Combining mobilizing agents with busulfan to reduce chemotherapy-based conditioning for hematopoietic stem cell transplantation

In the context of hematopoietic stem cell (HSC) transplantation, conditioning with myelo- and immune-ablative agents is used to eradicate the patient's diseased cells, generate space in the marrow and suppress immune reactions prior to the infusion of donor HSCs. While conditioning is required for effective and long-lasting HSC engraftment, currently used regimens are also associated with short and long-term side effects on extramedullary tissues and even mortality. Particularly in patients with severe combined immunodeficiency (SCID), who are generally less than 1-year old at the time of transplantation and often suffer from existing comorbidities. There is a pressing need for development of alternative, less toxic conditioning regimens. Hence, we here aimed to improve efficacy of currently used myeloablative protocols by combining busulfan with stem-cell niche-directed therapeutic agents (G-CSF or plerixafor) that are approved for clinical use in stem cell mobilization. T, B and myeloid cell recovery was analyzed in humanized NSG mice after different conditioning regimens. Increasing levels of human leukocyte chimerism were observed in a busulfan dose-dependent manner, showing comparable immune recovery as with total body irradiation in CD34-transplanted NSG mice. Notably, a better T cell reconstitution compared to TBI was observed after busulfan conditioning not only in NSG mice but also in SCID mouse models. Direct effects of reducing the stem cell compartment in the bone marrow were observed after G-CSF and plerixafor administration, as well as in combination with low doses of busulfan. Unfortunately, these direct effects on the stem population in the bone marrow were not reflected in increased human chimerism or immune recovery after CD34 transplantation in NSG mice. These results indicate moderate potential of reduced conditioning regimens for clinical use relevant for all allogeneic transplants.Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Explosive events - swirling transition region jets

In this paper, we extend our earlier work to provide additional evidence for an alternative scenario to explain the nature of so-called `explosive events'. The bi-directed, fast Doppler motion of explosive events observed spectroscopically in the transition region emission is classically interpreted as a pair of bidirectional jets moving upward and downward from a reconnection site. We discuss the problems of such a model. In our previous work, we focused basically on the discrepancy of fast Doppler motion without detectable motion in the image plane. We now suggest an alternative scenario for the explosive events, based on our observations of spectral line tilts and bifurcated structure in some events. Both features are indicative of rotational motion in narrow structures. We explain the bifurcation as the result of rotation of hollow cylindrical structures and demonstrate that such a sheath model can also be applied to explain the nature of the puzzling `explosive events'. We find that the spectral tilt, the lack of apparent motion, the bifurcation, and a rapidly growing number of direct observations support an alternative scenario of linear, spicular-sized jets with a strong spinning motion.Comment: 9 pages, 3 figures, accepted for publication in Solar Physic

Simultaneous NICER and NuSTAR observations of the Ultracompact X-ray Binary 4U 0614+091

We present the first joint NuSTAR and NICER observations of the ultracompact X-ray binary 4U 0614+091. This source shows quasiperiodic flux variations on the timescale of ∼days. We use reflection modeling techniques to study various components of the accretion system as the flux varies. We find that the flux of the reflected emission and the thermal components representing the disk and the compact object trend closely with the overall flux. However, the flux of the power-law component representing the illuminating X-ray corona scales in the opposite direction, increasing as the total flux decreases. During the lowest flux observation, we see evidence of accretion disk truncation from roughly 6 gravitational radii to 11.5 gravitational radii. This is potentially analogous to the truncation seen in black hole low-mass X-ray binaries, which tends to occur during the low/hard state at sufficiently low Eddington ratios

Oscillations and waves in solar spicules

Since their discovery, spicules have attracted increased attention as energy/mass bridges between the dense and dynamic photosphere and the tenuous hot solar corona. Mechanical energy of photospheric random and coherent motions can be guided by magnetic field lines, spanning from the interior to the upper parts of the solar atmosphere, in the form of waves and oscillations. Since spicules are one of the most pronounced features of the chromosphere, the energy transport they participate in can be traced by the observations of their oscillatory motions. Oscillations in spicules have been observed for a long time. However the recent high-resolutions and high-cadence space and ground based facilities with superb spatial, temporal and spectral capacities brought new aspects in the research of spicule dynamics. Here we review the progress made in imaging and spectroscopic observations of waves and oscillations in spicules. The observations are accompanied by a discussion on theoretical modelling and interpretations of these oscillations. Finally, we embark on the recent developments made on the presence and role of Alfven and kink waves in spicules. We also address the extensive debate made on the Alfven versus kink waves in the context of the explanation of the observed transverse oscillations of spicule axes

Migration of the Antarctic Polar Front through the mid-Pleistocene transition: evidence and climatic implications

The Antarctic Polar Front is an important biogeochemical divider in the Southern Ocean. Laminated diatom mat deposits record episodes of massive flux of the diatom Thalassiothrix antarctica beneath the Antarctic Polar Front and provide a marker for tracking the migration of the Front through time. Ocean Drilling Program Sites 1091, 1093 and 1094 are the only deep piston cored record hitherto sampled from the sediments of the circumpolar biogenic opal belt. Mapping of diatom mat deposits between these sites indicates a glacial-interglacial front migration of up to 6 degrees of latitude in the early / mid Pleistocene. The mid Pleistocene transition marks a stepwise minimum 7 degree northward migration of the locus of the Polar Front sustained for about 450 kyr until an abrupt southward return to a locus similar to its modern position and further south than any mid-Pleistocene locus. This interval from a “900 ka event” that saw major cooling of the oceans and a ?13C minimum through to the 424 ka Mid-Brunhes Event at Termination V is also seemingly characterised by 1) sustained decreased carbonate in the subtropical south Atlantic, 2) reduced strength of Antarctic deep meridional circulation, 3) lower interglacial temperatures and lower interglacial atmospheric CO2 levels (by some 30 per mil) than those of the last 400 kyr, evidencing less complete deglaciation. This evidence is consistent with a prolonged period lasting 450 kyr of only partial ventilation of the deep ocean during interglacials and suggests that the mechanisms highlighted by recent hypotheses linking mid-latitude atmospheric conditions to the extent of deep ocean ventilation and carbon sequestration over glacial-interglacial cycles are likely in operation during the longer time scale characteristic of the Mid-Pleistocene Transition. The cooling that initiated the “900 ka event” may have been driven by minima in insolation amplitude related to eccentricity modulation of precession that also affected low latitude climates as marked by threshold changes in the African monsoon system. The major thresholds in earth system behaviour through the Mid-Pleistocene Transition were likely governed by an interplay of the 100 kyr and 400 kyr eccentricity modulation of precession

Formation of a White-Light Jet within a Quadrupolar Magnetic Configuration

We analyze multi-wavelength and multi-viewpoint observations of a large-scale event viewed on 7 April 2011 originating from an active region complex. The activity leads to a white-light jet being formed in the outer corona. The topology and evolution of the coronal structures were imaged in high resolution using the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO). In addition, large field-of-view images of the corona were obtained using the Sun Watcher using Active Pixel System detector and Image Processing (SWAP) telescope onboard the PRoject for Onboard Autonomy (PROBA2) microsatellite, providing evidence for the connectivity of the coronal structures with outer coronal features that were imaged with the Large Angle Spectrometric Coronagraph (LASCO) C2 on Solar and Heliospheric Observatory (SOHO). The data-sets reveal an Eiffel-tower type jet configuration extending into a narrow jet in the outer corona. The event starts from the growth of a dark area in the central part of the structure. The darkening was also observed in projection on the disk by the Solar TErrestrial RElations Observatory-Ahead (STEREO-A) spacecraft from a different point of view. We assume that the dark volume in the corona descends from a coronal cavity of a flux rope that moved up higher in the corona but still failed to erupt. The quadrupolar magnetic configuration corresponds to a saddle-like shape of the dark volume and provides a possibility for the plasma to escape along the open field lines into the outer corona, forming the white-light jet.Comment: 15 pages, 10 figure

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Structure-function relationships of alpha lactalbumin

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN004142 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Design of chemoresistive silicon sensors for application in gas monitoring

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN019964 / BLDSC - British Library Document Supply CentreGBUnited Kingdo