High-efficiency, long-pulse operation of MW-level dual-frequency gyrotron, 84/126GHz, for the TCV Tokamak

The first unit of the dual-frequency gyrotron, 84126GHz/1MW/2s, for the upgrade of the TCV ECH system has been delivered and is presently being commissioned. During a first phase, long-pulse operation (TRF gt 0.5 mathrm{s}) has been achieved and powers in excess of 0.93MW/1.1s and 1MW/1.2s have been measured in the evacuated RF-load at the two frequencies, 84GHz (TE {17,5} mode) and 126GHz (TE {26,7} mode), respectively. Considering the different rf losses in the experimental setup, the power level generated in the gyrotron cavity is in excess of 1.1MW and 1.2MW, with a corresponding electronic efficiency of 35% and 36%. These values are in excellent agreement with the design parameters and would likely lead to a gyrotron total efficiency higher than 50% in case of implementation of a depressed collector. The gyrotron behavior is remarkably reliable and robust with the pulse length extension to 2s presently only limited by external auxiliary systems

Precancerous Stem Cells Have the Potential for both Benign and Malignant Differentiation

Cancer stem cells (CSCs) have been identified in hematopoietic and solid tumors. However, their precursors—namely, precancerous stem cells (pCSCs) —have not been characterized. Here we experimentally define the pCSCs that have the potential for both benign and malignant differentiation, depending on environmental cues. While clonal pCSCs can develop into various types of tissue cells in immunocompetent mice without developing into cancer, they often develop, however, into leukemic or solid cancers composed of various types of cancer cells in immunodeficient mice. The progress of the pCSCs to cancers is associated with the up-regulation of c-kit and Sca-1, as well as with lineage markers. Mechanistically, the pCSCs are regulated by the PIWI/AGO family gene called piwil2. Our results provide clear evidence that a single clone of pCSCs has the potential for both benign and malignant differentiation, depending on the environmental cues. We anticipate pCSCs to be a novel target for the early detection, prevention, and therapy of cancers

Bioinformatics Approach Reveals Evidence for Impaired Endometrial Maturation Before and During Early Pregnancy in Women Who Developed Preeclampsia

Impaired uterine invasion by extravillous trophoblast in early gestation is implicated in the genesis of preeclampsia, a potentially lethal malady of human pregnancy. However, reasons for extravillous trophoblast dysfunction remain unclear because of virtual inaccessibility of early placental and uterine tissues from women who develop preeclampsia, and the absence of animal models in which the disease spontaneously occurs. Consequently, the possibility that deficient or defective maturation of the endometrium (decidualization) may compromise extravillous trophoblast invasion in preeclampsia remains unexplored. Using a bioinformatics approach, we tested this hypothesis identifying 396 differentially expressed genes (DEG) in chorionic villous samples from women at ≈11.5 gestational weeks who developed severe preeclampsia symptoms 6 months later compared with chorionic villous samples from normal pregnancies. A large number, 154 or 40%, overlapped with DEG associated with various stages of normal endometrial maturation before and after implantation as identified by other microarray data sets (P=4.7×10−14). One-hundred and sixteen of the 154 DEG or 75% overlapped with DEG associated with normal decidualization in the absence of extravillous trophoblast, ie, late-secretory endometrium (LSE) and endometrium from tubal ectopic pregnancy (EP; P=4.2×10−9). Finally, 112 of these 154 DEG or 73% changed in the opposite direction in microarray data sets related to normal endometrial maturation (P=0.01), including 16 DEG upregulated in decidual (relative to peripheral blood) natural killer cells that were downregulated in chorionic villous samples from women who developed preeclampsia (P<0.0001). Taken together, these results suggest that insufficient or defective maturation of endometrium and decidual natural killer cells during the secretory phase and early pregnancy preceded the development of preeclampsia.Fil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto; ArgentinaFil: Post Uiterweer, Emiel D.. University of Utrecht; Países BajosFil: Jeyabalan, Arun. Magee Womens Hospital; Estados UnidosFil: Hogge, William A.. Magee Womens Hospital; Estados UnidosFil: Conrad, Kirk P.. University of Florida; Estados Unido

Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia

Loss-of-function mutations in telomerase complex genes can cause bone marrow failure, dyskeratosis congenita, and acquired aplastic anemia, both diseases that predispose to acute myeloid leukemia. Loss of telomerase function produces short telomeres, potentially resulting in chromosome recombination, end-to-end fusion, and recognition as damaged DNA. We investigated whether mutations in telomerase genes also occur in acute myeloid leukemia. We screened bone marrow samples from 133 consecutive patients with acute myeloid leukemia and 198 controls for variations in TERT and TERC genes. An additional 89 patients from a second cohort, selected based on cytogenetic status, and 528 controls were further examined for mutations. A third cohort of 372 patients and 384 controls were specifically tested for one TERT gene variant. In the first cohort, 11 patients carried missense TERT gene variants that were not present in controls (P < 0.0001); in the second cohort, TERT mutations were associated with trisomy 8 and inversion 16. Mutation germ-line origin was demonstrated in 5 patients from whom other tissues were available. Analysis of all 3 cohorts (n = 594) for the most common gene variant (A1062T) indicated a prevalence 3 times higher in patients than in controls (n = 1,110; P = 0.0009). Introduction of TERT mutants into telomerase-deficient cells resulted in loss of enzymatic activity by haploinsufficiency. Inherited mutations in TERT that reduce telomerase activity are risk factors for acute myeloid leukemia. We propose that short and dysfunctional telomeres limit normal stem cell proliferation and predispose for leukemia by selection of stem cells with defective DNA damage responses that are prone to genome instability

CW Experiments With the EU 1-MW, 170-GHz Industrial Prototype Gyrotron for ITER at KIT

The European 1-MW, 170-GHz continuous wave industrial prototype gyrotron for electron cyclotron resonance heating and current drive on international thermonuclear experimental reactor was during 2016 under test at the Karlsruhe Institute of Technology (KIT) test facility. In order to optimize the gyrotron operation, the tube was at first thoroughly tested in the short-pulse regime, with pulses that did not exceed 10 ms, for a wide range of operational parameters. Then, and after proper conditioning of the tube, the operation was extended to longer pulses with duration up to 180 s, which is the maximum pulselength possible at the KIT test facility. In this paper, we present in detail the achievements of the long-pulse experimental campaign

Megawatt power generation of the dual-frequency gyrotron for TCV at 84 and 126 GHz, in long pulses

In the frame of the TCV Tokamak upgrade, two 84/126 GHz/2 s dual frequency gyrotrons designed by SPC and KIT and manufactured by THALES will be added to the existing EC-System. The first unit has been delivered to EPFL-SPC and tested. In the commissioning configuration, a matching optics unit (MOU) is connected to the gyrotron window. The RF is then coupled to the HE11 mode of a 63.5mm corrugated waveguide and dissipated in a load procured by CNR after 4m of waveguide and 2 miter bends. Owing to the flexible triode gun design giving the possibility to adjust the pitch angle parameter, the specifications were met at both frequencies. At 84 GHz (TE17,5 mode), a power of 0.930 MW was measured in the calorimeter, with a pulse duration of 1.1 s. At the high frequency (126 GHz, TE26,7 mode), a power of 1.04 MW was reached for a pulse length of 1.2 s. Accounting for the load reflection and the ohmic losses in the various subcomponents of the transmission line and the tube, it is estimated that the output power at the gyrotron window is in excess of 1 MW at both frequencies, with an electronic efficiency of 32% and 34% at 84 GHz and 126 GHz respectively. The gyrotron behavior is remarkably robust and reproducible, and the pulse length is limited by external systems that will be improved shortly