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Mutations of calreticulin (CALR) are detected in 25–30% of patients with essential thrombocythemia (ET) or primary myelofibrosis and cause frameshifts that result in proteins with a novel C-terminal. We demonstrate that CALR mutations activated signal transducer and activator of transcription 5 (STAT5) in 293T cells in the presence of thrombopoietin receptor (MPL). Human megakaryocytic CMK11-5 cells and erythroleukemic F-36P-MPL cells with knocked-in CALR mutations showed increased growth and acquisition of cytokine-independent growth, respectively, accompanied by STAT5 phosphorylation. Transgenic mice expressing a human CALR mutation with a 52 bp deletion (CALRdel52-transgenic mice (TG)) developed ET, with an increase in platelet count, but not hemoglobin level or white blood cell count, in association with an increase in bone marrow (BM) mature megakaryocytes. CALRdel52 BM cells did not drive away wild-type (WT) BM cells in in vivo competitive serial transplantation assays, suggesting that the self-renewal capacity of CALRdel52 hematopoietic stem cells (HSCs) was comparable to that of WT HSCs. Therapy with the Janus kinase (JAK) inhibitor ruxolitinib ameliorated the thrombocytosis in TG mice and attenuated the increase in number of BM megakaryocytes and HSCs. Taken together, our study provides a model showing that the C-terminal of mutant CALR activated JAK-STAT signaling specifically downstream of MPL and may have a central role in CALR-induced myeloproliferative neoplasms.

The addition of the auxin 2,4-dichlorophenoxy acetic acid (2,4-D) to tobacco Bright-Yellow-2 (BY-2) cells cultured in 2,4-D-depleted medium induced dedifferentiation of starch-storing cells into dividing cells. The changes in cell growth, starch content, organellar DNA content, and the transcript levels for the ADP-glucose pyrophosphorylase gene during the dedifferentiation of starch-storing cells were examined. Cell proliferation, decrease in starch content, and increase in DNA content began from 12–18 h after 2,4-D application. RNA-gel blot analysis showed a decrease in the ADP-glucose pyrophosphorylase mRNA levels, within 6 h of the addition of 2,4-D. Furthermore, experiments using aphidicolin revealed that starch degradation is linked with cell division.

Microwave spectra of iodomethyl methyl ether and its 10 isotopic species have been measured. A least-squares analysis of the observed frequencies gave rotational and quartic centrifugal distortion constants and all the components of the nuclear quadrupole coupling constant tensor. The rsstructure has been well established from the moments of inertia calculated from the observed rotational constants. The observed nuclear quadrupole coupling constant tensor in the inertial principal axes system could be transformed into that in its own principal axes system. The directions of the χ principal axes in the molecule were found to be closely related to the signs of three off-diagonal χ components in the inertial principal axes system which could not be determined by the least-squares fit of the observed frequencies. The signs of the three off-diagonal χ components were concluded to be (+, +, −) for χab, χac, and χbc, respectively. The zaxis of the principal χ system is roughly along the CI bond, while the xaxis is no longer in the OCI plane but is inclined by about 6°30′ toward the side where the CH3group exists. The molecular structure and nuclear quadrupole coupling constant tensor of the present molecule were compared with those of the other halomethyl ethers, alkyl halides, and alkyl ethers.

By using human T-cell growth factor (TCGF), 10 cell lines were established from tissue samples of 10 patients with adult T-cell leukemia (ATL). Three cell lines were adapted to growth in medium lacking TCGF. The surface markers of all cell lines were characteristic of inducer/helper T cells, i.e., OKT3+, OKT4+, OKT6-, OKT8-, OKIa1+, and human Lyt2+ and Lyt3+, except that one cell line was OKT3-. The expression of the viral antigen was examined during establishment of 8 of the 10 cell lines. The viral antigen was not expressed in leukemic cells before cultivation. In 5 lines, the viral antigen was detected by immunofluorescent staining after a short period of cultivation. However, 3 cell lines, ATL-6A, ATL-9Y, and ATL-1K did not express the viral antigen during short-term culture: the ATL-6A and ATL-9Y cell lines became positive for the viral antigen after 5 and 2 months of cultivation, respectively; the ATL-1K cell line remained antigen-negative throughout a culture period of 13 months. Southern blot hybridization assay showed that all of the cell lines, including the viral antigen-negative ATL-1K cell line, contained the viral genome. Thus, the retrovirus was associated with all 10 cell lines established from ATL patients, but there was a heterogeneity in the expression time of the retroviral antigen in leukemic cells maintained in vitro. Our findings suggested that the expression of the viral antigen was not required for maintenance of the leukemic state in vivo and for growth of leukemic cells in vitro.

Microwave spectra of the trans-cisisomer of ethyl vinyl ether and its nine deuterated species were measured. A plausible molecular structure was obtained from the observed moments of inertia by an application of a diagnostic least-squares technique. The dipole moment and its direction were determined by the Stark effect measurements of several low Jtransitions for the normal and two deuterated species.

A comparison between non-selfconsistent single-particle Monte Carlo (MC) simulations and measurements of the output characteristics of an 0.1 µm n-MOSFET is presented. First the bulk MC model, which features a new simplified treatment of inelastic acoustic intravalley scattering, is validated by comparison with experimental literature data for mobilities and velocities. The dopant distribution of the MOSFET is obtained from a 2D process simulation, which is calibrated with SIMS and electrical measurements and fine-tuned by a comparison of the measured transfer characteristics in the subthreshold regime with a coupled Schro¨dinger drift-diffusion (DD) simulation. Then the quantum effect is replaced by a shift of the work function and the DD, hydrodynamic (HD) and MC models are adjusted to reproduce the measured drain current in the linear regime. The results of the three models in the non-linear regime are compared without further adjustment to the measured output characteristics. While good agreement is found for the MC model, the on-current is significantly overestimated by the HD model and underestimated by the DD model.