Epitaxial Growth of Thin Films -- a Statistical Mechanical Model

A theoretical framework is developed to describe experiments on the structure of epitaxial thin films, particularly niobium on sapphire. We extend the hypothesis of dynamical scaling to apply to the structure of thin films from its conventional application to simple surfaces. We then present a phenomenological continuum theory that provides a good description of the observed scattering and the measured exponents. Finally the results of experiment and theory are compared.Comment: 10 pages, 3 figures, minor revisions. accepted for publication in J Phys Condense Matte

Kritik der Strumaepidemiologie: I. Strumagröße

Der Vergleich von drei Methoden zum Nachweis von Schilddrüsenvergrößerungen bei 92 Patienten zeigt, daß die Sensitivität von sonographischer Volumetrie (93 %) und Palpation (91 %) besser als die der Röntgenaufnahmen (45 %) ist. Als Nachteil der Sonographie fiel das Fehlen des quantitativen Nachweises von retrosternalen Strumen ins Gewicht. Als Nachteil der Palpation und der Röntgen-Thoraxaufnahmen ergab sich die Häufigkeit sicher falsch-positiver Befunde von 8,7 bzw. 10,9 %.Comparison of three methods for demonstration of thyroid enlargement in 92 patients showed that the sensitivity of sonographic volumetrics (93 %) and palpation (91 %) is superior to radiography (45 %). Sonography has the disadvantage of lack of quantitative demonstration of retrosternal goitre. Palpation and chest radiograph had the disadvantage of a frequency of false positive findings in 8.7 and 10.9 %

Global carbon budget 2019

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere-the "global carbon budget"-is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions (EFF) are based on energy statistics and cement production data, while emissions from land use change (ELUC), mainly deforestation, are based on land use and land use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly and its growth rate (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) and terrestrial CO2 sink (SLAND) are estimated with global process models constrained by observations. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the last decade available (2009-2018), EFF was 9:5±0:5 GtC yr-1, ELUC 1:5±0:7 GtC yr-1, GATM 4:9±0:02 GtC yr-1 (2:3±0:01 ppm yr-1), SOCEAN 2:5±0:6 GtC yr-1, and SLAND 3:2±0:6 GtC yr-1, with a budget imbalance BIM of 0.4 GtC yr-1 indicating overestimated emissions and/or underestimated sinks. For the year 2018 alone, the growth in EFF was about 2.1% and fossil emissions increased to 10:0±0:5 GtC yr-1, reaching 10 GtC yr-1 for the first time in history, ELUC was 1:5±0:7 GtC yr-1, for total anthropogenic CO2 emissions of 11:5±0:9 GtC yr-1 (42:5±3:3 GtCO2). Also for 2018, GATM was 5:1±0:2 GtC yr-1 (2:4±0:1 ppm yr-1), SOCEAN was 2:6±0:6 GtC yr-1, and SLAND was 3:5±0:7 GtC yr-1, with a BIM of 0.3 GtC. The global atmospheric CO2 concentration reached 407:38±0:1 ppm averaged over 2018. For 2019, preliminary data for the first 6-10 months indicate a reduced growth in EFF of C0:6% (range of.0:2% to 1.5 %) based on national emissions projections for China, the USA, the EU, and India and projections of gross domestic product corrected for recent changes in the carbon intensity of the economy for the rest of the world. Overall, the mean and trend in the five components of the global carbon budget are consistently estimated over the period 1959-2018, but discrepancies of up to 1 GtC yr-1 persist for the representation of semi-decadal variability in CO2 fluxes. A detailed comparison among individual estimates and the introduction of a broad range of observations shows (1) no consensus in the mean and trend in land use change emissions over the last decade, (2) a persistent low agreement between the different methods on the magnitude of the land CO2 flux in the northern extra-tropics, and (3) an apparent underestimation of the CO2 variability by ocean models outside the tropics. This living data update documents changes in the methods and data sets used in this new global carbon budget and the progress in understanding of the global carbon cycle compared with previous publications of this data set (Le Quéré et al., 2018a, b, 2016, 2015a, b, 2014, 2013). The data generated by this work are available at https://doi.org/10.18160/gcp-2019 (Friedlingstein et al., 2019). © 2019 by the authors

Structural Properties of Polyglutamine Aggregates Investigated via Molecular Dynamics Simulations

Polyglutamine (polyQ) beta-stranded aggregates constitute the hallmark of Huntington disease. The disease is fully penetrant when Q residues are more than 36-40 ("disease threshold"). Here, based on a molecular dynamics study on polyQ helical structures of different shapes and oligomeric states, we suggest that the stability of the aggregates increases with the number of monomers, while it is rather insensitive to the number of Qs in each monomer. However, the stability of the single monomer does depend on the number of side-chain intramolecular H-bonds, and therefore oil the number of Qs. If such number is lower than that of the disease threshold, the beta-stranded monomers are unstable and hence may aggregate with lower probability, consistently with experimental findings. Our results provide a possible interpretation of the apparent polyQ length dependent-toxicity, and they do not support the so-called "structural threshold hypothesis", which supposes a transition from random coil to a beta-sheet structure only above the disease threshold

Longitudinal Imaging and Analysis of Neurons Expressing Polyglutamine-Expanded Proteins

Misfolded proteins have been implicated in most of the major neurodegenerative diseases, and identifying drugs and pathways that protect neurons from the toxicity of misfolded proteins is of paramount importance. We invented a form of automated imaging and analysis called robotic microscopy that is well suited to the study of neurodegeneration. It enables the monitoring of large cohorts of individual neurons over their lifetimes as they undergo neurodegeneration. With automated analysis, multiple endpoints in neurons can be measured, including survival. Statistical approaches, typically reserved for engineering and clinical medicine, can be applied to these data in an unbiased fashion to discover whether factors contribute positively or negatively to neuronal fate and to quantify the importance of their contribution. Ultimately, multivariate dynamic models can be constructed from these data, which can provide a systems-level understanding of the neurodegenerative disease process and guide the rationale for the development of therapies

Conformational Targeting of Fibrillar Polyglutamine Proteins in Live Cells Escalates Aggregation and Cytotoxicity

Misfolding- and aggregation-prone proteins underlying Parkinson's, Huntington's and Machado-Joseph diseases, namely alpha-synuclein, huntingtin, and ataxin-3 respectively, adopt numerous intracellular conformations during pathogenesis, including globular intermediates and insoluble amyloid-like fibrils. Such conformational diversity has complicated research into amyloid-associated intracellular dysfunction and neurodegeneration. To this end, recombinant single-chain Fv antibodies (scFvs) are compelling molecular tools that can be selected against specific protein conformations, and expressed inside cells as intrabodies, for investigative and therapeutic purposes.Using atomic force microscopy (AFM) and live-cell fluorescence microscopy, we report that a human scFv selected against the fibrillar form of alpha-synuclein targets isomorphic conformations of misfolded polyglutamine proteins. When expressed in the cytoplasm of striatal cells, this conformation-specific intrabody co-localizes with intracellular aggregates of misfolded ataxin-3 and a pathological fragment of huntingtin, and enhances the aggregation propensity of both disease-linked polyglutamine proteins. Using this intrabody as a tool for modulating the kinetics of amyloidogenesis, we show that escalating aggregate formation of a pathologic huntingtin fragment is not cytoprotective in striatal cells, but rather heightens oxidative stress and cell death as detected by flow cytometry. Instead, cellular protection is achieved by suppressing aggregation using a previously described intrabody that binds to the amyloidogenic N-terminus of huntingtin. Analogous cytotoxic results are observed following conformational targeting of normal or polyglutamine-expanded human ataxin-3, which partially aggregate through non-polyglutamine domains.These findings validate that the rate of aggregation modulates polyglutamine-mediated intracellular dysfunction, and caution that molecules designed to specifically hasten aggregation may be detrimental as therapies for polyglutamine disorders. Moreover, our findings introduce a novel antibody-based tool that, as a consequence of its general specificity for fibrillar conformations and its ability to function intracellularly, offers broad research potential for a variety of human amyloid diseases

Oncogenic Stress Induced by Acute Hyper-Activation of Bcr-Abl Leads to Cell Death upon Induction of Excessive Aerobic Glycolysis

In response to deregulated oncogene activation, mammalian cells activate disposal programs such as programmed cell death. To investigate the mechanisms behind this oncogenic stress response we used Bcr-Abl over-expressing cells cultivated in presence of imatinib. Imatinib deprivation led to rapid induction of Bcr-Abl activity and over-stimulation of PI3K/Akt-, Ras/MAPK-, and JAK/STAT pathways. This resulted in a delayed necrosis-like cell death starting not before 48 hours after imatinib withdrawal. Cell death was preceded by enhanced glycolysis, glutaminolysis, and amino acid metabolism leading to elevated ATP and protein levels. This enhanced metabolism could be linked to induction of cell death as inhibition of glycolysis or glutaminolysis was sufficient to sustain cell viability. Therefore, these data provide first evidence that metabolic changes induced by Bcr-Abl hyper-activation are important mediators of oncogenic stress-induced cell death