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It is generally expect-ed that for such molecules with multifunctional groups a hi-erarchical self-assembly process exists.During this processdirectional bonds (e.g., hydrogen bonds) determine the for-mation of supramolecular structures in the first place (atlow surface coverages), while weaker interactions (e.g., vander Waals (vdW) interactions) become more important withincreasing surface coverage and then direct the subsequentself-assembly of the supramolecules formed initially.Forthis kind of experiment, scanning tunneling microscopy(STM) has proven to be the technique of choice since itallows a direct, real-space determination of the symmetryproperties of the molecular network as well as the unit-mesh distances and angles at the atomic scale.However, toobtain further insight into the detailed molecular structuresfrom the STM images, to address questions such as the mo-lecular adsorption conformations and to distinguish the dif-ferent interactions in self-assembled structures, comparisonwith advanced theoretical modeling of the STM images isrequired.

Interleukin (IL)-21 is a recently discovered cytokine in early clinical development, which has shown anti-tumor activity in various animal models. In the present study, we examine the anti-tumor activity of IL-21 protein therapy in two syngeneic tumor models and its effect on the density of tumor infiltrating T cells. We treated mice bearing established subcutaneous B16 melanomas or RenCa renal cell carcinomas with intraperitoneal (i.p.) or subcutaneous (s.c.) IL-21 protein therapy and subsequently scored the densities of tumor infiltrating CD4(+) and CD8(+) T cells by immunohistochemistry. Whereas both routes of IL-21 administration significantly inhibited growth of small, established RenCa and B16 tumors, only s.c. therapy significantly inhibited the growth of large, established tumors. We found a greater bioavailability and significant drainage of IL-21 to regional lymph nodes following s.c. administration, which could account for the apparent increase in anti-tumor activity. Specific depletion of CD8(+) T cells with monoclonal antibodies completely abrogated the anti-tumor activity, whereas NK1.1(+) cell depletion did not affect tumor growth. In accordance, both routes of IL-21 administration significantly increased the density of tumor infiltrating CD8(+) T cells in both B16 and RenCa tumors; and in the RenCa model s.c. administration of IL-21 led to a significantly higher density of tumor infiltrating CD8(+) T cells compared to i.p. administration. The densities of CD4(+) T cells were unchanged following IL-21 treatments. Taken together, these data demonstrate that IL-21 protein has anti-tumor activity in established syngeneic tumors, and we show that IL-21 therapy markedly increases the density of tumor infiltrating CD8(+) T cells.

Background Inflammatory bowel disease (IBD) is a complex multi-factorial inflammatory disease with Crohn’s disease (CD) and ulcerative colitis (UC) being the two most common forms. A number of transcriptional profiling studies have provided compelling evidence that describe the role of protein-coding genes and microRNAs in modulating the immune responses in IBD. Methods In the present study, we performed a genome-wide transcriptome profiling of lncRNAs and protein-coding genes in 96 colon pinch biopsies (inflamed and non-inflamed) extracted from multiple colonic locations from 45 patients (CD = 13, UC = 20, controls = 12) using an expression microarray platform. Results In our study, we identified widespread dysregulation of lncRNAs and protein-coding genes in both inflamed and non-inflamed CD and UC compared to the healthy controls. In cases of inflamed CD and UC, we identified 438 and 745 differentially expressed lncRNAs, respectively, while in cases of the non-inflamed CD and UC, we identified 12 and 19 differentially expressed lncRNAs, respectively. We also observed significant enrichment (P-value

This paper presents a lead isotope investigation of a gold prospect south of the village Attu in the northern part of the Nagssugtoqidian orogen in central West Greenland. The Attu gold prospect is a replacement gold occurrence, related to a shear/mylonite zone along a contact between orthogneiss and amphibolite within the Nagssugtoqidian orogenic belt. The mineral occurrence is small, less than 0.5 m wide, and can be followed along strike for several hundred metres. The mineral assemblage is pyrite, chalcopyrite, magnetite and gold. The host rocks to the gold prospect are granulite facies ‘brown gneisses’ and amphibolites. Pb-isotopic data on magnetite from the host rocks yield an isochron in a 207Pb/204Pb vs. 206Pb/204Pb diagram, giving a date of 3162 ± 43 Ma (MSWD = 0.5). This date is interpreted to represent the age of the rocks in question, and is older than dates obtained from rocks elsewhere within the Nagssugtoqidian orogen. Pb-isotopic data on cataclastic magnetite from the shear zone lie close to this isochron, indicating a similar origin. The Pb-isotopic compositions of the ore minerals are similar to those previously obtained from the close-by ~2650 Ma Rifkol granite, and suggest a genetic link between the emplacement of this granite and the formation of the ore minerals in the shear/mylonite zone. Consequently, the age of the gold mineralisation is interpreted to be late Archaean.

Within the southern Nagssugtoqidian orogen in West Greenland metamorphic terrains of both Archaean and Palaeoproterozoic ages occur with metamorphic grade varying from low amphibolite facies to granulite facies. The determination of the relative ages of the different metamorphic terrains is greatly aided by the intrusion of the 2 Ga Kangâmiut dyke swarm along a NNE trend. In Archaean areas dykes cross-cut gneiss structures, and the host gneisses are in amphibolite to granulite facies. Along Itilleq strong shearing in an E–W-oriented zone caused retrogression of surrounding gneisses to low amphibolite facies. Within this Itivdleq shear zone Kangâmiut dykes follow the E–W shear fabrics giving the impression that dykes were reoriented by the shearing. However, the dykes remain largely undeformed and unmetamorphosed, indicating that the shear zone was established prior to dyke emplacement and that the orientation of the dykes here was governed by the shear fabric. Metamorphism and deformation north of Itilleq involve both dykes and host gneisses, and the metamorphic grade is amphibolite facies increasing to granulite facies at the northern boundary of the southern Nagssugtoqidian orogen. Here a zone of strong deformation, the Ikertôq thrust zone, coincides roughly with the amphibolite–granulite facies transition. Total magnetic field intensity anomalies from aeromagnetic data coincide spectacularly with metamorphic boundaries and reflect changes in content of the magnetic minerals at facies transitions. Even the nature of facies transitions is apparent. Static metamorphic boundaries are gradual whereas dynamic boundaries along deformation zones are abrupt.

The Archaean North Atlantic Craton of West Greenland collided at c. 1.9 Ga with a lesser-known Archaean craton to the north, to form the Nagssugtoqidian orogen. The Palaeoproterozoic metamorphic grade and strain intensity decrease northward through the orogen, allowing investigation of the reworked Archaean components in its northern part. Two Archaean supracrustal belts in this region – the Ikamiut and Kangilinaaq belts – are investigated here using field mapping, aeromagnetic data, zircon geochronology, and geochemistry. Both belts comprise quartzo-feldspathic and pelitic metasedimentary rocks, amphibolite, and minor calc-silicate rocks, anorthosite and ultramafic rocks. Pb-Pb and U-Pb dating of detrital zircons and host orthogneisses suggest deposition at c. 2800 Ma (Kangilinaaq belt) and after 2740 Ma (Ikamiut belt); both belts have zircons with Neoarchaean metamorphic rims. Metasedimentary rocks and orthogneisses at Ikamiut share similar steep REE signatures with strong LREE enrichment, consistent with local derivation of the sediment and deposition directly onto or proximal to the regional orthogneiss precursors. Zircon age data from Kangilinaaq indicate both local and distal sources for the sediment there. Geochemical data for Kangilinaaq amphibolites indicate bimodal, mixed felsic–mafic source rocks with island-arc basaltic affinities, consistent with a shelf or arc setting. Both belts experienced a similar tectono-metamorphic history involving Neoarchaean amphibolite facies peak metamorphism at c. 2740–2700 Ma, possibly due to continued emplacement of tonalitic and granodioritic magmas. Nagssugtoqidian lower amphibolite facies metamorphism at c. 1850 Ma was associated with development of the large-scale F2 folds and shear zones that control the present outcrop pattern. The observed differences in the sources of the Kangilinaaq and Ikamiut belts and their shared post-Archaean history suggest they were formed in different Neoarchaean environments proximal to and on a continental plate, and were amalgamated in a convergent margin setting shortly after their deposition.

The Nordre Strømfjord shear zone in the fjord Arfersiorfik, central West Greenland, consists of alternating panels of supracrustal rocks and orthogneisses which together form a vertical zone up to 7 km wide with sinistral transcurrent, ductile deformation, which occurred under middle amphibolite facies conditions. The pelitic and metavolcanic schists and paragneisses are all highly deformed, while the orthogneisses appear more variably deformed, with increasing deformation evident towards the supracrustal units. The c. 1.92 Ga Arfersiorfik quartz diorite is traceable for a distance of at least 35 km from the Inland Ice towards the west-south-west. Towards its northern contact with an intensely deformed schist unit it shows a similar pattern of increasing strain, which is accompanied by chemical and mineralogical changes. The metasomatic changes associated with the shear zone deformation are superimposed on a wide range of original chemical compositions, which reflect magmatic olivine and/or pyroxene as well as hornblende fractionation trends. The chemistry of the Arfersiorfik quartz diorite suite as a whole is comparable to that of Phanerozoic plutonic and volcanic rocks of calc-alkaline affinity.

The Archaean North Atlantic Craton of West Greenland collided at c. 1.9 Ga with a lesser-known Archaean craton to the north, to form the Nagssugtoqidian orogen. The Palaeoproterozoic metamorphic grade and strain intensity decrease northward through the orogen, allowing investigation of the reworked Archaean components in its northern part. Two Archaean supracrustal belts in this region – the Ikamiut and Kangilinaaq belts – are investigated here using field mapping, aeromagnetic data, zircon geochronology, and geochemistry. Both belts comprise quartzo-feldspathic and pelitic metasedimentary rocks, amphibolite, and minor calc-silicate rocks, anorthosite and ultramafic rocks. Pb-Pb and U-Pb dating of detrital zircons and host orthogneisses suggest deposition at c. 2800 Ma (Kangilinaaq belt) and after 2740 Ma (Ikamiut belt); both belts have zircons with Neoarchaean metamorphic rims. Metasedimentary rocks and orthogneisses at Ikamiut share similar steep REE signatures with strong LREE enrichment, consistent with local derivation of the sediment and deposition directly onto or proximal to the regional orthogneiss precursors. Zircon age data from Kangilinaaq indicate both local and distal sources for the sediment there. Geochemical data for Kangilinaaq amphibolites indicate bimodal, mixed felsic–mafic source rocks with island-arc basaltic affinities, consistent with a shelf or arc setting. Both belts experienced a similar tectono-metamorphic history involving Neoarchaean amphibolite facies peak metamorphism at c. 2740–2700 Ma, possibly due to continued emplacement of tonalitic and granodioritic magmas. Nagssugtoqidian lower amphibolite facies metamorphism at c. 1850 Ma was associated with development of the large-scale F2 folds and shear zones that control the present outcrop pattern. The observed differences in the sources of the Kangilinaaq and Ikamiut belts and their shared post-Archaean history suggest they were formed in different Neoarchaean environments proximal to and on a continental plate, and were amalgamated in a convergent margin setting shortly after their deposition.

This paper presents a lead isotope investigation of a gold prospect south of the village Attu in the northern part of the Nagssugtoqidian orogen in central West Greenland. The Attu gold prospect is a replacement gold occurrence, related to a shear/mylonite zone along a contact between orthogneissand amphibolite within the Nagssugtoqidian orogenic belt. The mineral occurrence is small, less than 0.5 m wide, and can be followed along strike for several hundred metres. The mineral assemblage is pyrite, chalcopyrite, magnetite and gold. The host rocks to the gold prospect are granulite facies ‘brown gneisses’ and amphibolites. Pb-isotopic data on magnetite from the host rocks yield an isochron in a 207Pb/204Pb vs. 206Pb/204Pb diagram, giving a date of 3162 ± 43 Ma (MSWD = 0.5). This date is interpreted to represent the age of the rocks in question, and is older than dates obtained from rocks elsewhere within the Nagssugtoqidian orogen. Pb-isotopic data on cataclastic magnetite from the shear zone lie close to this isochron, indicating a similar origin. The Pb-isotopic compositions of the ore minerals are similar to those previously obtained from the close-by ~2650 Ma Rifkol granite, and suggest a genetic link between the emplacement of this granite and the formation of the ore minerals in the shear/mylonite zone. Consequently, the age of the gold mineralisation is interpreted tobe late Archaean.

Within the southern Nagssugtoqidian orogen in West Greenland metamorphic terrains of both Archaean and Palaeoproterozoic ages occur with metamorphic grade varying from low amphibolites facies to granulite facies. The determination of the relative ages of the different metamorphic terrains is greatly aided by the intrusion of the 2 Ga Kangâmiut dyke swarm along a NNE trend. In Archaean areas dykes cross-cut gneiss structures, and the host gneisses are in amphibolite to granulite facies. Along Itilleq strong shearing in an E–W-oriented zone caused retrogression of surrounding gneisses to low amphibolite facies. Within this Itivdleq shear zone Kangâmiut dykes follow the E–W shear fabrics giving the impression that dykes were reoriented by the shearing. However, the dykes remain largely undeformed and unmetamorphosed, indicating that the shear zone was established prior to dyke emplacement and that the orientation of the dykes here was governed by the shear fabric. Metamorphism and deformation north of Itilleq involve both dykes and host gneisses, and the metamorphic grade is amphibolite facies increasing to granulite facies at the northern boundary of the southern Nagssugtoqidian orogen. Here a zone of strong deformation, the Ikertôq thrust zone, coincides roughly with the amphibolite–granulite facies transition. Total magnetic field intensity anomalies from aeromagnetic data coincide spectacularly with metamorphic boundaries and reflect changes in content of the magnetic minerals at facies transitions. Even the nature of facies transitions is apparent. Static metamorphic boundaries are gradual whereas dynamic boundaries along deformation zones are abrupt.

The Nordre Strømfjord shear zone in the fjord Arfersiorfik, central West Greenland, consists of alternating panels of supracrustal rocks and orthogneisses which together form a vertical zone up to 7 km wide with sinistral transcurrent, ductile deformation, which occurred under middle amphibolite facies conditions. The pelitic and metavolcanic schists and paragneisses are all highly deformed, while the orthogneisses appear more variably deformed, with increasing deformation evident towards the supracrustal units. The c. 1.92 Ga Arfersiorfik quartz diorite is traceable for a distance of at least 35 km from the Inland Ice towards the west-south-west. Towards its northern contact with an intensely deformed schist unit it shows a similar pattern of increasing strain, which is accompanied by chemical and mineralogical changes. The metasomatic changes associated with the shear zone deformation are superimposed on a wide range of original chemical compositions, which reflect magmatic olivine and/or pyroxene as well as hornblende fractionation trends. The chemistry of the Arfersiorfik quartz diorite suite as a whole is comparable to that of Phanerozoic plutonic and volcanic rocks of calc-alkaline affinity.

Visual inspection and comparison of lithological, topographical, geochemical and geophysical maps is a necessary (and often successful) way of interpreting geological features across poorly exposed or poorly explored areas. In mineral exploration, geochemical and geophysical maps are used to visually identify anomalies believed to reflect mineral occurrences. Outcropping mineral occurrences of a certain size can produce elevated concentrations of elements in stream sediment samples, or create magnetic or radioactive signals retrievable by airborne surveys. However, if the regional data are widely spaced, and if the occurrences are small or poorly exposed, the anomalies created may be too subtle to be recognised visually. In such cases, statistical data analyses may help identify deviations from background variations and trends in the data. Furthermore, visually based correlation between distribution patterns on maps is often limited to a few parameters, and multi-variable relationships are easily overlooked or not possible to deduce. Gold occurrences in Greenland occur in specific host rocks as a result of mineralising processes, e.g. hydrothermal activity, that have affected a larger area. Thus, the favourable environment for a gold occurrence may be reflected in regional scale survey data as subtle changes in certain geochemical and geophysical properties. If such changes, i.e. a multi-parameter signature for gold mineralisation, can be identified, the regional data can be searched for areas that might hold the same signature. This paper presents results gained in the application of a statistical spatial analysis method to investigate how known gold showings are expressed in a range of regional datasets from the Nuuk region, southern West Greenland. The main objective is to identify new areas with gold potential, and to quantify the signatures of the showings. The first tests based on this approach were reported in Nielsen et al. (2004) and Steensgaard et al. (2006).

An ideal mineral exploration program characterizes all types of data by describing its relationship to an integrated mineral deposit and exploration model. The model is used to interpret the minera ...

BACKGROUND: It is important to ensure that tools are valid and reliable in the context in which they are used. The development of age and country norms is part of this process.OBJECTIVES: The primary aim of the present study was to examine the performance of the Food Allergy Quality of Life Questionnaire - Parent Form (FAQLQ-PF) in a countrywide American sample of children with food allergy. The secondary aim was to compare age differences in impact across 9 European countries.METHODS: In a cross-sectional quantitative design, questionnaires were completed by the parents of 1029 food-allergic children (0-12 years). Participants were recruited via support groups and allergists. Data were analyzed by using multivariate analysis of variance and tests for internal consistency and validity. The average score was calculated for each age group in 15 studies in Ireland, Switzerland, the Netherlands, Spain, Portugal, Germany, Italy, Denmark, Israel, and the United Kingdom.RESULTS: The FAQLQ-PF has high convergent validity (child: r = 0.49, n = 695, P = .01; parent: r = 0.36, n = 696, P = .01) and discriminant validity, parent: t (719) = 4.67, P = .001 (anaphylaxis yes vs no); t (513), P = .009 (single vs multiple allergens). Internal consistency was excellent (r = 0.96). US health-related quality of life was worse than European health-related quality of life, as indicated by higher FAQLQ-PF scores in US samples. Burden increased with age in all populations.CONCLUSIONS: The FAQLQ-PF is appropriate for use in an American population. Findings will form the basis for further work in the development of an online manual with food allergy-normed age scores to allow for precise measurement, interpretation of scores, and comparison across countries and cultures, in clinical and research settings. (C) 2016 American Academy of Allergy, Asthma & Immunology

The growth of individual molecular building blocks can be carefullycontrolled by small modifications to a template surface. In theCommunication by F. Besenbacher and co-workers on the followingpages,thewidthofthelinesofaCu–Cu/Osupergratingareshowntodetermine the orientation in which molecules adsorb to the surface,andthussteertheiralignmentalongthetemplate.

Although the molecular signals underlying cardiac hypertrophy have been the subject of intense investigation, the extent of common and distinct gene regulation between different forms of cardiac hypertrophy remains unclear. We hypothesized that a general and comparative analysis of hypertrophic gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved in hypertrophic signalling. From gene expression analyses (8740 probe sets,n= 46) of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61 genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may be useful for prediction of a common therapeutic approach. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat

By means of STM imaging and manipulation, we show that violet Lander (VL) molecules (C108H104) act as nanoscale templates at the Cu(110) step edges, creating nanostructures to which the VLs are anchored. These nanostructures are longer and sometimes wider than those created by the related single Lander (SL) molecules due to the slightly different shape and size of the VL molecules. These results illustrate the possibility of controlling the formation of nanostructures on a surface on the atomic scale by means of a rational molecular design.

Sub-monolayer growth of a small chiral peptide, di- l -alanine, on Cu(1 1 0) was investigated by variable temperature scanning tunneling microscopy (STM). At low coverage and for temperatures above ≈−220 K the molecules nucleate along the [ 3 3 2] direction to form short, mainly one-dimensional islands. An increase in coverage leads to the formation of [ 3 3 2]-directed, elongated islands. Images with sub-molecular resolution reveal that the orientation of the molecules within one particular island depends on the deposition temperature. At higher coverage, up to one monolayer, the islands coalesce, giving rise to phase boundaries between domains of opposite orientation. An atomic-scale model for di- l -alanine on Cu(1 1 0) is presented.

The adsorption of large organic molecules on surfaces has recently been the subject of intensive investigation, both because of the molecules’ intrinsic physical and chemical properties, and for prospective applications in the emerging field of nanotechnology. Certain complex molecules are considered good candidates as basic building blocks for molecular electronics and nanomechanical devices. In general, molecular ordering on a surface is controlled by a delicate balance between intermolecular forces and molecule–substrate interactions. Under certain conditions, these interactions can be controlled to some extent, and sometimes even tuned by the appropriate choice of substrate material and symmetry. Several studies have indicated that, upon molecular adsorption, surfaces do not always behave as static templates, but may rearrange dramatically to accommodate different molecular species. In this context, it has been demonstrated that the scanning tunnelling microscope (STM) is a very powerful tool for exploring the atomic-scale realm of surfaces, and for investigating adsorbate–surface interactions. By means of high-resolution, fast-scanning STM unprecedented new insight was recently achieved into a number of fundamental processes related to the interaction of largish molecules with surfaces such as molecular diffusion, bonding of adsorbates on surfaces, and molecular self-assembly. In addition to the normal imaging mode, the STM tip can also be employed to manipulate single atoms and molecules in a bottom–up fashion, collectively or one at a time. In this way, molecule-induced surface restructuring processes can be revealed directly and nanostructures can be engineered with atomic precision to study surface quantum phenomena of fundamental interest. Here we will present a short review of some recent results, several of which were obtained by our group, in which several features of the complex interaction between large organic molecules and metal surfaces were revealed. The focus is on experiments performed using STM and other complementary surface-sensitive techniques.

Using a known dual PPARα/γ activator (5) as a structural template, SAR evaluations led to the identification of triple PPARα/γ/δ activators (18–20) with equal potency and efficacy on all three receptors. These compounds could become useful tools for studying the combined biological effects of PPARα/γ/δ activation.

The reliability of offshore wind turbines is highly influenced by the uncertainties related to the subsoil conditions. Traditionally, the evaluation of the dynamic structural behaviour is based on a computational model with deterministic soil properties. Using this approach, however, provides limited insight into thevariation of the estimate of the inherent modal properties and loads. In this paper, a comprehensive study is performed on the dynamic behaviour of an offshore wind turbine installed on a monopile foundation. Based on consistent lumped-parameter models calibrated to semi-analytical impedance functions of a monopile embedded in a stochastic linear viscoelastic soil layer, fully coupled aero-hydro-elastic simulations are conducted in the nonlinear multi-body code HAWC2. The probabilistic analysis accounts for the uncertainty of soil properties (e.g. damping and stiffness) and relies on a Monte Carlo method facilitating the derivation of the probability densities of the modal properties and the fatigue loading. The main conclusion of the presented work is that the dynamic structural behaviour of the wind turbine and its support structure is strongly affected by the stochastic soil properties. Lognormal and Gumbel distributed modal damping and side-side fatigue damage equivalent moments with a coefficient of variation of 30% and 8%, respectively, are observed. The reliability of offshore wind turbines is highly influenced by the uncertainties related to the subsoil conditions. Traditionally, the evaluation of the dynamic structural behaviour is based on a computational model with deterministic soil properties. Using this approach, however, provides limited insight into the variation of the estimate of the inherent modal properties and loads. In this paper, a comprehensive study is performed on the dynamic behaviour of an offshore wind turbine installed on a monopile foundation. Based on consistent lumped-parameter models calibrated to semi-analytical impedance functions of a monopile embedded in a stochastic linear viscoelastic soil layer, fully coupled aero-hydro-elastic simulations are conducted in the nonlinear multi-body code Hawc2. The probabilistic analysis accounts for the uncertainty of soil properties (e.g. damping and stiffness) and relies on a Monte Carlo method facilitating the derivation of the probability densities of the modal properties and the fatigue loading. The main conclusion of the presented work is that the dynamic structural behaviour of the wind turbine and its support structure is strongly affected by the stochastic soil properties. Lognormal and Gumbel distributed modal damping and accumulated side–side fatigue damage equivalent moments with a coefficient of variation of 30% and 8%, respectively, are observed.