J; Cooper, G; Cordelli, M; Cortiana, G; Cranshaw, J; Cudzewicz, R; Culbertson, R; Currat, C; Cyr, D; Dagenhart, D; Dal Monte, L; Da Ronco, S; D'Auria, S; Davila, R; Dawson, J; Dawson, T; De Barbaro, P; De Baun, C; De Cecco, S; Dell'Agnello, S; Dell'Orso, Mauro; De Maat, R; Demar, P; Demers, S; Demortier, L; Deninno, M; De Pedis, D; Derwent, P F; Derylo, G; Devlin, T; Dionisi, C; Dittmann, J R; Doksus, P; Dominguez, A; Donati, S; Donno, F; D'Onofrio, M; Dorigo, T; Downing, R; Drake, G; Drennan, C; Drollinger, V; Dunietz, Isard; Dyer, A; Ebina, K; Eddy, N; Ely, R; Engels, E; Erbacher, R D; Erdmann, M; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Feild, R G; Feindt, M; Fernández, J P; Ferretti, C; Field, R D; Fiori, I; Fischler, M; Flanagan, G; Flaugher, B; Flores-Castillo, L R; Foland, A D; Forrester, S; Foster, G W; Franklin, M; Frisch, H; Fromm, J; Fujii, Y; Furic, I; Galeotti, S; Galet, G; Gallas, A; Gallinaro, M; Ganel, O; García, C; García-Sciveres, M; Garfinkel, A F; Garwacki, M; Garzoglio, G; Gay, C; Gerberich, H; Gerdes, D W; Gerchtein, E; Gerstenslager, J; Giacchetti, L; Giagu, S; Giannetti, P; Gibson, A; Gillespie, G; Gingu, C; Ginsburg, C; Giolo, K; Giordani, M; Glagolev, V; Glenzinski, D A; Glossen, R; Gold, M; Goldschmidt, N; Goldstein, D B; Goldstein, J; Gómez, G; Goncharov, M; González, H; Gordon, S; Gorelov, I; Goshaw, A T; Gotra, Yu; Goulianos, K; Grado, J; Gregori, M; Gresele, A; Griffin, T; Grim, G; Grimm, C; Gromoll, S; Grosso-Pilcher, C; Gu, C; Guarino, V; Günther, M; Guimarães da Costa, J; Haber, C; Hahn, A; Hahn, K; Hahn, S R; Halkiadakis, E; Hall, C; Handler, R; Haney, M; Hao, W; Happacher, F; Hara, K; Hare, M; Harr, R F; Harrington, J; Harris, R M; Hartmann, F; Hatakeyama, K; Hauser, J; Hawke, T; Hays, C; Heider, E; Heinemann, B; Heinrich, J; Heiss, A; Hennecke, M; Herber, R; Herndon, M; Herren, M; Hicks, D; Hill, C; Hirschbuehl, D; Höcker, A; Hoff, J; Hoffman, K D; Hoftiezer, J H; Holloway, A; Holloway, L E; Holm, S; Holmgren, D; Hou, S; Houlden, M A; Howell, J; Hrycyk, M; Hubbard, P; Hughes, R E; Huffman, B T; Humbert, J; Huston, J; Ikado, K; Incandela, J R; Introzzi, G; Iori, M; Ishizawa, I; Issever, C; Ivanov, A; Iwata, Y; Iyutin, B; James, E; Jang, D; Jarrell, J; Jeans, D; Jensen, H; Jetton, R; Johnson, M; Jones, M; Jones, T; Jun, S Y; Junk, T R; Kallenbach, Jeff; Kamon, T; Kang, J; Karagoz-Unel, M; Karchin, P E; Kartal, S; Kasha, H; Kasten, M; Kato, Y; Kemp, Y; Kennedy, R D; Kephart, K; Kephart, R D; Khazins, D; Khotilovich, V; Kilminster, B; Kim, B J; Kim, D H; Kim, H S; Kim, J; Kim, M J; Kim, M S; Kim, S B; Kim, S H; Kim, T H; Kim, Y K; King, B T; Kirby, M; Kirk, M; Kirsch, L; Klein, R; Klimenko, S; Knapp, M; Knoblauch, D; Knuteson, B; Kobayashi, H; Koehn, P; Kondo, K; Kong, D J; Konigsberg, J; Kononenko, W; Kordas, K; Korn, A J; Korytov, A; Kotelnikov, K A; Kotwal, A; Kovalev, A; Kowalkowski, J B; Kraus, J; Kravchenko, I V; Kreymer, A; Kroll, J; Kruse, M; Krutelyov, V; Kuhlmann, S E; Kumar, A; Kuznetsova, N; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lamore, D; Lancaster, J; Lancaster, M; Lander, R; Lanfranco, G; Lannon, K; Lath, A; Latino, G; Lauhakangas, R; Lazzizzera, I; Le, Y; LeCompte, T J; Lee, J; Lee, K; Lee, S W; Lei, C M; Leininger, M; Leonardi, G L; Leonardo, N; Leone, S; Levshina, T; Lewis, F; Lewis, J D; Li, K; Lin, C S; Lindgren, M; Liss, T M; Litvintsev, D O; Liu, T; Liu, Y; Lobban, O; Lockyer, N S; Loginov, A; Loken, J; Loreti, M; Loskot, J; Loverre, P F; Lucchesi, D; Lukens, P; Lutz, P; Lyons, L; Lys, J; MacNerland, J; MacQueen, D; Madorsky, A; Madrak, R; Maeshima, K; Maksimovic, P; Malferrari, L; Mammini, P; Manca, G; Mandrichenko, I V; Manea, C; Marginean, R; Marrafino, J; Martin, A; Martin, M; Martin, V; Martínez, M; Maruyama, T; Matsunaga, H; Mayer, J; Mayers, G M; Mazzanti, P; McFarland, K S; McGivern, D; McIntyre, P M; McNamara, P; McNulty, R; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Meyer, A; Miao, T; Michael, N; Miller, J S; Miller, L; Miller, R; Miquel, R; Miscetti, S; Mitselmakher, G; Miyamoto, A; Miyazaki, Y; Mizicko, D; Moccia, S; Moggi, A; Moggi, N; Montero, S; Moore, R; Moore, T; Morris, L; Morsani, F; Moulik, T; Mukherjee, A; Mulhearn, M; Müller, T; Mumford, R; Munar, A; Murat, P; Murgia, S; Nachtman, J; Nagaslaev, V; Nahn, S; Nakamura, I; Nakano, I; Napier, A; Napora, R; Necula, V; Nelson, C; Nelson, T; Neu, C; Neubauer, M S; Neuberger, D; Newby, W; Newcomer, F M; Newman-Holmes, C; Niell, F; Nielsen, J; Nicollerat, A S; Nigmanov, T; Niu, H; Nodulman, L; Noe, W; Österberg, K; Ogawa, T; Oh, S; Oh, Y D; Ohl, K; Ohsugi, T; Oishi, R; Okusawa, T; Oldeman, R G C; Orava, Risto; Orejudos, W; Orr, S; Pagani, G; Pagliarone, C; Palmonari, F; Ramos, I; Panacek, S; Pantano, D; Paoletti, R; Papadimitriou, V; Pasetes, R; Pashapour, S; Passuello, D; Paterno, M; Patrick, J; Pauletta, G; Paulini, M; Pauly, T; Paus, C; Pavlicek, V; Pavlon, S; Pellett, D; Penzo, Aldo L; Perington, B; Petragnani, G; Petravick, D; Phillips, T J; Photos, F; Piacentino, G; Picciolo, C; Piccoli, L; Piedra, J; Pitts, K T; Plunkett, R; Pompos, A; Pondrom, L; Pope, G; Poukhov, O; Prakoshyn, F; Pratt, T; Profeti, A; Pronko, A G; Proudfoot, J; Punzi, G; Rademacker, J; Rafaelli, F; Rakitine, A; Rappoccio, S; Ratnikov, F; Rauch, J; Ray, H; Rechenmacher, R; Reia, S; Reichold, A; Rekovic, V; Renton, P B; Rescigno, M; Rimondi, F; Rinnert, K; Ristori, L; Riveline, M; Rivetta, C; Robertson, W J; Robson, A; Rodrigo, T; Rolli, S; Román, M; Rosenberg, S I; Rosenson, L; Roser, R; Rossin, R; Rott, C; Ruiz, A; Russ, J; Ryan, D; Saarikko, H; Sabik, S; Sadler, L; Safonov, A; Saint-Denis, R; Sakumoto, W K; Saltzberg, D; Sánchez, C; Sanders, H; Sanders, R; Sandrew, M; Sansoni, A; Santi, L; Sarkar, S; Sarraj, H; Sarraj, J; Sato, H; Savard, P; Schemitz, P; Schlabach, P; Schmidt, E E; Schmidt, J; Schmidt, M P; Schmitt, M; Schmitt, R; Schmitz, M; Schofield, G L; Schuh, K; Schultz, K; Scodellaro, L; Scott, L; Scribano, A; Scuri, F; Sedov, A; Segler, S; Seidel, S; Seiya, Y; Semenov, A; Semeria, F; Sexton-Kennedy, L; Sfiligoi, I; Shallenberger, J; Shapiro, M D; Shaw, T; Shears, T G; Shenai, A; Shepard, P F; Shimojima, M; Shochet, M J; Shon, Y; Shoun, M; Sidoti, A; Siegrist, J L; Sieh, C; Siket, M; Sill, A; Silva, R; Simaitis, V; Sinervo, P; Sirotenko, V I; Sissakian, A N; Skiba, A; Slaughter, A J; Sliwa, K; Smith, J; Snider, F D; Snihur, R; Somalwar, S V; Spalding, J; Spezziga, M; Spiegel, L; Spinella, F; Spiropulu, M; Stadie, H; Stanek, R; Stanfield, N; Stelzer, B; Stelzer-Chilton, O; Strologas, J; Stuart, D; Stuermer, W; Sukhanov, A; Sumorok, K; Sun, H; Suzuki, T; Syu, J; Szymulanski, A; Taffard, A C; Takach, S F; Takano, H; Takashima, R; Takeuchi, Y; Takikawa, K; Tamburello, P; Tanaka, M; Tanaka, R; Tang, D; Tanimoto, N; Tannenbaum, B; Tapprogge, Stefan; Taylor, R D; Teafoe, G; Tecchio, M; Teng, P K; Terashi, K; Terentieva, T; Tesarek, R J; Tether, S; Thom, J; Thomas, A; Thompson, A S; Thomson, E; Thurman-Keup, R M; Timm, S; Tipton, P; Tkaczyk, S M; Toback, D; Tollefson, K; Tonelli, D; Tonnesmann, M; Torretta, D; Trimby, C; Trischuk, W; Trumbo, J; Tseng, J; Tsuchiya, R; Tsuno, S; Tsybychev, D; Turini, N; Turner, M; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vacavant, L; Vaiciulis, T; Van Berg, R; Varganov, A V; Vataga, E; Vejcik, S; Velev, G V; Veramendi, G; Vickey, T; Vidal, R; Vila, I; Vilar, R; Vittone, M; Voirin, J; Vollmer, B; Vollrath, I; Volobuev, I P; Von der Mey, M; Votava, M; Wagner, R G; Wagner, R L; Wagner, W; Wallace, N; Walter, T; Walters, A; Wan, Z; Wandersee, A; Wang, M J; Wang, S M; Ward, B; Waschke, S; Waters, D; Watts, T; Weber, M; Weems, L; Wenzel, H; Wester, W; Whitehouse, B; Wickenberg, W; Wicklund, A B; Wicklund, E; Wigmans, R; Wike, C; Wilkes, T; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolter, M; Wong, M; Worcester, M; Worland, R; Worm, S; Wright, T; Wu, J; Wu, X; Würthwein, F; Wyatt, A; Yagil, A; Yamamoto, K; Yamashita, T; Yang, U K; Yao, W; Yarema, R J; Yeh, G P; Yi, K; Yocum, D R; Yoh, J K; Yoon, P; Yorita, K; Yoshida, T; Yu, I; Yu, S; Yu, Z; Yun, J C; Zalokar, M; Zanello, L; Zanetti, A; Zaw, I; Zetti, F; Zhou, J; Zimmerman, T; Zsenei, A; Zucchelli, S


    We present a measurement of the mass difference m(D+_s) - m(D+), where both the D+_s and D+ are reconstructed in the phi pi+ decay channel. This measurement uses 11.6 pb-1 of data collected by CDF II using the new displaced-track trigger. The mass difference is found to be: 99.41 +- 0.38 (stat) +- 0.21 (syst) MeV/c^2.

  19. Optimal Repair of MDS Codes in Distributed Storage via Subspace Interference Alignment

    Cadambe, Viveck R; Jafar, Syed A; Li, Jin


    It is well known that an (n,k) code can be used to store 'k' units of information in 'n' unit-capacity disks of a distributed data storage system. If the code used is maximum distance separable (MDS), then the system can tolerate any (n-k) disk failures, since the original information can be recovered from any k surviving disks. The focus of this paper is the design of a systematic MDS code with the additional property that a single disk failure can be repaired with minimum repair bandwidth, i.e., with the minimum possible amount of data to be downloaded for recovery of the failed disk. Previously, a lower bound of (n-1)/(n-k) units has been established by Dimakis et. al, on the repair bandwidth for a single disk failure in an (n,k) MDS code . Recently, the existence of asymptotic codes achieving this lower bound for arbitrary (n,k) has been established by drawing connections to interference alignment. While the existence of asymptotic constructions achieving this lower bound have been shown, finite code cons...

  20. Magie, Hexen und Strafverfolgung

    Arne Duncker


    Full Text Available In der Reihe „Historische Einführungen“ des Campus Verlags versucht Johannes Dillinger, die Entwicklung von Magie- und Hexereivorstellungen vom Mittelalter bis zur Gegenwart zu beschreiben. Die Hexenverfolgungen und -prozesse der Frühen Neuzeit und ihre Voraussetzungen nehmen dabei etwas mehr als die Hälfte der Gesamtdarstellung ein. Das Buch bietet in erster Linie eine Einführung in die neuere und neueste Sekundärliteratur und die dort besprochenen aktuellen Streitpunkte. In einem Teilabschnitt wird auch auf die Hexenverfolgung als Frauenverfolgung eingegangen und nach Ursachen für den hohen Frauenanteil unter den Verfolgten geforscht.

  1. Anerkennung und soziale Ungleichheit

    Annegret Ergenzinger


    Full Text Available Vor dem Hintergrund der Honneth’schen Stufentheorie der Anerkennung (von der Liebe in den Paar- und Nahbeziehungen über Achtung als Gleiche in den rechtlichen Bezügen des Staates, bis hin zur sozialen Wertschätzung von Leistung in der Wertegemeinschaft werden Anerkennung und Ungleichheit in Paarbeziehungen, Arbeitsorganisationen und im Sozialstaat empirisch und/oder analytisch im vorliegenden Sammelband untersucht. Empirische und theoretische Studien zeigen, dass die Kategorie Anerkennung in der sozialen Ungleichheitsforschung neue Erkenntnisse möglich macht. Dies gilt jedoch auch umgekehrt: Die Einbeziehung von weiteren historisch-kulturell eingebetteten Kategorien der Ungleichheit kontextualisieren und differenzieren die Theorie der Anerkennung.

  2. The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis

    Acute myeloid leukemia (AML) is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification), which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF-κB. Blockage of NF-κB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL

  3. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML.

    Wong, Terrence N; Miller, Christopher A; Klco, Jeffery M; Petti, Allegra; Demeter, Ryan; Helton, Nichole M; Li, Tiandao; Fulton, Robert S; Heath, Sharon E; Mardis, Elaine R; Westervelt, Peter; DiPersio, John F; Walter, Matthew J; Welch, John S; Graubert, Timothy A; Wilson, Richard K; Ley, Timothy J; Link, Daniel C


    There is interest in using leukemia-gene panels and next-generation sequencing to assess acute myelogenous leukemia (AML) response to induction chemotherapy. Studies have shown that patients with AML in morphologic remission may continue to have clonal hematopoiesis with populations closely related to the founding AML clone and that this confers an increased risk of relapse. However, it remains unknown how induction chemotherapy influences the clonal evolution of a patient's nonleukemic hematopoietic population. Here, we report that 5 of 15 patients with genetic clearance of their founding AML clone after induction chemotherapy had a concomitant expansion of a hematopoietic population unrelated to the initial AML. These populations frequently harbored somatic mutations in genes recurrently mutated in AML or myelodysplastic syndromes and were detectable at very low frequencies at the time of AML diagnosis. These results suggest that nonleukemic hematopoietic stem and progenitor cells, harboring specific aging-acquired mutations, may have a competitive fitness advantage after induction chemotherapy, expand, and persist long after the completion of chemotherapy. Although the clinical importance of these "rising" clones remains to be determined, it will be important to distinguish them from leukemia-related populations when assessing for molecular responses to induction chemotherapy. PMID:26631115

  4. The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis

    Dijk, Marianne van; Murphy, Eoin [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); Morrell, Ruth [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Knapper, Steven [Department of Haematology, School of Medicine, Cardiff University, Heath Park, CF14 4XN Cardiff (United Kingdom); O' Dwyer, Michael [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Samali, Afshin; Szegezdi, Eva, E-mail: [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland)


    Acute myeloid leukemia (AML) is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification), which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF-κB. Blockage of NF-κB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL.

  5. MYST2 acetyltransferase expression and Histone H4 Lysine acetylation are suppressed in AML.

    Sauer, Tim; Arteaga, Maria Francisca; Isken, Fabienne; Rohde, Christian; Hebestreit, Katja; Mikesch, Jan-Henrik; Stelljes, Matthias; Cui, Chunhong; Zhou, Fengbiao; Göllner, Stefanie; Bäumer, Nicole; Köhler, Gabriele; Krug, Utz; Thiede, Christian; Ehninger, Gerhard; Edemir, Bayram; Schlenke, Peter; Berdel, Wolfgang E; Dugas, Martin; Müller-Tidow, Carsten


    Chromatin-modifying enzymes are frequently altered in acute myeloid leukemia (AML). In the current study, we identified MYST2, a core histone acetyltransferase, to be suppressed in blast cells from AML patients compared with nonmalignant hematopoietic progenitor cells. Functionally, loss of MYST2 accelerated leukemic growth and colony formation, while forced expression of MYST2 induced H4K5 acetylation (H4K5Ac) and suppressed hematopoietic progenitor cell growth. Consistently, global H4K5Ac levels were frequently decreased in AML blasts. Low levels of H4K5Ac were most prominent in patients with complex karyotype AML and were associated with inferior overall survival in univariate but not multivariate analysis. ChIP-seq experiments in primary AML patients' blasts revealed widespread H4K5Ac deregulation, most prominent at gene promoters. Taken together, MYST2 is a repressed growth suppressor in AML mediating reduced acetylation of histone 4 at residue 5 and is associated with inferior AML patient survival. PMID:26072331

  6. Wissenschaft und Wiedervereinigung - Bilanz und offene Fragen

    Ash, Mitchell G.; Bierwisch, Manfred; Erhardt, Manfred; Ganten, Detlev; Grübel, Hartmut F.; Hertel, Ingolf; Kern, Horst F.; Klein, Dieter; Kocka, Jürgen; Krull , Wilhelm; Kuczynski, Thomas; Laitko, Hubert; Malycha, Andreas; Mayntz, Renate; Meyer, Hans Joachim


    Im 20. Jahr nach dem Mauerfall fand in der Berlin-Brandenburgischen Akademie der Wissenschaften vom 24. bis 25. November 2009 das Symposium „Wissenschaft und Wiedervereinigung. Bilanz und offene Fragen“ statt. Im Rahmen des Wissenschaftsjahres 2009 diskutierten Wissenschaftler und Wissenschaftspolitiker, ob bei der Vereinigung der beiden deutschen Wissenschaftssysteme Chancen genutzt oder verpasst wurden. Wie unterschiedlich oder ähnlich entwickelten sich die beiden getrennten Systeme bis zum...

  7. Energie- und Ressourceneffizienz in der Wärmebehandlung und Thermoprozesstechnik

    Fritsching, Udo


    Die effiziente Nutzung von Energie und Rohstoffen gewinnt in den allen Produktionsprozessen zunehmend an Bedeutung. Steigende Energiepreise und Umweltanforderungen sowie der zunehmende Kostendruck durch die Globalisierung zwingen auch klein- und mittelständische Unternehmen, sich mit dem Thema Energie- und Ressourceneffizienz verstärkt auseinanderzusetzen. Potentielle Effizienzsteigerungen in Prozessen und Anlagen gründen nach dem Stand der Technik auf innovativen Prozessen und Produkten und ...

  8. Angiomyolipoma (AML) without visible fat: Ultrasound, CT and MR imaging features with pathological correlation

    Hakim, Shaheed W.; Flood, Trevor A. [The Ottawa Hospital, University of Ottawa, Department of Anatomical Pathology, Ottawa, Ontario (Canada); Schieda, Nicola; Hodgdon, Taryn; McInnes, Matthew D.F.; Dilauro, Marc [The Ottawa Hospital, University of Ottawa, Department of Medical Imaging, Ottawa, Ontario (Canada)


    To compare imaging findings with histopathology in AML without visible fat (AML{sub wvf}). With IRB approval, we identified 18 AML{sub wvf} that underwent CT between 2002-2014. A radiologist measured NECT-attenuation, corticomedullary (CM) and nephrographic (NG) enhancement, echogenicity relative to renal cortex (RC) (N = 5), T2W (T2{sub AML}/T2{sub RC}) signal-intensity (SI), and chemical-shift SI ([SI{sub IN-PHASE} - SI{sub OPPOSED-PHASE}]/SI{sub IN-PHASE}) indices (N = 6). A pathologist re-evaluated 15/18 AML{sub wvf} for 1) < or > 25 % adipocytes/high-power-field (HPF), 2) ''many or few'' blood vessels. Comparisons were performed using chi-square and independent t-tests. 73.3 %(11/15) of AML{sub wvf} had <25 % adipocytes/HPF and 86.7 %(13/15) had ''many'' blood vessels. NECT-attenuation was 41.8(±6.9) HU. 61.1 %(11/18) of AML{sub wvf} were hyper-attenuating and 38.9 %(7/18) iso-attenuating; attenuation was associated with %-adipocytes/HPF, (p = 0.01). CM/NG enhancement were 63.3(±20.8)/51.7(±15.5) HU. 72.2 %(13/18) of AML{sub wvf} had wash-out enhancement, with no association with amount of blood vessels at pathology, (p = 0.68). No difference in echogenicity was noted by histology (p > 0.05). All AML{sub wvf} were T2-hypointense (SI ratio = 0.61 [±0.1]). 2/6 AML{sub wvf} showed SI drop on chemical-shift MRI; both were iso-attenuating and were associated with >25 % adipocytes/HPF (p = 0.04). AML{sub wvf} are typically T2-hypointense and hyper-attenuating with wash-out enhancement due to abundant smooth muscle and vessels respectively. Iso-attenuating AML{sub wvf} with microscopic fat on MRI contain more adipocytes/HPF. (orig.)

  9. Alternative splicing and genomic structure of the AML1 gene involved in acute myeloid leukemia.

    Miyoshi, H; Ohira, M; Shimizu, K; Mitani, K; Hirai, H; Imai, T.; Yokoyama, K.; Soeda, E; Ohki, M


    We previously isolated the AML1 gene, which is rearranged by the t(8;21) translocation in acute myeloid leukemia. The AML1 gene is highly homologous to the Drosophila segmentation gene runt and the mouse transcription factor PEBP2 alpha subunit gene. This region of homology, called the Runt domain, is responsible for DNA-binding and protein--protein interaction. In this study, we isolated and characterized various forms of AML1 cDNAs which reflect a complex pattern of mRNA species. Analysis o...

  10. Strahlungsmessung und Dosimetrie

    Krieger, Hanno


    „Strahlungsquellen und Dosimetrie“ ist Teil einer Lehrbuchreihe zur Strahlungsphysik und zum Strahlenschutz. Der erste Teil befasst sich mit den physikalischen Grundlagen der Strahlungsdetektoren und der Strahlungsmessung. Im zweiten Teil werden die Konzepte und Verfahren der klinischen Dosimetrie dargestellt. Der dritte Abschnitt erläutert ausführlich die Dosisverteilungen der klinisch angewendeten Strahlungsarten. Im vierten Teil werden weitere Messaufgaben der Strahlungsphysik einschließlich der Messsysteme für die Bildgebung mit Röntgenstrahlung dargestellt. Neben den grundlegenden Ausführungen enthält dieser Band im laufenden Text zahlreiche Tabellen und Grafiken zur technischen und medizinischen Radiologie, die bei der praktischen Arbeit sehr hilfreich sein können und 199 Übungsaufgaben mit Lösungen zur Vertiefung der Inhalte. Für die zweite Auflage wurden die Darstellungen der Elektronen- und der Protonendosimetrie sowie der bildgebenden Verfahren mit Computertomografen deutlich erweit...

  11. Globalisierung und (politische) Bildung

    Wilkiewicz, Zbigniew


    Der Autor skizziert zu Beginn die Bestandteile und Theoriekonzepte der Globalisierung sowie ihre Folgen für Umwelt, Wirtschaft, Staat, Gesellschaft und Kultur. Er diskutiert im Anschluss daran die Frage, ob eine alternative politische Bildung ein Gegengewicht zur neoliberalen Globalisierung darstellen kann. Er listet hierzu überblicksartig verschiedene Ansatzpunkte und Kernthemen aus der Pädagogik auf und weist vor allem auf die Bedeutung des globales Lernens hin. Er betont abschließend, dass...

  12. Informationskompetenz und Information Literacy

    Ingold, Marianne


    Informationskompetenz ist heute als Begriff , Konzept und praktisches Tätigkeitsfeld von Bibliotheken weltweit etabliert. Entstehung, Verbreitung und Entwicklung von „Informationskompetenz“ im deutschsprachigen Raum stehen in engem Zusammenhang mit dem in den USA und international seit den 1980er Jahren diskutierten und praktisch umgesetzten Konzept der „Information Literacy“. Auch wenn die beiden Begriffe in der Regel gleichbedeutend verwendet werden, zeigt ein Vergleich der vorwiegend aus e...

  13. HACCP Reproduktion und Geburt

    Früh, Barbara; Dippel, Sabine; Leeb, Christine


    Ein Ergebnis des COREPIG-Projektes sind HACCPbasierte Managementhilfen (Hazard Analysis Critical Control Points). Diese Hilfen unterstützen Landwirte betriebsspezifisch bei der Lösung und Vorbeugung von Problemen mit Endoparasiten, Problemen der Reproduktion und rund um die Geburt, bei Absetzdurchfall und Saugferkelsterblichkeit. Sie sind in Form von Microsoft Excel®-Dateien verfügbar. Es wird empfohlen, die Hilfen zusammen mit der Beraterin und/oder dem Veterinär anzuwenden. Jede Manag...

  14. Demografie und politischer Reduktionismus

    Kreitsch, Thomas


    Die Dissertation mit dem Thema „Demografie und politischer Reduktionismus – eine Diskursanalyse der Demografiepolitik in Deutschland“ knüpft an die Debatte um die Demografisierung an, die sich damit beschäftigt, dass gesellschaftliche Entwicklungen häufig zu sehr aus einer demografischen Perspektive betrachtet und beschrieben werden. Sie analysiert die zum Teil noch jungen Diskurse, die durch Akteure in Wissenschaft, Politik und Publizistik zu den demografiepolitischen Strategien und Aktivitä...

  15. Digital Zeichnen und Malen

    Christoph Kaindel


    Full Text Available Digitales Zeichnen und Malen hat gegenüber dem „analogen“ Vorteile wie auch Nachteile. In der folgenden, unvollständigen Liste stelle ich die technischen Vor- und Nachteile, die mir aufgefallen sind, gegenüber. Kommentare und Ergänzungen sind willkommen!

  16. Timothy Ley, M.D., Advocates for Personalized Medicine in AML - TCGA

    Oncologist Dr. Timothy Ley talks about how repurposing of existing drugs based on better understanding of the genetic basis of acute myeloid leukemia (AML) can help patients receive personalized care.

  17. What If the Leukemia Doesn't Respond or Comes Back After Treatment? (AML)

    ... your doctor about acute myeloid leukemia? What if acute myeloid leukemia doesn’t respond or comes back after treatment? For most types of acute myeloid leukemia If acute myeloid leukemia (AML) doesn’t go ...

  18. An acute myeloid leukemia gene, AML1, regulates hemopoietic myeloid cell differentiation and transcriptional activation antagonistically by two alternative spliced forms.

    T. Tanaka; Tanaka, K; Ogawa, S.; M. Kurokawa; Mitani, K; Nishida, J; Shibata, Y; Yazaki, Y.; Hirai, H


    The AML1 gene on chromosome 21 is disrupted in the (8;21)(q22;q22) and (3;21)(q26;q22) translocations associated with myelogenous leukemias and encodes a DNA binding protein. From the AML1 gene, two representative forms of proteins, AML1a and AML1b, are produced by alternative splicing. Both forms have a DNA binding domain but, unlike AML1b, AML1a lacks a putative transcriptional activation domain. Here we demonstrate that overexpressed AML1a totally suppresses granulocytic differentiation an...

  19. Improved Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) of Affinity Maturated and Fc-Engineered Antibodies Directed Against the AML Stem Cell Antigen CD96

    Mohseni Nodehi, Sahar


    Regardless of progress in the therapy of AML, there is no long-term cure for about 70% of AML patients. Leukemic stem cells seem to be an important key for the perpetuation of AML.Most currently used chemotherapeutic agents are not able to eliminate AML-LSCs. The combination of conventional therapies with AML-LSCs-directed therapies may eventually lead to a cure for AML patients.Recently expression of CD96 was reported on AML-LSCs, while only very low expression levels were found on normal HS...

  20. Beerdigung und Feuerbestattung in Bibel und Talmud

    Wiener, Adolf


    Fortsetzung des Aufsatzes u.d.T. "Beerdigung und Feuerbestattung in der Bibel / Schlußartikel von Rabbiner Dr. Wiener in Oppeln" s.a. Erwiderung "Die Erd- und Feuerbestattung / von Rabbiner Dr. Kohn in Inowrazlaw" s.a.

  1. Jersey: Financial Sector Assessment Program Update: Detailed Assessment of Observance of AML/CFT

    International Monetary Fund


    Jersey has put in place a comprehensive and robust Antimoney Laundering/Combating the Financing of Terrorism (AML/CFT) legal framework with a high level of compliance with almost all aspects of the Financial Action Task Force recommendations. The paper discusses a Detailed Assessment of Observance of AML/CFT report on Jersey. Both money laundering and financing of terrorism are criminalized largely in line with the international standard, and Jersey has implemented the provisions effectively.

  2. Intranuclear targeting of AML/CBFα regulatory factors to nuclear matrix-associated transcriptional domains

    Zeng, Congmei; McNeil, Sandra; Pockwinse, Shirwin; Nickerson, Jeffrey; Shopland, Lindsay; Lawrence, Jeanne B.; Penman, Sheldon; Hiebert, Scott; Lian, Jane B.; van Wijnen, André J.; Stein, Janet L.; Stein, Gary S.


    The AML/CBFα runt transcription factors are key regulators of hematopoietic and bone tissue-specific gene expression. These factors contain a 31-amino acid nuclear matrix targeting signal that supports association with the nuclear matrix. We determined that the AML/CBFα factors must bind to the nuclear matrix to exert control of transcription. Fusing the nuclear matrix targeting signal to the GAL4 DNA binding domain transactivates a genomically integrated GAL4 responsive reporter gene. These ...

  3. Forholdet mellom aml. § 14-12 og direktiv 2008/104/EC art. 4

    Trovåg, Kristin


    Masteroppgaven omhandler forholdet mellom aml. § 14-12 og direktiv 2008/104/EC art. 4 (vikarbyrådirektivet). Problemstillingen er om begrensningene for innleie av arbeidskraft fra bemanningsforetak i aml. § 14-12 første ledd er i overenstemmelse med de restriksjoner som lovlig kan begrunnes og gjennomføres etter vikarbyrådirektivet art. 4 nr. 1.

  4. How mRNA is misspliced in acute myelogenous leukemia (AML)?

    Mohamed, Aminetou Mint; Thénoz, Morgan; Solly, Françoise; Balsat, Marie; Mortreux, Franck; Wattel, Eric


    Approximately one-third of expressed genes are misspliced in AML, opening the possibility that additional factors than splicing factor mutations might cause RNA missplicing in these diseases. AML cells harbor a constellation of epigenetic modifications and regularly express large amounts of WT1 transcripts. Histone acetylation/methylation and DNA CpG methylation favor either exon skipping or inclusion, mainly through interfering with RNA Pol II-mediated elongation. This can result either from...

  5. Cognitive distortions based on MDS configuration and sketch mapping: a case study in Beijing

    Shen, Si; Xue, Lulu; Wu, Lun; Liu, Yu


    As an emerging field, cognitive map kept playing a significant role in geography these decades. To date, there are two dominant methods to externalize human's internal cognitive map, namely, multidimensional scaling (MDS) and skech mapping. However, among most recent researches on cognitive map, the differences between both methods are always ignored. The usage of one method over another is still under scrutiny. In order to shed light on the similarity or distinctions of MDS configuration and sketch mapping, we conducted an experiment on Beijing residents by requesting a sketch of the region within 3rd Ring and meanwhile extracting distance estimates between 8 landmarks. Employing the Bidimensional regression along with standard deviational ellipse, we studied the global and local distortions among two kinds of cognitive maps and quantitatively measure the overall and local cognitive maps distortions. Besides, we use Monte Carlo simulation method to calculate the radius of distortion for the Distortion Index (DI). It shows that the average cognitive distortion of habitants in Beijing is 2km to 3km, and the distortion takes 2nd-ring road as a border, displaying a southwest-northeast diagonal stretch and an east-west contracted tendency. The distortion in the two methods is remarkably both correlated with factors, such as travel frequency and years of residence. Comparing two methods, it turned out that sketch map was more consistent with real map, while the distortion orientations of sketch map resembled MDS configuration. Finally, we gave possible reasons with regard to above conclusions and advices for future usage of two methods.

  6. Auslandsadoptionen - Forschungsstand und Folgerungen

    Textor, Martin R.


    Die Übersicht über deutsch- und englischsprachige Studien über Auslandsadoptionen enthält Angaben über Schichtzugehörigkeit und Motive der Adoptiveltern, das Familienklima und die Eltern-Kind-Beziehungen. Auch werden Forschungsergebnisse über die gesundheitliche, körperliche, sprachliche, schulische, soziale und Persönlichkeitsentwicklung ausländischer Adoptivkinder referiert. Ferner wird über den Adoptionserfolg und über Verhaltensauffälligkeiten dieser Kinder berichtet. Schließlich werden K...

  7. Ting, Twitter und Tablet

    Schabos, Julia


    In der Leseförderung spielen klassische Medien eine wesentliche Rolle, werden aber zunehmend durch digitale Angebote ergänzt. Das Projekt „Lesen macht stark: Lesen und digitale Medien“ greift diese Entwicklung auf. Es bietet Bibliotheken mit fünf altersgerechten Aktionen die Gelegenheit, bewährte Veranstaltungsformate digital anzureichern und cross-medial zu arbeiten, denn Text- und Medienkompetenz sind wesentliche Voraussetzungen für die Meinungs- und Persönlichkeitsbildung von Kindern und J...

  8. Gold und Peanuts

    Hashmi, Stephen


    Die bisherigen Kenntnisse zur Gold-Katalyse lassen sich wie folgt zusammenfassen: 1. Gold-Katalysatoren reagieren rasch mit Kohlenstoff-Kohlenstoff-Mehrfachbindungen und sind somit besonders für einen Einsatz in der Organischen Chemie,der Chemie des Kohlenstoffs, geeignet. Dies lässt sich damit erklären, dass Gold und Kohlenstoff gemäß des Prinzips der harten und weichen Säuren und Basen („hard and soft acids and bases“, HSABPrinzip)beide als „weich“ klassifiziert werden und dieses Prinzi...

  9. The DVB Channel Coding Application Using the DSP Development Board MDS TM-13 IREF

    M. Slanina


    Full Text Available The paper deals with the implementation of the channel codingaccording to DVB standard on DSP development board MDS TM-13 IREF andPC. The board is based on Philips Nexperia media processor andintegrates hardware video ADC and DAC. The program libraries featuresused for MPEG based video compression are outlined and then thealgorithms of channel decoding (FEC protection against errors arepresented including the flowchart diagrams. The paper presents thepartial hardware implementation of the simulation system that coversselected phenomena of DVB baseband processing and it is used for realtime interactive demonstration of error protection influence ontransmitted digital video in laboratory and education.

  10. Adversarial Error Resilience in Distributed Storage Using MRD Codes and MDS Array Codes

    Silberstein, Natalia; Vishwanath, Sriram


    This paper presents a novel coding scheme for distributed storage systems containing nodes with adversarial errors. The key challenge in such systems is the propagation of the erroneous data from a single corrupted node to the rest of the system during node repair process. We present a concatenated coding scheme which is based on two types of codes: maximum rank distance (MRD) code as an outer code and optimal repair maximal distance separable (MDS) array code as an inner code. We prove that this coding scheme attains the upper bound on the resilience capacity, i.e., amount of data stored reliably in a system with a limited number of corrupted nodes.

  11. Extramedullary Acute Myeloid Leukemia (AML: Leukemic Pleural Effusion, Case Report and Review of the Literature



    Full Text Available Objective and Importance: Malignant pleural effusions occur in the setting of both solid and hematologic malignancies. Pleural effusion caused by leukemic infiltration is an unusual extramedullary manifestation of acute myeloid leukemia (AML with fewer than 20 cases reported.1-11 We report a case of pericardial and pleural effusions in a patient with AML and review the literature. Clinical presentation: In this case, a 55 year old man with previous history of myeloproliferative neoplasm (MPN experienced transformation AML, heralded by appearance of leukemic pleural effusions. The patient was identified to have leukemic pleural effusion based upon extended cytogenetic analysis of the pleural fluid, as morphologic analysis alone was insufficient. Intervention: The patient was treated with hypomethylator-based and intensive chemotherapy strategies, both of which maintained resolution of the effusions in the remission setting. Conclusion: Due to the rarity of diagnosis of leukemic pleural effusions, both cytogenetic and fluorescence in situ hybridization (FISH testing are recommended. Futhermore, systemic chemotherapy directed at the AML can lead to complete resolution of leukemic pleural effusions. Objective and ImportancePleural effusion caused by leukemic infiltration is an unusual extramedullary manifestation of acute myeloid leukemia (AML, but may be more common than previously thought. Fewer than 20 cases have been reported.1-11 We report a case of pericardial and pleural effusions in a patient with AML and review the literature.

  12. Patient-derived acute myeloid leukemia (AML) bone marrow cells display distinct intracellular kinase phosphorylation patterns

    Multiparametric analyses of phospho-protein activation in patients with acute myeloid leukemia (AML) offers a quantitative measure to monitor the activity of novel intracellular kinase (IK) inhibitors. As recent clinical investigation with FMS-like tyrosine-3 inhibitors demonstrated, targeting IK with selective inhibitors can have a modest clinical benefit. Because multiple IKs are active in patients with AML, multikinase inhibitors may provide the necessary inhibition profile to achieve a more sustained clinical benefit. We here describe a method of assessing the activation of several IKs by flow cytometry. In 40 different samples of patients with AML we observed hyper-activated phospho-proteins at baseline, which is modestly increased by adding stem cell factor to AML cells. Finally, AML cells had a significantly different phospho-protein profile compared with cells of the lymphocyte gate. In conclusion, our method offers a way to determine the activation status of multiple kinases in AML and hence is a reliable assay to evaluate the pharmacodynamic activity of novel multikinase inhibitors

  13. Flugmechanik und Flugregelung von Luftschiffen

    Kämpf, Bernhard G.


    In der vorliegenden Arbeit wird eine geschlossene algebraische Modellierung der Flugmechanik von Luftschiffen entwickelt und im Rahmen analytischer und numerischer Untersuchungen angewendet. Die Resultate geben eine allgemeine Einsicht in die flugmechanischen Eigenschaften von Luftschiffen und werden in den Entwurf einer Flugreglerstruktur umgesetzt. Neben der Darstellung der Gewichts- und Schubkräfte werden die aerostatischen und thermodynamischen Zusammenhänge dargestellt. Der Schwerpunk...

  14. c-Jun N-terminal kinase mediates AML1-ETO protein-induced connexin-43 expression

    AML1-ETO fusion protein, a product of leukemia-related chromosomal translocation t(8;21), was reported to upregulate expression of connexin-43 (Cx43), a member of gap junction-constituted connexin family. However, its mechanism(s) remains unclear. By bioinformatic analysis, here we showed that there are two putative AML1-binding consensus sequences followed by two activated protein (AP)1 sites in the 5'-flanking region upstream to Cx43 gene. AML1-ETO could directly bind to these two AML1-binding sites in electrophoretic mobility shift assay, but luciferase reporter assay revealed that the AML1 binding sites were not indispensable for Cx43 induction by AML1-ETO protein. Conversely, AP1 sites exerted an important role in this event. In agreement, AML1-ETO overexpression in leukemic U937 cells activated c-Jun N-terminal kinase (JNK), while its specific inhibitor SP600125 effectively abrogated AML1-ETO-induced Cx43 expression, indicating that JNK signaling pathway contributes to AML1-ETO induced Cx43 expression. These results would shed new insights for understanding mechanisms of AML1-ETO-associated leukemogenesis

  15. Tissue-specific upregulation of MDS/EVI gene transcripts in the intestine by thyroid hormone during Xenopus metamorphosis.

    Thomas C Miller

    Full Text Available BACKGROUND: Intestinal remodeling during amphibian metamorphosis resembles the maturation of the adult intestine during mammalian postembryonic development when the adult epithelial self-renewing system is established under the influence of high concentrations of plasma thyroid hormone (T3. This process involves de novo formation and subsequent proliferation and differentiation of the adult stem cells. METHODOLOGY/PRINCIPAL FINDINGS: The T3-dependence of the formation of adult intestinal stem cell during Xenopus laevis metamorphosis offers a unique opportunity to identify genes likely important for adult organ-specific stem cell development. We have cloned and characterized the ectopic viral integration site 1 (EVI and its variant myelodysplastic syndrome 1 (MDS/EVI generated via transcription from the upstream MDS promoter and alternative splicing. EVI and MDS/EVI have been implicated in a number of cancers including breast, leukemia, ovarian, and intestinal cancers. We show that EVI and MDS/EVI transcripts are upregulated by T3 in the epithelium but not the rest of the intestine in Xenopus laevis when adult stem cells are forming in the epithelium. CONCLUSIONS/SIGNIFICANCE: Our results suggest that EVI and MDS/EVI are likely involved in the development and/or proliferation of newly forming adult intestinal epithelial cells.

  16. Schwangerschaftshypertonie: Therapie und Nachsorge

    Homuth V


    Full Text Available Kurzfassung: Hypertensive Schwangerschaftserkrankungen komplizieren mehr als 10 % aller Schwangerschaften weltweit. Klinisch am bedeutsamsten sind die durch Hypertonie und Proteinurie nach der 20. Schwangerschaftswoche definierte schwangerschaftsinduzierte Präeklampsie und Pfropfpräeklampsie, insbesondere deren schwerste Verlaufsformen Eklampsie und HELLP-Syndrom. Sie gehören global unverändert zu den führenden Ursachen für fetale, neonatale und mütterliche Morbidität und Mortalität. Ihre Ätiologie ist unbekannt und daher ist mit Ausnahme der Beendigung der Schwangerschaft eine kausale Therapie nicht möglich. Insbesondere bleibt eine antihypertensive Therapie hinsichtlich der fetalen Entwicklung problematisch und sollte zur Vermeidung mütterlicher kardiovaskulärer Komplikationen erst bei Blutdruckwerten ≥ 170/110 mmHg begonnen werden, bei vorbestehendem Hochdruck oder Pfropfkonstellation (präexistente Nierenerkrankung, Diabetes mellitus bereits ab Blutdruckwerten von ≥ 160/ 100 mmHg. Zu beachten ist dabei die nur geringe Auswahl in der Schwangerschaft einsetzbarer Antihypertensiva, die sich im Wesentlichen auf Methyldopa, und bereits eingeschränkt auf den Betablocker Metoprolol sowie Dihydralazin und den Kalziumantagonisten Nifedipin begrenzt. Eine der wichtigsten Aufgaben nach der Entbindung ist die Gewährleistung und Förderung des Stillens. Aufgrund ausreichender medikamentöser Alternativen ist ein Abstillen wegen einer antihypertensiven Therapie nicht indiziert. Ergebnisse aktueller Untersuchungen zeigen, dass eine Hypertonie in der Schwangerschaft und ihre Komplikationen Frühgeburtlichkeit und vermindertes Geburtsgewicht einen bedeutsamen Risikofaktor für das Auftreten kardiovaskulärer Erkrankungen, wie Herzinfarkt und Schlaganfall, im späteren Leben darstellen. Daher sind für davon Betroffene frühzeitige Maßnahmen zur kardiovaskulären Prävention und lebenslangen Verlaufskontrolle zu fordern.

  17. Architekturvermittlung an Kinder und Jugendliche

    Nadansky, Martina


    In einer Zeit voller wirtschaftlicher und sozialer Brennpunkte mag die Auseinandersetzung mit Architektur nicht nahe liegen, wenn man den Aspekt der ästhetischen Gestaltung in den Vordergrund stellt. Architektur war und ist jedoch immer auch ein Seismograph der Gesellschaft, ihrer politischen, wirtschaftlichen und soziologischen Umstände und in sofern Ausdruck unseres höchsten Kulturgutes – des geistigen, emotionalen und sozial befriedigenden Zusammenlebens. Kinder und Jugendliche sind ein Te...

  18. A stable transcription factor complex nucleated by oligomeric AML1–ETO controls leukaemogenesis

    Sun, Xiao-Jian; Wang, Zhanxin; Wang, Lan; Jiang, Yanwen; Kost, Nils; Soong, T. David; Chen, Wei-Yi; Tang, Zhanyun; Nakadai, Tomoyoshi; Elemento, Olivier; Fischle, Wolfgang; Melnick, Ari; Patel, Dinshaw J.; Nimer, Stephen D.; Roeder, Robert G.


    Transcription factors are frequently altered in leukaemia through chromosomal translocation, mutation or aberrant expression. AML1–ETO, a fusion protein generated by the t(8;21) translocation in acute myeloid leukaemia, is a transcription factor implicated in both gene repression and activation. AML1–ETO oligomerization, mediated by the NHR2 domain, is critical for leukaemogenesis, making it important to identify co-regulatory factors that ‘read’ the NHR2 oligomerization and contribute to leukaemogenesis. Here we show that, in human leukaemic cells, AML1–ETO resides in and functions through a stable AML1–ETO-containing transcription factor complex (AETFC) that contains several haematopoietic transcription (co)factors. These AETFC components stabilize the complex through multivalent interactions, provide multiple DNA-binding domains for diverse target genes, co-localize genome wide, cooperatively regulate gene expression, and contribute to leukaemogenesis. Within the AETFC complex, AML1–ETO oligomerization is required for a specific interaction between the oligomerized NHR2 domain and a novel NHR2-binding (N2B) motif in E proteins. Crystallographic analysis of the NHR2–N2B complex reveals a unique interaction pattern in which an N2B peptide makes direct contact with side chains of two NHR2 domains as a dimer, providing a novel model of how dimeric/oligomeric transcription factors create a new protein-binding interface through dimerization/oligomerization. Intriguingly, disruption of this interaction by point mutations abrogates AML1–ETO-induced haematopoietic stem/progenitor cell self-renewal and leukaemogenesis. These results reveal new mechanisms of action of AML1–ETO, and provide a potential therapeutic target in t(8;21)-positive acute myeloid leukaemia.

  19. Loss of TLE1 and TLE4 from the del(9q) commonly deleted region in AML cooperates with AML1-ETO to affect myeloid cell proliferation and survival

    Dayyani, Farshid; Wang, Jianfeng; Yeh, Jing-Ruey J.; Ahn, Eun-Young; Tobey, Erica; Zhang, Dong-Er; Bernstein, Irwin D.; Peterson, Randall T.; Sweetser, David A.


    Deletions on chromosome 9q are seen in a subset of acute myeloid leukemia (AML) cases and are specifically associated with t(8;21) AML. We previously defined the commonly deleted region in del(9q) AML and characterized the genes in this interval. To determine the critical lost gene(s) that might cooperate with the AML1-ETO fusion gene produced by t(8;21), we developed a set of shRNAs directed against each gene in this region. Within this library, shRNAs to TLE1 and TLE4 were the only shRNAs c...

  20. Nitridoborate und Nitridocarbonate der Seltenerdelemente

    Neukirch, Michael


    Die vorliegende Arbeit befasst sich mit der Darstellung und Charakterisierung von Verbindungen im System A-B-C-N (A = EA, M oder SE). In diesem System sind Nitridoborate (Anionen aus B und N), Nitridocarbonate (Anionen aus C und N) und Tetracyanoborate (Anionen aus B, C und N) bekannt. Das Gebiet der Nitridoborate wurde im Rahmen dieser Arbeit um die Verbindungen YNi(BN) und SE(1-x)CaxNi(BN) mit SE = Tm (x = 0,3; 0,5 und 0,7) und Yb (x = 0,5) erweitert. Neben der röntgenographischen Chara...

  1. The Corepressor mSin3A Regulates Phosphorylation-Induced Activation, Intranuclear Location, and Stability of AML1

    Imai, Yoichi; Kurokawa, Mineo; Yamaguchi, Yuko; Izutsu, Koji; Nitta, Eriko; Mitani, Kinuko; Satake, Masanobu; Noda, Tetsuo; Ito, Yoshiaki; Hirai, Hisamaru


    The AML1 (RUNX1) gene, one of the most frequent targets of translocations associated with human leukemias, encodes a DNA-binding protein that plays pivotal roles in myeloid differentiation through transcriptional regulation of various genes. Previously, we reported that AML1 is phosphorylated on two serine residues with dependence on activation of extracellular signal-regulated kinase, which positively regulates the transcriptional activity of AML1. Here, we demonstrate that the interaction b...

  2. Arbeit und Nicht-Arbeit : Entgrenzungen und Begrenzungen von Lebensbereichen und Praxen


    "Mit dem Begriff der Entgrenzung lassen sich aktuelle Phänomene des Wandels von Arbeit und Arbeitskulturen fassen. Lange bestehende Standards von Arbeitsverträgen, Arbeitszeiten oder Arbeitsplätzen und -orten befinden sich in Auflösung oder werden ausgeweitet. Abgrenzungen von Arbeit und Arbeitslosigkeit, Familien- und Reproduktionsarbeit, von klassischer Lohnarbeit und Bürgerarbeit sowie gesellschaftlichem Engagement verlieren zunehmend an Schärfe. Die Grenzen der Bedeutung und des Verständn...

  3. Psychiatrische Erkrankungen und Wirtschaftskrisen

    Berghofer G


    Full Text Available Es besteht ein enger Zusammenhang von wirtschaftlichen Krisen und erhöhten Raten an Arbeitslosigkeit mit psychischen Erkrankungen wie Depressionen, Angstzuständen, Schlafstörungen und Alkoholismus sowie erhöhten Suizidraten. Gleichzeitig gibt es wirkungsvolle Maßnahmen, diesen schädlichen Gesundheitsauswirkungen von Wirtschaftskrisen effektiv entgegenzuwirken. Dazu gehören soziale und finanzielle Absicherungsprogramme, arbeitsmarktpolitische Förderangebote, Unterstützungsmaßnahmen für Familien und Entschuldungsprogramme. In Wirtschaftskrisen vorgenommene Kürzungen im Gesundheitswesen führen hingegen zu einer Verschlechterung der gesundheitlichen Versorgung und längerfristig zu erhöhten Gesundheitskosten. Um negativen gesundheitlichen Auswirkungen von Wirtschaftskrisen effektiv vorzubeugen, sollte daher präventiv in den Ausbau psychosozialer Angebote und medizinischer wie therapeutischer Versorgungseinrichtungen mit niederschwelligem Zugang investiert werden.

  4. Morbus Crohn und Psychosomatik

    Moser G


    Full Text Available Die psychosoziale Dimension bei Morbus Crohn soll in der Diagnostik und Therapie dieser chronisch entzündlichen Darmerkrankung berücksichtigt werden. Dieses Leiden trifft zumeist junge Individuen, nimmt einen chronischen Verlauf, ist mit tabuisierten Beschwerden verbunden und derzeit trotz intensiver Forschung unheilbar. Beeinträchtigte Lebensqualität und psychische Störungen wie Angst und Depressivität sind mögliche Folgen dieser Erkrankung. Die moderne psychosomatische Medizin bezieht sich auf das biopsychosoziale Modell, in dem parallel die biologischen, psychischen und sozialen Faktoren bei der Entstehung und dem Verlauf von Erkrankungen zu berücksichtigen sind. In der folgenden Übersichtsarbeit werden diese Faktoren für den Morbus Crohn dargestellt.

  5. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation

    Rishi, Loveena; Hannon, Maura; Salomè, Mara;


    α (C/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop...... cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C/EBPα and E2F1 to...

  6. Ethnografische Diskursanalyse und Sozialwissenschaften

    Macgilchrist, Felicitas; Hout, Tom Van


    Ethnografie und Diskursanalyse werden in den Sozialwissenschaften zunehmend kombiniert. In diesem Beitrag wird zunächst ein Überblick gegeben über das entstehende Feld der mit den Epistemologien und Methoden der Ethnografie und Diskursanalyse arbeitenden Forschung. Im zweiten Schritt werden zentral Aspekte eines neuen, computergestützten Ansatzes zur ethnografischen Diskursanalyse vorgestellt. Dieser mikroanalytische Ansatz bietet die Möglichkeit, Erkenntnisse über das Ringen um Deutungsmuste...

  7. Nachhaltige Bodenbewirtschaftung und Bodenschutz

    Ehrnsberger, Rainer


    Es werden aus bodenbiologischer Sicht die Funktion, Bedeutung und Gefährdung unserer Böden dargestellt und die Ziele einer nachhaltigen Bodenbewirtschaftung angesichts der allgemeinen Diskussion um "Sustainable Development" erläutert. Die Neuerungen des Bundes-Bodenschutzgesetzes von 1998 werden diskutiert und anhand der Ergebnisse einer Machbarkeitsstudie zum Thema "Erlebnisbereich Boden" dargelegt, wie die Ziele einer nachhaltigen Bodenbewirtschaftung gerade in einer neuen Dauerausstellung ...

  8. Information und Macht : Proceedings


    Die 12 Beiträge des vorliegenden Sammelbands versuchen quer zu bestehenden Disziplinen und Diskursen dem Zusammenhang von Information und Macht nachzugehen. Informationsforschung ist ein Forschungsfeld, das unterschiedliche disziplinäre Zugangsweisen - sie reichen von der Soziologie über Wirtschaftsinformatik bis zur Kunst - zu verbinden vermag. Die Autoren wollen die Fruchtbarkeit dieses inter- und intradisziplinären Unternehmens an den folgenden Themenkomplexen demonstrieren: (1) 'Informati...

  9. RFID: Grundlagen und Potenziale

    Overmeyer, Ludger; Vogeler, Stefan


    Die Radio Frequenz Identifikation (RFID) erlaubt es, Objekte mit Transpondern zu versehen und sie dadurch eindeutig zu identifizieren sowie drahtlos Daten auszutauschen. Das Potenzial der RFID erstreckt sich dabei weit über die einfache Identifikation von Objekten und bietet die Möglichkeit, Daten lokal zu speichern, sensorisch zu erfassen und am Objekt zu verarbeiten bzw. Steuerungs-entscheidungen zu treffen. Für die volle Ausschöpfung dieses Potenzials sind technologische Fragestellungen de...

  10. Resilienz - Konstrukt und Facetten

    Casper, Miriam


    Mit dieser Arbeit soll ein Beitrag zur Weiterentwicklung der Diskussion zum Thema Resilienz geleistet werden. Zielstellung ist es, zu einer Elaboration des Konstrukts und seiner Faktoren und Facetten beizutragen. Resilienz wird dabei als Persönlichkeitsmerkmal verstanden, das den Menschen befähigt, schwierige Lebenssituationen ohne anhaltende Beeinträchtigung zu überstehen (Duden, 2014). Die teststatistische Untersuchung der englischsprachigen RS-25 (Wagnild/Young, 1993) und der deutschsprach...

  11. Schwerpunktbericht: Migration und Gesundheit

    Razum, Oliver; Meesmann, Uta; Bredehorst, Maren; Brzoska, Patrick; Dercks, Tanja; Glodny, Susanne; Zeeb, Hajo; Schenk, Liane; Salman, Ramazan; Menkhaus, Björn; Ulrich, Ralf; Saß, Anke-Christine


    Fast ein Fünftel der Menschen in Deutschland hat einen Migrationshintergrund. Sie sind entweder selbst zugewandert oder Kinder und Enkel von Zuwanderern. Ein Migrationshintergrund bringt Chancen und Risiken mit sich, sowohl für die Lebenssituation als auch für die Gesundheit. Hinweis: Auf der RKI-Homepage können Sie Daten zum Schwerpunktbericht "Migration und Gesundheit" (ergänzende Wertetabellen zu den Abbildungen) herunterladen.

  12. Fotografie und atomare Katastrophe

    Bürkner, Daniel


    Die Dissertation setzt sich mit den fotografischen Repräsentationen der Atombombenabwürfe auf Hiroshima und Nagasaki sowie der Havarie des Kernkraftwerks Tschernobyl auseinander. Dabei werden künstlerische, dokumentarische und touristische Bilder analysiert, die sich der jeweiligen Strahlenkatastrophe oftmals erst Jahre nach dem Ereignis annehmen und ikonografische oder medial-materielle Bezüge zu ihr aufweisen. Es zeigen sich zentrale Strategien, atomare Katastrophen, seien sie militäri...

  13. Nachhaltigkeit und Menschenbilder

    Siebenhüner, Bernd


    "Die praktische Umsetzung der Nachhaltigkeit in Politik und Gesellschaft erfordert eine Reflexion der den unterschiedlichen Maßnahmen zugrunde liegendenden Menschenbilder, die jedoch stets sowohl normativ als auch deskriptiv-analytisch sind. Im Artikel werden Menschenbildentwürfe wie der homo oeconomicus, der homo sociologicus, der homo politicus, der homo oecologicus und der homo sustinens unter dem Blickwinkel ihrer Erklärungs- und Gestaltungsbeiträge erörtert." (Autorenreferat)

  14. Arbeitsbedingungen, Gesundheit und Arbeitsleistung

    Binnewies, Carmen; Sonnentag, Sabine


    Stress ist ein weit verbreitetes und zunehmendes Phänomen in der Arbeitswelt. Dass stressvolle Arbeitsbedingungen mit einer negativen Beeinträchtigung der Gesundheit einhergehen, wurde vielfach und relativ eindeutig durch die Forschung bestätigt. Für Arbeitsleistung zeigen sich in der Tendenz ebenfalls eher negative Zusammenhänge mit stressvollen Arbeitsbedingungen. Allerdings scheint es unter bestimmten Bedingungen auch keine oder auch positive Zusammenhänge zu geben und die Ergebnisse müsse...

  15. Kronos und der walfisch

    Janez Stanovnik


    Full Text Available Nach Hesiod, Theog. 154—210 entmannte Kronos seinen Vater Uranos, als sich dieser Gaia in der Nacht nahte, indem er ihm mit der von seiner Mutter gegebenen Sichel sein Glied abschnitt. Es ist bekannt, daß das Verhältnis zwischen Uranos und Kronos eine Dublette des Verhältnisses zwischen Kronos und seinen Kindern, insbesondere Zeus, ist. Laut der Theogonie hat auch Zeus dasselbe seinem Vater Kronos angetan: er hat ihn mit Honig trunken gemacht und ihn damn im Schlaf gefesselt und entmannt.

  16. Sternbilder und ihre Mythen

    Fasching, Gerhard

    Die Sternbilder, die seit alters her die Menschen in ihren Bann gezogen haben, und die damit verbundenen Mythen werden in zweifacher Weise vorgestellt. Erstens ist es die Absicht, dem Leser zu helfen, sich am Sternenhimmel zurechtzufinden, und zweitens will es ihm die Vielfalt der Bilder vermitteln, die damit verbunden sind. Am Anfang des Buches stehen die prächtigen Erzählungen aus Ovids Metamorphosen. Dann ist vom Sternenhimmel im Jahreskreis die Rede, um den Leser anzuregen, diesen fast unendlichen Bilderreichtum sich selbst durch eigene Beobachtungen zu erschließen. Ein umfangreicher Abschnitt behandelt die einzelnen Sternbilder und das hierzu überlieferte Wissen. Sternkarten und alte Kupferstiche aus dem Bestand der Österreichischen Nationalbibliothek zeigen, wie man sich in früheren Jahrhunderten den Sternenhimmel vorgestellt hat. Sternsagen und Mythen werden erzählt und auch das ptolemäische und das kopernikanische Weltsystem werden einander gegenübergestellt. Ausführliche Sachverzeichnisse mit über 3000 Suchbegriffen erleichtern den Zugang zu Stern- und Sternbildnamen und zur Mythologie.

  17. Lipidsenker, Statine und Fibrate

    Hoppichler F


    Full Text Available Eine Behandlung der Hyperlipidämie durch Diät und medikamentöse Lipidsenkung führt bekanntermaßen zu einer signifikanten Verringerung kardiovaskulärer Ereignisse. Neben dem lipidsenkenden Effekt führen Statine zur Stabilisierung atherosklerotischer Plaques und Fibrate bewirken eine deutliche Verringerung des Risikofaktors Fibrinogen. Der Effekt einer Kombination von Statinen und Fibraten wird in laufenden Studien, wie der FENICE und UKLDS untersucht, wobei letztere den Einfluß dieser Therapieformen auf das Gefäßrisiko beim diabetischen Patienten zum Inhalt hat.

  18. Digital Natives und Datenschutz

    Triz Heider


    Full Text Available Dieser Artikel lädt dazu ein, sich ein Bild der virtuellen Welt zu machen, ihre eingeborenen User zu verstehen, ihre Sprache und Kultur kennen zu lernen und damit einen Schritt zur Integration in „die digitale Gesellschaft“ (falls es sie gibt zu tun. Es findet eine Auseinandersetzung über die aktuelle Entwicklung des Internets, notwendige Kompetenzen Hilfesuchender und die Architektur von virtueller Beratung statt. Aspekte von Datenschutz und Privatsphäre runden die Ausführungen ab. Dabei werden sowohl aktuelle Themen angesprochen, als auch Vergleiche mit anderen, großen Internetangeboten wie SocialNetworks herangezogen.

  19. T-cell receptor Vbeta CDR3 oligoclonality frequently occurs in childhood refractory cytopenia (MDS-RC) and severe aplastic anemia

    Vries, A.C. de; Langerak, A.W.; Verhaaf, B.;


    (Very) severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V)SAA is a bone marrow (BM) failure syndrome characterized by immune-mediated destruction of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder, of which...

  20. Darstellung und Untersuchung von niederkoordinierten Platinimino-, Platinoxo- und Platinalkylidenborylkomplexen

    Brand, Johannes


    Diese Dissertation handelt von der Darstellung, Charakterisierung und Reaktivitätsuntersuchungen von neuartigen Platinalkylidenborylkomplexen und eines heteroleptischen Platiniminoborylkomplexes. Außerdem wurden Reaktivitätsuntersuchungen an einem Platinoxoborylkomplex durchgeführt und die erhaltenen Produkte wurden genau untersucht und charakterisiert.

  1. Improved MDS-based Sensor Localization Algorithm in Wireless Sensor Networks

    Yiqing Zhang


    Full Text Available Sensor localization technology is the principle problem for configuration and operation of wireless sensor network. Since existing multidimensional scaling localization algorithm has its limitation in localization accuracy, a novel method based on node distance correction (DCMDS is put forward. The improved multidimensional scaling-based sensor localization algorithm partly divides the location areas of the whole network. It achieves the relative position by distance information among the nodes. Then the distance estimations are corrected according to the distance information of anchor nodes. When the corrected estimations distance matrix is completed, relative position is recalculated with classical MDS algorithm. The optimized particle swarm optimization is used to acquire the final localization results. The performances of DCMDS algorithm were validated in different scenario. The experiments revealed that improved method has high accuracy in localization and low complexity for calculation and communication. It also enhances the extensibility of localization algorithms

  2. [Iron chelation therapy and its influence on the alleviation of EPO resistance in MDS patients].

    Zhang, Yao; Xiao, Chao; Gu, Shu-Cheng; Chang, Chun-Kang


    This study was aimed to investigate the changes of erythropoietin (EPO), hemoglobin(Hb) and recombinant EPO (rEPO) levels in MDS patients receiving iron chelation therapy, and to explore the relationship between EPO and serum ferritin(SF). A total of 172 MDS patients and 30 healthy controls were studied. The levels of SF, EPO, serum iron (SI), total iron binding capacity (TIBC), C-reaction protein (CRP) and Hb were measured respectively, the level of SF was adjusted according to the changes of CRP. Among them, there were 34 cases of low-risk (SF>1 000 mg/L) receiving deferoxamine therapy, whose changes of SF, EPO, SI, TIBC, Hb levels were detected and compared before and after treatment. Besides, the difference in the incidence of EPO resistance in iron overload group and non-iron overload group was assessed before and after therapy, and 58 cases of low-risk and EPO<1 000 U/L MDS patients were given rEPO therapy. The results showed that the level of EPO in non-iron overload group was higher than that in the normal control group (997.44 ± 473.48 vs 467.27 ± 238.49, P < 0.05). Obviously, the level of EPO in iron overload group was higher than that in non-iron overload group and control group (3257.59 ± 697.19 vs 997.44 ± 473.48, P = 0.012, 3257.59 ± 697.19 vs 467.27 ± 238.49, P = 0.002). Otherwise, the incidence of EPO resistance in iron overload group was higher than that in non-iron overload group (18/35 vs 2/23, P = 0.001), and the level of EPO and SF was positively related to each other in iron overload group (r = 0.310,P = 0.036). After receiving iron chelation therapy, the levels of SF, SI, TIBC and EPO in iron overload group were significantly lower than that before therapy (3942.38 ± 641.82 vs 2266.35 ± 367.31, P = 0.028;48.61 ± 10.65 vs 28.52 ± 12.61, P = 0.034;59.84 ± 12.62 vs 33.76 ± 15.43, P = 0.045;3808.01 ± 750.22 vs 1954.78 ± 473.18, P = 0.042). Moreover, the level of Hb increased (35 ± 18 vs 57 ± 21, P = 0.046) and the EPO resistance

  3. Analysis of local ionospheric variability based on SVD and MDS at low-latitude GNSS stations

    Dabbakuti, J. R. K. Kumar; Devanaboyina, Venkata Ratnam; Kanchumarthi, S. Ramesh


    Investigation of ionospheric anomalies during equatorial and low latitude is of major concern for modeling and global navigation satellite system (GNSS) applications. Total electron content (TEC) varies with the ionospheric conditions, which will lead to the errors in the global positioning system (GPS) measurements. It is therefore a method that is necessary to characterize the ionospheric anomalies for satellite-based navigation systems. In this study, characterization of ionospheric variations based on the singular value decomposition (SVD) and classical multidimensional scaling (MDS) methods was studied. The yearly and daily variations are decomposed from the GPS-TEC, international reference ionosphere (IRI) 2007 and IRI 2012 models TEC over the three low-latitude GNSS stations located at Koneru Lakshmaiah University (KLU-Guntur), Hyderabad and Bangalore, respectively. From the results, it is found that there is a strong correlation between GPS-TEC and IRI models. The correlation coefficient for the first three singular values is more than 0.86. From this, it is possible to reconstruct more than 85 % of the variability contained in global GPS-derived VTEC data (for year 2013) by using only the first three modes. The semiannual variation has maximum value during March-April and September-October and has minimum value during June-July. It is observed that the annual variations have maximum value in summer and minimum value in winter, and the amplitudes decrease with increasing latitude. Further, opposite latitudinal asymmetry among annual and semiannual variations for three GNSS stations is noticed. SVD and MDS methods clearly show time-varying characteristics and the absence of the winter anomaly at low-latitude GNSS stations.

  4. Isotopes and innovation: MDS Nordion's first fifty years, 1946-1996

    Few people realize that Canada leads in the world in the production of radio isotopes, the raw material of nuclear medicine and high-tech scanners, and in their use in medicine and industry. In Isotopes and Innovation the author gives an in-depth look at MDS Nordion, a company that started as the radium sales department of Eldorado Mining and Refining, the Canadian uranium producer that was a key strategic resource for the Allies during the race to build the nuclear bomb, and went on to become the world?s leading producer of radioisotopes. When radium began to be used as a cancer treatment, Eldorado quickly became familiar with the medical marketplace and adept at developing products that could solve clinical problems and, more important, save lives. When Canadian nuclear reactors at Chalk River began producing radioisotopes that outperformed radium, Eldorado's radium sales department was transferred to a new crown corporation, Atomic Energy of Canada Limited, created to manage Canada's nuclear research establishment. The new company developed many useful applications for radioisotopes, including cobalt-60 cancer therapy machines and industrial sterilization plants. Bought by Medical Data Services Inc. in the early 1990s, MDS Nordion was a runaway success, creator and sole proprietor of several market-leading products. Isotopes and Innovation describes how a company capitalized on the byproducts of Canada's unique nuclear research program to attain a commanding international position in extremely specialized and demanding high-tech markets, a saga in which innovative research and enterprising global marketing have brought commercial success and saved countless lives around the world

  5. Epilepsie und psychiatrische Erkrankungen

    Baumgartner C


    Full Text Available Psychiatrische Erkrankungen treten bei Epilepsiepatienten signifikant häufiger auf als in der Allgemeinbevölkerung und als bei Patienten mit anderen chronischen Erkrankungen. Die Depression stellt die häufigste psychiatrische Begleiterkrankung bei Epilepsie dar. Die Häufigkeit von Depressionen korreliert mit der Anfallskontrolle: Sie liegt zwischen 3 und 9 % bei gut kontrollierter Epilepsie, jedoch zwischen 20 und 55 % bei Patienten mit therapieresistenten Epilepsien. Umgekehrt ist bei Patienten mit neu diagnostizierten Epilepsien anamnestisch signifikant häufiger eine Depression zu erheben als in einem Vergleichskollektiv. Diese bidirektionale Beziehung zwischen Epilepsie und Depression könnte durch gemeinsame Pathomechanismen beider Erkrankungen erklärt werden. Obwohl das Vorliegen und der Schweregrad einer Depression die wichtigsten Prädiktoren für die Lebensqualität bei Epilepsiepatienten darstellen, werden Depressionen bei Epilepsiepatienten unterdiagnostiziert und unterbehandelt. Eine psychopharmakologische Behandlung sollte bei Vorliegen einer Begleitdepression deshalb unverzüglich initiiert werden, das epileptogene Potential von Antidepressiva stellt dabei ein vernachlässigbares Risiko dar. Die Prävalenz psychotischer Störungen bei Epilepsiepatienten liegt zwischen 2 und 8 %, wobei sogenannte episodische Psychosen (iktale, postiktale und Alternativpsychosen, die in einem zeitlichen Bezug zum Anfallsgeschehen stehen, und chronische Psychosen (interiktale Psychosen ohne zeitlichen Bezug zu den Anfällen, unterschieden werden können. Die Prävalenz von Angststörungen bei Epilepsiepatienten liegt zwischen 15 und 25 %. Man kann zwischen präiktaler, iktaler, postiktaler und interiktaler Angst unterscheiden.

  6. Investigation of porosity and fractal properties of the sintered metal and semiconductor layers in the MDS capacitor structure

    Skatkov Leonid; Gomozov Valeriy; Bayrachniy Boris


    MDS capacitor (metal - dielectric - semiconductor) is a structure in which metal plate is represented by compact bulk-porous pellets of niobium sintered powder, and semiconductor plate - by pyrolytic layer of MnO2. In the present paper we report the results of investigation of microporosity of sintered Nb and pyrolytic MnO2 and also the fractal properties of semiconductor layer.

  7. AML suppresses hematopoiesis by releasing exosomes that contain microRNAs targeting c-MYB.

    Hornick, Noah I; Doron, Ben; Abdelhamed, Sherif; Huan, Jianya; Harrington, Christina A; Shen, Rongkun; Cambronne, Xiaolu A; Chakkaramakkil Verghese, Santhosh; Kurre, Peter


    Exosomes are paracrine regulators of the tumor microenvironment and contain complex cargo. We previously reported that exosomes released from acute myeloid leukemia (AML) cells can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors. We found that the systemic loss of hematopoietic function is also in part a consequence of AML exosome-directed microRNA (miRNA) trafficking to HSPCs. Exosomes isolated from cultured AML or the plasma from mice bearing AML xenografts exhibited enrichment of miR-150 and miR-155. HSPCs cocultured with either of these exosomes exhibited impaired clonogenicity, through the miR-150- and miR-155-mediated suppression of the translation of transcripts encoding c-MYB, a transcription factor involved in HSPC differentiation and proliferation. To discover additional miRNA targets, we captured miR-155 and its target transcripts by coimmunoprecipitation with an attenuated RNA-induced silencing complex (RISC)-trap, followed by high-throughput sequencing. This approach identified known and previously unknown miR-155 target transcripts. Integration of the miR-155 targets with information from the protein interaction database STRING revealed proteins indirectly affected by AML exosome-derived miRNA. Our findings indicate a direct effect of AML exosomes on HSPCs that, through a stroma-independent mechanism, compromises hematopoiesis. Furthermore, combining miRNA target data with protein-protein interaction data may be a broadly applicable strategy to define the effects of exosome-mediated trafficking of regulatory molecules within the tumor microenvironment. PMID:27601730

  8. Milch, Milchprodukte, Analoge und Speiseeis

    Coors, Ursula

    Die Produktpalette Milch und Erzeugnisse aus Milch beinhaltet Konsummilch, die aus Milch oder Bestandteilen der Milch hergestellten Milcherzeugnisse wie Sauermilch-, Joghurt-, Kefir-, Buttermilch-, Sahne-, Kondensmilch-, Trockenmilch- und Molkenerzeugnisse, Milchmisch- und Molkenmischprodukte (Produkte mit beigegebenen Lebensmitteln), Milchzucker, Milcheiweißerzeugnisse, Milchfette und Käse.

  9. Chemie metastabiler Anionen : Synthese und Charakterisierung neuer Auride und Ozonide

    Nuß, Hannelore


    Die vorliegende Arbeit beschreibt die Synthese und Charakterisierung neuer Ozonid- und Auridverbindungen, sowie Verbindungen des Quadratatdianions. Fünf neue Ozonidverbindungen wurden ausgehend von den Alkalimetallozoniden KO_3, RbO_3 und CsO_3 durch Umsetzung mit verschiedenen Kronenetherliganden in flüssigem Ammoniak hergestellt. Das Verhältnis zwischen Ligandendurchmesser und Kationenradius bestimmt dabei die Art der Komplexierung des Metallzentrums und damit auch die Packung der Kompl...

  10. An Implementation and Evaluation of the AMLS Method for SparseEigenvalue Problems

    Gao, Weiguo; Li, Xiaoye S.; Yang, Chao; Bai, Zhaojun


    We describe an efficient implementation and present aperformance study of an algebraic multilevel sub-structuring (AMLS)method for sparse eigenvalue problems. We assess the time and memoryrequirements associated with the key steps of the algorithm, and compareitwith the shift-and-invert Lanczos algorithm in computational cost. Oureigenvalue problems come from two very different application areas: theaccelerator cavity design and the normal mode vibrational analysis of thepolyethylene particles. We show that the AMLS method, when implementedcarefully, is very competitive with the traditional method in broadapplication areas, especially when large numbers of eigenvalues aresought.

  11. Markttransformation und politische Instrumente

    Irrek, Wolfgang; Thomas, Stefan

    Was die Energieabnehmerinnen und -abnehmer in privaten Haushalten, öffentlichen Einrichtungen und Unternehmen im Grunde benötigen, ist nicht Energie, sondern die Befriedigung ihrer energierelevanten Bedürfnisse (z. B. eine warme Wohnung, kühles Bier, Informationsübertragung oder Kraftanwendung).

  12. Rundfunk und Fernsehen


    Rundfunk meint die rein akustische Verbreitung von Musik- und Wortsendungen (sog. Hörfunk) mittels elektromagnetischer Wellen sowie die Organisationseinrichtungen für Sendung und Empfang (Radio-Verkehrs-Aktien-Gesellschaft [RAVAG], Radio Wien, Reichsrundfunk, Rundfunk, Österreichischer [ORF]), Fernsehen das optisch-akustische Analogon dazu.

  13. Manuelle und elektronische Vorgangssteuerung

    Schwickert, Axel C.; Rey, Louis-Ferdinand


    Sequentielle Vorgangsbearbeitung und manuelle Vorgangssteuerung sind typische Kennzeichen verrichtungsorientierter Organisationen. Hier werden einzelne Vorgänge und Vorgangsschritte mit Unterstützung allenfalls traditioneller EDV-Systeme von spezialisierten Sachbearbeitern arbeitsteilig abgearbeitet. Auf der Kritik der tradierten manuellen Vorgangssteuerung aufbauend, wird die elektronische Vorgangssteuerung in einer prozeßorientierten Organisation dargestellt. Die prozeßorientierte Vorgangss...

  14. Von Menschenbildern und Hirnmodellen

    Koukkou, M


    Haben die beeindruckenden Erkenntnisse der Hirnforschung das Menschenbild verändert, auf das sich die Psychiatrie beruft? Ist die Befürchtung berechtigt, dass dadurch der Beziehungsaspekt und das Biographische in Psychiatrie und Psychotherapie an Bedeutung verlieren? Diesen Fragen geht Martha Koukkou im folgenden Text nach.

  15. Steuern und Governance

    Eduard Müller


    Full Text Available ENGLISH: Taxation, in the modern state, has long been a mass phenomenon with an interdisciplinary outlook. On the macro level of the state, a new generation of administrative reforms has crystallized under the label “good public governance”. These reforms seek to resolve regulatory interdependence of state and non - state actors by way of cooperation and interaction. In parallel, on the micro level of businesses, “corporate governance” – voluntary compliance with legal and ethical standards – has become an increasingly important issue. With a view to tax law and tax collection, these developments open up new possibilities to raise tax compliance by means of consensual and cooperative instruments and, accordingly, address taxation as a mass phenomenon. DEUTSCH: Besteuerung ist im modernen Staat ein Massenphänomen und längst interdisziplinär ausgerichtet. Auf der Makro-Ebene des Staates hat sich unter dem Begriff Good Public Governance eine neue Generation von Staats- und Verwaltungsreformen herausgebildet, die Regelungsbeziehungen von staatlichen und nichtstaatlichen Akteuren durch Kooperationen und Interaktionen zu lösen versucht. Parallel dazu hat auf der Mikro-Ebene der Unternehmen mit dem Thema Corporate Governance die freiwillige Einhaltung von rechtlichen und ethischen Regeln an Bedeutung gewonnen. Für das Steuerrecht und den Steuervollzug resultieren aus diesen Entwicklungen neue Möglichkeiten, durch Nutzung konsens- und kooperationsorientierter Instrumente die Tax Compliance zu erhöhen und so dem Massenphänomen Besteuerung gerecht zu werden.

  16. The MDS Mortality Risk Index: The evolution of a method for predicting 6-month mortality in nursing home residents

    Parker-Oliver Debra


    Full Text Available Abstract Background Accurate prognosis is vital to the initiation of advance care planning particularly in a vulnerable, at risk population such as care home residents. The aim of this paper is to report on the revision and simplification of the MDS Mortality Rating Index (MMRI for use in clinical practice to predict the probability of death in six months for care home residents. Methods The design was a secondary analysis of a US Minimum Data Set (MDS for long term care residents using regression analysis to identify predictors of mortality within six months. Results Using twelve easy to collect items, the probability of mortality within six months was accurately predicted within the MDS database. The items are: admission to the care home within three months; lost weight unintentionally in past three months; renal failure; chronic heart failure; poor appetite; male; dehydrated; short of breath; active cancer diagnosis; age; deteriorated cognitive skills in past three months; activities of daily living score. Conclusion A lack of recognition of the proximity of death is often blamed for inappropriate admission to hospital at the end of an older person's life. An accurate prognosis for older adults living in a residential or nursing home can facilitate end of life decision making and planning for preferred place of care at the end of life. The original MMRI was derived and validated from a large database of long term care residents in the USA. However, this simplification of the revised index (MMRI-R may provide a means for facilitating prognostication and end of life discussions for application outside the USA where the MDS is not in use. Prospective testing is needed to further test the accuracy of the MMRI-R and its application in the UK and other non-MDS settings.

  17. ELMO1 is upregulated in AML CD34+ stem/progenitor cells, mediates chemotaxis and predicts poor prognosis in normal karyotype AML.

    Capala, Marta E; Vellenga, Edo; Schuringa, Jan Jacob


    Both normal as well leukemic hematopoietic stem cells critically depend on their microenvironment in the bone marrow for processes such as self-renewal, survival and differentiation, although the exact pathways that are involved remain poorly understood. We performed transcriptome analysis on primitive CD34+ acute myeloid leukemia (AML) cells (n = 46), their more differentiated CD34- leukemic progeny, and normal CD34+ bone marrow cells (n = 31) and focused on differentially expressed genes involved in adhesion and migration. Thus, Engulfment and Motility protein 1 (ELMO1) was identified amongst the top 50 most differentially expressed genes. ELMO1 is a crucial link in the signaling cascade that leads to activation of RAC GTPases and cytoskeleton rearrangements. We confirmed increased ELMO1 expression at the mRNA and protein level in a panel of AML samples and showed that high ELMO1 expression is an independent negative prognostic factor in normal karyotype (NK) AML in three large independent patient cohorts. Downmodulation of ELMO1 in human CB CD34+ cells did not significantly alter expansion, progenitor frequency or differentiation in stromal co-cultures, but did result in a decreased frequency of stem cells in LTC-IC assays. In BCR-ABL-transduced human CB CD34+ cells depletion of ELMO1 resulted in a mild decrease in proliferation, but replating capacity of progenitors was severely impaired. Downregulation of ELMO1 in a panel of primary CD34+ AML cells also resulted in reduced long-term growth in stromal co-cultures in two out of three cases. Pharmacological inhibition of the ELMO1 downstream target RAC resulted in a severely impaired proliferation and survival of leukemic cells. Finally, ELMO1 depletion caused a marked decrease in SDF1-induced chemotaxis of leukemic cells. Taken together, these data show that inhibiting the ELMO1-RAC axis might be an alternative way to target leukemic cells. PMID:25360637

  18. ELMO1 Is Upregulated in AML CD34+ Stem/Progenitor Cells, Mediates Chemotaxis and Predicts Poor Prognosis in Normal Karyotype AML

    Capala, Marta E.; Vellenga, Edo; Schuringa, Jan Jacob


    Both normal as well leukemic hematopoietic stem cells critically depend on their microenvironment in the bone marrow for processes such as self-renewal, survival and differentiation, although the exact pathways that are involved remain poorly understood. We performed transcriptome analysis on primitive CD34+ acute myeloid leukemia (AML) cells (n = 46), their more differentiated CD34− leukemic progeny, and normal CD34+ bone marrow cells (n = 31) and focused on differentially expressed genes in...

  19. Thermodynamik grundlagen und technische anwendungen

    Baehr, Hans Dieter


    Für die aktualisierte 14. Auflage des bewährten Lehrbuchs der Technischen Thermodynamik wurde das Kapitel über Wärmekraftanlagen gründlich bearbeitet und durch einen Abschnitt zur Energiewandlung ergänzt: Die Energiebedarfsstruktur von Deutschland wird erläutert, und die möglichen Energiewandlungspfade werden diskutiert. Schwerpunkt des Buches ist die ausführliche und auch dem Anfänger verständliche Darstellung der Grundlagen der Thermodynamik mit der sorgfältigen Einführung der thermodynamischen Begriffe und den fundamentalen Bilanzgleichungen für Energie, Entropie und Exergie. Die thermodynamischen Eigenschaften reiner Fluide und fluider Gemische werden eingehend erläutert. Darauf aufbauend wird die Thermodynamik der Gemische und der chemischen Reaktionen entwickelt. Auch die thermodynamischen Aspekte wichtiger energie- und verfahrenstechnischer Anwendungen werden praxisnah behandelt: - Strömungs- und Arbeitsprozesse, - thermische Stofftrennverfahren, - Verbrennungsprozesse und Verbrennungsk...

  20. Zinkbedarf und Risiko und Nutzen einer Zinksupplementierung

    Wolfgang Maret


    Full Text Available Der Körper eines erwachsenen Menschen enthält 2 – 3 g Zink, von denen pro Tag etwa 0,1% ersetzt werden. Auf dieser Basis und gestützt auf Schätzungen bezüglich der Bioverfügbarkeit von Zink werden Ernährungsempfehlungen für augenscheinlich gesunde Personen gegeben. Das Fehlen chemischer, funktioneller und/oder körperlicher Anzeichen eines Zinkmangels gilt dabei als Hinweis auf eine adäquate Versorgung. Spezifischere Daten sind jedoch nur selten vorhanden. Veränderungen hinsichtlich der Auswahl und Verfügbarkeit von Nahrungsmitteln sowie neue Methoden der Zubereitung, Konservierung und Aufbereitung machen u. U. die Neubewertung älterer Daten erforderlich. Konservative Schätzungen legen nahe, dass bei ≥ 25% der Weltbevölkerung das Risiko für einen Zinkmangel besteht. Die meisten Betroffenen sind arm und konsumieren nur selten Nahrungsmittel, die reich an gut bioverfügbarem Zink sind, sondern eher solche, die einen hohen Gehalt an Inhibitoren der Zinkabsorption aufweisen und/oder kaum bioverfügbares Zink enthalten. Im Gegensatz dazu hat bei vergleichsweise Wohlhabenden die Auswahl der Nahrungsmittel entscheidenden Einfluss auf das Risiko für einen Zinkmangel. Ein weiteres Problem, ebenfalls speziell bei vergleichsweise Wohlhabenden, ist das Risiko einer chronischen Zinkintoxikation durch übermäßige Einnahme von Zinksupplementen. Insbesondere kann eine hohe Aufnahme von Zink verglichen mit Kupfer zu Kupfermangel führen. Eine bedeutende Herausforderung, die im Hinblick auf den maximalen Nutzen für die Gesundheit bisher noch nicht gemeistert worden ist, besteht darin, dass die empfohlene Tagesdosis (recommended dietary allowance, RDA und die Referenzdosis (RfD für eine sichere Aufnahme von Zink sehr nahe beieinander liegen. Aktuelle Empfehlungen berücksichtigen weder die zahlreichen Nahrungsmittelbestandteile, die die Bioverfügbarkeit von Zink und Kupfer beeinflussen, noch die Wahrscheinlichkeit einer Vergiftung durch

  1. Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML


    Relapsed Acute Lymphoblastic Leukemia (ALL); Refractory Acute Lymphoblastic Leukemia (ALL); Relapsed Acute Myelogenous Leukemia (AML); Refractory Acute Myelogenous Leukemia (AML); Relapsed Mixed Lineage Leukemia; Refractory Mixed Lineage Leukemia; Relapsed Biphenotypic Leukemia; Refractory Biphenotypic Leukemia; Chronic Myelogenous Leukemia (CML) in Blast Crisis

  2. 30 CFR 874.17 - AML agency procedures for reclamation projects receiving less than 50 percent government funding.


    ... accordance with the provisions of 30 CFR subchapter R; (3) Develop specific-site reclamation requirements... 30 Mineral Resources 3 2010-07-01 2010-07-01 false AML agency procedures for reclamation projects... RECLAMATION REQUIREMENTS § 874.17 AML agency procedures for reclamation projects receiving less than...

  3. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts

    Dombret, Hervé; Seymour, John F.; Butrym, Aleksandra; Wierzbowska, Agnieszka; Selleslag, Dominik; Jang, Jun Ho; Kumar, Rajat; Cavenagh, James; Schuh, Andre C.; Candoni, Anna; Récher, Christian; Sandhu, Irwindeep; Bernal del Castillo, Teresa; Al-Ali, Haifa Kathrin; Martinelli, Giovanni


    Azacitidine increased median overall survival by 3.8 months vs current commonly used AML treatments (10.4 vs 6.5 months; P = .1009).Azacitidine safety in patients age ≥65 years with AML (>30% blasts) was consistent with its known safety profile in other trials.

  4. Zusammenfassung Workshop und Umfrageergebnisse "Bedarf und Anforderungen an Ressourcen für Text und Data Mining"

    Sens, Irina; Katerbow, Matthias; Schöch, Christof; Mittermaier, Bernhard


    Zusammenfassung des Workshops und Visualisierung der Umfrageerbegnisse der Umfrage "Bedarf und Anforderungen an Ressourcen für Text und Data Mining" der Schwerpunktinitiative "Digitale Information" der Allianz der deutschen Wissenschaftsorganisationen, Arbeitsgruppe Text und Data Mining

  5. MDS-RA、MgA与M6的骨髓细胞形态学鉴别诊断%Differential diagnostic of bone marrow morphocytology in the patients with MDS-RA,MgA and M6

    于远军; 张敏


    Objechve: To analyze the bone marrow morphocytology in the patients with MDS-RA. MgA and M6, deepen our understanding of related diseases. Methods: 25 cases diagnosed in our hospital and Shanghai Ruijin Hospital were analyzed. Results: MDS-RA of the bone marrow showed active or significantly active proliferation, occasionally showed by poplasia.The ratio of G/E in bone marrow often reduced and more than two series were dysplastic. MgA of the bone marrow showed significantly active proliferation The ratio of G/E in bone marrow often reduced and the bone marrow cells had a change of giants. M6 of the bone marrow showed significantly active proliferation The ratio of G/E in bone marrow were often inverse. Erythrocytes were significantly dysplastic and the more ratio of blastocytes was found. Conclusion: MDS-RA, MgA and M6 of the bone marrow showed in common that erythrocytes were significantly active proliferation and the bone marrow cells had a change of giants. The differentia shows that the bone marrow of MDS-RA and M6 are dysplastic and have the different ratio of blastocytes. The bone marrow cells of MgA have a change of giants and the ratio of blastocytes is not high.%目的:分析MDS-RA、MgA及M6患者骨髓细胞形态特点,以提高对相关疾病的认识.方法:对在我院及上海瑞金医院确诊的25例MDS-RA,MgA及M6患者的骨髓细胞形态进行分析.结果:MDS-RA骨髓增生活跃或明显活跃,偶见增生减低,粒红比常减低,常见两系以上病态;MgA骨髓增生明显活跃,粒红比常减低,粒红两系出现巨幼样变;M6骨髓增生明显活跃,粒红比常倒置,红系明显病态,原始细胞增多.结论:MDS-RA,MgA及M6的骨髓象共同点:都会出现红系明显增生,出现巨幼样病态改变.不同点:MDS-RA与M6主要是各系病态造血明显,通常以原始细胞比例不同进行鉴别.而MgA主要表现为各系的巨幼样变,且原始细胞比例不高.

  6. Antepartuales fetales Elektrokardiogramm und Kardiotokographie

    Prechtl, Eva Maria


    Es wurden 65 Patientinnen zwischen der 17. und 41. Schwangerschaftswoche unter Berücksichtigung der Hauptpathologien "intauterine Wachstumsretardierung" und "Gestationsdiabetes" simultan mit Hilfe der Kineto-Kardiotokographie (KCTG) und des fetalen abdominalen EKGs (AECG) untersucht. Neben dem direkten Vergleich von KCTG- und AECG-Messung wurde die Registrierqualität des AECG hinsichtlich verschiedener Einflussgrößen untersucht und eine Analyse der errechneten Durchschnitts-EKGs vorgenommen. ...

  7. Digitale Lesekompetenz und digitale Kultur

    Jung, Meike


    Konzept, Veranstaltungen und Vermittlung in der Stadtbibliothek Stuttgart Unter dem Begriff „digitale Lesekompetenz“ schaut die Stadtbibliothek Stuttgart unter die glänzenden Medienoberflächen. Sie thematisiert die Nutzungsqualitäten und Auswirkungen der digitalen Medien sowie die gesellschaftlichen und persönlichen Konsequenzen. Medien- und Recherchekompetenz, Datenschutz, Privatsphäre und Sicherheit im Netz sind Themen, die von der Stadtbibliothek Stuttgart gemeinsam mit einem Netzwerk v...

  8. Lipide und Diabetes

    Riedl M


    Full Text Available 2010 werden weltweit ca. 220 Millionen Menschen von Diabetes betroffen sein, und die Inzidenz und Prävalenz steigen weiter an. Die meisten dieser Patienten (90 % leiden an Typ-2-Diabetes, der ein 2- bis 4fach höheres Risiko für Herz-Kreislauf-Erkrankungen mit sich bringt. Die pathogenetische Erklärung für das erhöhte atherosklerotische Risiko beim Diabetes ist noch immer kontroversiell. Von allen Risikofaktoren scheint die derzeit am besten modulierbare Größe in bezug auf Atherosklerose und Diabetes die Dyslipidämie zu sein. Sie ist charakterisiert durch ein moderat erhöhtes Gesamt- und Low Density Lipoprotein (LDL-Cholesterin, erhöhte Triglyzeride und ein niedriges High Density Lipoprotein (HDL. Post-hoc-Analysen der Subgruppen der primären Interventionsstudien Helsinki Heart Study und AFCAPS/TexCAPS und der sekundären Interventionsstudien CARE, 4S, LIPID und VA-HIT sowie die DAIS-Studie zeigen eine hohe Wahrscheinlichkeit, daß Lipidreduktion das makrovaskuläre Risiko auch bei Diabetikern senkt. Die erhöhte Inzidenz für Herz-Kreislauf-Erkrankungen bei Diabetes, die größere Sterblichkeitsziffer und die erhöhte 1-Jahres-Mortalität bei Patienten mit Myokardinfarkt deuten stark darauf hin, daß die präventive Senkung der Lipidspiegel bei Diabetikern mit dem Ziel der Erreichung der Werte für die Sekundärprävention erfolgen sollte. Derzeit laufen mehrere randomisierte, doppelblinde, placebokontrollierte Studien mit Statinen an Diabetikern, wie die ASPEN-, die CARDS- und die ALLHAT-Studie, die hoffentlich Antwort auf derzeit offene Fragen geben werden.

  9. c-Myc regulates expression of NKG2D ligands ULBP1/2/3 in AML and modulates their susceptibility to NK-mediated lysis

    Nanbakhsh, Arash; Pochon, Cécile; Mallavialle, Aude; Amsellem, Sophie; Bourhis, Jean Henri; Chouaib, Salem


    AML cells resistant to cytarabine are more susceptible to NK-mediated cell lysis.c-Myc regulates ULBP1/2/3 expression and interferes with NK cell susceptibility in primary cytarabine resistant AML blasts.

  10. KRAS (G12D Cooperates with AML1/ETO to Initiate a Mouse Model Mimicking Human Acute Myeloid Leukemia

    Shanmin Zhao


    Full Text Available Background/Aims: It has been demonstrated that KRAS mutations represent about 90% of cancer-associated mutations, and that KRAS mutations play an essential role in neoplastic transformation. Cancer-associated RAS mutations occur frequently in acute myeloid leukemia (AML, suggesting a functional role for Ras in leukemogenesis. Methods: We successfully established a mouse model of human leukemia by transplanting bone marrow cells co-transfected with the K-ras (G12D mutation and AML1/ETO fusion protein. Results: Mice transplanted with AML/ETO+KRAS co-transduced cells had the highest mortality rate than mice transplanted with AML/ETO- or KRAS-transduced cells (115d vs. 150d. Upon reaching a terminal disease stage, EGFP-positive cells dominated their spleen, lymph nodes, peripheral blood and central nervous system tissue. Immunophenotyping, cytologic analyses revealed that AML/ETO+KRAS leukemias predominantly contained immature myeloid precursors (EGFP+/c-Kit+/Mac-1-/Gr-1-. Histologic analyses revealed that massive leukemic infiltrations were closely packed in dense sheets that effaced the normal architecture of spleen and thymus in mice transplanted with AML1/ETO + KRAS co-transduced cells. K-ras mRNA and protein expression were upregulated in bone marrow cells of the K-ras group and AML1/ETO + Kras group. The phosphorylation of MEK/ERK was significantly enhanced in the AML1/ETO + Kras group. The similar results of the AML1/ETO + Nras group were consistent with those reported previously. Conclusion: Co-transduction of KrasG12D and AML1/ETO induces acute monoblastic leukemia. Since expression of mutant K-ras alone was insufficient to induce leukemia, this model may be useful for investigating the multi-step leukemogenesis model of human leukemia.