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To make best use of the exceptional good weather conditions at Chajnantor we developed CHAMP+, a two time seven pixel dual-color heterodyne array for operation in the 350 and 450 µm atmospheric windows. CHAMP+ uses state-of-the-art SIS-mixers provided by our collaborators at SRON. To maximize its performance, optical single sideband filter are implemented for each of the two subarrays, and most of the optics is operated cold (20K) to minimize noise contributions. The instrument can be operated remotely, under full computer control of all components. The autocorrelator backend, currently in operation with 2 × 1GHz of bandwidth for each of the 14 heterodyne channels, will be upgraded by a new technologies FFT spectrometer array in mid 2008. CHAMP+ has been commissioned successfully in late 2007. We will review the performance of the instrument "in the field," and present its characteristics as measured on-sky.
Survival of patients with pediatric acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-SCT) is mainly compromised by leukemia relapse, carrying dismal prognosis. As novel individualized therapeutic approaches are urgently needed, we performed whole-exome sequencing of leukemic blasts of 10 children with post–allo-SCT relapses with the aim of thoroughly characterizing the mutational landscape and identifying druggable mutations. We found that post–allo-SCT ALL relapses display highly diverse and mostly patient-individual genetic lesions. Moreover, mutational cluster analysis showed substantial clonal dynamics during leukemia progression from initial diagnosis to relapse after allo-SCT. Only very few alterations stayed constant over time. This dynamic clonality was exemplified by the detection of thiopurine resistance-mediating mutations in the nucleotidase NT5C2 in 3 patients’ first relapses, which disappeared in the post–allo-SCT relapses on relief of selective pressure of maintenance chemotherapy. Moreover, we identified TP53 mutations in 4 of 10 patients after allo-SCT, reflecting acquired chemoresistance associated with selective pressure of prior antineoplastic treatment. Finally, in 9 of 10 children’s post–allo-SCT relapse, we found alterations in genes for which targeted therapies with novel agents are readily available. We could show efficient targeting of leukemic blasts by APR-246 in 2 patients carrying TP53 mutations. Our findings shed light on the genetic basis of post–allo-SCT relapse and may pave the way for unraveling novel therapeutic strategies in this challenging situation.
3-Hydroxyisobutyrate Dehydrogenase (HIBADH) deficiency - a novel disorder of valine metabolism
(2021)
3-Hydroxyisobutyric acid (3HiB) is an intermediate in the degradation of the branched-chain amino acid valine. Disorders in valine degradation can lead to 3HiB accumulation and its excretion in the urine. This article describes the first two patients with a new metabolic disorder, 3-hydroxyisobutyrate dehydrogenase (HIBADH) deficiency, its phenotype and its treatment with a low-valine diet. The detected mutation in the HIBADH gene leads to nonsense-mediated mRNA decay of the mutant allele and to a complete loss-of-function of the enzyme. Under strict adherence to a low-valine diet a rapid decrease of 3HiB excretion in the urine was observed. Due to limited patient numbers and intrafamilial differences in phenotype with one affected and one unaffected individual, the clinical phenotype of HIBADH deficiency needs further evaluation.
Project Management
(2023)
Companies are increasingly developing into dynamic and project-oriented organizations. Globalization, innovations and organizational dynamics require more and more projects, and thus a more project-oriented corporate organization and management. As a rule, managers as well as employees already work parallel to their line function in projects or completely from project to project.
At the same time, cross-company and especially international value chains lead to the cooperation of cross-departamental and intercultural teams. For this, the specialists and executives need above all knowledge and experience in project management and the corresponding concepts as well as in the special form of cooperation, team development and communication. Because the most problems in project management are not caused by project goals and methods, but by the many different problem-solving behavior and attitudes, e.g. between engineers and business people, different departments or the different country cultures. The international IT project specialist Tom DeMarco puts it in a nutshell (in Peopleware - Productive Projects and Teams: The major problems of our work are not so much technological as socio-logical in nature. In terms of content here, in contrast to traditional professional textbooks, not only the technologies are priority, but also the social and intercultural aspects of project work.
The book is aimed equally at students of all disciplines with a focus on managerial and project-related work as well as practitioners and entrepreneurs in all private business sectors as well as in NGOs, public projects or PPPs as public-private partnership.