Simulation of milling cells in shell through the cam module Compas‐3D v18

У роботі проведено комп’ютерне моделювання фрезерування карманів дослідної оболонки корпусу ракетно‐космічного призначення із алюмінієвого сплаву. При моделюванні застосована програма «Модуль ЧПУ. Фрезерная обработка», що є інтегрована в систему тривимірного моделювання КОМПАС‐3D v18. Показано, що з трьох стратегій фрезерування карманів («зігзаг», «еквідистанта», «по рядках») найбільш продуктивною є стратегія «зігзаг».The computer simulation of the milling of cells of the experimental shell of the rocket space housing of aluminum alloy. For simulation, we use the program "CNC Module. Milling Processing", which is integrated into Compas‐3D v18. It is shown that of the three pocket milling strategies ("zigzag", "equidistant", "line by line") the most productive is the "zigzag" strategy

Significant association of cutaneous adverse events with hydroxyurea: results from a prospective non-interventional study in BCR-ABL1-negative myeloproliferative neoplasms (MPN) - on behalf of the German Study Group-MPN

Despite the successes achieved with molecular targeted inhibition of the oncogenic driver Bcr-Abl in chronic myeloid leukemia (CML), the majority of patients still require lifelong tyrosine kinase inhibitor (TKI) therapy. This is primarily caused by resisting leukemic stem cells (LSCs), which prevent achievement of treatment-free remission in all patients. Here we describe the ITIM (immunoreceptor tyrosine-based inhibition motif)-containing Fc gamma receptor IIb (FcγRIIb, CD32b) for being critical in LSC resistance and show that targeting FcγRIIb downstream signaling, by using a Food and Drug Administration-approved BTK inhibitor, provides a successful therapeutic approach. First, we identified FcγRIIb upregulation in primary CML stem cells. FcγRIIb depletion caused reduced serial re-plaiting efficiency and cell proliferation in malignant cells. FcγRIIb targeting in both a transgenic and retroviral CML mouse model provided in vivo evidence for successful LSC reduction. Subsequently, we identified BTK as a main downstream mediator and targeting the Bcr-Abl-FcγRIIb-BTK axis in primary CML CD3

Publisher Correction: Significant association of cutaneous adverse events with hydroxyurea: results from a prospective non-interventional study in BCR-ABL1-negative myeloproliferative neoplasms (MPN) - on behalf of the German Study Group-MPN

Stegelmann F, Wille K, Marchi H, et al. Publisher Correction: Significant association of cutaneous adverse events with hydroxyurea: results from a prospective non-interventional study in BCR-ABL1-negative myeloproliferative neoplasms (MPN) - on behalf of the German Study Group-MPN. Leukemia. 2021

Inactivation of polycomb repressive complex 2 components in myeloproliferative and myelodysplastic/myeloproliferative neoplasms

The polycomb repressive complex 2 (PRC2) is a highly conserved histone H3 lysine 27 methyltransferase that regulates the expression of developmental genes. Inactivating mutations of the catalytic component of PRC2, EZH2, are seen in myeloid disorders. We reasoned that the other two core PRC2 components SUZ12 and EED may also bemutational targets in these diseases, as well as associated factors such as Jarid2. SUZ12 mutations were identified in 1 of 2 cases with myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with 17q aUPD and 2 of 2 myelofibrosis cases with focal 17q11 deletions. All three were missense mutations affecting the highly conserved VEFS domain. Analysis of a further 146 MDS/MPN cases revealed an additional VEFS domain mutant, yielding a total mutation frequency of 2/148 (1.4%). We did not find mutations of Jarid2 or EED in association with aUPD for chromosome 6p or 11q, respectively, however screening unselected cases identified missense mutations in EED (1/148; 1%) and Jarid2 (3/148; 2%). All three SUZ12 mutations tested and the EED mutation reduced PRC2 histone methyltransferase activity in vitro, thus demonstrating that PRC2 function may be compromised in myeloid disorders by mutation of distinct genes