Training deep quantum neural networks.

Neural networks enjoy widespread success in both research and industry and, with the advent of quantum technology, it is a crucial challenge to design quantum neural networks for fully quantum learning tasks. Here we propose a truly quantum analogue of classical neurons, which form quantum feedforward neural networks capable of universal quantum computation. We describe the efficient training of these networks using the fidelity as a cost function, providing both classical and efficient quantum implementations. Our method allows for fast optimisation with reduced memory requirements: the number of qudits required scales with only the width, allowing deep-network optimisation. We benchmark our proposal for the quantum task of learning an unknown unitary and find remarkable generalisation behaviour and a striking robustness to noisy training data

Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche

Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1hi monocytes (MOs), Gr-1lo MOs, and macrophages (MΦ) based on differential expression of Gr-1, CD115, F4/80, and CD169. Using MO and MΦ conditional depletion models, we found that reductions in BM mononuclear phagocytes led to reduced BM CXCL12 levels, the selective down-regulation of HSC retention genes in Nestin+ niche cells, and egress of HSCs/progenitors to the bloodstream. Furthermore, specific depletion of CD169+ MΦ, which spares BM MOs, was sufficient to induce HSC/progenitor egress. MΦ depletion also enhanced mobilization induced by a CXCR4 antagonist or granulocyte colony-stimulating factor. These results highlight two antagonistic, tightly balanced pathways that regulate maintenance of HSCs/progenitors in the niche during homeostasis, in which MΦ cross talk with the Nestin+ niche cell promotes retention, and in contrast, SNS signals enhance egress. Thus, strategies that target BM MΦ hold the potential to augment stem cell yields in patients that mobilize HSCs/progenitors poorly

Year in review in Intensive Care Medicine 2009: II. Neurology, cardiovascular, experimental, pharmacology and sedation, communication and teaching

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Mesenchymal stem cell: keystone of the hematopoietic stem cell niche and a stepping-stone for regenerative medicine

Mesenchymal stem cells (MSCs) are self-renewing precursor cells that can differentiate into bone, fat, cartilage, and stromal cells of the bone marrow. Recent studies suggest that MSCs themselves are critical for forming a niche that maintains hematopoietic stem cells (HSCs). The ease by which human MSC-like and stromal progenitor cells can be isolated from the bone marrow and other tissues has led to the rapid development of clinical investigations exploring their anti-inflammatory properties, tissue preservation capabilities, and regenerative potential. However, the identity of genuine MSCs and their specific contributions to these various beneficial effects have remained enigmatic. In this article, we examine the definition of MSCs and discuss the importance of rigorously characterizing their stem cell activity. We review their role and that of other putative niche constituents in the regulation of bone marrow HSCs. Additionally, how MSCs and their stromal progeny alter immune function is discussed, as well as potential therapeutic implications

Circadian Adrenergic Regulation of Bone Marrow Endothelial Adhesion Molecule Expression Impacts Progenitor Recruitment and Engraftment Efficiency

Abstract Abstract 398 Previous studies have revealed that hematopoietic stem cells (HSCs) are released into peripheral blood in a circadian manner in a process controlled by the sympathetic nervous system (SNS) through the regulation of CXCL12 levels in the bone marrow (BM) (Mendez-Ferrer et. al. Nature 2008;452:442). Here, we have evaluated the constitutive recruitment of hematopoietic cells back to the BM. We have observed using high-speed multichannel fluorescence intravital microscopy (MFIM) significant circadian oscillations in the number of adherent BM cells in sinusoids with a nadir in the morning (Zeitgeber time, ZT5: 0.97 ± 0.17 adherent cells/ 100 μm2 vessel area) and a peak at night (ZT13: 2.54 ± 0.53 adherent cells/100 μm2, p = 0.007) after adoptive transfer on a 12 hour light-12 hour darkness cycle. Flow cytometric analyses revealed that the majority (∼70 %) of homed BM cells were Gr-1+ Mac-1+ myeloid cells. To investigate the underlying mechanisms, we have examined the expression levels of P- and E-selectins and VCAM-1, essential homing receptors for progenitor cells in the BM, and found that their mRNA and protein expression on BM endothelium oscillated over the course of a day with the peak expression overlapping the time of the highest cell adhesion numbers (ZT13). To examine the role of the SNS in this process, we surgically sympathectomized mice by unilateral section of the superior cervical ganglion (SCGx) whose neurons project into the calvarial vasculature, while performing sham surgery on the contralateral side. Sympathectomy abolished circadian fluctuations in the number of adoptively transferred adherent cells to the denervated calvarial BM compared to the control side in the same animals (nerve-intact side: ZT5 / ZT13: 1.66 ± 0.10 / 2.41 ± 0.08 cells / 100 μm2, p&lt;0.0001; SCGx: ZT5 / ZT13: 1.65 ± 0.09 vs 1.63 ± 0.09 / 100 μm2 vessel area, p=0.90). We then ascertained further the role of adrenergic signals by evaluating mice deficient in b-adrenergic receptors. We found that the oscillations in cell adhesion molecule expression were markedly reduced in β2 (Adrb2-/-) and β3 (Adrb3-/-) adrenergic receptor deficient mice. These results suggest that hematopoietic cell recruitment to the BM is under circadian control, which is dependent on oscillating expression of endothelial selectins and VCAM-1, and regulated by the SNS. To test the relevance of circadian leukocyte recruitment, we investigated whether isoproterenol, a pan-b-adrenergic agonist commonly used in the clinic, could promote hematopoietic progenitor recruitment and thus BM reconstitution after BM transplantation (BMT). Treatment with isoproterenol (5 mg/kg) for 5 days significantly up-regulated expression of P-selectin (1.2-fold increase; p = 0.027), E-selectin (1.5-fold increase; P = 0.003) and VCAM-1 (2.3-fold increase; P=0.006) on BM endothelium in irradiated recipients as determined by flow cytometry of Tie-2+ PECAM-1+ endothelial cells. Consequently, homing of BM cells was dramatically increased (control / isoproterenol: 2.4 ± 0.2 ×104/4.9 ± 0.4 × 104 donor cells/femur; p = 0.0002) as was the number of recruited hematopoietic progenitors (17.0 ± 3.5/74.1 ± 18.8 CFU-C/femur; p = 0.017). In addition, the recovery of mature myeloid cells in peripheral blood was significantly accelerated in 3 weeks after transplantation of 5 × 104 BM cells (0.38 ± 0.21 × 103/1.64 ± 0.50 ×103/μl; p = 0.024). Of importance, using limiting numbers of BM cells (2.5 × 104) for transplantation, isoproterenol treatment markedly improved the survival (median survival time 10 vs 18 days, percent survival at 4 weeks post-BMT 5.8 vs 35.2%; p = 0.0097). These results indicate that the circadian timing of donor cell infusion and/or manipulation of adrenergic signals in the BM microenvironment may improve transplantation outcome through enhanced engraftment efficiency. Disclosures: No relevant conflicts of interest to declare. </jats:sec