70 research outputs found
Asymmetric Phase Shifts in the U.S. Industrial Production Cycles
We identify the cyclical turning points of 74 U.S. manufacturing industries and uncover new empirical regularities: (i) Cyclical phase shifts are highly concentrated around the aggregate turning points; (ii) In contrast to the conventional notion of a sudden stop and slow recovery, troughs are much more concentrated than peaks; (iii) Occurrences of phase shifts across industries support the spillovers through input-output linkages; (iv) The common macroeconomic shocks, such as exogenous changes in the federal funds rate, government spending, and oil prices, are significant drivers of industrial phase shifts; (v) Both monetary and fiscal policy shocks are more effective in recessions.Business cycles; Comovement; Turning points; Asymmetries
Generating Autologous Hematopoietic Cells from Human Induced Pluripotent Stem Cells through Ectopic Expression of Transcription Factors
Purpose of review: Hematopoietic cell transplantation (HCT) is a successful treatment modality for patients with malignant and nonmalignant disorders, usually when no other treatment option is available. The cells supporting long-term reconstitution after HCT are the hematopoietic stem cells (HSCs), which can be limited in numbers. Moreover, finding an appropriate human leukocyte antigen-matched donor can be problematic. If HSCs can be stably produced in large numbers from autologous or allogeneic cell sources, it would benefit HCT. Induced pluripotent stem cells (iPSCs) established from patients’ own somatic cells can be differentiated into hematopoietic cells in vitro. This review will highlight recent methods for regulating human (h) iPSC production of HSCs and more mature blood cells.
Recent findings: Advancements in transcription factor-mediated regulation of the developmental stages of in-vivo hematopoietic lineage commitment have begun to provide an understanding of the molecular mechanism of hematopoiesis. Such studies involve not only directed differentiation in which transcription factors, specifically expressed in hematopoietic lineage-specific cells, are overexpressed in iPSCs, but also direct conversion in which transcription factors are introduced into patient-derived somatic cells which are dedifferentiated to hematopoietic cells. As iPSCs derived from patients suffering from genetically mutated diseases would express the same mutated genetic information, CRISPR-Cas9 gene editing has been utilized to differentiate genetically corrected iPSCs into normal hematopoietic cells.
Summary: IPSCs provide a model for molecular understanding of disease, and also may function as a cell population for therapy. Efficient differentiation of patient-specific iPSCs into HSCs and progenitor cells is a potential means to overcome limitations of such cells for HCT, as well as for providing in-vitro drug screening templates as tissue-on-a-chip models
Three-dimensional imaging of cell and extracellular matrix elasticity using quantitative micro-elastography
Funding: Australian Research Council; Cancer Council Western Australia; Industrial Transformation Training Centre; The William and Marlene Schrader Trust of the University of Western Australia.Recent studies in mechanobiology have revealed the importance of cellular and extracellular mechanical properties in regulating cellular function in normal and disease states. Although it is established that cells should be investigated in a three-dimensional (3-D) environment, most techniques available to study mechanical properties on the microscopic scale are unable to do so. In this study, for the first time, we present volumetric images of cellular and extracellular elasticity in 3-D biomaterials using quantitative micro-elastography (QME). We achieve this by developing a novel strain estimation algorithm based on 3-D linear regression to improve QME system resolution. We show that QME can reveal elevated elasticity surrounding human adipose-derived stem cells (ASCs) embedded in soft hydrogels. We observe, for the first time in 3-D, further elevation of extracellular elasticity around ASCs with overexpressed TAZ; a mechanosensitive transcription factor which regulates cell volume. Our results demonstrate that QME has the potential to study the effects of extracellular mechanical properties on cellular functions in a 3-D micro-environment.Publisher PDFPeer reviewe
MiR-9 Controls Chemotactic Activity of Cord Blood CD34⁺ Cells by Repressing CXCR4 Expression
Improved approaches for promoting umbilical cord blood (CB) hematopoietic stem cell (HSC) homing are clinically important to enhance engraftment of CB-HSCs. Clinical transplantation of CB-HSCs is used to treat a wide range of disorders. However, an improved understanding of HSC chemotaxis is needed for facilitation of the engraftment process. We found that ectopic overexpression of miR-9 and antisense-miR-9 respectively down- and up-regulated C-X-C chemokine receptor type 4 (CXCR4) expression in CB-CD34+ cells as well as in 293T and TF-1 cell lines. Since CXCR4 is a specific receptor for the stromal cell derived factor-1 (SDF-1) chemotactic factor, we investigated whether sense miR-9 and antisense miR-9 influenced CXCR4-mediated chemotactic mobility of primary CB CD34+ cells and TF-1 cells. Ectopic overexpression of sense miR-9 and antisense miR-9 respectively down- and up-regulated SDF-1-mediated chemotactic cell mobility. To our knowledge, this study is the first to report that miR-9 may play a role in regulating CXCR4 expression and SDF-1-mediated chemotactic activity of CB CD34+ cells
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Dispersion retrieval from multi-level ultra-deep reactive-ion-etched microstructures for terahertz slow-wave circuits
A multi-level microstructure is proposed for terahertz slow-wave circuits, with dispersion relation retrieved by scattering parameter measurements. The measured return loss shows strong resonances above the cutoff with negligible phase shifts compared with finite element analysis. Splitting the circuit into multi levels enables a low aspect ratio configuration that alleviates the loading effect of deep-reactive-ion etching on silicon wafers. This makes it easier to achieve flat-etched bottom and smooth sidewall profiles. The dispersion retrieved from the measurement, therefore, corresponds well to the theoretical estimation. The result provides a straightforward way to the precise determination of dispersions in terahertz vacuum electronics.</jats:p
Visible Wavelength Color Filters using Dielectric Subwavelength Gratings for Backside-illuminated CMOS Image Sensor Technologies
We report transmissive color filters based on subwavelength dielectric gratings that can replace conventional dye-based color filters used in backside-illuminated CMOS image sensor (BSI CIS) technologies. The filters are patterned in an 80-nm-thick poly-silicon film on a 115-nm-thick SiO_2 spacer layer. They are optimized for operating at the primary RGB colors, exhibit peak transmittance of 60-80%, and an almost insensitive response over a ±20° angular range. This technology enables shrinking of the pixel sizes down to near a micrometer
Visible Wavelength Color Filters Using Dielectric Subwavelength Gratings for Backside-Illuminated CMOS Image Sensor Technologies
Engineering bio-inspired microenvironments for stem cell proliferation and skeletal differentiation
Interactions of cells with their extracellular matrix (ECM) play an important role in development, disease progression, and regeneration. The material properties of ECM such as geometry, chemistry, hydrophobicity, mechanics, and microstructure play an important role in regulating various cellular processes and tissue morphogenesis. Thus there is a surge of interest in determining the effect of various material properties on cell fate and tissue formation. Beyond providing fundamental understandings, these efforts can also led to development of effective scaffolds (structural support for cell culture) as scaffold engineering is an integral part of in vitro cell cultures, tissue engineering, and transplants/implants. The central focus of this thesis is design of polymer- based biomaterials as synthetic matrices for cell culture and understands how cell-matrix interactions affect tissue formation, stem cell differentiation and self-renewal. The first two chapters focuses on synthesis and characterization of three dimensional hydrogels having interconnected macroporous network structures of poly(ethylene glycol) using cryogelation techniques, where I have developed a novel, green strategy to create monolithic structures with heterogeneous and homogenous networks. I have also developed a process to create three- dimensional structures with different internal architecture while maintaining the same porosity. These 3D structures were then used to understand effect of scaffold porosity, pore structure, etc play an important role in cell proliferation, differentiation, and tissue formation using cartilage tissue engineering as a model system. We also harnessed the potential of cell-matrix interactions to develop defined, synthetic matrices to expand human embryonic stem cells in vitro without introducing any detrimental effects. Employing a number of hydrogels I have determined the effect of various physico-chemical cues (bulk and interfacial properties) on adhesion, growth, colony formation, and self-renewal of human embryonic stem cells. Poly[acrylamide-co-sodium 4-vinylbenzenesulfonate] hydrogels having a moderate hydrophobicity (water contact angle of 23°) and bulk rigidity of 343.7kPa have supported in vitro growth of a number of hPSCs (HUES9, HUES6, and iPSCs) in defined medium (StemPro®) for more than 20 passages. These studies are discussed in chapter
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