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Purpose An electric field (EF) can be used to change the mechanical properties of cells and skin tissues. We demonstrate EF-induced elasticity changes in human dermal fibroblasts (HDFs) and a human skin equivalent and identify the underlying principles related to the changes. Methods HDFs and human skin equivalent were stimulated with electric fields of 1.0 V/cm. Change in cellular elasticity was determined by using atomic force microscopy. Effects of EF on the biomechanical and chemical properties of a human skin equivalent were analyzed. In cells and tissues, the effects of EF on biomarkers of cellular elasticity were investigated at the gene and protein levels. Results In HDFs, the cellular elasticity was increased and the expression of biomarkers of cellular elasticity was regulated by the EF. Expression of the collagen protein in the human skin equivalent was changed by EF stimulation; however, changes in density and microstructure of the collagen fibrils were not significant. The viscoelasticity of the human skin equivalent increased in response to EF stimulation, but molecular changes were not observed in collagen. Conclusions Elasticity of cells and human skin equivalent can be regulated by electrical stimulation. Especially, the change in cellular elasticity was dependent on cell age.

Laser melting of polycrystalline metals starts at the internal grain boundaries and propagates into the grains., Melting is a fundamental process of matter that is still not fully understood at the microscopic level. Here, we use time-resolved x-ray diffraction to examine the ultrafast melting of polycrystalline gold thin films using an optical laser pump followed by a delayed hard x-ray probe pulse. We observe the formation of an intermediate new diffraction peak, which we attribute to material trapped between the solid and melted states, that forms 50 ps after laser excitation and persists beyond 500 ps. The peak width grows rapidly for 50 ps and then narrows distinctly at longer time scales. We attribute this to a melting band originating from the grain boundaries and propagating into the grains. Our observation of this intermediate state has implications for the use of ultrafast lasers for ablation during pulsed laser deposition.

Three-dimensional (3D) reconstruction of highly functional tissues is of great importance in advancing the clinical benefit of tissue engineering and regenerative medicine. In the last quarter century, many studies have found that by engineering a 3D microenvironment that resembles the in vivo tissue condition, cells exhibit behaviors and functions that reflect those of native tissue. Biomaterial scaffolds are a central technology for providing 3D microenvironments in vitro, and, in conjunction with diverse design and cell seeding advents, have produced highly functional and complex 3D tissues. Here, we describe a new approach to creating 3D cell-dense tissue-like constructs without a biomaterial scaffold. Cell sheet technology with cell sheet layering strategies generates highly cell dense, engineered tissue capable of direct crosstalk with the tissue-engraftment surface, in addition to paracrine-mediated signaling. In this chapter, we will introduce methods of reconstructing 3D tissue using cell sheet technology and the advantages of a scaffold-free design.

X-ray computed micro-tomography (μCT) is one of the most advanced and common non-destructive techniques in the field of medical imaging and material science. It allows recreating virtual models (3D models), without destroying the original objects, by measuring three-dimensional X-ray attenuation coefficient maps of samples on the (sub) micrometer scale. The quality of the images obtained using μCT is strongly dependent on the performance of the associated X-ray detector i.e. to the acquisition of information of the X-ray beam traversing the patient/sample being precise and accurate. Detectors for μCT have to meet the requirements of the specific tomography procedure in which they are going to be used. In general, the key parameters are high spatial resolution, high dynamic range, uniformity of response, high contrast sensitivity, fast acquisition readout and support of high frame rates. At present the detection devices in commercial μCT scanners are dominated by charge-coupled devices (CCD), photodiode arrays, CMOS acquisition circuits and more recently by hybrid pixel detectors. Monolithic CMOS imaging sensors, which offer reduced pixel sizes and low electronic noise, are certainly excellent candidates for μCT and may be used for the development of novel high-resolution imaging applications. The uses of monolithic CMOS based detectors such as the PERCIVAL detector are being recently explored for synchrotron and FEL applications. PERCIVAL was developed to operate in synchrotron and FEL facilities in the soft X-ray regime from 250 eV to 1 keV and it could offer all the aforementioned technical requirements needed in μCT experiments. In order to adapt the system for a typical tomography application, a scintillator is required, to convert incoming X-ray radiation (∼ tens of KeV) into visible light which may be detected with high efficiency. Such a taper-based scintillator was developed and mounted in front of the sensitive area of the PERCIVAL imager. In this presentation we will report the setup of the detector system and preliminary results of first μCTs of reference objects, which were performed in the TomoLab at ELETTRA.

The purpose of this study was to identify the factors affecting depression in patients with hand injuries. The participants were 100 outpatients with hand microsurgery in C hospital in Gyeonggi_do. The data were analyzed using Pearson's correlation, t-test, ANOVA, and multiple regression with SPSS/W...

Background In most stem cell therapy strategies reported to date, stem cells are introduced to damaged tissue sites to repair and regenerate the original tissue structure and function. MSC therapeutic efficacies are inconsistent, largely attributed to transplanted MSC difficulties both in engrafting at tissue sites and in retaining their therapeutic functions from suspension formulations. MSC functional components, including cell adhesion and cell–cell junction proteins, and ECM that contribute to essential cellular therapeutic effects, are damaged or removed by proteolytic enzymes used in stem cell harvesting strategies from culture. To overcome these limitations, methods to harvest and transplant cells without disrupting critical stem cell functions are required. Cell sheet technology, exploiting temperature-responsive cell culture surfaces, permits cell harvest without cell protein damage. This study is focused on phenotypic traits of MSC sheets structurally and functionally to understand therapeutic benefits of cell sheets. Methods/results This study verified cleaved cellular proteins (vinculin, fibronectin, laminin, integrin β-1, and connexin 43) and increased apoptotic cell death produced under standard trypsin harvesting treatment in a time-dependent manner. However, MSC sheets produced without trypsin using only temperature-controlled sheet harvest from culture plastic exhibited intact cellular structures. Also, MSCs harvested using enzymatic treatment (i.e., chemical disruption) showed higher pYAP expression compared to MSC sheets. Conclusion Retention of cellular structures such as ECM, cell–cell junctions, and cell–ECM junctions is correlated with human umbilical cord mesenchymal stem cell (hUC-MSC) survival after detachment from cell culture surfaces. Retaining these proteins intact in MSC cultures using cell sheet technology is proposed to enhance stem cell survival and their function in stem cell-based therapy.

본 연구는 결혼예비세대인 미혼 남녀의 성역할태도, 자아존중감, 진로결정자기효능감이 결혼인식에 미치는 영향을 파악하기 위해 시도되었다. 서울 및 경기 거주 미혼 남녀 150명을 대상으로 분석한 결과, 대상자의 결혼인식은 점수범위 1~5점에서 3.77±.91점, 성역할태도 4.15±1.32점(점수범위 1~5), 자아존중감은 점수범위 1~4점에서 3.01±1.65점, 진로결정자기효능감 4.09±1.79점(점수범위 1~5)으로 나타났다. 미혼 남녀의 결혼인식은 자아존중감(r=.199, p=.018), 진로결정 자기효능감(r=.333, p

The hard X-ray free-electron laser at the Pohang Accelerator Laboratory (PAL-XFEL) in the Republic of Korea achieved saturation of a 0.144 nm free-electron laser beam on 27 November 2016, making it the third hard X-ray free-electron laser in the world, following the demonstrations of the Linac Coherent Light Source (LCLS) and the SPring-8 Angstrom Compact Free Electron Laser (SACLA). The use of electron-beam-based alignment incorporating undulator radiation spectrum analysis has allowed reliable operation of PAL-XFEL with unprecedented temporal stability and dispersion-free orbits. In particular, a timing jitter of just 20 fs for the free-electron laser photon beam is consistently achieved due to the use of a state-of-the-art design of the electron linear accelerator and electron-beam-based alignment. The low timing jitter of the electron beam makes it possible to observe Bi(111) phonon dynamics without the need for timing-jitter correction, indicating that PAL-XFEL will be an extremely useful tool for hard X-ray time-resolved experiments. The Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL) in South Korea has now entered operation with a timing jitter of just 20 fs.

Background Previous studies have revealed that gypenosides (GPS) improve the symptoms of anxiety disorders in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rat model of Parkinson’s disease (PD). The present study aimed to investigate the effects of GPS on memory deficits in an MPTP-lesioned mouse model of PD treated with L-3,4-dihydroxyphenylalanine (L-DOPA). Methods MPTP (30 mg/kg/day, 5 days)-lesioned mice were treated with GPS (50 mg/kg) and/or L-DOPA (10 and 25 mg/kg) for 21 days. After the final treatments, behavioral changes were assessed in all mice using passive avoidance and elevated plus-maze tests. We then evaluated the biochemical influences of GPS treatment on levels of tyrosine hydroxylase (TH), dopamine, N-methyl-D-aspartate (NMDA) receptors, extracellular signal-regulated kinase (ERK1/2), and cyclic AMP-response element binding protein (CREB) phosphorylation. Results MPTP-lesioned mice exhibited deficits associated with habit learning and spatial memory, which were further aggravated by treatment with L-DOPA (25 mg/kg). However, treatment with GPS (50 mg/kg) ameliorated memory deficits. Treatment with GPS (50 mg/kg) also improved L-DOPA (25 mg/kg)-treated MPTP lesion-induced decreases in retention latency on the passive avoidance test, as well as levels of TH-immunopositive cells and dopamine in the substantia nigra and striatum. GPS treatment also attenuated increases in retention transfer latency on the elevated plus-maze test and in NMDA receptor expression, as well as decreases in the phosphorylation of ERK1/2 and CREB in the hippocampus. Treatment with L-DOPA (10 mg/kg) also ameliorated deficits in habit learning and spatial memory in MPTP-lesioned mice, and this effect was further enhanced by treatment with GPS (50 mg/kg). Conclusion GPS ameliorate deficits in habit learning and spatial memory by modulating the dopaminergic neuronal and N-methyl-D-aspartate receptor-mediated signaling systems in MPTP-lesioned mice treated with L-DOPA. GPS may serve as an adjuvant therapeutic agent for memory deficits in patients with PD receiving L-DOPA.

Mechanical properties of a single cell are closely related to the fate and functions of the cell. Changes in mechanical properties may cause diseases or cell apoptosis. Selective cytotoxic effects of nonthermal atmospheric pressure micro-dielectric barrier discharge (DBD) plasma have been demonstrated on cancer cells. In this work, changes in the mechanical properties of a single cell induced by nonthermal atmospheric pressure micro-DBD plasma were investigated using atomic force microscopy (AFM). Two cervical cancer cell lines (HeLa and SiHa) and normal human fibroblast cells (HFBs) were exposed to micro-DBD plasma for various exposure times. The elasticity of a single cell was determined by force-distance curve measurement using AFM. Young's modulus was decreased by plasma treatment for all cells. The Young's modulus of plasma-treated HeLa cells was decreased by 75% compared to nontreated HeLa cells. In SiHa cells and HFBs, elasticity was decreased slightly. Chemical changes induced by the plasma treatment, which were observed by Raman spectroscopy, were also significant in HeLa cells compared to SiHa cells and HFBs. These results suggested that the molecular changes induced by micro-DBD plasma were related to cell mechanical changes.

This study investigated the effects of ethanol extract from Gynostemma pentaphyllum (GP-EX) on memory deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) (MPTP-lesioned mice). MPTP (30 mg/kg/day, 5 days)-lesioned mice showed deficits of habit learning memory and spatial memory, which were further aggravated by treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) (25 mg/kg, 21 days). However, treatment with GP-EX (50 mg/kg, 21 days) ameliorated memory deficits in MPTP-lesioned mice treated with L-DOPA (25 mg/kg): GP-EX prevented the decreases in retention latency time in the passive avoidance test and tyrosine hydroxylase-immunopositive cells and dopamine levels in the nigrostriatum. GP-EX also reduced increases in retention transfer latency time of the elevated plus-maze test and expression of N-methyl-D-aspartate (NMDA) receptor and improved decreases in phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus in the same models. By contrast, L-DOPA treatment (10 mg/kg, 21 days) ameliorated memory deficits in MPTP-lesioned mice, which were further improved by GP-EX treatment. These results suggest that GP-EX ameliorates habit learning memory deficits by activating dopaminergic neurons and spatial memory deficits by modulating NMDA receptor-ERK1/2-CREB system in MPTP-lesioned mice treated with L-DOPA. GP-EX may serve as an adjuvant phytonutrient for memory deficits in PD.

This study investigated the effects of (-)-sesamin on memory deficits induced by chronic electric footshock (EF)-induced stress in mice. Mice were treated with (-)-sesamin (25 and 50mg/kg, p.o., daily for 21day) prior to chronic EF stress (0.6mA, 1s every 5s for 3min, daily for 21day). Transfer retention latencies in the elevated plus maze test and N-methyl-d-aspartate (NMDA) receptor (type 1) phosphorylation in the hippocampus increased with chronic EF stress, and they were reduced by treatment with (-)-sesamin at both doses. Phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-responsive element binding protein (CREB), which were reduced by chronic EF stress, were increased by treatment with (-)-sesamin. Retention latencies in the passive avoidance test and dopamine levels in the substantia nigra-striatum were also reduced by chronic EF stress, and similarly recovered with (-)-sesamin treatment. These results suggest that (-)-sesamin ameliorates the effects of chronic EF stress-induced spatial and habit learning memory deficits by modulating both NMDA receptor and dopaminergic neuronal systems.

The mechanical properties of single cells have been recently identified as the basis of an emerging approach in medical applications because they are closely related to the biological processes of cells and, ultimately, human health conditions. In this article, we provide a brief review of the intrinsic mechanical properties of single cells related to cancer and aging. The mechanical properties can be used as biomarkers for early cancer diagnosis because cancer cells have a lower Young's modulus, indicating higher elasticity or softness than their counterpart normal cells. The metastatic potential of cancer cells is inversely correlated with their elastic properties. Aging induces stiffness through an increased amount of cytoskeletal fiber. Changes in the mechanical properties also show potential for drug screening. Although there are several challenges to be met before clinical applications can be made, such mechanical properties of single cells may provide new approaches to human diseases.

Cell sheet technology exploits temperature responsive cell culture dishes (TRCDs) as versatile cell harvesting methods to yield contiguous cell monolayers robustly held together by cell-cell junctions, receptors, and endogenous extracellular matrix. More than 15 years of clinical data using autologous-sourced cell sheets demonstrate enhanced therapeutic properties through increased cell retention at target tissue sites. Recently, several preclinical studies have also been reported using mesenchymal stem cell (MSC) sheets in wound healing, cardiac ischemia therapies, and pancreatic regeneration. However, optimized MSC sheet fabrication conditions have not yet been reported. In this study, we identified specific conditions for reliable human MSC sheet fabrication by comparing cell growth media supplements (fetal bovine serum [FBS] and human platelet lysate [hPL]). Human umbilical cord-derived MSCs cultured in FBS and hPL exhibit different actin cytoskeletal structures related to their cell morphologies and adhesion. MSCs cultured in FBS media showed stable cell adhesion on TRCDs with flattened cell shapes and aligned actin cytoskeletal structure. This stable cell adhesion enables production of consistent MSC cell sheets, with controlled cell sheet detachment. Conversely, cell sheet fabrication in hPL media exhibits poor reproducibility being more sensitive to temperature- and culture time-induced release due to weak cell adhesion. These findings suggest that stable MSC adhesion to TRCDs is important to reliable MSC sheet fabrication methods and that MSC growth media supplementation directly affects cell adhesion during culture.

Temperature-responsive polymer grafted tissue culture dishes release cells as confluent living sheets in response to small changes in temperature, with recovered cell sheets retaining cell–cell communications, functional extracellular matrices and tissue-like behaviors. These features promote tissue regeneration and improve transplantation efficacy in various tissues including cartilage, heart, kidney, liver, endometrium, cornea, middle ear, periodontium, and esophageal living sheet transplants. However, the functional effects of cell sheets for salivary gland regeneration to treat hyposalivation have not yet been studied. Thus, the present study aims to both establish the viability of thermoresponsive cell sheets for use in salivary glands and then explore the delivery option (i.e., single vs. multiple layers) that would result in the most complete tissue growth in terms of cell differentiation and recovered tissue integrity. Results indicate that single cell sheets form polarized structures that maintain cell–cell junctions and secretory granules in vitro while layering of two-single cell sheets forms a glandular-like pattern in vitro. Moreover, double layer cell sheets enhance tissue formation, cell differentiation and saliva secretion in vivo. In contrast, single cell sheets demonstrated only modest gains relative to the robust growth seen with the double layer variety. Together, these data verify the utility of thermoresponsive cell sheets for use in salivary glands and indicates the double layer form to provide the best option in terms of cell differentiation and recovered tissue integrity, thereby offering a potential new therapeutic strategy for treating hyposalivation.

Cells are dynamic structures that continually generate and sustain mechanical forces within their environments. Cells respond to mechanical forces by changing their shape, moving, and differentiating. These reactions are caused by intracellular skeletal changes, which induce changes in cellular mechanical properties such as stiffness, elasticity, viscoelasticity, and adhesiveness. Interdisciplinary research combining molecular biology with physics and mechanical engineering has been conducted to characterize cellular mechanical properties and understand the fundamental mechanisms of mechanotransduction. In this review, we focus on the role of cytoskeletal proteins in cellular mechanics. The specific role of each cytoskeletal protein, including actin, intermediate filaments, and microtubules, on cellular elasticity is summarized along with the effects of interactions between the fibers.

This is the first report, to our knowledge, of the preparation of an injectable in situ–forming click-crosslinked hyaluronic acid (Cx-HA) hydrogel (Cx-HA-CM) containing chemical immobilized cytomodulin-2 (CM), a chondrogenic differentiation factor, and on the utility of human periodontal ligament stem cells (hPLSCs) as a cell source for cartilage tissue engineering. hPLSCs served here as a stem cell source tolerant to ex vivo manipulation. CM induced in vitro chondrogenic differentiation of hPLSCs comparable to induction with traditional TGF-β. Cx-HA was prepared via a click-reaction between tetrazine-modified HA and transcyclooctene-modified HA. Cx-HA displayed significantly more features of a stiff hydrogel than HA. Cx-HA had a three-dimensional porous interconnected structure, absorbed a large volume of biological medium, and showed excellent biocompatibility. In contrast to HA, the Cx-HA hydrogel persisted in vitro and in vivo for an extended period, as evidenced by in vivo near-infrared fluorescence imaging. CM covalently linked to Cx-HA (Cx-HA-CM) remained inside Cx-HA for a prolonged period compared with CM physically loaded onto Cx-HA [Cx-HA (+CM)]. Cx-HA-CM also caused better chondrogenic differentiation of hPLSCs, as evidenced by Alcian blue and Safranin O staining, and greater increases in the expression of type II collagen, glycosaminoglycan content and SOX9, aggrecan, and type 2α1 collagen mRNA levels. Thus, compared to Cx-HA (+CM), the hPLSC-loaded Cx-HA-CM hydrogel induced greater chondrogenic differentiation of hPLSCs via CM that was retained in the hydrogel for a much longer period of time. Injectable polymers that spontaneously form three-dimensional porous scaffolds may make it easier to repair cartilage tissue in arthritis sufferers. Recent findings have shown that periodontal stem cells harvested from tissue surrounding human teeth can differentiate into cartilage cells when seeded onto scaffolds containing bioactive peptides. Moon Suk Kim from Ajou University in Suwon, South Korea, and colleagues have now improved this approach by chemically attaching peptides that mimic natural growth factors to water-filled polymers called hydrogels. Cell culture experiments demonstrated that this new material improved resistance against breakdown compared with hydrogels containing physically absorbed bioactive peptides. By injecting live mice with injectable polymers, the team induced hydrogels via click-crosslink into a subcutaneous scaffold loaded with periodontal stem cells. Hydrogels revealed the formation of cartilagelike tissues over four weeks without causing inflammation. In this work, we confirmed that an in situ–forming click-crosslinked hyaluronic acid (Cx-HA) hydrogel with chemical immobilization of cytomodulin-2 (CM) (Cx-HA-CM) and human periodontal ligament stem cells (hPLSCs) have a good potential for cartilage tissue engineering. The CM that is retained inside the Cx-HA hydrogel for a long time synergistically induces chondrogenic differentiation of hPLSCs. Therefore, such an injectable formulation of the Cx-HA-CM–based hydrogel proposed in this work provides an opportunity to satisfy the unmet need for (pre)clinical repair of damaged articular cartilage.

Neurite outgrowth is the differentiation process by which neurons establish synapses. In the dentate gyrus of the hippocampus, new neurons are constantly produced and undergo neurite outgrowth to form synapses, and this process is involved in cognitive ability. Therefore, if an agent could modulate neurite outgrowth, it could potentially be developed as a compound for modulating cognitive ability. In this study, we examined whether coniferaldehyde, a natural compound, regulates neurite outgrowth in Neuro2a cells. We ascertained morphological changes and measured the percentage of neurite-bearing cells and neurite lengths. Coniferaldehyde significantly increased the percentage of neurite-bearing cells, and the length of neurites in a concentration-dependent manner, without inducing cell death. We then have identified that, coniferaldehyde activates the extracellular signals-regulated Kinase 1 and 2 (ERK1/2), and further noted that, U0126, an ERK1/2 inhibitor, blocks coniferaldehyde-facilitated neurite outgrowth. Moreover, Subchronic administration of CA enhanced learning and memory, and increased neurite length of newborn neurons in the hippocampus. These results suggest that coniferaldehyde induces neurite outgrowth by a process possibly mediated by ERK1/2 signaling and enhances learning and memory.

Background Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by autoantibody production and mesenchymal stem cells (MSCs) have emerged as a promising new therapy for the treatment of SLE. MSCs are adult stem cells isolated from various human tissues including bone marrow, adipose tissue, umbilical cord blood, and skeletal muscle; MSCs can differentiate into various cell types and can potentially replace damaged cells in vivo. MSCs suppress T cell proliferation and cytokine production, reduce B cell proliferation and antibody secretion, decrease the generation and function of dendritic cells, and reduce the activity of natural killer cells. MSCs also enhance the activity of regulatory T (Treg) cells. MSCs are thought to inhibit T cell functions by two different mechanisms: by producing soluble mediators and by direct cellcell contacts. The soluble immunosuppressive factors produced by MSCs include IL-10, nitric oxide (NO), tumor growth factor (TGF)-, prostaglandin E2 (PGE2), and indoleamine 2,3-dioxygenase (IDO), all of which can inhibit the functions of major immune cells. Yet, much remains to be learned about the contact-dependent T cell inhibition by MSCs. Methods We examined the in vivo efficacy of MSCs in lupus-prone MRL/lpr mouse model and examined how MSCs inhibit MRL/lpr T cells by using time-lapse imaging at the single level. Results In this study, we show that transfer of human MSCs increased MRL/lpr mouse survival, decreased T cell infiltration in the kidneys, and reduced T cell cytokine expression. In vitro, allogeneic mouse MSCs inhibited MRL/lpr T cell proliferation and cytokine production. Time-lapse imaging revealed that MSCs recruited MRL/lpr T cells establishing long-lasting cellular contacts by enhancing T cell VCAM-1 expression in a CCL2-dependent manner. In contrast, CCL2 deficient MSCs did not induce T cell migration and VCAM-1 expression, resulting in insufficient cell-cell contact. Consequently, CCL2 deficient MSCs did not inhibit IFN- production by T cells and upon transfer no longer prolonged survival of MRL/lpr mice. Conclusions Taken together, our imaging study demonstrates that CCL2 enables the prolonged MSC-T cell interactions needed for sufficient suppression of autoreactive T cells and helps to understand how MSCs ameliorate symptoms in lupus-prone MRL/lpr mice. Funding Source(s): This study was supported by grants funded by the KoreanGovernment (NRF-2017R1A5A2015541 and NRF-2017M3A9B4050336).

We characterize the spatial and temporal coherence properties of hard X-ray pulses from the Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL, Pohang, Korea). The measurement of the single-shot speckle contrast, together with the introduction of corrections considering experimental conditions, allows obtaining an intrinsic degree of transverse coherence of 0.85 ± 0.06. In the Self-Amplified Spontaneous Emission regime, the analysis of the intensity distribution of X-ray pulses also provides an estimate for the number of longitudinal modes. For monochromatic and pink (i.e. natural bandwidth provided by the first harmonic of the undulator) beams, we observe that the number of temporal modes is 6.0 ± 0.4 and 90.0 ± 7.2, respectively. Assuming a coherence time of 2.06 fs and 0.14 fs for the monochromatic and pink beam respectively, we estimate an average X-ray pulse duration of 12.6 ± 1.0 fs.

Background Transforming growth factor-β (TGF-β) is a major regulator of extracellular matrix (ECM) events, particularly collagen production. Aim We explored whether the expression of matrix metalloproteinases (MMPs) and collagen are transcriptionally regulated by the TGF-β and Smad signaling pathways, and the roles played by NF-κB and mitogen-activated protein kinase (MAPK) signaling in normal, aged, human dermal fibroblasts. Methods We quantified mRNA and protein expression using real-time PCR and immunoblotting of proteins from cells in passage 5-15. Results The levels of mRNAs encoding TGF-β1, TGF-β3, and TGF-β receptor type I (TGFβ RI) decreased with increasing passage number. The levels of mRNAs encoding TGF-β2, TGFβ RII, and TGFβ RIII increased to passage 10 but decreased by passage 15. The levels of mRNAs encoding Smad-2, -3, -4, and -7 decreased with increasing passage number. The level of mRNA encoding MMP-1 increased with increasing passage number, and the levels of mRNAs encoding MMP-2, TIMP-1, and TIMP-2 increased to passage 10 but decreased by passage 15. The levels of mRNAs encoding collagen types I and II decreased with increasing passage number. At the protein level, NF-κB, IκBα, p38, ERK, Akt, and JNK became increasingly phosphorylated at higher passage numbers. Conclusion Our results suggest that reductions in the expression levels of MMPs and collagen types I and III in aging human dermal fibroblasts reflect reduced expression of TGF-β/Smad and TGF-β receptors, thus compromising the TGF-β receptor-binding capacity of fibroblasts; the NF-κB and Akt-JNK/MAPK signaling pathways may play active roles in this process.

2019 26th IEEE International Conference on Electronics, Circuits and Systems (ICECS), Genoa, Italy, 27 Nov 2019 - 29 Nov 2019; ... IEEE International Symposium on Circuits and Systems proceedings 51, 50 (2019). doi:10.1109/ICECS46596.2019.8964996, High brilliance synchrotrons and Free Electron Lasers (FELs) require high performing detector systems to realise their full potential. High dynamic range, low noise and high frame rate are all of great importance. In this paper we describe the P2M CMOS sensor, designed for soft X-ray detection at such facilities. We refer to previous work on test devices demonstrating a noise of 5Me- and quantum efficiency of >80% at 400eV (and with good sensitivity even below this value). Initial test results on the first Front Side Illuminated (FSI) 2 Megapixel device are also presented, and an outline of future work is described., Published by Inst. of Electr. and Electronics Engineers, New York, N.Y.

In this paper, we are presenting the Percival detector, a monolithic CMOS Imager for detection of soft x-rays in Synchrotron Rings and Free Electron Lasers. The imager consists in a 2D array of many (2M) small (27um pitch) pixels, without dead or blind zones in the imaging area. The imager achieves low noise and high dynamic range by means of an adaptive-gain in-pixel circuitry, that has been validated on prototypes. The imager features on-chip Analogue-to-Digital conversion to 12+1 bits, and has a readout speed which is compatible with most of Free Electron Laser Facilities. For direct detection of low-energy x-rays, the imager is back-illuminated and post-processed to achieve 100% fill factor.

Malaria is a pathogenic disease in mammal species and typically causes destruction of red blood cells (RBCs). The malaria-infected RBCs undergoes alterations in morphology and its rheological properties, and the altered rheological properties of RBCs have a significant impact on disease pathophysiology. In this study, we investigated detailed topological and biomechanical properties of RBCs infected with malaria Plasmodium berghei ANKA using atomic force microscopy. Mouse (BALB/c) RBCs were obtained on Days 4, 10, and 14 after infection. We found that malaria-infected RBCs changed significantly in shape. The RBCs maintained a biconcave disk shape until Day 4 after infection and then became lopsided on Day 7 after infection. The central region of RBCs began to swell beginning on Day 10 after infection. More schizont stages were present on Days 10 and 14 compared with on Day 4. The malaria-infected RBCs also showed changes in mechanical properties and the cytoskeleton. The stiffness of infected RBCs increased 4.4-4.6-fold and their cytoskeletal F-actin level increased 18.99-67.85% compared with the control cells. The increase in F-actin depending on infection time was in good agreement with the increased stiffness of infected RBCs. Because more schizont stages were found at a late period of infection at Days 10 and 14, the significant changes in biomechanical properties might contribute to the destruction of RBCs, possibly resulting in the release of merozoites into the blood circulation.

Thermoresponsive cell culture plates release cells as confluent living sheets in response to small changes in temperature, with recovered cell sheets retaining functional extracellular matrix proteins and tight junctions, both of which indicate formation of intact and functional tissue. Our recent studies demonstrated that cell sheets are highly effective in promoting mouse submandibular gland (SMG) cell differentiation and recovering tissue integrity. However, these studies were performed only at early time points and extension of the observation period is needed to investigate duration of the cell sheets. Thus, the goal of this study was to demonstrate that treatment of wounded mouse SMG with cell sheets is capable of increasing salivary epithelial integrity over extended time periods. The results indicate that cell sheets promote tissue organization as early as eight days after transplantation and that these effects endure through Day 20. Furthermore, cell sheet transplantation in wounded SMG induces a significant time-dependent enhancement of cell polarization, differentiation and ion transporter expression. Finally, this treatment restored saliva quantity to pre-wounding levels at both eight and twenty days post-surgery and significantly improved saliva quality at twenty days post-surgery. These data indicate that cell sheets engineered with thermoresponsive cell culture plates are useful for salivary gland regeneration and provide evidence for the long-term stability of cell sheets, thereby offering a potential new therapeutic strategy for treating hyposalivation.

Diverse intrinsic and extrinsic mechanical factors have a strong influence on the regulation of stem cell fate. In this work, we examined recent literature on the effects of mechanical environments on stem cells, especially on differentiation of mesenchymal stem cells (MSCs). We provide a brief review of intrinsic mechanical properties of single MSC and examined the correlation between the intrinsic mechanical property of MSC and the differentiation ability. The effects of extrinsic mechanical factors relevant to the differentiation of MSCs were considered separately. The effect of nanostructure and elasticity of the matrix on the differentiation of MSCs were summarized. Finally, we consider how the extrinsic mechanical properties transfer to MSCs and then how the effects on the intrinsic mechanical properties affect stem cell differentiation.