Surface analysis by time-of-flight secondary ion mass spectrometry, X-ray photoelectron spectroscopy and scanning tunnelling microscopy has been applied to provide new insight on Mo effects on the ...composition and nanostructure of the passive films grown in sulfuric acid on well-controlled Fe-17Cr-14.5Ni-2.3Mo(100) austenitic stainless steel single crystal surfaces. A duplex hydroxylated oxide matrix, 1.8-1.9 nm thick, is formed with a strong partition between Cr(
iii
) and Fe(
iii
) in the inner and outer layers, respectively. Cr(
iii
) is increasingly enriched by preferential iron oxide dissolution upon passivation and ageing. Ni, only present as oxide traces in the film, is enriched in the alloy underneath. Mo, mostly present as Mo(
iv
) in the Cr-rich inner layer prior to anodic polarisation, becomes increasingly enriched (up to 16% of cations) mostly as Mo(
vi
) in the Fe-rich outer layer of the passive film, with ageing promoting this effect. Metallic Mo is not significantly enriched below the passive film produced from the native oxide covered surface. Mo does not markedly impact the nanogranular morphology of the native oxide film nor its local thickness variations assigned to substrate site effects on Cr(
iii
) enrichment. Site specific preferential passivation still takes place at the (native) oxide-covered step edges of the alloy surface, and transient dissolution remains preferentially located on the terraces. Nanostructures, possibly Mo-containing, and healing local depressions formed by transient dissolution during passivation, appear as a specific effect of the Mo presence. Another Mo effect, observed even after 20 h of passivation, is to prevent crystallisation at least in the Fe-rich outer part of the passive film where it is concentrated mostly as Mo(
vi
) (
i.e.
molybdate) species.
Maintenance of skeletal muscle structure and function requires innervation by motor neurons, such that denervation causes muscle atrophy. We show that myogenin, an essential regulator of muscle ...development, controls neurogenic atrophy. Myogenin is upregulated in skeletal muscle following denervation and regulates expression of the E3 ubiquitin ligases MuRF1 and atrogin-1, which promote muscle proteolysis and atrophy. Deletion of myogenin from adult mice diminishes expression of MuRF1 and atrogin-1 in denervated muscle and confers resistance to atrophy. Mice lacking histone deacetylases (HDACs) 4 and 5 in skeletal muscle fail to upregulate myogenin and also preserve muscle mass following denervation. Conversely, forced expression of myogenin in skeletal muscle of HDAC mutant mice restores muscle atrophy following denervation. Thus, myogenin plays a dual role as both a regulator of muscle development and an inducer of neurogenic atrophy. These findings reveal a specific pathway for muscle wasting and potential therapeutic targets for this disorder.
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► Myogenin, a key regulator of myogenesis, controls muscle atrophy upon denervation ► Adult mice lacking myogenin are resistant to muscle atrophy upon denervation ► Myogenin transcriptionally activates E3 ubiquitin ligases, which promote atrophy ► Mice lacking histone deacetylases 4 and 5 mimic mice lacking myogenin
Response times on test items are easily collected in modern computerized testing. When collecting both (binary) responses and (continuous) response times on test items, it is possible to measure the ...accuracy and speed of test takers. To study the relationships between these two constructs, the model is extended with a multivariate multilevel regression structure which allows the incorporation of covariates to explain the variance in speed and accuracy between individuals and groups of test takers. A Bayesian approach with Markov chain Monte Carlo (MCMC) computation enables straightforward estimation of all model parameters. Model-specific implementations of a Bayes factor (BF) and deviance information criterium (DIC) for model selection are proposed which are easily calculated as byproducts of the MCMC computation. Both results from simulation studies and real-data examples are given to illustrate several novel analyses possible with this modeling framework.
Histone variant H3.3 plays novel roles in development as compared to canonical H3 proteins and is the most commonly mutated histone protein of any kind in human disease. Here we discuss how gene ...targeting studies of the two H3.3-coding genes H3f3a and H3f3b have provided important insights into H3.3 functions including in gametes as well as brain and lung development. Knockouts have also provided insights into the important roles of H3.3 in maintaining genomic stability and chromatin organization, processes that are also affected when H3.3 is mutated in human diseases such as pediatric tumors and neurodevelopmental syndromes. Overall, H3.3 is a unique histone linking development and disease via epigenomic machinery.
The evolution of the defect structure and microstructure of heavily Gd-doped ceria (Ce
RE
O
, 0.313 ≤ μ ≤ 0.438) for different synthetic pathways is investigated here to explore the way defects ...interact with each other in a composition range known to effectively hamper the application of the material as an electrolyte. Synchrotron radiation powder diffraction is exploited by combining conventional Rietveld analysis with the Pair Distribution Function to get a multiscale picture of defect structures, and it is combined with Raman spectroscopy to assess local scale interactions. Samples were prepared via both the sol-gel route and coprecipitation of oxalates by sintering the powders at different temperatures to obtain samples with different defect distributions and crystallite sizes, investigated using electron microscopy and Whole Powder Pattern Modelling from diffraction data. As a general scheme, increasing the doping amount transforms the fluorite structure of ceria into C-type Gd
O
. For samples annealed at and above 900 °C, containing crystals at least ∼100 nm in size, this transformation occurs through a mechanism involving first the formation of distorted Gd-rich droplets on the local scale, then the growth of extended C-type nanodomains. Nanoparticles, resulting from thermal treatments at lower temperature, are less distorted on the local scale and transform abruptly upon doping, without forming larger dopant-rich aggregations, from fluorite to the C-type. The annealing temperature not only acts on the sintering of the crystallites, it is also found to promote a radical change in the microstructure as a consequence of the preferential aggregation of oxygen vacancies.
The mechanical properties of medium-carbon steel bond onto low-carbon steel by explosive welding are correlated to the microstructure of the steels. In the investigated weld there is a wavy interface ...including melt pockets exhibiting ultra-high hardness. It is found that the bonding is of high quality, reflected by the fact that in tensile testing with the bonding zone perpendicular to the tensile direction fracture happens in the medium-carbon steel.
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•Medium carbon steel was bonded onto low carbon steel by explosive welding.•The bonding zone exhibits a wavy structure with melt pockets.•The bonding zone shows very high hardness values.•Fracture occurs in the low carbon steel upon tensile testing.
The fact that polarisation lidars measure a depolarisation signal in liquid clouds due to the occurrence of multiple scattering is well known. The degree of measured depolarisation depends on the ...lidar characteristics (e.g. wavelength and receiver field of view) as well as the cloud macrophysical (e.g. cloud-base altitude) and microphysical (e.g. effective radius, liquid water content) properties. Efforts seeking to use depolarisation information in a quantitative manner to retrieve cloud properties have been undertaken with, arguably, limited practical success. In this work we present a retrieval procedure applicable to clouds with (quasi-)linear liquid water content (LWC) profiles and (quasi-)constant cloud-droplet number density in the cloud-base region. Thus limiting the applicability of the procedure allows us to reduce the cloud variables to two parameters (namely the derivative of the liquid water content with height and the extinction at a fixed distance above cloud base). This simplification, in turn, allows us to employ a fast and robust optimal-estimation inversion using pre-computed look-up tables produced using extensive lidar Monte Carlo (MC) multiple-scattering simulations. In this paper, we describe the theory behind the inversion procedure and successfully apply it to simulated observations based on large-eddy simulation (LES) model output. The inversion procedure is then applied to actual depolarisation lidar data corresponding to a range of cases taken from the Cabauw measurement site in the central Netherlands. The lidar results were then used to predict the corresponding cloud-base region radar reflectivities. In non-drizzling condition, it was found that the lidar inversion results can be used to predict the observed radar reflectivities with an accuracy within the radar calibration uncertainty (2–3 dBZ). This result strongly supports the accuracy of the lidar inversion results. Results of a comparison between ground-based aerosol number concentration and lidar-derived cloud-droplet number densities are also presented and discussed. The observed relationship between the two quantities is seen to be consistent with the results of previous studies based on aircraft-based in situ measurements.
Elevated serum IgE levels are associated with allergic disorders, parasitosis and specific immunologic abnormalities. In addition, epidemiological and mechanistic evidence indicates an association ...between IgE‐mediated immune surveillance and protection from tumour growth. Intriguingly, recent studies reveal a correlation between IgE deficiency and increased malignancy risk. This is the first review discussing IgE levels and links to pathological conditions, with special focus on the potential clinical significance of ultra‐low serum IgE levels and risk of malignancy. In this Position Paper we discuss: (a) the utility of measuring total IgE levels in the management of allergies, parasitosis, and immunodeficiencies, (b) factors that may influence serum IgE levels, (c) IgE as a marker of different disorders, and d) the relationship between ultra‐low IgE levels and malignancy susceptibility. While elevated serum IgE is generally associated with allergic/atopic conditions, very low or absent IgE may hamper anti‐tumour surveillance, indicating the importance of a balanced IgE‐mediated immune function. Ultra‐low IgE may prove to be an unexpected biomarker for cancer risk. Nevertheless, given the early stage of investigations conducted mostly in patients with diseases that influence IgE levels, in‐depth mechanistic studies and stratification of malignancy risk based on associated demographic, immunological and clinical co‐factors are warranted.
The hypothalamus-pituitary-thyroid feedback control is a dynamic, adaptive system. In situations of illness and deprivation of energy representing type 1 allostasis, the stress response operates to ...alter both its set point and peripheral transfer parameters. In contrast, type 2 allostatic load, typically effective in psychosocial stress, pregnancy, metabolic syndrome, and adaptation to cold, produces a nearly opposite phenotype of predictive plasticity. The non-thyroidal illness syndrome (NTIS) or thyroid allostasis in critical illness, tumors, uremia, and starvation (TACITUS), commonly observed in hospitalized patients, displays a historically well-studied pattern of allostatic thyroid response. This is characterized by decreased total and free thyroid hormone concentrations and varying levels of thyroid-stimulating hormone (TSH) ranging from decreased (in severe cases) to normal or even elevated (mainly in the recovery phase) TSH concentrations. An acute versus chronic stage (wasting syndrome) of TACITUS can be discerned. The two types differ in molecular mechanisms and prognosis. The acute adaptation of thyroid hormone metabolism to critical illness may prove beneficial to the organism, whereas the far more complex molecular alterations associated with chronic illness frequently lead to allostatic overload. The latter is associated with poor outcome, independently of the underlying disease. Adaptive responses of thyroid homeostasis extend to alterations in thyroid hormone concentrations during fetal life, periods of weight gain or loss, thermoregulation, physical exercise, and psychiatric diseases. The various forms of thyroid allostasis pose serious problems in differential diagnosis of thyroid disease. This review article provides an overview of physiological mechanisms as well as major diagnostic and therapeutic implications of thyroid allostasis under a variety of developmental and straining conditions.
Objective
Evidence suggests that chronic high levels of behavioral inhibition are a precursor of social anxiety disorder. The authors sought to identify early risk factors for, and developmental ...pathways to, chronic high inhibition among school-age children and the association of chronic high inhibition with social anxiety disorder by adolescence.
MethodA community sample of 238 children was followed from birth to grade 9. Mothers, teachers, and children reported on the children's behavioral inhibition from grades 1 to 9. Lifetime history of psychiatric disorders was available for the subset of 60 (25%) children who participated in an intensive laboratory assessment at grade 9. Four early risk factors were assessed: female gender; exposure to maternal stress during infancy and the preschool period; and at age 4.5 years, early manifestation of behavioral inhibition and elevated afternoon salivary cortisol levels.
ResultsAll four risk factors predicted greater and more chronic inhibition from grades 1 to 9, and together they defined two developmental pathways. The first pathway, in girls, was partially mediated by early evidence of behavioral inhibition and elevated cortisol levels at age 4.5 years. The second pathway began with exposure to early maternal stress and was also partially mediated by childhood cortisol levels. By grade 9, chronic high inhibition was associated with a lifetime history of social anxiety disorder.
ConclusionsChronic high levels of behavioral inhibition are associated with social anxiety disorder by adolescence. The identification of two developmental pathways suggests the potential importance of considering both sets of risk factors in developing preventive interventions for social anxiety disorder.
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