Immune checkpoint blockade therapy has been successful in treating some types of cancers but has not shown clinical benefits for treating leukemia 1 . This result suggests that leukemia exploits unique escape mechanisms. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukemia cells. It remains unknown whether these receptors can initiate immune-related primary signaling in tumor cells. Here we show that LILRB4, an ITIM-containing receptor and a monocytic leukemia marker, supports tumor cell infiltration into tissues and suppresses T cell activity via ApoE/LILRB4/SHP-2/uPAR/Arginase-1 signaling axis in acute myeloid leukemia (AML) cells. Blocking LILRB4 signaling using knockout and antagonistic antibody approaches impeded AML development. Thus, LILRB4 orchestrates tumor invasion pathways in monocytic leukemia cells by creating an immune-suppressive microenvironment. LILRB4 represents a compelling target for treatment of monocytic AML.

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Airborne LiDAR is one of the most effective and reliable means of terrain data collection. Using LiDAR data for digital elevation model (DEM) generation is becoming a standard practice in spatial related areas. However, the effective processing of the raw LiDAR data and the generation of an efficient and high-quality DEM remain big challenges. This paper reviews the recent advances of airborne LiDAR systems and the use of LiDAR data for DEM generation, with special focus on LiDAR data filters, interpolation methods, DEM resolution, and LiDAR data reduction. Separating LiDAR points into ground and non-ground is the most critical and difficult step for DEM generation from LiDAR data. Commonly used and most recently developed LiDAR filtering methods are presented. Interpolation methods and choices of suitable interpolator and DEM resolution for LiDAR DEM generation are discussed in detail. In order to reduce the data redundancy and increase the efficiency in terms of storage and manipulation, LiDAR data reduction is required in the process of DEM generation. Feature specific elements such as breaklines contribute significantly to DEM quality. Therefore, data reduction should be conducted in such a way that critical elements are kept while less important elements are removed. Given the high-density characteristic of LiDAR data, breaklines can be directly extracted from LiDAR data. Extraction of breaklines and integration of the breaklines into DEM generation are presented.

BackgroundAdult hematopoietic stem cells (HSCs) are maintained in a microenvironment, known as niche in the endosteal regions of the bone marrow. This stem cell niche with low oxygen tension requires HSCs to adopt a unique metabolic profile. We have recently demonstrated that mouse long-term hematopoietic stem cells (LT-HSCs) utilize glycolysis instead of mitochondrial oxidative phosphorylation as their main energy source. However, the metabolic phenotype of human hematopoietic progenitor and stem cells (HPSCs) remains unknown.ResultsWe show that HPSCs have a similar metabolic phenotype, as shown by high rates of glycolysis, and low rates of oxygen consumption. Fractionation of human mobilized peripheral blood cells based on their metabolic footprint shows that cells with a low mitochondrial potential are highly enriched for HPSCs. Remarkably, low MP cells had much better repopulation ability as compared to high MP cells. Moreover, similar to their murine counterparts, we show that Hif-1α is upregulated in human HPSCs, where it is transcriptionally regulated by Meis1. Finally, we show that Meis1 and its cofactors Pbx1 and HoxA9 play an important role in transcriptional activation of Hif-1α in a cooperative manner.ConclusionsThese findings highlight the unique metabolic properties of human HPSCs and the transcriptional network that regulates their metabolic phenotype.Electronic supplementary materialThe online version of this article (doi:10.1186/s13578-015-0020-3) contains supplementary material, which is available to authorized users.

In-and Cd-doped Cu 9 S 5 and reported that the electrical conductivity was reduced and the thermal power was improved when In and Cd were added to Cu 9 S 5 . However, they did not report the thermal conductivity and ZT value. [ 30 ] In our previous work, we reported that the ZT value of pristine Cu 9 S 5 reached 0.3 at 673 K and the ZT for the optimized sintering temperature sample could be further enhanced to 0.5 because of the existence of a second Cu 1.96 S phase and a considerable number of pores. [ 18 ] Dennler et al. [ 31 ] systematically studied the thermal stability and electrical stability of CuS, Cu 9 S 5, and Cu 2 S. The results showed that the CuS is not stable at temperatures beyond 240 °C either in air or N 2 . Experiments also showed that Cu 2 S is not electrically stable because both cracks and copper whiskers were observed in a Cu 2 S sample after long-time current stress tests (24 A cm −2 /24 h). In contrast, CuS and Cu 9 S 5 samples did not show any degradation in the electrical stability test, even when current densities were increased to as high as 48 A cm −2 . However, the Seebeck coeffi cient, electrical resistivity, crystal structure, and stoichiometry remained constant. [ 31 ] This indicates that only Cu 9 S 5 is both thermally and electrically stable.High-performance TE materials should simultaneously own large Seebeck coeffi cients, high electrical conductivity, and low thermal conductivity, but these three parameters are interrelated with each other. It is diffi cult to improve all the parameters at the same time, for instance, an improvement of electrical conductivity will normally lead to the deterioration in the Secbeck coeffi cient and thermal conductivity. [ 4 ] The main challenges for enhancing TE properties of Cu 9 S 5 -based materials are to improve the Seebeck coeffi cient via carrier concentration optimization. In this work, Na x Cu 9 S 5 ( x = 0, 0.025, 0.05, 0.15, 0.25) nanopowders with an average size of 3 nm were prepared by mechanical alloying (MA). The nanopowders were then sintered to bulk materials by spark plasma sintering (SPS) technology. Metallic Na was doped to Cu 9 S 5 to reduce carrier concentration and improve the Seebeck coeffi cient. Besides, nanopores and nanograins were observed unexpectedly in the Na-doped bulk samples, leading to a signifi cantly reduced thermal conductivity. Overall, a peak ZT value of 1.1 was achieved at 773 K in the composition of Na 0.05 Cu 9 S 5 . Figure 1 a,b shows the transmission electron microscope (TEM) and high-resolution transmission electron microscope (HRTEM) images (inset of Figure 1 b) of Na 0.05 Cu 9 S 5 powders obtained by MA method. Under the low magnifi cation mode, it can be seen that Na 0.05 Cu 9 S 5 powders disperse homogeneously on the microgrid support membrane, show a particle size smaller than 5 nm and an average size of 3 nm. This extremely small particle size obtained directly by MA method is quite astonishing, since the typical particle size of MAed powders is around several hundred nanometer to several micr...

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Key Points• Paired immunoglobulin-like receptor B negatively regulates platelet activation.Murine paired immunoglobulin-like receptors B (PIRB), as the ortholog of human leukocyte immunoglobulin-like receptor B2 (LILRB2), is involved in a variety of biological functions. Here, we found that PIRB and LILRB2 were expressed in mouse and human platelets, respectively. PIRB intracellular domain deletion (PIRB-TM) mice had thrombocythemia and significantly higher proportions of megakaryocytes in bone marrow. Agonist-induced aggregation and spreading on immobilized fibrinogen were facilitated in PIRB-TM platelets. The rate of clot retraction in platelet-rich plasma containing PIRB-TM platelets was also increased. Characterization of signaling confirmed that PIRB associated with phosphatases Shp1/2 in platelets. The phosphorylation of Shp1/2 was significantly downregulated in PIRB-TM platelets stimulated with collagen-related peptide (CRP) or on spreading. The results further revealed that the phosphorylation levels of the linker for activation of T cells, SH2 domain-containing leukocyte protein of 76kDa, and phospholipase C were enhanced in PIRB-TM platelets stimulated with CRP. The phosphorylation levels of FAK Y397 and integrin b3 Y759 were also enhanced in PIRB-TM platelet spread on fibrinogen. The PIRB/LILRB2 ligand angiopoietin-like-protein 2 (ANGPTL2) was expressed and stored in platelet a-granules. ANGPTL2 inhibited agonist-induced platelet aggregation and spreading on fibrinogen. The data presented here reveal that PIRB and its ligand ANGPTL2 possess an antithrombotic function by suppressing collagen receptor glycoprotein VI and integrin aIIbb3-mediated signaling. (Blood. 2014;124(15):2421-2430 Introduction Platelets, which are derived from megakaryocytes, circulate in mammalian blood and play essential roles in hemostasis, angiogenesis, inflammation, and metastasis, 1-3 contain a variety of receptors on their surface. The immunoglobulin superfamily (IgSF) is a large group of cell surface proteins that are involved in the adhesion, binding, or recognition of cells. 4 Several IgSF members expressed on the platelet surface regulate platelet adhesion, activation, and aggregation. Among those receptors, platelet collagen receptor glycoprotein VI (GPVI) has short cytoplasmic domains lacking signaling motifs, but it transmits activating signals by linking to immunoreceptor tyrosine-based activation motif (ITAM) of the Fc receptor g chain (FcRg chain). 5 The GPVI/FcRg chain complex can propagate potent signaling causing aIIbb3 activation and platelet aggregation and thereby play an important role in hemostasis and thrombosis formation. 6 In contrast to GPVI, platelet endothelial cell adhesion molecule-1, a platelet surface IgSF member with 6 extracellular Ig domains and a cytoplasmic immunoreceptor tyrosinebased inhibitory motif (ITIM), mildly inhibits human or mouse platelet activation by collagen, adenosine 59-diphosphate (ADP), or thrombin. 7 Similarly, antibody-mediated cross-linking of G6B, a platelet surface IgS...

Orthophotos (or orthoimages if in digital form) have long been recognised as a supplement or alternative to standard maps. The increasing applications of orthoimages require efforts to ensure the accuracy of produced orthoimages. As digital photogrammetry technology has reached a stage of relative maturity and stability, the availability of high quality ground control points (GCPs) and digital elevation models (DEMs) becomes the central issue for successfully implementing an image orthorectification project. Concerns with the impacts of the quality of GCPs and DEMs on the quality of orthoimages inspire researchers to look for more reliable approaches to acquire high quality GCPs and DEMs for orthorectification. Light Detection and Ranging (LiDAR), an emerging technology, offers capability of capturing high density three dimensional points and generating high accuracy DEMs in a fast and cost-effective way. Nowadays, highly developed computer technologies enable rapid processing of huge volumes of LiDAR data. This leads to a great potential to use LiDAR data to get high quality GCPs and DEMs to improve the accuracy of orthoimages. This paper presents methods for utilizing LiDAR intensity images to collect high accuracy ground coordinates of GCPs and for utilizing LiDAR data to generate a high quality DEM for digital photogrammetry and orthorectification processes. A comparative analysis is also presented to assess the performance of proposed methods. The results demonstrated the feasibility of using LiDAR intensity image-based GCPs and the LiDAR-derived DEM to produce high quality orthoimages.