Undifferentiated human mesenchymal stem cells (hMSCs) are highly sensitive to mechanical strain: transcriptionally controlled early osteo-chondrogenic response in vitro

SummaryObjectivePhysical cues play a crucial role in skeletogenesis and osteochondral regeneration. Although human mesenchymal stem cells (hMSCs) offer considerable therapeutic potential, little is known about the molecular mechanisms that control their differentiation. We hypothesized that mechanical strain might be an inherent stimulus for chondrogenic and/or osteogenic differentiation in undifferentiated hMSCs, where c-Fos (FOS) might play a major role in mechanotransduction.MethodhMSCs from 10 donors were intermittently stimulated by cyclic tensile strain (CTS) at 3000 μstrain for a period of 3 days. Differential gene expression of strained and unstrained hMSCs was analysed by real-time RT-PCR for several marker genes, including the transcription factors FOS, RUNX2, SOX9, and others. Additionally, alkaline phosphatase activity (ALP) was determined kinetically.ResultsThe application of CTS significantly stimulated the expression levels of the early chondrogenic and osteogenic marker genes (SOX9, LUM, DCN; RUNX2, SPARC, SPP1, ALPL); this was accompanied by stimulation of ALP activity (+38%±12 standard error of mean, P<0.05). Matrix analysis revealed that the osteo-chondrogenic response followed a coordinated expression pattern, in which FOS was attributed to early osteogenic but not chondrogenic differentiation.ConclusionUndifferentiated hMSCs are highly sensitive to mechanical strain with a transcriptionally controlled osteo-chondrogenic differentiation response in vitro

Анализ пожарной опасности предприятий по переработке и выпуску упаковочных материалов из пластика

В статье освящаются вопросы, касающиеся предприятий по переработке и выпуску упаковочных материалов из пластика, а так же анализ их пожарной опасности.The article highlights the issues related to enterprises for the processing and production of plastic packaging materials, as well as an analysis of their fire hazards

Neutron Scattering and the B_{1g} Phonon in the Cuprates

The momentum dependent lineshape of the out-of-phase oxygen vibration as measured in recent neutron scattering measurements is investigated. Starting from a microscopic coupling of the phonon vibration to a local crystal field, the phonon lineshift and broadening is calculated as a function of transfered momentum in the superconducting state of YBa$_{2}$Cu$_{3}$O$_{7}$. It is shown that the anisotropy of the density of states, superconducting energy gap, and the electron-phonon coupling are all crucial in order to explain these experiments.Comment: new figures and discussio

Optimal phase estimation in quantum networks

We address the problem of estimating the phase phi given N copies of the phase rotation u(phi) within an array of quantum operations in finite dimensions. We first consider the special case where the array consists of an arbitrary input state followed by any arrangement of the N phase rotations, and ending with a POVM. We optimise the POVM for a given input state and fixed arrangement. Then we also optimise the input state for some specific cost functions. In all cases, the optimal POVM is equivalent to a quantum Fourier transform in an appropriate basis. Examples and applications are given.Comment: 9 pages, 2 figures; this is an extended version of arXiv:quant-ph/0609160. v2: minor corrections in reference

Interstitial cell migration: integrin-dependent and alternative adhesion mechanisms

Adhesion and migration are integrated cell functions that build, maintain and remodel the multicellular organism. In migrating cells, integrins are the main transmembrane receptors that provide dynamic interactions between extracellular ligands and actin cytoskeleton and signalling machineries. In parallel to integrins, other adhesion systems mediate adhesion and cytoskeletal coupling to the extracellular matrix (ECM). These include multifunctional cell surface receptors (syndecans and CD44) and discoidin domain receptors, which together coordinate ligand binding with direct or indirect cytoskeletal coupling and intracellular signalling. We review the way that the different adhesion systems for ECM components impact cell migration in two- and three-dimensional migration models. We further discuss the hierarchy of these concurrent adhesion systems, their specific tasks in cell migration and their contribution to migration in three-dimensional multi-ligand tissue environments

An In Vitro Barrier Model of the Human Submandibular Salivary Gland Epithelium Based on a Single Cell Clone of Cell Line HTB-41: Establishment and Application for Biomarker Transport Studies

The blood–saliva barrier (BSB) consists of the sum of the epithelial cell layers of the oral mucosa and salivary glands. In vitro models of the BSB are inevitable to investigate and understand the transport of salivary biomarkers from blood to saliva. Up to now, standardized, cell line-based models of the epithelium of the submandibular salivary gland are still missing for this purpose. Therefore, we established epithelial barrier models of the submandibular gland derived from human cell line HTB-41 (A-253). Single clone isolation resulted in five different clones (B2, B4, B9, D3, and F11). Clones were compared to the parental cell line HTB-41 using measurements of the transepithelial electrical resistance (TEER), paracellular marker permeability assays and analysis of marker expression for acinar, ductal, and myoepithelial cells. Two clones (B9, D3) were characterized to be of acinar origin, one clone (F11) to be of myoepithelial origin and one isolation (B4) derived from two cells, to be presumably a mixture of acinar and ductal origin. Clone B2, presumably of ductal origin, showed a significantly higher paracellular barrier compared to other clones and parental HTB-41. The distinct molecular identity of clone B2 was confirmed by immunofluorescent staining, qPCR, and flow cytometry. Experiments with ferritin, a biomarker for iron storage, demonstrated the applicability of the selected model based on clone B2 for transport studies. In conclusion, five different clones originating from the submandibular gland cell line HTB-41 were successfully characterized and established as epithelial barrier models. Studies with the model based on the tightest clone B2 confirmed its suitability for transport studies in biomarker research

The Heavy Photon Search test detector

The Heavy Photon Search (HPS), an experiment to search for a hidden sector photon in fixed target electroproduction, is preparing for installation at the Thomas Jefferson National Accelerator Facility (JLab) in the Fall of 2014. As the first stage of this project, the HPS Test Run apparatus was constructed and operated in 2012 to demonstrate the experiment׳s technical feasibility and to confirm that the trigger rates and occupancies are as expected. This paper describes the HPS Test Run apparatus and readout electronics and its performance. In this setting, a heavy photon can be identified as a narrow peak in the e+e− invariant mass spectrum above the trident background or as a narrow invariant mass peak with a decay vertex displaced from the production target, so charged particle tracking and vertexing are needed for its detection. In the HPS Test Run, charged particles are measured with a compact forward silicon microstrip tracker inside a dipole magnet. Electromagnetic showers are detected in a PbW04 crystal calorimeter situated behind the magnet, and are used to trigger the experiment and identify electrons and positrons. Both detectors are placed close to the beam line and split top-bottom. This arrangement provides sensitivity to low-mass heavy photons, allows clear passage of the unscattered beam, and avoids the spray of degraded electrons coming from the target. The discrimination between prompt and displaced e+e− pairs requires the first layer of silicon sensors be placed only 10 cm downstream of the target. The expected signal is small, and the trident background huge, so the experiment requires very large statistics. Accordingly, the HPS Test Run utilizes high-rate readout and data acquisition electronics and a fast trigger to exploit the essentially 100% duty cycle of the CEBAF accelerator at JLab

Hole concentration and phonon renormalization in Ca-doped YBa_2Cu_3O_y (6.76 < y < 7.00)

In order to access the overdoped regime of the YBa_2Cu_3O_y phase diagram, 2% Ca is substituted for Y in YBa_2Cu_3O_y (y = 7.00,6.93,6.88,6.76). Raman scattering studies have been carried out on these four single crystals. Measurements of the superconductivity-induced renormalization in frequency (Delta \omega) and linewidth (\Delta 2\gamma) of the 340 cm^{-1} B_{1g} phonon demonstrate that the magnitude of the renormalization is directly related to the hole concentration (p), and not simply the oxygen content. The changes in \Delta \omega with p imply that the superconducting gap (\Delta_{max}) decreases monotonically with increasing hole concentration in the overdoped regime, and \Delta \omega falls to zero in the underdoped regime. The linewidth renormalization \Delta 2\gamma is negative in the underdoped regime, crossing over at optimal doping to a positive value in the overdoped state.Comment: 18 pages; 5 figures; submitted to Phys. Rev. B Oct. 24, 2002 (BX8292