Mo-Si-B alloys, as a more and more frequently considered high-temperature material, face the challenge of machining complex shapes. In the present work, the feasibility of printing pre-alloyed ...Mo-Si-B powder materials via laser metal deposition (LMD) process was firstly demonstrated. Mo-Si-B powder was manufactured via gas atomization (GA) process out of solid raw materials meeting the requirements for additive manufacturing (AM) regarding flowability and particle size. Investigations of the powder particles after GA and detailed analyses of the printability and microstructural evolution of the multi-phase Moss-Mo3Si-Mo5SiB2 built are presented. As a result, distinct zones resulting from the layer-wise LMD process were observed next to a microstructure of primarily solidified Moss phases embedded in fine dispersed eutectic regions. The hardness of the LMD processed material is shown to be comparable with Mo-Si-B alloys produced by ingot metallurgy (IM).
•Mo-Si-B powder was successfully produced by gas atomization out of raw materials.•Flowability and particle size meet the requirements for additive manufacturing.•Printing via laser metal deposition (LMD) was successfully conducted.•Multi-phase Moss-Mo3Si-Mo5SiB2 builts are characterized by SEM and EBSD.
Highlights • In comparison with matched controls, VEMPs were consistently altered in patients with Parkinson’s Disease (PD) and severity of abnormalities progressively increased with stage of ...disease. • In PD significant correlation was found between VEMP alterations and both postural instability and REM sleep behavior disorder. • Combined use of VEMPs may provide insights into pathophysiological dynamics of brainstem involvement at the earliest phases of PD.
Rigidity and preorganisation are believed to be required for high affinity in multiply bonded supramolecular complexes as they help reduce the entropic penalty of the binding event. This comes at the ...price that such rigid complexes are sensitive to small geometric mismatches. In marked contrast, nature uses more flexible building blocks. Thus, one might consider putting the rigidity/high‐affinity notion to the test. Multivalent crown/ammonium complexes are ideal for this purpose as the monovalent interaction is well understood. A series of divalent complexes with different spacer lengths and rigidities has thus been analysed to correlate chelate cooperativities and spacer properties. Too long spacers reduce chelate cooperativity compared to exactly matching ones. However, in contrast to expectation, flexible guests bind with chelate cooperativities clearly exceeding those of rigid structures. Flexible spacers adapt to small geometric host–guest mismatches. Spacer–spacer interactions help overcome the entropic penalty of conformational fixation during binding and a delicate balance of preorganisation and adaptability is at play in multivalent complexes.
Adaptability beats rigidity: Thermochemical (ITC) and computational (DFT) analyses on various crown/ammonium complexes with different guest–spacer lengths and flexibilities revealed a delicate interplay of preorganisation and adaptability. Flexible and rigid spacers equally suffer entropic penalty upon binding, but flexible spacers are able to compensate for mismatches between host and guest. Furthermore, spacer–spacer interactions render flexible spacers favourable.
Epithelial cells must adhere to the extracellular matrix (ECM) for survival, as detachment from matrix triggers apoptosis or anoikis. Integrins are major mediators of adhesion between cells and ECM ...proteins, and transduce signals required for cell survival. Recent evidence suggests that integrin receptors are coupled to growth factor receptors in the regulation of multiple biological functions; however, mechanisms involved in coordinate regulation of cell survival are poorly understood and mediators responsible for anoikis have not been well characterized. Here, we identify the pro-apoptotic protein Bim as a critical mediator of anoikis in epithelial cells. Bim is strongly induced after cell detachment and downregulation of Bim expression by RNA interference (RNAi) inhibits anoikis. Detachment-induced expression of Bim requires a lack of β1-integrin engagement, downregulation of EGF receptor (EGFR) expression and inhibition of Erk signalling. Overexpressed EGFR was uncoupled from integrin regulation, resulting in the maintenance of Erk activation in suspension, and a block in Bim expression and anoikis. Thus, Bim functions as a key sensor of integrin and growth factor signals to the Erk pathway, and loss of such coordinate regulation may contribute to tumour progression.
Objective: (1) To assess cognitive function and cerebral magnetic resonance imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to monitor disease evolution, cognitive ...dysfunction, and cerebral lesion burden over time (mean 8.5 year follow up period); (3) to study the relation between clinical, neuropsychological, and MRI data. On follow up assessment, visual and auditory oddball event related potentials (ERPs) were recorded as psychophysiological evaluation of cognitive status. Correlations between neuropsychological, MRI, and ERP data were also analysed. Methods: Neuropsychological study assessed verbal and non-verbal IQ, deterioration index (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial short-term and long term memory. MRI assessment detected presence of demyelinating lesions by using a semiquantitative method as well as cortical and subcortical atrophy over time. Results: Attention, short-term and long term visuospatial memory were mildly impaired at baseline and remained unaltered longitudinally. At retesting a significant worsening of verbal long term memory (p=0.023), DI presence (p=0.041) and the increase of supratentorial and subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions as well as cortical atrophy correlated significantly with attention and memory tests at baseline. Follow up assessment revealed significant correlation between cortical atrophy and attention as well as visuospatial short-term memory; spatial long term memory correlated significantly with lesions in body of lateral ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more visual P300 (58.4 % of cases) than auditory wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI and auditory P300 latency with frontal horn and brain stem lesions. Conclusions: These findings revealed mild cognitive impairment in MS patients particularly consistent with slowing information processing over time. Increased MRI lesions do not correlate with the clinical course of the disease and cognitive deficit evolution. Thus, cognitive dysfunction could be related to disease peculiarity and not to the time course. Correlations between P300, neuropsychological, and MRI findings provide further information about ERP application to examine cognitive impairment in MS and probably to investigate their neural origin.
Abstract
We report on the realization of an extremely sensitive x-ray polarization microscope, allowing to detect tiniest polarization changes of 1 in 100 billion (10
−11
) with a
μ
m-size focused ...beam. The extreme degree of polarization purity places the most stringent requirements on the orientation of the polarizer and analyzer crystals as well as the composition and the form fidelity of the lenses, which must not exhibit any birefringence. The results show that these requirements are currently only met by polymer lenses. Highly sensitive scanning x-ray polarization microscopy thus is established as a new method. It can provide new insights in a wide range of applications ranging from quantum electrodynamics and quantum optics to x-ray spectroscopy, materials research, and laser physics.
A thorough thermodynamic analysis by isothermal titration calorimetry of allosteric and chelate cooperativity effects in divalent crown ether/ammonium complexes is combined with DFT calculations ...including implicit solvent on the one hand and large‐scale molecular dynamics simulations with explicit solvent molecules on the other. The complexes studied exhibit binding constants up to 2×106 m−1 with large multivalent binding enhancements and thus strong chelate cooperativity effects. Slight structural changes in the spacers, that is, the exchange of two ether oxygen atoms by two isoelectronic methylene groups, cause significantly stronger binding and substantially increased chelate cooperativity. The analysis is complemented by the examination of solvent effects and allosteric cooperativity. Such a detailed understanding of the binding processes will help to efficiently design and construct larger supramolecular architectures with multiple multivalent building blocks.
Balancing the cooperativity scales: The exchange of two ether oxygen atoms by two isoelectronic methylene units in divalent crown ether/ammonium complexes significantly enhances the chelate cooperativity of the complex (see figure). A joint experimental and theoretical approach (isothermal titration calorimetry (ITC), solution‐phase DFT calculations and molecular dynamics (MD) simulations) provides detailed insight into the binding mechanisms of divalent complexes.
Dichroism is one of the most important optical effects in both the visible and the X‐ray range. Besides absorption, scattering can also contribute to dichroism. This paper demonstrates that, based on ...the example of polyimide, materials can show tiny dichroism even far from electronic resonances due to scattering. Although the effect is small, it can lead to a measurable polarization change and might have influence on highly sensitive polarimetric experiments.
Aligned molecules, for example in polyimide foils, lead to small dichroism even far from resonances, which can be revealed by high‐precision X‐ray polarimetry.
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