Aluminum with dispersed nanoparticles by laser additive manufacturing.

While laser-printed metals do not tend to match the mechanical properties and thermal stability of conventionally-processed metals, incorporating and dispersing nanoparticles in them should enhance their performance. However, this remains difficult to do during laser additive manufacturing. Here, we show that aluminum reinforced by nanoparticles can be deposited layer-by-layer via laser melting of nanocomposite powders, which enhance the laser absorption by almost one order of magnitude compared to pure aluminum powders. The laser printed nanocomposite delivers a yield strength of up to 1000 MPa, plasticity over 10%, and Young's modulus of approximately 200 GPa, offering one of the highest specific Young's modulus and specific yield strengths among structural metals, as well as an improved specific strength and thermal stability up to 400 °C compared to other aluminum-based materials. The improved performance is attributed to a high density of well-dispersed nanoparticles, strong interfacial bonding between nanoparticles and Al matrix, and ultrafine grain sizes

Targeting translation initiation by synthetic rocaglates for treating MYC-driven lymphomas.

MYC-driven lymphomas, especially those with concurrent MYC and BCL2 dysregulation, are currently a challenge in clinical practice due to rapid disease progression, resistance to standard chemotherapy, and high risk of refractory disease. MYC plays a central role by coordinating hyperactive protein synthesis with upregulated transcription in order to support rapid proliferation of tumor cells. Translation initiation inhibitor rocaglates have been identified as the most potent drugs in MYC-driven lymphomas as they efficiently inhibit MYC expression and tumor cell viability. We found that this class of compounds can overcome eIF4A abundance by stabilizing target mRNA-eIF4A interaction that directly prevents translation. Proteome-wide quantification demonstrated selective repression of multiple critical oncoproteins in addition to MYC in B-cell lymphoma including NEK2, MCL1, AURKA, PLK1, and several transcription factors that are generally considered undruggable. Finally, (-)-SDS-1-021, the most promising synthetic rocaglate, was confirmed to be highly potent as a single agent, and displayed significant synergy with the BCL2 inhibitor ABT199 in inhibiting tumor growth and survival in primary lymphoma cells in vitro and in patient-derived xenograft mouse models. Overall, our findings support the strategy of using rocaglates to target oncoprotein synthesis in MYC-driven lymphomas.P30 CA036727 - NCI NIH HHS; R24 GM111625 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HHS; LB506 - Nebraska Department of Health and Human Services (Nebraska DHHS)Accepted manuscriptSupporting documentatio

A droplet-based microfluidic platform enables high-throughput combinatorial optimization of cyanobacterial cultivation

Cyanobacteria are fast-growing, genetically accessible, photoautotrophs. Therefore, they have attracted interest as sustainable production platforms. However, the lack of techniques to systematically optimize cultivation parameters in a high-throughput manner is holding back progress towards industrialization. To overcome this bottleneck, here we introduce a droplet-based microfluidic platform capable of one- (1D) and two-dimension (2D) screening of key parameters in cyanobacterial cultivation. We successfully grew three different unicellular, biotechnologically relevant, cyanobacteria: Synechocystis sp. PCC 6803, Synechococcus elongatus UTEX 2973 and Synechococcus sp. UTEX 3154. This was followed by a highly-resolved 1D screening of nitrate, phosphate, carbonate, and salt concentrations. The 1D screening results suggested that nitrate and/or phosphate may be limiting nutrients in standard cultivation media. Finally, we use 2D screening to determine the optimal N:P ratio of BG-11. Application of the improved medium composition in a high-density cultivation setup led to an increase in biomass yield of up to 15.7%. This study demonstrates that droplet-based microfluidics can decrease the volume required for cyanobacterial cultivation and screening up to a thousand times while significantly increasing the multiplexing capacity. Going forward, microfluidics have the potential to play a significant role in the industrial exploitation of cyanobacteria

The Caenorhabditis elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion.

Cell invasion allows cells to migrate across compartment boundaries formed by basement membranes. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells. Anchor cell (AC) invasion in C. elegans is an excellent in vivo model to study the regulation of cell invasion during development. Here, we have examined the function of egl-43, the homolog of the human Evi1 proto-oncogene (also called MECOM), in the invading AC. egl-43 plays a dual role in this process, firstly by imposing a G1 cell cycle arrest to prevent AC proliferation, and secondly, by activating pro-invasive gene expression. We have identified the AP-1 transcription factor fos-1 and the Notch homolog lin-12 as critical egl-43 targets. A positive feedback loop between fos-1 and egl-43 induces pro-invasive gene expression in the AC, while repression of lin-12 Notch expression by egl-43 ensures the G1 cell cycle arrest necessary for invasion. Reducing lin-12 levels in egl-43 depleted animals restored the G1 arrest, while hyperactivation of lin-12 signaling in the differentiated AC was sufficient to induce proliferation. Taken together, our data have identified egl-43 Evi1 as an important factor coordinating cell invasion with cell cycle arrest

Numerical approximation of some time optimal control problems

International audienceIn this work we study the numerical approximation of the solutions of a class of abstract parabolic time optimal control problems. Our main results assert that, provided that the target is a closed ball centered at the origin and of positive radius, the optimal time and the optimal controls of the approximate time optimal problems converge to the optimal time and to the optimal controls of the original problem. In order to prove our main theorem, we provide a nonsmooth data error estimate for abstract parabolic systems

Economic value of trees in the estate of the Harewood House stately home in the United Kingdom

The estates of stately homes or manor houses are an untapped resource for assessing the ecosystem services provided by trees. Many of these estates have large collections of trees with clear value in terms of carbon storage, runoff prevention, and pollution removal along with additional benefits to biodiversity and human health. The estate of Harewood House in North Yorkshire represents an ideal example of such a stately home with a mixture of parkland and more formally planted gardens. The trees in each type of garden were analysed for height, diameter at breast height and light exposure. The data were then processed in iTrees software to generate economic benefits for each tree in both gardens. The analysis found that the larger North Front parkland garden had greater total benefits but the more densely planted formal West Garden had the greater per hectare value. In total, the trees on Harewood House estate are estimated to provide approximately £29 million in ecosystem service benefits. This study is the first to analyse the trees of stately homes for economic benefits and highlights that the trees are a valuable commodity for the estates. This should be considered in future planning and management of such estates

Probing the Physics of Narrow Line Regions in Active Galaxies III: Accretion and Cocoon Shocks in the LINER NGC1052

We present Wide Field Spectrograph (WiFeS) integral field spectroscopy and HST FOS spectroscopy for the LINER galaxy NGC 1052. We infer the presence of a turbulent accretion flow forming a small-scale accretion disk. We find a large-scale outflow and ionisation cone along the minor axis of the galaxy. Part of this outflow region is photoionised by the AGN, and shares properties with the ENLR of Seyfert galaxies, but the inner ($R \lesssim 1.0$~arcsec) accretion disk and the region around the radio jet appear shock excited. The emission line properties can be modelled by a "double shock" model in which the accretion flow first passes through an accretion shock in the presence of a hard X-ray radiation, and the accretion disk is then processed through a cocoon shock driven by the overpressure of the radio jets. This model explains the observation of two distinct densities ($\sim10^4$ and $\sim10^6$ cm$^{-3}$), and provides a good fit to the observed emission line spectrum. We derive estimates for the velocities of the two shock components and their mixing fractions, the black hole mass, the accretion rate needed to sustain the LINER emission and derive an estimate for the jet power. Our emission line model is remarkably robust against variation of input parameters, and so offers a generic explanation for the excitation of LINER galaxies, including those of spiral type such as NGC 3031 (M81).Comment: Accepted for publication in Astrophysical Journal. 16 pages, 12 figure

Organic biogeochemistry in West Mata, NE Kau hydrothermal vent fields

Author Posting. © American Geophysical Union, 2021. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 22(4), (2021): e2020GC009481, https://doi.org/10.1029/2020GC009481.The impact of submarine hydrothermal systems on organic carbon in the ocean—one of the largest fixed carbon reservoirs on Earth—could be profound. Yet, different vent sites show diverse fluid chemical compositions and the subsequent biological responses. Observations from various vent sites are to evaluate hydrothermal systems' impact on the ocean carbon cycle. A response cruise in May 2009 to an on-going submarine eruption at West Mata Volcano, northeast Lau Basin, provided an opportunity to quantify the organic matter production in a back-arc spreading hydrothermal system. Hydrothermal vent fluids contained elevated dissolved organic carbon, particulate organic carbon (POC), and particulate nitrogen (PN) relative to background seawater. The δ13C-POC values for suspended particles in the diffuse vent fluids (−15.5‰ and −12.3‰) are distinct from those in background seawater (−23 ± 1‰), indicative of unique carbon synthesis pathways of the vent microbes from the seawater counterparts. The first dissolved organic nitrogen concentrations reported for diffuse vents were similar to or higher than those for background seawater. Enhanced nitrogen fixation and denitrification removed 37%–89% of the total dissolved nitrogen in the recharging background seawater in the hydrothermal vent flow paths. The hydrothermal plume samples were enriched in POC and PN, indicating enhanced biological production. The total “dark” organic carbon production within the plume matches the thermodynamic prediction based on available reducing chemical substances supplied to the plume. This research combines the measured organic carbon contents with thermodynamic modeled results and demonstrates the importance of hydrothermal activities on the water column carbon production in the deep ocean.This project was supported by N.S.F. (OCE0929881, J. P. Cowen and K. H. Rubin), the NOAA PMEL VENTS (now Earth-Ocean Interactions) Program and the Joint Institute for the Study of the Atmosphere and Ocean (JISAO) under NOAA Cooperative Agreement No. NA10OAR4320148, and the UH NASA Astrobiology Institute. The Ministry of Science and Technology of Taiwan award (MOST 107-2611-M-002-002, and MOST 108-2611-M-002-006 to H.-T. Lin). Ministry of Education (M.O.E.) Republic of China (Taiwan) 109L892601 to H.-T. Lin. SOEST contributions no. 11285, C-DEBI contribution no. 563. PMEL contribution no. 3996, JISAO contribution 2183