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Glancing angle deposition of sculptured thin metal films at room temperature
Metallic thin films consisting of separated nanostructures are fabricated by evaporative glancing angle deposition at room temperature. The columnar microstructure of the Ti and Cr columns is investigated by high resolution transmission electron microscopy and selective area electron diffraction. The morphology of the sculptured metallic films is studied by scanning electron microscopy. It is found that tilted Ti and Cr columns grow with a single crystalline morphology, while upright Cr columns are polycrystalline. Further, the influence of continuous substrate rotation on the shaping of Al, Ti, Cr and Mo nanostructures is studied with view to surface diffusion and the shadowing effect. It is observed that sculptured metallic thin films deposited without substrate rotation grow faster compared to those grown with continuous substrate rotation. A theoretical model is provided to describe this effect
Glancing angle deposition of sculptured thin metal films at room temperature
Metallic thin films consisting of separated nanostructures are fabricated by evaporative glancing
angle deposition at room temperature. The columnar microstructure of the Ti and Cr columns is
investigated by high resolution transmission electron microscopy and selective area electron
diffraction. The morphology of the sculptured metallic films is studied by scanning electron
microscopy. It is found that tilted Ti and Cr columns grow with a single crystalline morphology,
while upright Cr columns are polycrystalline. Further, the influence of continuous substrate
rotation on the shaping of Al, Ti, Cr and Mo nanostructures is studied with view to surface
diffusion and the shadowing effect. It is observed that sculptured metallic thin films deposited
without substrate rotation grow faster compared to those grown with continuous substrate
rotation. A theoretical model is provided to describe this effec
How advances in cryo-electron tomography have contributed to our current view of bacterial cell biology
Microbial Biotechnolog
Buried graphene heterostructures for electrostatic doping of low-dimensional materials
The fabrication and characterization of steep slope transistor devices based on low-dimensional materials requires precise electrostatic doping profiles with steep spatial gradients in order to maintain maximum control over the channel. In this proof-of-concept study we present a versatile graphene heterostructure platform with three buried individually addressable gate electrodes. The platform is based on a vertical stack of embedded titanium and graphene separated by an intermediate oxide to provide an almost planar surface. We demonstrate the functionality and advantages of the platform by exploring transfer and output characteristics at different temperatures of carbon nanotube field-effect transistors with different electrostatic doping configurations. Furthermore, we back up the concept with finite element simulations to investigate the surface potential. The presented heterostructure is an ideal platform for analysis of electrostatic doping of low-dimensional materials for novel low-power transistor devices
An antibody that prevents serpin polymerisation acts by inducing a novel allosteric behavior
Serpins are important regulators of proteolytic pathways with an antiprotease activity that involves a conformational transition from a metastable to a hyperstable state. Certain mutations permit the transition to occur in the absence of a protease; when associated with an intermolecular interaction, this yields linear polymers of hyperstable serpin molecules, which accumulate at the site of synthesis. This is the basis of many pathologies termed the serpinopathies. We have previously identified a monoclonal antibody (mAb4B12) that, in single-chain form, blocks α1-Antitrypsin (α1-AT) polymerisation in cells. Here, we describe the structural basis for this activity. The mAb4B12 epitope was found to encompass residues Glu32, Glu39 and His43 on helix A and Leu306 on helix I. This is not a region typically associated with the serpin mechanism of conformational change, and correspondingly the epitope was present in all tested structural forms of the protein. Antibody binding rendered β-sheet A - on the opposite face of the molecule - more liable to adopt an 'open' state, mediated by changes distal to the breach region and proximal to helix F. The allosteric propagation of induced changes through the molecule was evidenced by an increased rate of peptide incorporation and destabilisation of a preformed serpin-enzyme complex following mAb4B12 binding. These data suggest that prematurely shifting the β-sheet A equilibrium towards the 'open' state out of sequence with other changes suppresses polymer formation. This work identifies a region potentially exploitable for a rational design of ligands that is able to dynamically influence α1-AT polymerisation
Application of magnetic resonance imaging in transgenic and chemical mouse models of hepatocellular carcinoma
<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The molecular mechanisms underlying hepatocarcinogenesis are still poorly understood. Genetically modified mice are powerful tools to further investigate the mechanisms of HCC development. However, this approach is limited due to the lack of non-invasive detection methods in small rodents. The aim of this study was to establish a protocol for the non-invasive analysis of hepatocarcinogenesis in transgenic mice using a clinical 1.5 Tesla Magnetic Resonance Imaging scanner.</p> <p>Results</p> <p>As a model system we used hepatocyte-specific c-myc transgenic mice developing hepatocellular carcinoma at the age of 12-15 months. The scans of the murine livers included axial T2-weighted turbo-spin echo (TSE) images, axial T1-weighted and contrast enhanced T1-weighted gradient echo (fast field echo, FFE) and sagittal true Fast Imaging with Steady state Precession (true-FISP) images. Application of contrast agent was performed via tail vein-catheter and confirmed by evaluation of the altered longitudinal relaxation T1 time before and after application. Through technical adaptation and optimization we could detect murine liver lesions with a minimum diameter of approximately 2 mm and provided histopathological evidence that these MR findings correspond to hepatocellular carcinoma. Tumor growth was repeatedly measured using sequential MRI with intervals of 5 weeks and subsequent volumetric analysis facilitating direct comparison of tumor progression between individual animals. We finally demonstrated that our protocol is also applicable in the widely- used chemical model of N-nitrosodiethylamine-induced hepatocarcinogenesis.</p> <p>Conclusion</p> <p>Our protocol allows the non-invasive, early detection of HCC and the subsequent continuous monitoring of liver tumorgenesis in transgenic mice thereby facilitating future investigations of transgenic tumor mouse models of the liver.</p
Pharmacological inhibition of cyclin-dependent kinases triggers anti-fibrotic effects in hepatic stellate cells in vitro
Liver fibrosis is a wound healing process in response to chronic liver injury, which is characterized by the accumulation of extracellular collagen produced by Hepatic Stellate Cells (HSCs). This process involves cell cycle re-entry and proliferation of normally quiescent HSCs controlled by cyclins and associated cyclin-dependent kinases (Cdks). Cdk2 mediates the entry and progression through S-phase in complex with E-and A-type cyclins. We have demonstrated that cyclin E1 is essential for liver fibrogenesis in mice, but it is not known if this is dependent on Cdk2 or related Cdks. Here, we aimed to evaluate the benefit of the pan-Cdk inhibitor CR8 for treatment of liver fibrosis in vitro. CR8-treatment reduced proliferation and survival in immortalized HSC lines and in addition attenuated pro-fibrotic properties in primary murine HSCs. Importantly, primary murine hepatocytes were much more tolerant against the cytotoxic and anti-proliferative effects of CR8. We identified CR8 dosages mediating anti-fibrotic effects in primary HSCs without affecting cell cycle activity and survival in primary hepatocytes. In conclusion, the pharmacological pan-Cdk inhibitor CR8 restricts the pro-fibrotic properties of HSCs, while preserving proliferation and viability of hepatocytes at least in vitro. Therefore, CR8 and related drugs might be beneficial for the treatment of liver fibrosis
Structural Analysis of a Nitrogenase Iron Protein from Methanosarcina acetivorans: Implications for CO2 Capture by a Surface-Exposed [Fe4S4] Cluster.
Nitrogenase iron (Fe) proteins reduce CO2 to CO and/or hydrocarbons under ambient conditions. Here, we report a 2.4-Å crystal structure of the Fe protein from Methanosarcina acetivorans (MaNifH), which is generated in the presence of a reductant, dithionite, and an alternative CO2 source, bicarbonate. Structural analysis of this methanogen Fe protein species suggests that CO2 is possibly captured in an unactivated, linear conformation near the [Fe4S4] cluster of MaNifH by a conserved arginine (Arg) pair in a concerted and, possibly, asymmetric manner. Density functional theory calculations and mutational analyses provide further support for the capture of CO2 on MaNifH while suggesting a possible role of Arg in the initial coordination of CO2 via hydrogen bonding and electrostatic interactions. These results provide a useful framework for further mechanistic investigations of CO2 activation by a surface-exposed [Fe4S4] cluster, which may facilitate future development of FeS catalysts for ambient conversion of CO2 into valuable chemical commodities.IMPORTANCE This work reports the crystal structure of a previously uncharacterized Fe protein from a methanogenic organism, which provides important insights into the structural properties of the less-characterized, yet highly interesting archaeal nitrogenase enzymes. Moreover, the structure-derived implications for CO2 capture by a surface-exposed [Fe4S4] cluster point to the possibility of developing novel strategies for CO2 sequestration while providing the initial insights into the unique mechanism of FeS-based CO2 activation
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