Identification and characterization of FAM124B as a novel component of a CHD7 and CHD8 containing complex

BACKGROUND: Mutations in the chromodomain helicase DNA binding protein 7 gene (CHD7) lead to CHARGE syndrome, an autosomal dominant multiple malformation disorder. Proteins involved in chromatin remodeling typically act in multiprotein complexes. We previously demonstrated that a part of human CHD7 interacts with a part of human CHD8, another chromodomain helicase DNA binding protein presumably being involved in the pathogenesis of neurodevelopmental (NDD) and autism spectrum disorders (ASD). Because identification of novel CHD7 and CHD8 interacting partners will provide further insights into the pathogenesis of CHARGE syndrome and ASD/NDD, we searched for additional associated polypeptides using the method of stable isotope labeling by amino acids in cell culture (SILAC) in combination with mass spectrometry. PRINCIPLE FINDINGS: The hitherto uncharacterized FAM124B (Family with sequence similarity 124B) was identified as a potential interaction partner of both CHD7 and CHD8. We confirmed the result by co-immunoprecipitation studies and showed a direct binding to the CHD8 part by direct yeast two hybrid experiments. Furthermore, we characterized FAM124B as a mainly nuclear localized protein with a widespread expression in embryonic and adult mouse tissues. CONCLUSION: Our results demonstrate that FAM124B is a potential interacting partner of a CHD7 and CHD8 containing complex. From the overlapping expression pattern between Chd7 and Fam124B at murine embryonic day E12.5 and the high expression of Fam124B in the developing mouse brain, we conclude that Fam124B is a novel protein possibly involved in the pathogenesis of CHARGE syndrome and neurodevelopmental disorders

Continuous method of producing silicon carbide fibers

This invention pertains to a method for production of polycrystalline ceramic fibers from silicon oxycarbide (SiCO) ceramic fibers wherein the method comprises heating an amorphous ceramic fiber containing silicon and carbon in an inert environment comprising a boron oxide and carbon monoxide at a temperature sufficient to convert the amorphous ceramic fiber to a polycrystalline ceramic fiber. By having carbon monoxide present during the heating of the ceramic fiber, it is possible to achieve higher production rates on a continuous process

Model pathway diagrams for the representation of mathematical models

Mathematical models are the foundation of numerical simulation of optoelectronic devices. We present a concept for a machine-actionable as well as human-understandable representation of the mathematical knowledge they contain and the domain-specific knowledge they are based on. We propose to use theory graphs to formalize mathematical models and model pathway diagrams to visualize them. We illustrate our approach by application to the van Roosbroeck system describing the carrier transport in semiconductors by drift and diffusion. We introduce an approach for the block-based composition of models from simpler components

Comparison of nanoindentation results obtained with Berkovich and cube-corner indenters

There is increasing interest in using sharp cube corner indenters in nanoindentation experiments to study plastic properties. In combination with finite element methods it is for instance possible to extract stress-strain curves from load-displacement curves measured with differently shaped pyramidal indenters. Another example is the fracture toughness of coatings, which can be studied using cracks produced during indentation with cube corner tips. We have carried out indentation experiments with Berkovich and cube corner indenters on eight different materials with different mechanical properties. To gain information about the formation of pile-up and cracks, indentation experiments with cube corner indenter were performed inside a Scanning Electron Microscope (SEM) using a custom-built SEMMicroindenter. The results show that reliable hardness and modulus values can be measured using cube corner indenters. However, the fit range of the unloading curve has a much bigger influence on the results for the cube corner than for the Berkovich tip. The unloading curves of a cube corner measurement should therefore be carefully inspected to determine the region of smooth curvature and the unloading fit range chosen warily. Comparison of the modulus results shows that there is no significant difference between cube corner and Berkovich measurements. Also for hardness, no fundamental difference is observed for most of the investigated materials. Exceptions are materials like silicon nitride, cemented carbide or glassy carbon, where a clear difference to the hardness reference value has been observed although the modulus difference is not pronounced

Introduction to the Special Issue on the New Arctic Ocean

One hundred and thirty years ago, Fridtjof Nansen, the Norwegian polar explorer and scientist, set off on a bold three-year journey to investigate the unknown Arctic Ocean. The expedition relied on a critical technological development: a small, strong, and maneuverable vessel, powered by sail and an engine, with an endurance of five years for twelve men. His intellectual curiosity and careful observations led to an early glimpse of the Arctic Ocean’s circulation and its unique ecosystem. Some of Nansen’s findings on sea ice and the penetration of Atlantic Water into the Arctic Ocean established a benchmark against which we have measured profound changes over the past few decades. In contrast, little was known about the Arctic Ocean’s ecosystem processes prior to the onset of anthropogenic climate change. Nansen’s successes, which paved the way for subsequent research, were gained in part from Indigenous Greenlanders who taught him how to survive in this harsh environment.</jats:p

Localized Basis for Effective Lattice Hamiltonians: Lattice Wannier Functions

A systematic method is presented for constructing effective Hamiltonians for general phonon-related structural transitions. The key feature is the application of group theoretical methods to identify the subspace in which the effective Hamiltonian acts and construct for it localized basis vectors, which are the analogue of electronic Wannier functions. The results of the symmetry analysis for the perovskite, rocksalt, fluorite and A15 structures and the forms of effective Hamiltonians for the ferroelectric transition in $PbTiO_3$ and $BaTiO_3$, the oxygen-octahedron rotation transition in $SrTiO_3$, the Jahn-Teller instability in $La_{1-x}(Ca,Sr,Ba)_xMnO_3$ and the antiferroelectric transition in $PbZrO_3$ are discussed. For the oxygen- octahedron rotation transition in $SrTiO_3$, this method provides an alternative to the rotational variable approach which is well behaved throughout the Brillouin zone. The parameters appearing in the Wannier basis vectors and in the effective Hamiltonian, given by the corresponding invariant energy expansion, can be obtained for individual materials using first- principles density-functional-theory total energy and linear response techniques, or any technique that can reliably calculate force constants and distortion energies. A practical approach to the determination of these parameters is presented and the application to ferroelectric $PbTiO_3$ discussed.Comment: extensive revisions in presentation, 32 pages, Revtex, 7 Postscript figure

Characterisation of exacerbation risk and exacerbator phenotypes in the POET-COPD trial

Background: Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce. Methods: Post-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint. Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or &gt;= 2 exacerbations during study treatment), irrespective of study treatment. A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation. Results: In total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators. Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses. Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and &gt;= 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers. The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality. Conclusion: The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer surviva

Episodic warming of near-bottom waters under the Arctic sea ice on the central Laptev Sea shelf

A multiyear mooring record (2007–2014) and satellite imagery highlight the strong temperature variability and unique hydrographic nature of the Laptev Sea. This Arctic shelf is a key region for river discharge and sea ice formation and export and includes submarine permafrost and methane deposits, which emphasizes the need to understand the thermal variability near the seafloor. Recent years were characterized by early ice retreat and a warming near-shore environment. However, warming was not observed on the deeper shelf until year-round under-ice measurements recorded unprecedented warm near-bottom waters of +0.6°C in winter 2012/2013, just after the Arctic sea ice extent featured a record minimum. In the Laptev Sea, early ice retreat in 2012 combined with Lena River heat and solar radiation produced anomalously warm summer surface waters, which were vertically mixed, trapped in the pycnocline, and subsequently transferred toward the bottom until the water column cooled when brine rejection eroded stratification