Plasmonic nanostructures are widely used for various sensing applications by monitoring changes in refractive index through optical spectroscopy or as substrates for surface enhanced Raman spectroscopy. However, in most practical situations conventional surface plasmon resonance is preferred for biomolecular interaction analysis because of its high resolution in surface coverage and the simple single-material planar interface. Still, plasmonic nanostructures may find unique sensing applications, for instance when the nanoscale geometry itself is of interest. This calls for new methods to prepare nanoscale particles and cavities with controllable dimensions and curvature. In this work, we present two types of plasmonic nanopores where the solid support underneath a nanohole array has been etched, thereby creating cavities denoted as ‘nanowells’ or ‘nanocaves’ depending on the degree of anisotropy (dry or wet etch). The refractometric sensitivity is shown to be enhanced upon removing the solid support because of an increased probing volume and a shift of the asymmetric plasmonic field towards the liquid side of the finite gold film. Furthermore, the structures exhibit different spectral changes upon binding inside the cavities compared to the gold surface, which means that the structures can be used for location-specific detection. Other sensing applications are also suggested.

Various forms of carbon are known to perform well as biomaterials in a variety of applications and an improved understanding of their interactions with biomolecules, cells, and tissues is of interest for improving and tailoring their performance. Nanoplasmonic sensing (NPS) has emerged as a powerful technique for studying the thermodynamics and kinetics of interfacial reactions. In this work, the in situ adsorption of two proteins, bovine serum albumin and fibrinogen, were studied at carbon surfaces with differing chemical and optical properties using nanoplasmonic sensors. The carbon material was deposited as a thin film onto NPS surfaces consisting of 100 nm Au nanodisks with a localized plasmon absorption peak in the visible region. Carbon films were fully characterized by X-ray photoelectron spectroscopy, atomic force microscopy, and spectroscopic ellipsometry. Two types of material were investigated: amorphous carbon (a-C), with high graphitic content and high optical absorptivity, and hydrogenated amorphous carbon (a-C:H), with low graphitic content and high optical transparency. The optical response of the Au/carbon NPS elements was modeled using the finite difference time domain (FDTD) method, yielding simulated analytical sensitivities that compare well with those observed experimentally at the two carbon surfaces. Protein adsorption was investigated on a-C and a-C:H, and the protein layer thicknesses were obtained from FDTD simulations of the expected response, yielding values in the 1.83.3 nm range. A comparison of the results at a-C and a-C:H indicates that in both cases fibrinogen layers are thicker than those formed by albumin by up to 80%.

Obesity is a highly heritable disorder but the genetic associations reported to date account for only a small percentage of the inherited variation in body mass index. Two groups report deletions on chromosome16p11.2 that may explain part of the 'missing heritability' in terms of 'high-penetrance' mutations that are rare but when present are very often associated with severe obesity. This is in contrast to more common gene defects that are less closely associated with clinical symptoms. Bochukova et al. identified rare recurrent copy number variants in 300 patients with severe early-onset obesity, caused by deletions involving several genes including SH2B1, known to be involved in leptin and insulin signalling. Many of the patients also suffered neurodevelopmental disorders. Walters et al. identified deletions of at least 593 kilobases on chromosome 16p11.2 in 31 patients with a previously unrecognized type of extreme obesity. The strategy they used to identify the lesion — using small well-phenotyped cohorts of extreme phenotypes with targeted follow-up in genome-wide association studies and population cohorts — shows promise as a means of identifying 'missing heritability' in complex metabolic diseases more generally. Recently, numerous single nucleotide polymorphisms have been identified as being associated with obesity, but these loci together account for only a small fraction of the known heritable component. Here, an association is reported between rare deletions of at least 593 kilobases at 16p11.2 and a highly penetrant form of obesity. The strategy used of combining study of extreme phenotypes with targeted follow-up is promising for identifying missing heritability in obesity. Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western ‘obesogenic’ environment and a strong genetic contribution1. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component1. Thus, the ‘common disease, common variant’ hypothesis is increasingly coming under challenge2. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) ≥ 40 kg m-2 or BMI standard deviation score ≥ 4; P = 6.4 × 10-8, odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the ‘power of the extreme’4 in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.

Mesoscopically ordered mesoporous silica materials have attracted a wide interest since their discovery in the early 1990’s due to their diverse potential applications areas; including catalysis, filtration and chromatography. Supramolecular surfactant aggregates are used as structure directing agents for inorganics during condensation, leading to mesoscopically ordered surfactant-inorganic composites. Porosity can be induced in the inorganic part by removal of the surfactant portion through thermal or chemical means. By controlling the synthesis conditions and choice of structure directing agents, the system can be engineered to fit numerous functions of preference. As the purely siliceous mesoporous materials have been shown to be biocompatible, or sometimes even bioactive, there is an increasing interest in this class of materials for applications in the field of bioceramics, especially as bone substitute materials. Furthermore, the highly organized porous silica matrix could be used as a potential controlled drug release system. Another attractive advantage is that amorphous silica is degradable in an aqueous solution, and thus problems related to the removal of the material after use can be avoided. In this article, a few of the most common forms of drug delivery mechanism from ceramic drug carrier systems are investigated. Furthermore, some examples are given on different mesoporous silica systems as drug delivery devices and how factors such as pore size, pore connectivity and surface affect the drug loading and the release (diffusion) rate.

Spray drying is a widely used process to produce pharmaceutical powders. In traditional spray drying, the particle size distribution is wide and not well controlled. Using EHD atomization for spray drying offers a possibility to tailor the particle size and morphology. In conventional EHD spray drying, the generated particles are charged and need to be discharged to avoid Rayleigh breakup. Discharging adds complexity to the process and eliminates the possibility to collect the powder using an electric field. The present work describes a novel EHD spray drying setup based on a low-voltage nozzle. The low-voltage nozzle imparts moderate charge to the droplets, which makes discharging unnecessary. The charged particles can be controlled and collected by using an auxiliary electric field. The EHD spray dryer has been characterized in terms of particle size, particle morphology, process output, and yield. The size distribution of the generated particles is very narrow. Both porous and completely spherical particles can be produced. The yield of small-scale bench-top equipment was 20%, which is similar to the yield of a small-scale conventional spray dryer. The effective output with five nozzles was 75 mg/hr of dry powder. Because of the repelling forces associated with the unipolarly charged droplets, the number of nozzles can be increased without risking coalescence.

In two recent papers (J. Andersson, S. Areva, B. Spliethoff and M. Linden, Biomaterials, 2005, 26, 6827-6835 and J. Andersson, E. Johannessen, S. Areva, M. Jarn and M. Linden, J. Nanosci. Nanotechnol., 2006, 6, 2438-2444) we have presented new means of synthesizing silica-calcium phosphate ( hydroxyapatite or tricalcium phosphate) composite materials, where the calcium phosphate is covered by a mesoporous layer of silica. These materials are bifunctional biomaterials, as they can be used both as drug carrier matrices and osteoconductive materials. Some of these materials, especially if synthesized according to a one-pot method, exhibit a very high in vitro bioactivity, and nucleate and grow calcium phosphate on their surfaces in less than 24 h if exposed to a simulated body fluid. In the present study, we have carried out a thorough characterization of the one-pot sol-gel derived composite materials by the means of solid state Si-29 magic angle spinning (MAS) NMR, P-31 MAS NMR, Na-23 MAS NMR, and transfer of population in double resonance (TRAPDOR) NMR spectroscopy, scanning electron microscopy, and transmission electron microscopy. The aim of the study is to relate the material properties to the in vitro bioactivity. The reason for high bioactivity of the composites cannot be ascribed to the silica content, but primarily to the presence of a highly soluble second calcium phosphate phase, NaCaPO4, co-existing with the hydroxyapatite in the hybrid material. Furthermore, the hydroxyapatite becomes increasingly calcium deficient with increasing silica content, which adds to increase the bioactivity. Also the overall crystallinity of the apatitic calcium phosphate phase could contribute to the bioactivity of the composites in vitro.

Predator cues and diet, when studied separately, have been shown to affect body shape of organisms. Previous studies show that the morphological responses to predator absence/presence and diet may be similar, and hence could confound the interpretation of the causes of morphological differences found between groups of individuals. In this study, we simultaneously examined the effect of these two factors on body shape and performance in crucian carp in a laboratory experiment. Crucian carp (Carassius carassius) developed a shallow body shape when feeding on zooplankton prey and a deep body shape when feeding on benthic chironomids. In addition, the presence of chemical cues from a pike predator affected body shape, where a shallow body shape was developed in the absence of pike and a deep body shape was developed in the presence of pike. Foraging activity was low in the presence of pike cues and when chironomids were given as prey. Our results thereby suggest that the change in body shape could be indirectly mediated through differences in foraging activity. Finally, the induced body shape changes affected the foraging efficiency, where crucians raised on a zooplankton diet or in the absence of pike cues had a higher foraging success on zooplankton compared to crucian raised on a chironomid diet or in the presence of pike. These results suggest that body changes in response to predators can be associated with a cost, in terms of competition for resources.

This paper describes a method by which a porous silica coating layer can be obtained on different apatite particles through a simple sol-gel synthesis route. Sol-gel derived powders of hydroxyapatite (HAP) and beta tricalciumphosphate (beta-TCP) were coated with a mesoporous silica using C16TAB (hexadecyltrimethylammonium bromide) as a template in order to induce mesophase formation. Further calcination of the material removes the template from the mesophase and leaves a highly ordered hexagonal arranged mesoporous silica structure with a core of HAP/beta-TCP. The phase purity of the SiO2/apatite composites has been thoroughly investigated by the means of FT-IR, XRD, and solid state 31P MAS NMR. The phase purity of these materials is shown to be dependent on the solubility properties of the used apatites. The hybrid materials are suitable as a multifunctional biomaterial where osteoconductive properties can be combined with drug delivery.

We discuss the volume fraction of a model of non - overlapping convex grains. It is obtained from thinning a Poisson process where each point has a weight and is the centre of a grain, by removing any grain that is overlapped by one of larger or equal weight. In the limit as the intensity of the Poisson process tends to infinity, the model can be identified with the intact grains in the dead leaves model if the weights are independent of the grain sizes. In this case we can show that the volume fraction is at most 1/2(d) for d = 1 or 2 if the shape is fixed, but the size and the orientation are random. The upper bound is achieved for centrally symmetric sets of the same size and orientation. For general d we can show the upper bound, 1/2(d), for spherical grains with two - point radius distribution. If dependence between weight and size is allowed, it is possible to achieve a volume fraction arbitrarily close to one.

Question: Does cannibalism lead to resource polymorphism in young Arctic charr (Salvelinus alpinus. Pisces)?Hypothesis: Cannibals should evoke a low-activity morph that is well adapted to benthivory but not planktivory, and which differs in morphology compared with a planktivorous morph.Methods: We reared young-of-the-year charr in laboratory aquaria with and without larger cannibalistic charr present. Thereafter, we measured foraging efficiency on pelagic and benthic resources, swimming speed when foraging, and morphology of the young charr.Conclusions: Living among cannibals did not affect the morphology of the young charr. It also did not affect the foraging efficiency of the young charr on the benthic resource. However, individuals from cannibal treatments swam closer and had lower foraging efficiency on the pelagic resource.

BACKGROUND TP53 has been described as a prognostic factor in many malignancies, including breast cancer. Whether it also might be a predictive factor with reference to chemo- and endocrine therapy is more controversial. PATIENTS AND METHODS We investigated relapse-free (RFS), breast cancer-corrected (BCCS) and overall survival (OS) related to TP53 status in node-positive breast cancer patients that had received polychemotherapy [cyclophosphamide, methotrexate, 5-fluorouracil (CMF)] and/or endocrine therapy (tamoxifen). Sequence analyses of the whole TP53 coding region was performed in 376 patients operated on for primary breast cancer with axillary lymph node metastases between 1984 and 1989 (median follow-up time 84 months). RESULTS TP53 mutations were found in 105 patients (28%). We found 90 (82%) of the 110 mutations in the more frequently analysed exons 5-8, while the other 20 (18%) were located in exons 3-4 and 9-10, respectively. Univariate analyses showed TP53 to be a significant prognostic factor with regard to RFS, BCCS and OS in patients who received adjuvant CMF. CONCLUSIONS TP53 mutations might induce resistance to certain modalities of breast cancer therapy. Sequence-determined TP53 mutation was of negative prognostic value in the total patient population and in the CMF treated patients.

In this study, a degradable, hierarchically porous silica/apatite composite material is developed from a simple low-temperature synthesis. Mesoporosity is induced in the silica portion by the use of supramolecular templating. The template is further removed by calcination. Firstly, hydroxyapatite is synthesized through a sol–gel method at near room temperature conditions. After the mineralization process, the crystal surface is coated with a mesoporous silica matrix using the templates already present in the bulk solution. The material is characterized by XRD, N2-sorption, FT–IR, SEM/EDS, and TEM. The coating layer is distributed fairly homogeneously over the apatite surface and the coating thickness is easily adjustable and dependent on the amount of added silica precursor. The hybrid material is shown to efficiently induce calcium phosphate formation under in vitro conditions and simultaneously work as a carrier system for drugs.

The aim of the present study is to investigate the influence of the variation of metal grain sizes on fatigue lives. The grain structure is simulated from a Poisson–Voronoi model and the short crack growth model of Navarro and de los Rios is applied. The resulting fatigue life decreased with increasing component size, probably reflecting the fact that with increasing number of grains there is a larger probability of finding a large grain where the crack starts. The standard deviation of the logarithm of the lives was in the order of 0.2–0.4, i.e. the variation in grain size explains only part of the observed variance in real fatigue data.

Intraspecific competition for resources is strongly influenced by the size of competitors. In this study, we estimated the size‐scaling of the foraging capacities on zooplankton and benthic macroinvertebrates in Arctic char (Salvelinus alpinus) to link size‐dependent performance to effects from competition. The competitive interactions between two size‐classes (YOY and 1‐y) of char were then studied in a large‐scale pond experiment and in two small subarctic lakes. The attack rate function on zooplankton was hump‐shaped whereas the attack rate on benthic chironomids increased monotonically with size. The size‐scaling exponent's for zooplankton and chironomids were 0.65 and 0.30, respectively, leading to that critical resource density (CRD) and maximum growth resource density (GMRD) increases with size, suggesting an exploitative competitive advantage of small individuals over large. Correspondingly, large (1‐y) char growth was negatively affected by cohort competition whereas small (YOY) char growth was not. Diets of both size classes were dominated by macroinvertebrates with large overlap in prey size suggesting only small gape size advantages for large char. Small char fed to a larger extend on cladocerans which, due to the hump‐shaped foraging efficiency function on zooplankton, were a relatively more profitable resource for small than large char.Estimates of CRD and GmRD were in correspondence with observed growth responses and resource estimates for zooplankton, whereas for macroinvertebrates only qualitatively correspondence with foraging estimates and char performance was found. Although we were able to explain our results with exploitative competition only, we suggest a general need for size‐dependent foraging estimates on prey in more complex habitats in order to quantitatively link performance and resource abundances. Interference and size‐dependent resource use as mechanisms for observed stable population dynamics in char was not supported by this study and instead a low per capita fecundity and early cannibalism on recruits are suggested to be potential mechanisms that may stabilize char dynamics.

Resource polymorphism has been suggested to be a platform for speciation. In some cases resource polymorphism depends on phenotypic plasticity but in other cases on genetic differences between morphotypes, which in turn has been suggested to be the ongoing development of a species pair. Here we study environmentally induced morphological differences in two age classes of Arctic char (Salvelinus alpinus) influencing char performance and diet in relation to resource availability. We found that structurally complex habitats with relatively lower zooplankton densities gave rise to individuals with a deeper body, and a downward positioned tip of the snout compared with individuals from structurally simple habitats with relatively higher zooplankton densities for both age classes. Environment also had an effect on foraging efficiency on zooplankton, with fish from structurally simple habitats had a higher foraging rate than fish from structurally complex habitats. Diet analyses showed that resource use in char mainly depends on the relative abundance of different resources. Therefore, to gain further understanding of resource polymorphism we suggest that future studies must include population dynamic feedbacks by the resources on the consumers. (c) 2005 The Linnean Society of London.

SiO2-based bioceramics, MCM-41-type SiO2 and the bioactive glass S53P4, in composites with poly(D,L)lactide were studied in the simulated body fluid. The parameters controlling ion dissolutions and calcium phosphate formation were studied and the data was used to create multicomposites with locally varying properties (e.g., CaP formation on the other side, uninhibited silica dissolution and possibility to drug release from the other side of composite).

Many of the photosynthetic genes are conserved among all higher plants, indicating that there is strong selective pressure to maintain the genes of each protein. However, mutants of these genes often lack visible growth phenotypes, suggesting that they are important only under certain conditions or have overlapping functions. To assess the importance of specific genes encoding the light-harvesting complex (LHC) proteins for the survival of the plant in the natural environment, we have combined two different scientific traditions by using an ecological fitness assay on a set of genetically modified Arabidopsis plants with differing LHC protein contents. The fitness of all of the LHC-deficient plants was reduced in some of the growth environments, supporting the hypothesis that each of the genes has been conserved because they provide ecological flexibility, which is of great adaptive value given the highly variable conditions encountered in nature.