Objectives: To summarize the effects of the bone marrow niche on hematopoiesis and leukemogenesis and discuss the chemotherapy resistance that can arise from interactions between the niche and ...leukemia stem cells.
Methods: We review the major roles of the bone marrow niche in cell proliferation, adhesion and drug resistance. The signaling pathways and major molecular participants in the niche are discussed. We also address potential niche-targeting strategies for the treatment of acute myeloid leukemia (AML).
Results: The bone marrow niche supports normal hematopoiesis and affects acute myeloid leukemia (AML) initiation, progression and chemotherapy resistance.
Discussion: AML is a group of heterogeneous malignant diseases characterized by the excessive proliferation of hematopoietic stem and/or progenitor cells. Even with intensive chemotherapy regimens and stem cell transplantation, the overall survival rate for AML is poor. The bone marrow niches of malignant cells are remodeled into a leukemia-permissive environment, and these reformed niches protect AML cells from chemotherapy-induced cell death. Inhibiting the cellular and molecular interactions between the niche and leukemia cells is a promising direction for targeted therapies for AML treatment.
Conclusions: Interactions between leukemia cells and the bone marrow niche influence hematopoiesis, leukemogenesis, and chemotherapy resistance in AML and require ongoing study. Understanding the mechanisms that underlie these interactions will help identify rational niche-targeting therapies to improve treatment outcomes in AML patients.
Fully Homomorphic encryption-based Merkle Tree (FHMT) is a novel technique for streaming authenticated data structures (SADS) to achieve the streaming verifiable computation. By leveraging the ...computing capability of fully homomorphic encryption, FHMT shifts almost all of the computation tasks to the server, reaching nearly no overhead for the client. Therefore, FHMT is an important technique to construct a more efficient lightweight ADS for resource-limited clients. But the typical FHMT cannot support the dynamic scenario very well because it cannot expend freely since its height is fixed. We now present our fully dynamic FHMT construction, which is a construction that is able to authenticate an unbounded number of data elements and improves upon the state-of-the-art in terms of computational overhead. We divided the algorithms of the DFHMT with the following phases: initialization, insertion, tree expansion, query and verification. The DFHMT removes the drawbacks of the static FHMT. In the initialization phase, it is not required for the scale of the tree to be determined, and the scale of the tree can be adaptively expanded during the data-appending phase. This feature is more suitable for streaming data environments. We analyzed the security of the DFHMT, and point out that DFHMT has the same security with FHMT. The storage, communication and computation overhead of DFHMT is also analyzed, the results show that the client uses simple numerical multiplications and additions to replace hash operations, which reduces the computational burden of the client; the length of the authentication path in DFHMT is shorter than FHMT, which reduces storage and communication overhead. The performance of DFHMT was compared with other construction techniques of SADS via some tests, the results show that DFHMT strikes the performance balance between the client and server, which has some performance advantage for lightweight devices.
Additive manufacturing (AM) or 3-D printing refers to a new class of technologies that actively construct products directly from any 3-D digital model. In the future, the broader applications of AM ...will require a cost reduction of AM machines. Currently, the products fabricated by low-end machines, such as those fabricated using fused deposition modeling (FDM) processes, suffer from the issue of low dimensional accuracy due to multiple error sources. To properly manage error sources for improved prevision, this paper proposes a novel strategy for error compensation in the FDM processes. First, we consecutively attribute the dimensional inaccuracy to two major error sources that affect the geometric shape of the product: 1) positioning error of the extruder and 2) shape deformation induced by processing error, including material phase change and other variations that occur. The extruder positioning error is characterized by a Kriging model, while the modeling of shape deformation due to processing error follows the method developed by Huang et al. Second, using error equivalence concept, we transform the positioning error into the equivalent amount of design input error. Finally, we adjust the design to compensate for the overall shape deviation. To validate this strategy, we conduct a designed experiment for the shape deviation prediction and the compensation. The experimental results successfully demonstrate the effectiveness of the proposed three-step strategy to manage multiple error sources in the FDM processes.
The mechanisms underlying development processes and functional dynamics of neural circuits are far from understood. Long non-coding RNAs (lncRNAs) have emerged as essential players in defining ...identities of neural cells, and in modulating neural activities. In this review, we summarized latest advances concerning roles and mechanisms of lncRNAs in assembly, maintenance and plasticity of neural circuitry, as well as lncRNAs' implications in neurological disorders. We also discussed technical advances and challenges in studying functions and mechanisms of lncRNAs in neural circuitry. Finally, we proposed that lncRNA studies would advance our understanding on how neural circuits develop and function in physiology and disease conditions.
This paper gives foundational results for the application of quasistationarity to Monte Carlo inference problems. We prove natural sufficient conditions for the quasi-limiting distribution of a ...killed diffusion to coincide with a target density of interest. We also quantify the rate of convergence to quasi-stationarity by relating the killed diffusion to an appropriate Langevin diffusion. As an example, we consider in detail a killed Ornstein–Uhlenbeck process with Gaussian quasi-stationary distribution.
The production and expansion of intermediate progenitors (IPs) are essential for neocortical neurogenesis during development and over evolution. Here, we have characterized an epigenetic circuit that ...precisely controls neurogenic programs, particularly properties of IPs, during neocortical development. The circuit comprises a long non-coding RNA (LncBAR) and the BAF (SWI/SNF) chromatin-remodeling complex, which transcriptionally maintains the expression of Zbtb20. LncBAR knockout neocortex contains more deep-layer but fewer upper-layer projection neurons. Intriguingly, loss of LncBAR promotes IP production, but paradoxically prolongs the duration of the cell cycle of IPs during mid-later neocortical neurogenesis. Moreover, in LncBAR knockout mice, depletion of the neural progenitor pool at embryonic stage results in fewer adult neural progenitor cells in the subventricular zone of lateral ventricles, leading to a failure in adult neurogenesis to replenish the olfactory bulb. LncBAR binds to BRG1, the core enzymatic component of the BAF chromatin-remodeling complex. LncBAR depletion enhances association of BRG1 with the genomic locus of, and suppresses the expression of, Zbtb20, a transcription factor gene known to regulate both embryonic and adult neurogenesis. ZBTB20 overexpression in LncBAR-knockout neural precursors reverses compromised cell cycle progressions of IPs.
The electrical conduction and dielectric (capacitive) properties of electrolyte-filled carbon paste electrochemical electrodes are reported, with the carbon, electrolyte (15% H2SO4), ...carbon–electrolyte interface and carbon–contact(metal) interface contributions fully decoupled for the first time. Without full decoupling and with the carbon contributions neglected, the carbon–electrolyte specific interfacial capacitance would be much over-estimated and the carbon–electrolyte interfacial resistivity would be much under-estimated. The carbons and electrolyte are comparable in both dielectric constant and resistivity. The specific contact capacitance is increased and the contact resistivity is decreased by adding the electrolyte to a carbon. The electrolyte is more effective than water in enhancing carbon–liquid and paste–contact interfaces. Conductivity is attractive for batteries and supercapacitors; strong dielectric properties are attractive for supercapacitors but not batteries. Exfoliated graphite provides handleability and excellent volumetric and interfacial conductivities. It gives low carbon dielectric constant, but contributes to the interfacial capacitances. Activated graphite nanoplatelet (GNP) gives high carbon and paste dielectric constants and high specific contact capacitance. Activated carbon gives poor volumetric and interfacial conductivities. Exfoliated graphite is even better than carbon black for batteries; GNP is even better than activated carbon for supercapacitors; an exfoliated-graphite/GNP mixture is suitable for both; natural graphite is not competitive for either.
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