Thermal Conductivity Measurements with Galvanic Metallization Lines on Porosified LTCC Applying the 3-Omega Technique

AbstractThe reduction of the thermal conductivity of low temperature co-fired ceramics (LTCC) caused by a porosification process originally developed for the local modification of the permittivity is determined by the 3ω measurement technique. Therefore, metallization lines of small width down to 20μm are applied by galvanic pulse plating onto the roughened LTCC surface. By this deposition technology it is possible, to cover the pores without any depth penetration. Compared to the ‘as fired’ state, a reduction in thermal conductivity of up to 70% is measured independent of the LTCC type

Subglacial Drainage Evolution Modulates Seasonal Ice Flow Variability of Three Tidewater Glaciers in Southwest Greenland

B.J.D was funded in the form of a PhD studentship provided by the Scottish Association for Geosciences, Environment and Society (SAGES) and the University of St Andrews, UK. J.M.L is supported by a UKRI Future Leaders Fellowship (Grant No. MR/S017232/1). D.F would like to acknowledge the support of this work through the EPSRC and ESRC Centre for Doctoral Training on Quantification and Management of Risk and Uncertainty in Complex Systems Environments Grant No. (EP/L015927/1).Surface‐derived meltwater can access the bed of the Greenland Ice Sheet, causing seasonal velocity variations. The magnitude, timing and net impact on annual average ice flow of these seasonal perturbations depends on the hydraulic efficiency of the subglacial drainage system. We examine the relationships between drainage system efficiency and ice velocity, at three contrasting tidewater glaciers in southwest Greenland during 2014‐2019, using high‐resolution remotely sensed ice velocities, modelled surface melting, subglacial discharge at the terminus and results from buoyant plume modelling. All glaciers underwent a seasonal speed‐up, which usually coincided with surface melt‐onset, and subsequent slow‐down, which usually followed inferred subglacial channelisation. The amplitude and timing of these speed variations differed between glaciers, with the speed‐up being larger and more prolonged at our fastest study glacier. At all glaciers, however, the seasonal variations in ice flow are consistent with inferred changes in hydraulic efficiency of the subglacial drainage system, and qualitatively indicative of a flow regime in which annually‐averaged ice velocity is relatively insensitive to inter‐annual variations in meltwater supply – so‐called ‘ice flow self‐regulation’. These findings suggest that subglacial channel formation may exert a strong control on seasonal ice flow variations, even at fast‐flowing tidewater glaciers.Publisher PDFPeer reviewe

Electrical Hole Transport Properties of an Ambipolar Organic Compound With Zn-Atoms on a Crystalline Silicon Heterostructure

In this paper, we investigate the electrical hole transport properties of an organic/inorganic heterostructure consisting of a thin organic film, that combines hole and electron conducting molecules around a bridging Zn-atom, deposited on top of an n-type crystalline silicon substrate. Current-voltage characteristics and capacitance voltage measurements have been used for the determination of the organic layer dielectric and hole conduction parameters

Modification of amorphous and microcrystalline silicon film properties after irradiation with MeV and GeV protons

It is well known that the degree of crystallinity has a prominent influence on the stability of Silicon under proton irradiation. Amorphous silicon films are much more stable than mono- or polycrystalline silicon substrates or microcrystalline silicon thin films. In particular it has been shown, that in a micromorph tandem solar cell irradiated with protons in the lower MeV energy range only the microcrystalline diode showed a pronounced decrease in photocurrent after irradiation1. The proton irradiation induced damage in thick crystalline silicon samples has a maximum at beam energies between 1MeV and 4MeV and decreases for further increasing proton energies. However, irradiating an amorphous silicon/crystalline silicon heterojunction solar cell with a relatively dose of 24GeV, we observed a very strong drop in conversion efficiency with only minor recovery after sample annealing. In literature it has been reported 2, that the degradation of amorphous silicon is negligible for proton energies above 100MeV. In order to clarify to which extent also the thin film top layer of the hetero solar cell is affected by the proton irradiation, we exposed a variety of thin film silicon samples either to a 1.7MeV beam with a dose of 5.1012 protons/cm2 or to a 24GeV beam with a dose of 5 .1013 protons/cm2. The investigated intrinsic, p-type and n-type amorphous and microcrystalline silicon films have been deposited by conventional plasma deposition under variation of the silane / hydrogen gas phase ratio. Raman measurements have been done in order to determine the order of crystallinity obtained under various deposition conditions. We observed even at 24GeV a clear modification in the electrical characteristics of the films. Temperature dependent measurements of the dark current revealed in particular for all doped samples a significant increase of the activation energy, that might be explained by a decrease of the dopant efficiency, while for intrinsic a-Si:H layers the increasing activation energy is due to deep defect creation

Five years of experience in the Epigenetics and Chromatin Clinic : what have we learned and where do we go from here?

Funding Information: None of the authors had specific funding for this publication, but JRH is supported by grants from the NIH/NICHD 1K23HD101646, the Kabuki Syndrome Foundation, the Rubinstein-Taybi Syndrome Children’s Foundation, the Sekel-Breidenstein Family Fund, and the Kennedy Krieger IDDRC NIH P50HD103538. HTB is supported by the Louma G. Foundation, the Icelandic Research Fund (#217988, #195835, #206806) and the Icelandic Technology Development Fund (#2010588), and JAF is supported by the National Institutes of Health, specifically the National Institute for Child Health and Human Development (NICHD; K08HD086250), the Maryland Stem Cell Research Fund (2022-MSCRFL-5846), and a Johns Hopkins Catalyst Award. CWG receives support from NIH T32GM136577. Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.The multidisciplinary Epigenetics and Chromatin Clinic at Johns Hopkins provides comprehensive medical care for individuals with rare disorders that involve disrupted epigenetics. Initially centered on classical imprinting disorders, the focus shifted to the rapidly emerging group of genetic disorders resulting from pathogenic germline variants in epigenetic machinery genes. These are collectively called the Mendelian disorders of the epigenetic machinery (MDEMs), or more broadly, Chromatinopathies. In five years, 741 clinic visits have been completed for 432 individual patients, with 153 having confirmed epigenetic diagnoses. Of these, 115 individuals have one of 26 MDEMs with every single one exhibiting global developmental delay and/or intellectual disability. This supports prior observations that intellectual disability is the most common phenotypic feature of MDEMs. Additional common phenotypes in our clinic include growth abnormalities and neurodevelopmental issues, particularly hypotonia, attention-deficit/hyperactivity disorder (ADHD), and anxiety, with seizures and autism being less common. Overall, our patient population is representative of the broader group of MDEMs and includes mostly autosomal dominant disorders impacting writers more so than erasers, readers, and remodelers of chromatin marks. There is an increased representation of dual function components with a reader and an enzymatic domain. As expected, diagnoses were made mostly by sequencing but were aided in some cases by DNA methylation profiling. Our clinic has helped to facilitate the discovery of two new disorders, and our providers are actively developing and implementing novel therapeutic strategies for MDEMs. These data and our high follow-up rate of over 60% suggest that we are achieving our mission to diagnose, learn from, and provide optimal care for our patients with disrupted epigenetics.Peer reviewe

Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.

New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved

Determining the Orientation of Protegrin-1 in DLPC Bilayers Using an Implicit Solvent-Membrane Model

Continuum models that describe the effects of solvent and biological membrane molecules on the structure and behavior of antimicrobial peptides, holds a promise to improve our understanding of the mechanisms of antimicrobial action of these peptides. In such methods, a lipid bilayer model membrane is implicitly represented by multiple layers of relatively low dielectric constant embedded in a high dielectric aqueous solvent, while an antimicrobial peptide is accounted for by a dielectric cavity with fixed partial charge at the center of each one of its atoms. In the present work, we investigate the ability of continuum approaches to predict the most probable orientation of the β-hairpin antimicrobial peptide Protegrin-1 (PG-1) in DLPC lipid bilayers by calculating the difference in the transfer free energy from an aqueous environment to a membrane-water environment for multiple orientations. The transfer free energy is computed as a sum of two terms; polar/electrostatic and non-polar. They both include energetic and entropic contributions to the free energy. We numerically solve the Poisson-Boltzmann equation to calculate the electrostatic contribution to the transfer free energy, while the non-polar contribution to the free energy is approximated using a linear solvent accessible surface area relationships. The most probable orientation of PG-1 is that with the lowest relative transfer free energy. Our simulation results indicate that PG-1 assumes an oblique orientation in DLPC lipid bilayers. The predicted most favorable orientation was with a tilt angle of 19°, which is in qualitative agreement with the experimentally observed orientations derived from solid-state NMR data

Aberrant Epigenetic Silencing Is Triggered by a Transient Reduction in Gene Expression

Aberrant epigenetic silencing plays a major role in cancer formation by inactivating tumor suppressor genes. While the endpoints of aberrant silencing are known, i.e., promoter region DNA methylation and altered histone modifications, the triggers of silencing are not known. We used the tet-off system to test the hypothesis that a transient reduction in gene expression will sensitize a promoter to undergo epigenetic silencing.The tet responsive promoter (P(TRE)) was used to drive expression of the selectable human HPRT cDNA in independent transfectants of an Hprt deficient mouse cell line. In this system, high basal HPRT expression is greatly reduced when doxycycline (Dox) is added to the culture medium. Exposure of the P(TRE)-HPRT transfectants to Dox induced HPRT deficient clones in a time dependent manner. A molecular analysis demonstrated promoter region DNA methylation, loss of histone modifications associated with expression (i.e., H3 lysine 9 and 14 acetylation and lysine 4 methylation), and acquisition of the repressive histone modification H3 lysine 9 methylation. These changes, which are consistent with aberrant epigenetic silencing, were not present in the Dox-treated cultures, with the exception of reduced H3 lysine 14 acetylation. Silenced alleles readily reactivated spontaneously or after treatment of cells with inhibitors of histone deacetylation and/or DNA methylation, but re-silencing of reactivated alleles did not require a new round of Dox exposure. Inhibition of histone deacetylation inhibited both the induction of silencing and re-silencing, whereas inhibition of DNA methylation had no such effect.This study demonstrates that a transient reduction in gene expression triggers a pathway for aberrant silencing in mammalian cells and identifies histone deacetylation as a critical early step in this process. DNA methylation, in contrast, is a secondary step in the silencing pathway under study. A model to explain these observations is offered

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome:phenotype comparison in two related syndromes

Background Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. Methods Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. Results Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. Conclusions Results show significant between and within syndrome variability. DifferentNFIXvariants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit

Structural Insight into the Rotational Switching Mechanism of the Bacterial Flagellar Motor

Structural analysis of a clockwise-biased rotation mutant of the bacterial flagellar rotor protein FliG provides a new model for the arrangement of FliG subunits in the motor, and novel insights into rotation switching