Sub-Nyquist Field Trial Using Time Frequency Packed DP-QPSK Super-Channel Within Fixed ITU-T Grid

Sub-Nyquist time frequency packing technique was demonstrated for the first time in a super channel field trial transmission over long-haul distances. The technique allows a limited spectral occupancy even with low order modulation formats. The transmission was successfully performed on a deployed Australian link between Sydney and Melbourne which included 995 km of uncompensated SMF with coexistent traffic. 40 and 100 Gb/s co-propagating channels were transmitted together with the super-channel in a 50 GHz ITU-T grid without additional penalty. The super-channel consisted of eight sub-channels with low-level modulation format, i.e. DP-QPSK, guaranteeing better OSNR robustness and reduced complexity with respect to higher order formats. At the receiver side, coherent detection was used together with iterative maximum-a-posteriori (MAP) detection and decoding. A 975 Gb/s DP-QPSK super-channel was successfully transmitted between Sydney and Melbourne within four 50GHz WSS channels (200 GHz). A maximum potential SE of 5.58 bit/s/Hz was achieved with an OSNR=15.8 dB, comparable to the OSNR of the installed 100 Gb/s channels. The system reliability was proven through long term measurements. In addition, by closing the link in a loop back configuration, a potential SE*d product of 9254 bit/s/Hz*km was achieved

Achieving a Molecular Remission before Allogeneic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia: Impact on Relapse and Long Term Outcome

Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The prognostic value of measurable levels of minimal residual disease (MRD) at time of conditioning is a matter of debate. We analyzed the predictive relevance of MRD levels before transplantation on the clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2 consecutive prospective clinical trials. MRD evaluation before transplantation was available for 65 of the 73 patients who underwent an alloHSCT in CR1. A complete or major molecular response at time of conditioning was achieved in 24 patients (37%), whereas 41 (63%) remained carriers of any other positive MRD level in the bone marrow. MRD negativity at time of conditioning was associated with a significant benefit in terms of risk of relapse at 5 years, with a relapse incidence of 8% compared with 39% for patients with MRD positivity (P\u2009=\u2009.007). However, thanks to the post-transplantation use of tyrosine kinase inhibitors (TKIs), disease-free survival was 58% versus 41% (P\u2009=\u2009.17) and overall survival was 58% versus 49% (P\u2009=\u2009.55) in MRD-negative compared with MRD-positive patients, respectively. The cumulative incidence of nonrelapse mortality was similar in the 2 groups. Achieving a complete molecular remission before transplantation reduces the risk of leukemia relapse even though TKIs may still rescue some patients relapsing after transplantation

Myeloablative conditioning with thiotepa-busulfan-fludarabine does not improve the outcome of patients transplanted with active leukemia: final results of the GITMO prospective trial GANDALF-01

The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population

Guanosine effect on cholesterol efflux and apolipoprotein E expression in astrocytes

The main source of cholesterol in the central nervous system (CNS) is represented by glial cells, mainly astrocytes, which also synthesise and secrete apolipoproteins, in particular apolipoprotein E (ApoE), the major apolipoprotein in the brain, thus generating cholesterol-rich high density lipoproteins (HDLs). This cholesterol trafficking, even though still poorly known, is considered to play a key role in different aspects of neuronal plasticity and in the stabilisation of synaptic transmission. Moreover, cell cholesterol depletion has recently been linked to a reduction in amyloid beta formation. Here we demonstrate that guanosine, which we previously reported to exert several neuroprotective effects, was able to increase cholesterol efflux from astrocytes and C6 rat glioma cells in the absence of exogenously added acceptors. In this effect the phosphoinositide 3 kinase/extracellular signal-regulated kinase 1/2 (PI3K/ERK1/2) pathway seems to play a pivotal role. Guanosine was also able to increase the expression of ApoE in astrocytes, whereas it did not modify the levels of ATP-binding cassette protein A1 (ABCA1), considered the main cholesterol transporter in the CNS. Given the emerging role of cholesterol balance in neuronal repair, these effects provide evidence for a role of guanosine as a potential pharmacological tool in the modulation of cholesterol homeostasis in the brain

Thyroid hormone effects on mouse oocyte maturation and granulosa cell aromatase activity

In the present study we evaluated the role of T-3 on the in vitro processes of mouse cumulus cell-oocyte complex expansion, oocyte meiotic maturation, and granulosa cell aromatase activity. Results obtained from cumuli oophori isolated from immature and adult mice ovaries demonstrated that T-3 at all concentrations tested (0.1-100 nM) did not affect basal or FSH-induced cumulus expansion or interfere with oocyte meiotic maturation up to metaphase II stage. On the contrary, T-3 inhibited in a time- and dose-dependent manner FSH-induced aromatase activity in cultured granulosa cells obtained from either adult or immature female mice. The half-maximal dose (ED50) of T-3 inhibition was 0.87 +/- 0.21 nM, which is in agreement with the reported dissociation constant of T-3 nuclear receptor (K-d = 0.4-5 nM) in mammalian granulosa cells. Time-course experiments demonstrated higher sensitivity to T-3 of adult granulosa cells with respect to immature granulosa cells in culture. Indeed, in immature granulosa cells T-3 inhibition became significantly evident only after 6 days of hormonal treatment, whereas in adult granulosa cells the inhibitory effect was present after only 2 days of treatment. (Bu)(2)cAMP- or 3-isobutyl-1-methyl-xanthine-stimulated aromatase activity was also significantly decreased by T-3, thus suggesting that the inhibition was downstream from cAMP formation. Lastly, analysis of aromatase messenger RNA (mRNA) levels by semiquantitative RT-PCR demonstrated the ability of FSH to increase aromatase mRNA level in cultured granulosa cells by 2.4 +/- 0.5-fold. In agreement with the effect on enzyme activity, the stimulatory effect of FSH on aromatase mRNA level was greatly reduced after T-3 cotreatment. In conclusion, T-3 inhibition of aromatase activity may be of physiological relevance in the complex multihormonal regulation of mammalian follicle development and may contribute to explaining the alteration in female reproductive functions after thyroid hormone hypo- or hypersecretion

The importance of InSAR data post-processing for the interpretation of geomorphological processes

A-DInSAR (Advanced Differential Synthetic Aperture Radar Interferometry) is widely acknowledged as one of the most powerful remote sensing tools for measuring Earth’s surface displacements over large areas, and in particular landslides. The Persistent Scatterer Interferometry (PS-InSAR or PSI) is a common A-DInSAR multitemporal technique, which allows retrieving displacement measurements with sub-centimetric precision. Characterization and interpretation of landslides can greatly benefit from the application of A-DInSAR post-processing tools, especially when extremely slow-moving phenomena are not detectable by classical geomorphological investigations, or when complex displacement patterns need to be highlighted. Detailed representations of the spatial and temporal evolution of the processes provide useful constraints during the planning stages of reconstructions and for land use purposes. The present study is part of a broader national project, focused on updating and monitoring landslide-prone slopes interacting with urban centres in the Central Apennines (Italy), by using both geomorphological and A-DInSAR analysis. Therefore, although field surveys permitted the systematic updating of the available landslide inventories, in most cases, clear indications of displacement were outlined only by the SAR interferometry results. In this regard, the preliminary results of the ongoing research focus on specific post-processing analyses of interferometric data performed in the study area. A specific PS-toolbox software, developed by NHAZCA S.r.l. as a set of post-processing plugins for the open-source software QGIS, was specifically designed to enhance spatial and temporal deformation trends of the PSI results, as well as for visualizing the differences between multi-satellite datasets. Moreover, the PS-toolbox allowed depicting subtle surface patterns within the landslide area, shedding light on kinematics and style of activity of slope instabilities. In complex morphological conditions, as the Apennines mountainous regions, the geometric distortions and the site coverage percentage can lead to a lack of information. Therefore, we compared the coverage of PSs and the accuracy of the surface velocity maps produced using different InSAR tool packages on both Sentinel-1 and COSMO-SkyMed scenes. Thus, the comparison of the resulting datasets allowed their validation in terms of measured displacements and reliability for further processing