254 research outputs found
Bacterial contamination of anesthesia machines’ internal breathing-circuit-systems
Background: Bacterial contamination of anesthesia breathing machines and their potential hazard for pulmonary infection and cross-infection among anesthetized patients has been an infection control issue since the 1950s. Disposable equipment and bacterial filters have been introduced to minimize this risk. However, the machines’ internal breathing-circuit-system has been considered to be free of micro-organisms without providing adequate data supporting this view. The aim of the study was to investigate if any micro-organisms can be yielded from used internal machines’ breathing-circuit-system. Based on such results objective reprocessing intervals could be defined
Slabs of stabilized jellium: Quantum-size and self-compression effects
We examine thin films of two simple metals (aluminum and lithium) in the
stabilized jellium model, a modification of the regular jellium model in which
a constant potential is added inside the metal to stabilize the system for a
given background density. We investigate quantum-size effects on the surface
energy and the work function. For a given film thickness we also evaluate the
density yielding energy stability, which is found to be slightly higher than
the equilibrium density of the bulk system and to approach this value in the
limit of thick slabs. A comparison of our self-consistent calculations with the
predictions of the liquid-drop model shows the validity of this model.Comment: 7 pages, 6 figures, to appear in Phys. Rev.
Investigations of Optical Coherence Properties in an Erbium-doped Silicate Fiber for Quantum State Storage
We studied optical coherence properties of the 1.53 m telecommunication
transition in an Er-doped silicate optical fiber through spectral
holeburning and photon echoes. We find decoherence times of up to 3.8 s at
a magnetic field of 2.2 Tesla and a temperature of 150 mK. A strong
magnetic-field dependent optical dephasing was observed and is believed to
arise from an interaction between the electronic Er spin and the
magnetic moment of tunneling modes in the glass. Furthermore, we observed
fine-structure in the Erbium holeburning spectrum originating from
superhyperfine interaction with Al host nuclei. Our results show that
Er-doped silicate fibers are promising material candidates for quantum
state storage
Relaxation and reconstruction on (111) surfaces of Au, Pt, and Cu
We have theoretically studied the stability and reconstruction of (111)
surfaces of Au, Pt, and Cu. We have calculated the surface energy, surface
stress, interatomic force constants, and other relevant quantities by ab initio
electronic structure calculations using the density functional theory (DFT), in
a slab geometry with periodic boundary conditions. We have estimated the
stability towards a quasi-one-dimensional reconstruction by using the
calculated quantities as parameters in a one-dimensional Frenkel-Kontorova
model. On all surfaces we have found an intrinsic tensile stress. This stress
is large enough on Au and Pt surfaces to lead to a reconstruction in which a
denser surface layer is formed, in agreement with experiment. The
experimentally observed differences between the dense reconstruction pattern on
Au(111) and a sparse structure of stripes on Pt(111) are attributed to the
details of the interaction potential between the first layer of atoms and the
substrate.Comment: 8 pages, 3 figures, submitted to Physical Review
Development and validation of novel clinical endpoints in intermediate age-related macular degeneration in MACUSTAR
Background
Currently, no validated clinical endpoints for treatment studies exist for intermediate age-related macular degeneration (iAMD).
Objective
The European MACUSTAR study aims to develop and clinically validate adequate clinical endpoints for future treatment studies in iAMD and to identify early determinants of disease progression to late stage AMD.
Material and methods
The MACUSTAR study protocol was developed by an international consortium of researchers from academia, the pharmaceutical industry and medical device companies. The MACUSTAR project is funded by the Innovative Medicines Initiative 2 (IMI2) of the European Union.
Results
The MACUSTAR study consists of a cross-sectional and a longitudinal investigation. A total of 750 subjects with early, intermediate and late AMD as well as control subjects with no signs of AMD will be included with a follow-up period of 3 years. Overall, 20 European study centers are involved.
Conclusion
The MACUSTAR project will generate large high-quality datasets, which will allow clinical validation of novel endpoints for future interventional trials in iAMD. The aim is that these endpoints will be accepted as suitable for medication approval studies by the regulatory authorities and that understanding of the disease process will be improved
MicroRNAs in pulmonary arterial remodeling
Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH
Spurious transcription causing innate immune responses is prevented by 5-hydroxymethylcytosine
Generation of functional transcripts requires transcriptional initiation at regular start sites, avoiding production of aberrant and potentially hazardous aberrant RNAs. The mechanisms maintaining transcriptional fidelity and the impact of spurious transcripts on cellular physiology and organ function have not been fully elucidated. Here we show that TET3, which successively oxidizes 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and other derivatives, prevents aberrant intragenic entry of RNA polymerase II pSer5 into highly expressed genes of airway smooth muscle cells, assuring faithful transcriptional initiation at canonical start sites. Loss of TET3-dependent 5hmC production in SMCs results in accumulation of spurious transcripts, which stimulate the endosomal nucleic-acid-sensing TLR7/8 signaling pathway, thereby provoking massive inflammation and airway remodeling resembling human bronchial asthma. Furthermore, we found that 5hmC levels are substantially lower in human asthma airways compared with control samples. Suppression of spurious transcription might be important to prevent chronic inflammation in asthma
MicroRNAs Dynamically Remodel Gastrointestinal Smooth Muscle Cells
Smooth muscle cells (SMCs) express a unique set of microRNAs (miRNAs) which regulate and maintain the differentiation state of SMCs. The goal of this study was to investigate the role of miRNAs during the development of gastrointestinal (GI) SMCs in a transgenic animal model. We generated SMC-specific Dicer null animals that express the reporter, green fluorescence protein, in a SMC-specific manner. SMC-specific knockout of Dicer prevented SMC miRNA biogenesis, causing dramatic changes in phenotype, function, and global gene expression in SMCs: the mutant mice developed severe dilation of the intestinal tract associated with the thinning and destruction of the smooth muscle (SM) layers; contractile motility in the mutant intestine was dramatically decreased; and SM contractile genes and transcriptional regulators were extensively down-regulated in the mutant SMCs. Profiling and bioinformatic analyses showed that SMC phenotype is regulated by a complex network of positive and negative feedback by SMC miRNAs, serum response factor (SRF), and other transcriptional factors. Taken together, our data suggest that SMC miRNAs are required for the development and survival of SMCs in the GI tract
MicroRNA-145 Regulates Chondrogenic Differentiation of Mesenchymal Stem Cells by Targeting Sox9
Chondrogenic differentiation of mesenchymal stem cells (MSCs) is accurately regulated by essential transcription factors and signaling cascades. However, the precise mechanisms involved in this process still remain to be defined. MicroRNAs (miRNAs) regulate various biological processes by binding target mRNA to attenuate protein synthesis. To investigate the mechanisms for miRNAs-mediated regulation of chondrogenic differentiation, we identified that miR-145 was decreased during transforming growth factor beta 3 (TGF-β3)-induced chondrogenic differentiation of murine MSCs. Subsequently, dual-luciferase reporter gene assay data demonstrated that miR-145 targets a putative binding site in the 3′-UTR of SRY-related high mobility group-Box gene 9 (Sox9) gene, the key transcription factor for chondrogenesis. In addition, over-expression of miR-145 decreased expression of Sox9 only at protein levels and miR-145 inhibition significantly elevated Sox9 protein levels. Furthermore, over-expression of miR-145 decreased mRNA levels for three chondrogenic marker genes, type II collagen (Col2a1), aggrecan (Agc1), cartilage oligomeric matrix protein (COMP), type IX collagen (Col9a2) and type XI collagen (Col11a1) in C3H10T1/2 cells induced by TGF-β3, whereas anti-miR-145 inhibitor increased the expression of these chondrogenic marker genes. Thus, our studies demonstrated that miR-145 is a key negative regulator of chondrogenic differentiation by directly targeting Sox9 at early stage of chondrogenic differentiation
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