Vitamin K-Dependent Carboxylase in Skin

Vitamin K-dependent carboxylase is demonstrated in skin microsomes from humans, rats, rabbits, and mice. This enzyme converts a number of distinct protein-bound glutamic acid residues into γ-carboxyglutamic acid residues, which strongly interact with Ca++ ions. The enzymatic activity (expressed per mg protein) in skin is about 20% of that in liver. Vitamin K-dependent carboxylase is present in both epidermal and dermal tissue. It is demonstrated that warfarin treatment in mice results in an accumulation of noncarboxylated precursor proteins in both dermal and epidermal microsomes. Most probably this effect of warfarin is not restricted to mice, but occurs also in the skin of patients under oral anticoagulant therapy. A possible relation between vitamin K-dependent skin carboxylase and the γ-carboxyglutamic acid-containing protein in calcified nodules from patients with scleroderma and dermatomyositis is discussed

Atomic scale analysis of N dopants in InAs

The band gap of most III-V semiconductors is strongly reduced with the introduction of only a few percent of N, even if the III-N alloy has a much bigger band gap. N impurities in InAs introduce an impurity state around 1 eV above the conduction-band minimum, much deeper in the band than in other III-V materials. Topographic scanning tunneling spectroscopy measurements (STS) and areal spectroscopy measurements performed on N atoms up to two layers below the (110) surface of InAs show a reduction of the resonance energy of the N atom with increasing depth. This is attributed to tip induced band bending, pulling the N states up at positive bias and acting most strongly on surface N atoms. STS measurements obtained on undoped InAs and N-doped InAs show a band-gap reduction of <0.1 eV. Spacial imaging of features corresponding to N dopants up to two layers below the surface are also compared to density functional theory simulations and show excellent correspondence. Spectroscopy maps of N atoms up to two layers below the surface provide a high-resolution spatial and spectroscopic view of the N atoms. Here the characteristic shape of the N atoms in different layers below the surface is observed as an enhancement of the dI/dV signal compared to the InAs background. At energies above the enhancement a reduction of the dI/dV is observed, which has the same shape and size as the enhancement. This shows that the redistribution of density of states caused by the N impurities is mainly energetic in nature

An atomic scale study of Si-doped AlAs by cross-sectional scanning tunneling microscopy and density functional theory

Silicon (Si) donors in GaAs have been the topic of extensive studies since Si is the most common and well understood n-type dopant in III-V semiconductor devices and substrates. The indirect bandgap of AlAs compared to the direct one of GaAs leads to interesting effects when introducing Si dopants. Here we present a study of cross-sectional scanning tunneling microscopy (X-STM) and density functional theory (DFT) calculations to study Si donors in AlAs at the atomic scale. Based on their crystal symmetry and contrast strengths, we identify Si donors up to four layers below the (110) surface of AlAs. Interestingly, their short-range local density of states (LDOS) is very similar to Si atoms in the (110) surface of GaAs. Additionally we show high-resolution images of Si donors in all these layers. For empty state imaging, the experimental and simulated STM images based on DFT show excellent agreement for Si donor up to two layers below the surface

Mental and perceptual feedback in the development of creative flow

Sketching is considered by artists and designers to be a vital tool in the creative process. However, research shows that externalisation during the creative process (i.e., sketching) is not necessary to create effectively. This study examines whether sketching may play a more important role in the subjective experience of creativity by facilitating the deeply focused, optimal state of consciousness termed ‘flow’ (being ‘in the zone’). The study additionally explored whether sketching affects flow by easing cognitive load or by providing a clearer sense of self-feedback. Participants carried out the creative mental synthesis task (combining sets of simple shapes into creative drawings), experimentally simulating the visual creative process. Ideas were generated either mentally before committing to a final drawing, or with external perceptual support through sketching, and cognitive load was varied by using either three- or five-shape sets. The sketching condition resulted in greater experience of flow and lower perceived task difficulty. However, cognitive load did not affect flow and there was no interaction between load and sketching conditions. These findings are the first to empirically demonstrate that sketching increases flow experience, and that this is not dependent on an associated reduction in overall working memory load

N-nH complexes in GaAs studied at the atomic scale by cross-sectional scanning tunneling microscopy

Hydrogenation of nitrogen (N) doped GaAs allows for reversible tuning of the bandgap and the creation of site controlled quantum dots through the manipulation of N-nH complexes, N-nH complexes, wherein a nitrogen atom is surrounded by n hydrogen (H) atoms. Here we employ cross-sectional scanning tunneling microscopy (X-STM) to study these complexes in the GaAs (110) surface at the atomic scale. In addition to that we performed density functional theory (DFT) calculations to determine the atomic properties of the N-nH complexes. We argue that at or near the (110) GaAs surface two H atoms from N-nH complexes dissociate as an H$_2$ molecule. We observe multiple features related to the hydrogenation process, of which a subset is classified as N-1H complexes. These N-1H related features show an apparent reduction of the local density of states (LDOS), characteristic to N atoms in the GaAs (110) surface with an additional apparent localized enhancement of the LDOS located in one of three crystal directions. N-nH features can be manipulated with the STM tip. Showing in one case a switching behavior between two mirror-symmetric states and in another case a removal of the localized enhancement of the LDOS. The disappearance of the bright contrast is most likely a signature of the removal of an H atom from the N-nH complex.Comment: 11 pages, 12 figure

Defining decision thresholds for judgments on health benefits and harms using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) frameworks : A protocol for a randomised methodological study (GRADE-THRESHOLD)

Introduction The Grading of Recommendations Assessment, Development and Evaluation (GRADE) and similar Evidence to Decision (EtD) frameworks require its users to judge how substantial the effects of interventions are on desirable and undesirable people-important health outcomes. However, decision thresholds (DTs) that could help understand the magnitude of intervention effects and serve as reference for interpretation of findings are not yet available. The objective of this study is an approach to derive and use DTs for EtD judgments about the magnitude of health benefits and harms. We hypothesise that approximate DTs could have the ability to discriminate between the existing four categories of EtD judgments (Trivial, Small, Moderate, Large), support panels of decision-makers in their work, and promote consistency and transparency in judgments. Methods and analysis We will conduct a methodological randomised controlled trial to collect the data that allow deriving the DTs. We will invite clinicians, epidemiologists, decision scientists, health research methodologists, experts in Health Technology Assessment (HTA), members of guideline development groups and the public to participate in the trial. Then, we will investigate the validity of our DTs by measuring the agreement between judgments that were made in the past by guideline panels and the judgments that our DTs approach would suggest if applied on the same guideline data. Ethics and dissemination The Hamilton Integrated Research Ethics Board reviewed this study as a quality improvement study and determined that it requires no further consent. Survey participants will be required to read a consent statement in order to participate in this study at the beginning of the trial. This statement reads: You are being invited to participate in a research project which aims to identify indicative DTs that could assist users of the GRADE EtD frameworks in making judgments. Your input will be used in determining these indicative thresholds. By completing this survey, you provide consent that the anonymised data collected will be used for the research study and to be summarised in aggregate in publication and electronic tools. PROTOCOL registration number NCT05237635

The role and impact of mental simulation in design

Although theories of mental simulations have used different formulations of the premises of 'thought experiments', they can be fitted under a minimalist hypothesis stating that mental simulations are run under situations of uncertainty to turn that uncertainty into approximate answers. Three basic assumptions of mental simulations were tested by using naturalistic data from engineering design. Results from the design protocols showed (1) initial representations in mental simulation had higher than base-rate uncertainty, (2) uncertainty in mental simulations were lowered after simulation runs, (3) resulting representations had more approximations than base-rate or initial representations. Further, the reference to external representational systems (sketches and prototypes) was examined. It was found that prototypes had fewer technical/functional simulations compared to sketches or unsupported cognition. Although prototypes were associated with more approximation than unsupported cognition, the different external representation categories did not differ in information uncertainty. The results support the minimalist hypothesis of mental simulations. Copyright © 2008 John Wiley & Sons, Ltd