Investigation of the anisotropy and scaling of the phase structure function of a spatially coherent light beam propagating through convective air turbulence.

We report on applications of moiré deflectometry in measurements of the anisotropy and scaling of the phase structure function (PSF), obtained after passing a laser beam through an indoor enclosure containing convective air turbulence. We combine the use of two telescopes, with a two-channel wavefront sensor based on moiré deflectometry, to attain high sensitivity and resolution to fluctuations in the wavefront phase, caused by turbulent fluctuations in the enclosure. The measurements of the wavefront PSF along two directions perpendicular to the direction of the light beam propagation at different heater temperatures show that the convective air turbulence is anisotropic turbulence, where the value of the anisotropy increases with increasing temperature gradient. Various models are fitted to the measured PSFs, and we find that the turbulent is also non-Kolmogorov, in which, for the separation distances of two points on the wavefront less than 10 cm, the von Kármán PSF is the best fit to the experimental data. For higher values of separations, the experimental data do not fit with existing models. By fitting the von Kármán PSF on the data, we estimate values of the refractive index structure constant, Cn2, as well as the outer scale of the turbulence. The value of the outer scale decreases with increasing temperature of the heater up to approximately 50°C, where it saturates, while the value of Cn2 monotonically increases. Over the complete range of heater temperatures, from 40°C to 160°C, the Rayleigh number, Ra, for the enclosed air flow varied from 5.80×108

Mercury goes Solid at room temperature at nanoscale and a potential Hg waste storage.

While room temperature bulk mercury is liquid, it is solid in its nano-configuration (Ønano-Hg ≤ 2.5 nm). Conjugating the nano-scale size effect and the Laplace driven surface excess pressure, Hg nanoparticles of Ønano-Hg ≤ 2.4 nm embedded in a 2-D turbostratic Boron Nitride (BN) host matrix exhibited a net crystallization at room temperature via the experimentally observed (101) and (003) diffraction Bragg peaks of the solid Hg rhombohedral α-phase. The observed crystallization is correlated to a surface atomic ordering of 7 to 8 reticular atomic plans of the rhombohedral α-phase. Such a novelty of size effect on phase transition phenomena in Hg is conjugated to a potential Hg waste storage technology. Considering the vapor pressure of bulk Hg, Room Temperature (RT) Solid nano-Hg confinement could represent a potential green approach of Hg waste storage derived from modern halogen efficient light technology.

Turbulent convection and large scale circulation in a cube with rough horizontal surfaces.

Large-eddy simulations of thermal convection are presented and discussed for a cube with rough horizontal surfaces. Two types of roughness are considered: uniformly placed pyramids, and grooves aligned parallel to one set of sidewalls. The Rayleigh number is 10^{8}, the Prandtl number 0.7, and the aspect ratio 1, as in a previous study [N. Foroozani, J. J. Niemela, V. Armenio, and K. R. Sreenivasan, Phys. Rev. E 95, 033107 (2017)10.1103/PhysRevE.95.033107], except that the meshes here are finer. When the thermal boundary layers are sufficiently large relative to the characteristic roughness height, i.e., for hydrodynamically smooth conditions, the mean properties of the large scale circulation (LSC) are qualitatively similar to the case of smooth surfaces. In particular, the LSC is always aligned along one of the diagonals of the cube. When the boundaries are hydrodynamically rough, the same result holds true only for the case of pyramidal structures; for grooved surfaces, the LSC is forced to be parallel to the sidewalls on average, alternating rapidly between the two diagonals of the cube with a mean period of the order 10 turnover times. Our analysis suggests that the difference from the pyramidal case is due to the breaking of the horizontal x-z symmetry under conditions of hydrodynamical roughness, and the corresponding directional concentration of plume emission along the grooves, from which the LSC is generated, providing a strong restoring force. Furthermore, in this study we observed a small reduction in heat transport for both roughness configurations which is in good agreement with past studies.

Reorientations of the large-scale flow in turbulent convection in a cube.

Large-eddy simulations of turbulent Rayleigh-Bénard convection were conducted for a fluid of Prandtl number Pr=0.7 confined in a cube, for Rayleigh numbers of 10^{6} and 10^{8}. The model solves the unsteady Navier-Stokes equations under the Boussinesq approximation, using a dynamic Smagorinsky model with a Lagrangian averaging technique for the subgrid terms. Under fully developed conditions the flow topology is characterized by a large-scale circulation (LSC) developing in a plane containing one of the diagonals of the cell, while two counter-rotating vortices consequently develop in the other diagonal plane, resulting in a strong inflow at the horizontal midplane. This flow structure is not static, with the LSC undergoing nonperiodic reorientations, or switching, between the two diagonal planes; hence, we supplement the observations of the three-dimensional time-averaged flow structures with single point measurements (time series) to shed light on the dynamics of the reorientations. For all observations, this switching results from a lateral rotation of the LSC in which some finite time spent in a transient state where the large-scale circulation is parallel to one set of side walls; there are, importantly, no observations consistent with so-called cessations of the LSC, in which it decays and then reforms in another plane without such a rotation. The average switching rate for the LSC is in excellent agreement with the results of Bai et al. [K. Bai, D. Ji, and E. Brown, Phys. Rev. E 93, 023117 (2016)PLEEE81539-375510.1103/PhysRevE.93.023117].

Thermoelectric and Structural Characterization of Al-Doped ZnO/Y2O3 Multilayers.

The influence of Y2O3 nanolayers on thermoelectric performance and structure of 2% Al-doped ZnO (AZO) thin films has been studied. Multilayers based on five 50 nm thick AZO layers alternated with few nanometers thick Y2O3 layers were prepared by pulsed laser deposition on Al2O3 single crystals by alternate ablation of AZO target and Y2O3 target. The number of laser shots on Y2O3 target was maintained very low (5, 10 and 15 pulses in three separate experiments. The main phase (AZO) presents polycrystalline orientation and typical columnar growth not affected by the presence of Y2O3 nanolayers. The multilayer with 15 laser shots of Y2O3 showed best thermoelectric performance with electrical conductivity σ 48 S/cm and Seebeck coefficient S = −82 µV/K, which estimate power factor (S2·σ) about 0.03 × 10−3 W m−1 K−2 at 600 K. The value of thermal conductivity (κ) was found 10.03 W m−1 K−1 at 300 K, which is one third of typical value previously reported for bulk AZO. The figure of merit, ZT = S2·σ·T/κ, is calculated 9.6 × 10−4 at 600 K. These results demonstrated the feasibility of nanoengineered defects insertion for the depression of thermal conductivity.

Loss of B Cells in Patients with Heterozygous Mutations in IKAROS.

BACKGROUND: Common variable immunodeficiency (CVID) is characterized by late-onset hypogammaglobulinemia in the absence of predisposing factors. The genetic cause is unknown in the majority of cases, and less than 10% of patients have a family history of the disease. Most patients have normal numbers of B cells but lack plasma cells. METHODS: We used whole-exome sequencing and array-based comparative genomic hybridization to evaluate a subset of patients with CVID and low B-cell numbers. Mutant proteins were analyzed for DNA binding with the use of an electrophoretic mobility-shift assay (EMSA) and confocal microscopy. Flow cytometry was used to analyze peripheral-blood lymphocytes and bone marrow aspirates. RESULTS: Six different heterozygous mutations in IKZF1, the gene encoding the transcription factor IKAROS, were identified in 29 persons from six families. In two families, the mutation was a de novo event in the proband. All the mutations, four amino acid substitutions, an intragenic deletion, and a 4.7-Mb multigene deletion involved the DNA-binding domain of IKAROS. The proteins bearing missense mutations failed to bind target DNA sequences on EMSA and confocal microscopy; however, they did not inhibit the binding of wild-type IKAROS. Studies in family members showed progressive loss of B cells and serum immunoglobulins. Bone marrow aspirates in two patients had markedly decreased early B-cell precursors, but plasma cells were present. Acute lymphoblastic leukemia developed in 2 of the 29 patients. CONCLUSIONS: Heterozygous mutations in the transcription factor IKAROS caused an autosomal dominant form of CVID that is associated with a striking decrease in B-cell numbers. (Funded by the National Institutes of Health and others.).

Plant stanol content remains stable during storage of cholesterol-lowering functional foods.

Plant stanols reduce the absorption of both dietary and biliary cholesterol. The aim of this study was to examine the stability of plant stanols in the form of plant stanol esters in spreads and biscuits stored under typical storage conditions. The plant stanol content of two commercial margarine-type spreads, containing 35% and 60% absorbable fat, was 6.5 and 6.4 g/100 g after production and remained unaltered when stored at 6 °C for a shelf life of 18 and 22 weeks, respectively. Comparable results were obtained for plant stanol ester ingredient stored under the same conditions and for plant stanol ester-containing biscuits stored at room temperature for up to 74 weeks. Furthermore, the peroxide value and free fatty acids showed that the quality of the food products remained good. The present study demonstrated that plant stanol esters as an ingredient and when added in food products, are stable whilst stored under the appropriate conditions.

Investigation into local cell mechanics by atomic force microscopy mapping and optical tweezer vertical indentation.

Investigating the mechanical properties of cells could reveal a potential source of label-free markers of cancer progression, based on measurable viscoelastic parameters. The Young's modulus has proved to be the most thoroughly studied so far, however, even for the same cell type, the elastic modulus reported in different studies spans a wide range of values, mainly due to the application of different experimental conditions. This complicates the reliable use of elasticity for the mechanical phenotyping of cells. Here we combine two complementary techniques, atomic force microscopy (AFM) and optical tweezer microscopy (OTM), providing a comprehensive mechanical comparison of three human breast cell lines: normal myoepithelial (HBL-100), luminal breast cancer (MCF-7) and basal breast cancer (MDA-MB-231) cells. The elastic modulus was measured locally by AFM and OTM on single cells, using similar indentation approaches but different measurement parameters. Peak force tapping AFM was employed at nanonewton forces and high loading rates to draw a viscoelastic map of each cell and the results indicated that the region on top of the nucleus provided the most meaningful results. OTM was employed at those locations at piconewton forces and low loading rates, to measure the elastic modulus in a real elastic regime and rule out the contribution of viscous forces typical of AFM. When measured by either AFM or OTM, the cell lines' elasticity trend was similar for the aggressive MDA-MB-231 cells, which were found to be significantly softer than the other two cell types in both measurements. However, when comparing HBL-100 and MCF-7 cells, we found significant differences only when using OTM.

Mutations in PIK3CD can cause hyper IgM syndrome (HIGM) associated with increased cancer susceptibility.

Autosomal dominant gain of function mutations in the gene encoding PI3K p110δ were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, CMV and/or EBV viremia and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM. Here we describe three patients in two families who were diagnosed with HIGM at a young age and were recently found to carry heterozygous mutations in PIK3CD. These patients had an abnormal circulating B cell distribution featuring a preponderance of early transitional (T1) B cells and plasmablasts. When stimulated in vitro, PIK3CD mutated B cells were able to secrete class-switched immunoglobulins. This finding implies that the patients' elevated serum IgM levels were unlikely a product of an intrinsic B cell functional inability to class switch. All three patients developed malignant lymphoproliferative syndromes that were not associated with EBV. Thus, we identified a novel subset of patients with PIK3CD mutations associated with HIGM, despite indications of preserved in vitro B cell class switch recombination, as well as susceptibility to non-EBV-associated malignancies.

Influence of container shape on scaling of turbulent fluctuations in convection.

We perform large-eddy simulations of turbulent convection in a cubic cell for Rayleigh numbers, Ra, between 10(6) and 10(10) and the molecular Prandtl number, Pr=0.7. The simulations were carried out using a second-order-accurate finite-difference method in which subgrid-scale fluxes of momentum and heat were both parametrized using a Lagrangian and dynamic Smagorinsky model. The scaling of the root-mean-square fluctuations of density (temperature) and velocity measured in the cell center are in excellent agreement with the scaling measured in the laboratory experiments of Daya and Ecke [Phys. Rev. Lett. 87, 184501 (2001)] and differ substantially from that observed in cylindrical cells. We also observe the time-averaged spatial distributions of the local heat flux and density fluctuations, and find that they are strongly inhomogeneous in the horizontal midplane, with the largest density gradients occurring at the corners at the midheight, where hot and cold plumes mix in the form of strong counter-rotating eddies.

QSAR models for anti-androgenic effect--a preliminary study.

Three modelling systems (MultiCase®, LeadScope® and MDL® QSAR) were used for construction of androgenic receptor antagonist models. There were 923-942 chemicals in the training sets. The models were cross-validated (leave-groups-out) with concordances of 77-81%, specificity of 78-91% and sensitivity of 51-76%. The specificity was highest in the MultiCase® model and the sensitivity was highest in the MDL® QSAR model. A complementary use of the models may be a valuable tool when optimizing the prediction of chemicals for androgenic receptor antagonism. When evaluating the fitness of the model for a particular application, balance of training sets, domain definition, and cut-offs for prediction interpretation should also be taken into account. Different descriptors in the modelling systems are illustrated with hydroxyflutamide and dexamethasone as examples (a non-steroid and a steroid anti-androgen, respectively). More research concerning the mechanism of anti-androgens would increase the possibility for further optimization of the QSAR models. Further expansion of the basis for the models is in progress, including the addition of more drugs.

QSAR models for P450 (2D6) substrate activity.

Human Cytochrome P450 (CYP) is a large group of enzymes that possess an essential function in metabolising different exogenous and endogenous compounds. Humans have more than 50 different genes encoding CYP enzymes, among these a gene encoding for the CYP isoenzyme 2D6, a CYP able to metabolise drugs and other chemicals. A training set of 747 chemicals primarily based on in vivo human data for the CYP isoenzyme 2D6 was collected from the literature. QSAR models focusing on substrate/non-substrate activity were constructed by the use of MultiCASE, Leadscope and MDL quantitative structure-activity relationship (QSAR) modelling systems. They cross validated (leave-groups-out) with concordances of 71%, 81% and 82%, respectively. Discrete organic European Inventory of Existing Commercial Chemical Substances (EINECS) chemicals were screened to predict an approximate percentage of CYP 2D6 substrates. These chemicals are potentially present in the environment. The biological importance of the CYP 2D6 and the use of the software mentioned above were discussed.

Molecular characterization of patients with X-linked Hyper-IgM syndrome: description of two novel CD40L mutations.

Type 1, X-linked Hyper-IgM syndrome (HIGM1) is caused by mutations in the gene encoding the CD154 protein, also known as CD40 ligand (CD40LG). CD40L is expressed in activated T cells and interacts with CD40 receptor expressed on B lymphocytes and dendritic cells. Affected patients present cellular and humoral immune defects, with infections by intracellular, opportunistic and extracellular pathogens. In the present study we investigated the molecular defects underlying disease in four patients with HIGM1. We identified four distinct CD40L mutations, two of them which have not been previously described. P1 harboured the novel p.G227X mutation which abolished CD40L expression. P2 had a previously described frame shift deletion in exon 2 (p.I53fsX65) which also prevented protein expression. P3 demonstrated the previously known p.V126D change in exon 4, affecting the TNF homology (TNFH) domain. Finally, P4 evidenced the novel p.F229L mutation also located in the TNFH domain. In silico analysis of F229L predicted the change to be pathological, affecting the many hydrophobic interactions of this residue. Precise molecular diagnosis in HIGM syndrome allows reliable detection of carriers, making genetic counselling and prenatal diagnosis possible.

QSAR models for reproductive toxicity and endocrine disruption in regulatory use--a preliminary investigation.

A special challenge in the new European Union chemicals legislation, Registration, Evaluation and Authorisation of Chemicals, will be the toxicological evaluation of chemicals for reproductive toxicity. Use of valid quantitative structure-activity relationships (QSARs) is a possibility under the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data and epidemiological human studies), dominant lethal effect in rodents (in vivo) and Drosophila melanogaster sex-linked recessive lethal effect. A structure set of 57,014 European Inventory of Existing Chemical Substances (EINECS) chemicals was screened. A total of 5240 EINECS chemicals, corresponding to 9.2%, were predicted as reproductive toxicants by one or more of the models. The chemicals predicted positive for reproductive toxicity will be submitted to the Danish Environmental Protection Agency as scientific input for a future updated advisory classification list with advisory classifications for concern for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption.

Formation of the "superconducting" core in turbulent thermal convection.

A sinusoidal temperature perturbation is superimposed on the bottom plate of a cylindrical convection cell, and its decay is measured at the cell midheight. Rayleigh numbers up to Ra=10(13) and aspect ratios 1 and 4 are considered. The technique allows a dynamic measurement of the height of the layer interposed between the superconducting core and the boundary. This deduced height is in good agreement with results from recent numerical simulations.

Conservation planning in forest landscapes of Fennoscandia and an approach to the challenge of countdown 2010.

Effective management of biodiversity in production landscapes requires a conservation approach that acknowledges the complexity of ecological and cultural systems in time and space. Fennoscandia has experienced major loss of forest biodiversity caused by intensive forestry. Therefore, the Countdown 2010 initiative to halt the loss of biodiversity in Europe is highly relevant to forest management in this part of the continent. As a contribution to meeting the challenge posed by Countdown 2010, we developed a spatially explicit conservation-planning exercise that used regional knowledge on forest biodiversity to provide support for managers attempting to halt further loss of biological diversity in the region. We used current data on the distribution of 169 species (including 68 red-listed species) representing different forest habitats and ecologies along with forest data within the frame of modern conservation software to devise a map of priority areas for conservation. The top 10% of priority areas contained over 75% of red-listed species locations and 41% of existing protected forest areas, but only 58% of these top priorities overlapped with core areas identified previously in a regional strategy that used more qualitative methods. We argue for aggregating present and future habitat value of single management units to landscape and regional scales to identify potential bottlenecks in habitat availability linked to landscape dynamics. To address the challenge of Countdown 2010, a general framework for forest conservation planning in Fennoscandia needs to cover different conservation issues, tools, and data needs.

Fluctuations of temperature gradients in turbulent thermal convection.

Broad theoretical arguments are proposed to show, formally, that the magnitude G of the temperature gradients in turbulent thermal convection at high Rayleigh numbers obeys the same advection-diffusion equation that governs the temperature fluctuation T , except that the velocity field in the new equation is substantially smoothed. This smoothed field leads to a -1 scaling of the spectrum of G in the same range of scales for which the spectral exponent of T lies between -7/5 and -5/3 . This result is confirmed by measurements in a confined container with cryogenic helium gas as the working fluid for Rayleigh number Ra=1.5x 10(11) . Also confirmed is the logarithmic form of the autocorrelation function of G . The anomalous scaling of dissipation-like quantities of T and G are identical in the inertial range, showing that the analogy between the two fields is quite deep.

Critical fluctuation of wind reversals in convective turbulence.

The irregular reversals of wind direction in convective turbulence are found to have fluctuating intervals that can be related, under certain circumstances, to critical behavior. In particular, by focusing on its temporal evolution, the net magnetization of a two-dimensional Ising lattice of finite size is observed to fluctuate in the same way. Detrended fluctuation analysis of the wind reversal time series results in a scaling behavior that agrees remarkably well with that of the Ising problem. The specific properties found here, as well as the lack of an external tuning parameter, also suggest that the wind reversal phenomenon exhibits signs of self-organized criticality.

Resilience and vulnerability of northern regions to social and environmental change.

The arctic tundra and boreal forest were once considered the last frontiers on earth because of their vast expanses remote from agricultural land-use change and industrial development. These regions are now, however, experiencing environmental and social changes that are as rapid as those occurring anywhere on earth. This paper summarizes the role of northern regions in the global system and provides a blueprint for assessing the factors that govern their sensitivity to social and environmental change.

"Clusterization" and intermittency of temperature fluctuations in turbulent convection.

Temperature time traces are obtained in turbulent thermal convection at high Rayleigh numbers. Measurements are made in the midplane of the apparatus, near the sidewall but outside the boundary layer. A telegraph approximation for temperature traces is generated by setting the fluctuation amplitude to 1 or 0 depending on whether or not it exceeds the mean value. Unlike the standard diagnostics of intermittency, the telegraph approximation allows one to distinguish the tendency of events to cluster (clusterization) from their large-scale variability in amplitude. A qualitative conclusion is that amplitude intermittency might mitigate clusterization effects.