Isolation of dental stem cell-enriched populations from continuously growing mouse incisors

Continuous growth of the rodent incisor is enabled by epithelial and mesenchymal stem cells (ESCs and MSCs) which unceasingly replenish enamel and dentin, respectively, that wear by persistent animal gnawing. Lineage tracing studies have provided evidence that ESCs contribute to all epithelial lineages of the tooth in vivo. Meanwhile, in the mouse incisor, MSCs continuously contribute to odontoblast lineage and tooth growth. However, in vitro manipulation of ESCs has shown little progress, mainly due to lack of appropriate protocol to successfully isolate, culture, expand, and differentiate ESCs in vitro without using the co-culture system. In this chapter we describe the isolation of the Sox2-GFP+ cell population that is highly enriched in ESCs. Isolated cells can be used for various types of analyses, including in vitro culture, single cell-related analyses, etc. Furthermore, we describe ways to obtain populations enriched in the incisor MSCs using FACS sorting of antibody-labeled cells. Easily accessible FACS sorting enables easy and relatively fast isolation of the cells labeled by the fluorescent protein. © Springer Science+Business Media, LLC, part of Springer Nature 2019.Peer reviewe

Ptch2 is a Potential Regulator of Mesenchymal Stem Cells

Ptch receptors 1 and 2 mediate Hedgehog signaling pivotal for organ development and homeostasis. In contrast to embryonic lethal Ptch1(-/-) phenotype, Ptch2(-/-) mice display no effect on gross phenotype. In this brief report, we provide evidence of changes in the putative incisor mesenchymal stem cell (MSC) niches that contribute to accelerated incisor growth, as well as intriguing changes in the bones and skin which suggest a role for Ptch2 in the regulation of MSCs and their regenerative potential. We employed histological, immunostaining, and computed tomography (mu CT) analyses to analyze morphological differences between Ptch2(-/-) and wild-type incisors, long bones, and skins. In vitro CFU and differentiation assays were used to demonstrate the MSC content and differentiation potential of Ptch2(-/-) bone marrow stromal cells. Wound healing assay was performed in vivo and in vitro on 8-week-old mice to assess the effect of Ptch2 on the wound closure. Loss of Ptch2 causes increases in the number of putative MSCs in the continuously growing incisor, associated with increased vascularization observed in the tooth mesenchyme and the neurovascular bundle. Increased length and volume of Ptch2(-/-) bones is linked with the increased number and augmented in vitro differentiation potential of MSCs in the bone marrow. Dynamic changes in the Ptch2(-/-) skin thickness relate to changes in the mesenchymal compartment and impact the wound closure potential. The effects of Ptch2 abrogation on the postnatal MSCs suggest a crucial role for Ptch2 in Hedgehog signaling regulation of the organ regenerative potential.Peer reviewe

Dataset of measured and commented pantograph electric arcs in DC railways

DC railways are characterized by particularly intense arcing caused by pantograph detachment, due to the large current intensity and the general implementation of onboard resonant filters, whose transient response is triggered by electric transients including electric arcs. Electric arc depends on the train speed (the relative speed between the sliding contact over the pantograph and the hot spot on the catenary system), the intensity of the collected pantograph current and the line voltage level. Electric arcs are broadband in nature and can trigger the system transient response dominated by the resonant filter, besides interfering with the operation of onboard equipment (such as for energy conversion and metering)

Predicting Neutron Production from Cosmic-ray Muons

Fast neutrons from cosmic-ray muons are an important background to underground low energy experiments. The estimate of such background is often hampered by the difficulty of measuring and calculating neutron production with sufficient accuracy. Indeed substantial disagreement exists between the different analytical calculations performed so far, while data reported by different experiments is not always consistent. We discuss a new unified approach to estimate the neutron yield, the energy spectrum, the multiplicity and the angular distribution from cosmic muons using the Monte Carlo simulation package FLUKA and show that it gives a good description of most of the existing measurements once the appropriate corrections have been applied.Comment: 8 pages, 7 figure

Entanglement of spin waves among four quantum memories

Quantum networks are composed of quantum nodes that interact coherently by way of quantum channels and open a broad frontier of scientific opportunities. For example, a quantum network can serve as a `web' for connecting quantum processors for computation and communication, as well as a `simulator' for enabling investigations of quantum critical phenomena arising from interactions among the nodes mediated by the channels. The physical realization of quantum networks generically requires dynamical systems capable of generating and storing entangled states among multiple quantum memories, and of efficiently transferring stored entanglement into quantum channels for distribution across the network. While such capabilities have been demonstrated for diverse bipartite systems (i.e., N=2 quantum systems), entangled states with N > 2 have heretofore not been achieved for quantum interconnects that coherently `clock' multipartite entanglement stored in quantum memories to quantum channels. Here, we demonstrate high-fidelity measurement-induced entanglement stored in four atomic memories; user-controlled, coherent transfer of atomic entanglement to four photonic quantum channels; and the characterization of the full quadripartite entanglement by way of quantum uncertainty relations. Our work thereby provides an important tool for the distribution of multipartite entanglement across quantum networks.Comment: 4 figure

Measurement-Induced Entanglement for Excitation Stored in Remote Atomic Ensembles

A critical requirement for diverse applications in Quantum Information Science is the capability to disseminate quantum resources over complex quantum networks. For example, the coherent distribution of entangled quantum states together with quantum memory to store these states can enable scalable architectures for quantum computation, communication, and metrology. As a significant step toward such possibilities, here we report observations of entanglement between two atomic ensembles located in distinct apparatuses on different tables. Quantum interference in the detection of a photon emitted by one of the samples projects the otherwise independent ensembles into an entangled state with one joint excitation stored remotely in 10^5 atoms at each site. After a programmable delay, we confirm entanglement by mapping the state of the atoms to optical fields and by measuring mutual coherences and photon statistics for these fields. We thereby determine a quantitative lower bound for the entanglement of the joint state of the ensembles. Our observations provide a new capability for the distribution and storage of entangled quantum states, including for scalable quantum communication networks .Comment: 13 pages, 4 figures Submitted for publication on August 31 200

Left ventricular ejection fraction and cardiac biomarkers for dynamic prediction of cardiotoxicity in early breast cancer

BACKGROUND/PURPOSE: This study aims to quantify the utility of monitoring LVEF, hs-cTnT, and NT-proBNP for dynamic cardiotoxicity risk assessment in women with HER2+ early breast cancer undergoing neoadjuvant/adjuvant trastuzumab-based therapy. MATERIALS AND METHODS: We used joint models of longitudinal and time-to-event data to analyze 1,136 echocardiography reports and 326 hs-cTnT and NT-proBNP measurements from 185 women. Cardiotoxicity was defined as a 10% decline in LVEF below 50% and/or clinically overt heart failure. RESULTS: Median pre-treatment LVEF was 64%, and 19 patients (10%) experienced cardiotoxicity (asymptomatic n = 12, during treatment n = 19). The pre-treatment LVEF strongly predicted for cardiotoxicity (subdistribution hazard ratio per 5% increase in pre-treatment LVEF = 0.68, 95%CI: 0.48–0.95, p = 0.026). In contrast, pre-treatment hs-cTnT and NT-proBNP were not consistently associated with cardiotoxicity. During treatment, the longitudinal LVEF trajectory dynamically identified women at high risk of developing cardiotoxicity (hazard ratio per 5% LVEF increase at any time of follow-up = 0.36, 95% CI: 0.2–0.65, p = 0.005). Thirty-four patients (18%) developed an LVEF decline ≥ 5% from pre-treatment to first follow-up (“early LVEF decline”). One-year cardiotoxicity risk was 6.8% in those without early LVEF decline and pre-treatment LVEF ≥ 60% (n = 117), 15.9% in those with early LVEF decline or pre-treatment LVEF 5% during trastuzumab-based therapy. The longitudinal LVEF trajectory but not hs-cTnT or NT-proBNP allows for a dynamic assessment of cardiotoxicity risk in this setting

Hyperactive gp130/STAT3-driven gastric tumourigenesis promotes submucosal tertiary lymphoid structure development

Tertiary lymphoid structures (TLSs) display phenotypic and functional characteristics of secondary lymphoid organs, and often develop in tissues affected by chronic inflammation, as well as in certain inflammation-associated cancers where they are prognostic of improved patient survival. However, the mechanisms that govern the development of tumour-associated TLSs remain ill-defined. Here, we observed tumour-associated TLSs in a preclinical mouse model (gp130F/F) of gastric cancer, where tumourigenesis is dependent on hyperactive STAT3 signalling through the common IL-6 family signalling receptor, gp130. Gastric tumourigenesis was associated with the development of B and T cell-rich submucosal lymphoid aggregates, containing CD21+ cellular networks and high endothelial venules. Temporally, TLS formation coincided with the development of gastric adenomas and induction of homeostatic chemokines including Cxcl13, Ccl19 and Ccl21. Reflecting the requirement of gp130-driven STAT3 signalling for gastric tumourigenesis, submucosal TLS development was also STAT3-dependent, but independent of the cytokine IL-17 which has been linked with lymphoid neogenesis in chronic inflammation and autoimmunity. Interestingly, upregulated lymphoid chemokine expression and TLS formation were also observed in a chronic gastritis model induced by Helicobacter felis infection. Tumour-associated TLSs were also observed in patients with intestinal-type gastric cancer, and a gene signature linked with TLS development in gp130F/F mice was associated with advanced clinical disease, but was not prognostic of patient survival. Collectively, our in vivo data reveal that hyperactive gp130-STAT3 signalling closely links gastric tumourigenesis with lymphoid neogenesis, and while a TLS gene signature was associated with advanced gastric cancer in patients, it did not indicate a favourable prognosis