Superior expansion of long-term hematopoietic stem cells using StemPro™ HSC medium kit

The use of CD34+ hematopoietic stem cells (HSC) for transplantation has been limited due to the low CD34+ cell numbers in tissue sources such as peripheral blood and cord blood. Two strategies have been employed to increase the CD34+ cell dosage. These include mobilization of HSC into peripheral blood via injection of G-CSF, and ex vivo expansion of CD34+ cells. A major limitation of current systems used for the expansion of HSC is that ex vivo culture leads to expansion and differentiation of cells, at the expense of the most primitive pluripotent long-term HSC. This has limited the clinical application of ex vivo expanded HSC, since short-term progenitor cells only provide transient protection, ultimately reducing the positive health outcomes, increasing the duration of hospitalizations, and health care costs per patient. Development of a culture system that expands, both short term progenitor cells and long-term HSC would enable immune protection during the early phase of recovery, and provide a suitable solution for transfusion-independent hematopoiesis. Therefore, we have developed an HSC culture medium that enables the expansion of both long-term HSC and short-term progenitor cells, while maintaining their functional properties. We conducted several iterative rounds of Design of Experiments (DOE) involving multifactorial analysis, and mathematical modeling methods. The DOEs allowed us to identify optimal combinations and concentrations of essential media components, small molecules, and growth factors. The performance of candidate HSC expansion media were evaluated after 7 days of culture, upon which the CD34+ cells and CD34+CD90+CD45RA- cells (long-term HSC) were quantified. We were successful in developing a media system- StemPro™ HSC Medium Kit-which is xeno-free, serum-free medium that expands both long term CD34+CD90+CD45RA- HSC and short term CD34+. The expression of aldehyde dehydrogenase was conducted to identify primitive stem cells, and colony-forming unit assays were performed to assess the in vitro differentiation capacity of expanded cells. We plan to determine whether the expanded cells are engraftable by transplanting the cells into immuno-deficient mice. Taken together, we seek to highlight our design philosophy in HSC culture media development, and we believe our efforts are critical for the successful utilization of hematopoietic stem cell transplants in translational cell therapies

Multiplicity of northern bright O-type stars with optical long baseline interferometry

The study of the multiplicity of massive stars gives hints on their formation processes and their evolutionary paths, which are still not fully understood. Large separation binaries (>50 milliseconds of arc, mas) can be probed by adaptive-optics-assisted direct imaging and sparse aperture masking, while close binaries can be resolved by photometry and spectroscopy. However, optical long baseline interferometry is mandatory to establish the multiplicity of Galactic massive stars at the separation gap between 1 and 50 mas. In this paper, we aim to demonstrate the capability of the new interferometric instrument MIRC-X, located at the CHARA Array, to study the multiplicity of O-type stars and therefore probe the full range of separation for more than 120 massive stars (H<7.5 mag). We initiated a pilot survey of bright O-type stars (H<6.5mag) observable with MIRC-X. We observed 29 O-type stars, including two systems in average atmospheric conditions around a magnitude of H=7.5 mag. We systematically reduced the obtained data with the public reduction pipeline of the instrument. We analyzed the reduced data using the dedicated python software CANDID to detect companions. Out of these 29 systems, we resolved 19 companions in 17 different systems with angular separations between ~0.5 and 50 mas. This results in a multiplicity fraction fm=17/29=0.59+/-0.09, and an average number of companions fc=19/29=0.66+/-0.13. Those results are in agreement with the results of the SMASH+ survey in the Southern Hemisphere. Thirteen of these companions have been resolved for the first time, including the companion responsible for the nonthermal emission in Cyg OB2-5 A and the confirmation of the candidate companion of HD 47129 suggested by SMASH+. A large survey on more than 120 northern O-type stars (H<7.5) is possible with MIRC-X and will be fruitful.Comment: 15 pages, 9 figures, 5 tables, accepted in A&

The Role of Additive Neurogenesis and Synaptic Plasticity in a Hippocampal Memory Model with Grid-Cell Like Input

Recently, we presented a study of adult neurogenesis in a simplified hippocampal memory model. The network was required to encode and decode memory patterns despite changing input statistics. We showed that additive neurogenesis was a more effective adaptation strategy compared to neuronal turnover and conventional synaptic plasticity as it allowed the network to respond to changes in the input statistics while preserving representations of earlier environments. Here we extend our model to include realistic, spatially driven input firing patterns in the form of grid cells in the entorhinal cortex. We compare network performance across a sequence of spatial environments using three distinct adaptation strategies: conventional synaptic plasticity, where the network is of fixed size but the connectivity is plastic; neuronal turnover, where the network is of fixed size but units in the network may die and be replaced; and additive neurogenesis, where the network starts out with fewer initial units but grows over time. We confirm that additive neurogenesis is a superior adaptation strategy when using realistic, spatially structured input patterns. We then show that a more biologically plausible neurogenesis rule that incorporates cell death and enhanced plasticity of new granule cells has an overall performance significantly better than any one of the three individual strategies operating alone. This adaptation rule can be tailored to maximise performance of the network when operating as either a short- or long-term memory store. We also examine the time course of adult neurogenesis over the lifetime of an animal raised under different hypothetical rearing conditions. These growth profiles have several distinct features that form a theoretical prediction that could be tested experimentally. Finally, we show that place cells can emerge and refine in a realistic manner in our model as a direct result of the sparsification performed by the dentate gyrus layer

A tabletop x-ray tomography instrument for nanometer-scale imaging: demonstration of the 1,000-element transition-edge sensor subarray

We report on the 1,000-element transition-edge sensor (TES) x-ray spectrometer implementation of the TOMographic Circuit Analysis Tool (TOMCAT). TOMCAT combines a high spatial resolution scanning electron microscope (SEM) with a highly efficient and pixelated TES spectrometer to reconstruct three-dimensional maps of nanoscale integrated circuits (ICs). A 240-pixel prototype spectrometer was recently used to reconstruct ICs at the 130 nm technology node, but to increase imaging speed to more practical levels, the detector efficiency needs to be improved. For this reason, we are building a spectrometer that will eventually contain 3,000 TES microcalorimeters read out with microwave superconducting quantum interference device (SQUID) multiplexing, and we currently have commissioned a 1,000 TES subarray. This still represents a significant improvement from the 240-pixel system and allows us to begin characterizing the full spectrometer performance. Of the 992 maximimum available readout channels, we have yielded 818 devices, representing the largest number of TES x-ray microcalorimeters simultaneously read out to date. These microcalorimeters have been optimized for pulse speed rather than purely energy resolution, and we measure a FWHM energy resolution of 14 eV at the 8.0 keV Cu K$\alpha$ line.Comment: 5 pages, 4 figures, submitted to IEEE Transactions on Applied Superconductivit

Geobiology of the late Paleoproterozoic Duck Creek Formation, Western Australia

The ca. 1.8 Ga Duck Creek Formation, Western Australia, preserves 1000 m of carbonates and minor iron formation that accumulated along a late Paleoproterozoic ocean margin. Two upward-deepening stratigraphic packages are preserved, each characterized by peritidal precipitates at the base and iron formation and carbonate turbidites in its upper part. Consistent with recent studies of Neoarchean basins, carbon isotope ratios of Duck Creek carbonates show no evidence for a strong isotopic depth gradient, but carbonate minerals in iron formations can be markedly depleted in C-13. In contrast, oxygen isotopes covary strongly with depth; delta O-18 values as positive as 2%. VPDB in peritidal facies systematically decline to values of 6 to 16% in basinal rocks, reflecting, we posit, the timing of diagenetic closure. The Duck Creek Formation contains microfossils similar to those of the Gunflint Formation, Canada; they are restricted to early diagenetic cherts developed in basinal facies, strengthening the hypothesis that such fossils capture communities driven by iron metabolism. Indeed, X-ray diffraction data indicate that the Duck Creek basin was ferruginous throughout its history. The persistence of ferruginous waters and iron formation deposition in Western Australia for at least several tens of millions of years after the transition to sulfidic conditions in Laurentia suggests that the late Paleoproterozoic expansion of sulfidic subsurface waters was globally asynchronous