Liver stellate cells: magnificent characteristics in human cell biology

Hepatic stellate cells (HSCs), a mesenchymal cell type in hepatic parenchyma, have unique features with respect to their cellular origin, morphology, and function. Normal, quiescent HSCs function as major vitamin A-storing cells containing over 80% of total vitamin A in the body to maintain vitamin A homeostasis. HSCs are located between parenchymal cell plates and sinusoidal endothelial cells, and extend well-developed, long processes surrounding sinusoids in vivo as pericytes. However, HSCs are known to be ‘activated’ or ‘transdifferentiated’ to myofibroblast-like phenotype lacking cytoplasmic lipid droplets and long processes in pathological conditions such as liver fibrosis and cirrhosis, as well as merely during cell culture after isolation. HSCs are the predominant cell type producing extracellular matrix (ECM) components as well as ECM degrading metalloproteases in hepatic parenchyma, indicating that they play a pivotal role in ECM remodeling in both normal and pathological conditions. Recent findings have suggested that HSCs have a neural crest origin from their gene expression pattern similar to neural cell type and/or smooth muscle cells and myofibroblasts. The morphology and function of HSCs are regulated by ECM components as well as by cytokines and growth factors in vivo and in vitro. Liver regeneration after partial hepatectomy might be an invaluable model to clarify the HSC function in elaborate organization of liver tissue by cell-cell and cell-ECM interaction and by growth factor and cytokine regulation

Unique protective function of Kupffer cells

Kupffer cells The most important function of Kupffer cells is defense against infections and tumor cells. Kupffer cells act as antigen presenting cells and as effector cells that act directly by phagocytosis, or indirectly by activation of other cells, e.g. NK cells. Though Kupffer cells are constantly acting as scavengers, they can be activated through different pathways. Firstly, soluble mediators can trigger their activation. IFN-γ is the prototypical macrophage activating factor. It is central to the development of Th1-dominated immune responses, and it affects not only macrophages in an autocrine fashion, but other immune cells as well.One of the key events during innate immune reactions is the production of IL-12, mainly by macrophages. IL-12 induces NK cells to rapidly secrete IFN-γ, which then in turn activates macrophages early in the immune response. It also induces IFN-γ production by T cells. IL- 18, which is produced by Kupffer cells and other cell types, is also involved in enhancing IFN-γ production by T cells. Macrophages also secrete IFN-γ upon stimulation with IL-12 and IL-18 together. It is known that IFN-γ is a possible reducer of metastasis of colon cancer in the liver. Macrophages can also be activated by direct interaction with micro-organisms or bacterial products such as lipopoly-saccharide, glucan, muramyl dipeptide and lipid A[52]. A pivotal role for IFN-γ in the clearance of various intracellular pathogens has been amply demonstrated. It has been described that macrophages release the cytotoxic radical, NO. In vitro studies suggested that NO induces mitochondrial dysfunction in tumor cells followed by membrane barrier dysfunction in the liver sinusoid. Another important cytotoxic factor released by activated macrophages is tumor necrosis factor alpha (TNF-α), which is produced in both soluble and membrane-bound forms. After binding to its receptor, apoptosis can be induced in the target cell.Cytotoxicity of macrophages can be classified into antibody-dependent and antibody-independent cell-mediated cytotoxicity. Both pathways are contact dependent and induce tumor cell death after a number of hours. Antibody-dependent cell-mediated cytotoxicity is based on the recognition of an antibody-coated target by Fc receptors on the effector cells. Upon cross-linking of the Fc receptor, secretion of cytotoxic mediators occurs. Secretion of reactive oxygen species, IL-1 and TNF-α are probably involved. Antibody-independent cell-mediated cytotoxicity involves binding to the macrophage followed by translocation of the lysosomal organelles to the target. Moreover, cytotoxicity towards tumor targets involves cytolysis and phagocytosis.In certain pathophysiologic conditions, apoptosis is chaotic and non-selective, may be massive and occurs persistently over an extended period of time. A large number of apoptotic bodies produced are phagocytosed by Kupffer cells. It has recently been reported that engulfment of apoptotic bodies results in the generation of death ligands, such as FasL and TNF-α on the membrane of the Kupffer cells, but engulfment of latex beads does not produce a similar response. This means that uptake of apoptotic bodies induces an additional immunologic response involving liver inflammation and fibrosis

Does the shock wave in a highly ionized non-isothermal plasma really exist?

Here, we study the structure of a highly ionizing shock wave in a gas of high atmospheric pressure. We take into account the gas ionization when the gas temperature reaches few orders above ionization potential. It is shown that after gasdynamic temperature-raising shock and formation of a highly-ionized nonisothermal collisionless plasma Te≫Ti , only the solitary ion-sound wave (soliton) can propagate in this plasma. In such a wave, the charge separation occurs: electrons and ions form the double electric layer with the electric field. The shock wave form, its amplitude, and front width are derived

Atomic fluctuations lifting the energy degeneracy in Si/SiGe quantum dots

Electron spins in Si/SiGe quantum wells suffer from nearly degenerate conduction band valleys, which compete with the spin degree of freedom in the formation of qubits. Despite attempts to enhance the valley energy splitting deterministically, by engineering a sharp interface, valley splitting fluctuations remain a serious problem for qubit uniformity, needed to scale up to large quantum processors. Here, we elucidate and statistically predict the valley splitting by the holistic integration of 3D atomic-level properties, theory and transport. We find that the concentration fluctuations of Si and Ge atoms within the 3D landscape of Si/SiGe interfaces can explain the observed large spread of valley splitting from measurements on many quantum dot devices. Against the prevailing belief, we propose to boost these random alloy composition fluctuations by incorporating Ge atoms in the Si quantum well to statistically enhance valley splitting.BUS/Quantum DelftQCD/Scappucci LabQCD/Vandersypen LabBUS/TNO STAFFQN/Vandersypen La

CMOS-based cryogenic control of silicon quantum circuits

The most promising quantum algorithms require quantum processors that host millions of quantum bits when targeting practical applications1. A key challenge towards large-scale quantum computation is the interconnect complexity. In current solid-state qubit implementations, an important interconnect bottleneck appears between the quantum chip in a dilution refrigerator and the room-temperature electronics. Advanced lithography supports the fabrication of both control electronics and qubits in silicon using technology compatible with complementary metal oxide semiconductors (CMOS)2. When the electronics are designed to operate at cryogenic temperatures, they can ultimately be integrated with the qubits on the same die or package, overcoming the ‘wiring bottleneck’3–6. Here we report a cryogenic CMOS control chip operating at 3 kelvin, which outputs tailored microwave bursts to drive silicon quantum bits cooled to 20 millikelvin. We first benchmark the control chip and find an electrical performance consistent with qubit operations of 99.99 per cent fidelity, assuming ideal qubits. Next, we use it to coherently control actual qubits encoded in the spin of single electrons confined in silicon quantum dots7–9 and find that the cryogenic control chip achieves the same fidelity as commercial instruments at room temperature. Furthermore, we demonstrate the capabilities of the control chip by programming a number of benchmarking protocols, as well as the Deutsch–Josza algorithm10, on a two-qubit quantum processor. These results open up the way towards a fully integrated, scalable silicon-based quantum computer.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.QCD/Vandersypen LabQuTechQCD/Sebastiano LabQuantum & Computer EngineeringQCD/Scappucci LabBUS/TNO STAFFQCD/Veldhorst LabQuantum Circuit Architectures and TechnologyElectronicsQN/Vandersypen La

A Scalable Cryo-CMOS 2-to-20GHz Digitally Intensive Controller for 4×32 Frequency Multiplexed Spin Qubits/Transmons in 22nm FinFET Technology for Quantum Computers

Quantum computers (QC), comprising qubits and a classical controller, can provide exponential speed-up in solving certain problems. Among solid-state qubits, transmons and spin-qubits are the most promising, operating « 1K. A qubit can be implemented in a physical system with two distinct energy levels representing the |0) and |1) states, e.g. the up and down spin states of an electron. The qubit states can be manipulated with microwave pulses, whose frequency f matches the energy level spacing E = hf (Fig. 19.1.1). For transmons, f 6GHz, for spin qubits f20GHz, with the desire to lower it in the future. Qubit operations can be represented as rotations in the Bloch sphere. The rotation axis is set by the phase of the microwave signal relative to the qubit phase, which must be tracked for coherent operations. The pulse amplitude and duration determine the rotation angle. A π-rotation is typically obtained using a 50ns Gaussian pulse for transmons and a 500ns rectangular pulse for spin qubits with powers of -60dBm and -45dBm, respectively.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.OLD QCD/Charbon LabQCD/Vandersypen LabQCD/Scappucci LabQCD/Veldhorst LabQN/Vandersypen LabElectronics(OLD)Applied Quantum Architecture