New avenues for residual stress analysis in ultrathin atomic layer deposited free-standing membranes through release of micro-cantilevers.

The fabrication of thinnest, yet undeformed membrane structures with nanometer resolution is a prerequisite for a variety of Microelectromechanical systems (MEMS). However, functionally relevant thin films are susceptible to growth-generated stress. To tune the performance and reach large aspect ratios, knowledge of the intrinsic material properties is indispensable. Here, we present a new method for stress evaluation through releasing defined micro-cantilever segments by focused ion beam (FIB) milling from a predefined free-standing membrane structure. Thereby, the cantilever segment is allowed to equilibrate to a stress-released state through measurable strain in the form of a resulting radius of curvature. This radius can be back-calculated to the residual stress state. The method was tested on a 20 nm and 50 nm thick tunnel-like ALD Image 1 membrane structure, revealing a significant amount of residual stress with 866 MPa and 6104 MPa, respectively. Complementary finite element analysis to estimate the stress distribution in the structure showed a 97% and 90% agreement in out-of-plane deflection for the 20 nm and 50 nm membranes, respectively. This work reveals the possibilities of releasing entire membrane segments from thin film membranes with a significant amount of residual stress and to use the resulting bending behavior for evaluating stress and strain by measuring their deformation.

Malnutrition risk and oropharyngeal dysphagia in the chronic post-stroke phase.

Background: Oropharyngeal dysphagia (OD) and malnutrition are associated with poor clinical outcomes after stroke. The present study evaluated (1) malnutrition risk and OD-related characteristics in patients with chronic post-stroke OD, and (2) the relationship between on the one hand OD severity and on the other hand functional oral intake and dysphagia-specific quality of life. Methods: A cross-sectional study was conducted in a Dutch interdisciplinary outpatient clinic for OD. The standardized examination protocol comprised: clinical ear, nose, and throat examination, body mass index, the short nutritional assessment questionnaire (SNAQ), a standardized fiberoptic endoscopic evaluation of swallowing (FEES), the functional oral intake scale (FOIS), and the MD Anderson dysphagia inventory (MDADI). Results: Forty-two consecutive patients with chronic post-stroke OD were included. Mean (±SD) age and BMI of the population were 69.1 (±8.7) years and 26.8 (±4.1) kg/m2 respectively. Seventeen (40.4%) patients presented a moderate to high risk of malnutrition (SNAQ score≥2). The FEES examination showed moderate to severe OD in 28 (66.7%) patients. The severity of OD was significantly related to the FOIS score but not to the MDADI scores. Conclusion: In this specific sample of referred stroke patients, moderate to severe OD and moderate to high risk of malnutrition were common. Despite the use of clinical practice guidelines on stroke and a normal nutritional status at first sight, repeated screening for malnutrition and monitoring the severity and management of OD remain important elements in the care of patients with chronic post-stroke OD.

Atomic-scale 3D imaging of individual dopant atoms in an oxide semiconductor.

The physical properties of semiconductors are controlled by chemical doping. In oxide semiconductors, small variations in the density of dopant atoms can completely change the local electric and magnetic responses caused by their strongly correlated electrons. In lightly doped systems, however, such variations are difficult to determine as quantitative 3D imaging of individual dopant atoms is a major challenge. We apply atom probe tomography to resolve the atomic sites that donors occupy in the small band gap semiconductor Er(Mn,Ti)O3 with a nominal Ti concentration of 0.04 at. %, map their 3D lattice positions, and quantify spatial variations. Our work enables atomic-level 3D studies of structure-property relations in lightly doped complex oxides, which is crucial to understand and control emergent dopant-driven quantum phenomena.

Low Levels of Branched Chain Amino Acids, Eicosapentaenoic Acid and Micronutrients Are Associated with Low Muscle Mass, Strength and Function in Community-Dwelling Older Adults.

BACKGROUND: Sarcopenia, the age-related decrease in muscle mass and function can result in adverse health outcomes and subsequent loss of independence. Inadequate nutrition is an important contributor to the aetiology of sarcopenia, and dietary strategies are studied to prevent or delay this geriatric syndrome. OBJECTIVE: The present study investigated whether there is an association between biochemical nutrient status markers, muscle parameters and sarcopenia in community-dwelling older adults. DESIGN: Data from the cross-sectional Maastricht Sarcopenia study (MaSS) were used, in which skeletal muscle index (SMI), 4 meter gait speed, 5 times chair stand and handgrip strength were assessed among older adults (n=227). Sarcopenia was defined following the algorithm of the European Working Group on Sarcopenia in Older People. Fasted blood samples were analyses on amino acids levels, RBC phospholipid profile, 25-hydroxyvitamin D (25(OH)D), α-tocopherol, magnesium and homocysteine were determined in fasted blood levels. Generalized linear modelling and logistic regression were used for data analysis. RESULTS: Lower blood levels of essential amino acids (EAA), total branched-chain amino acids (BCAA) and leucine were associated with lower SMI (P<0.001), strength (P<0.001) and longer time to complete the chair stand (P<0.05), whereas no association was found for total amino acids (TAA). Lower levels of eicosapentaenoic acid (EPA), 25(OH)D and homocysteine were associated with lower muscle parameter values (P<0.05). No significant associations were found for SFA, MUFA, PUFA, n-3 and n-6 fatty acids, docosahexaenoic acid (DHA), α-tocopherol-cholesterol ratio and magnesium. Sarcopenia was more frequent among those with lower levels of leucine, BCAA, EAA, EPA, 25(OH)D and higher levels of homocysteine (P<0.05). Age and BMI were identified as relevant covariates. A robust association was only found for lower gait speed and lower 25(OH)D levels. CONCLUSION: Compromised muscle parameters are associated with low blood values of specific amino acids, fatty acids, vitamin D and high homocysteine.

Association between Oropharyngeal Dysphagia and Malnutrition in Dutch Nursing Home Residents: Results of the National Prevalence Measurement of Quality of Care.

OBJECTIVES: Nursing home residents often suffer from multi-morbidities and geriatric syndromes leading to lower quality of life or mortality. Oropharyngeal dysphagia (OD) and malnutrition are profound conditions in this complex profile of multi-morbidities and are associated with deprived mental -and physical health status, e.g. aspiration pneumonia or dehydration. This study aimed to assess the association between OD and malnutrition in Dutch nursing home residents. DESIGN: Data for this cross-sectional study were obtained from the annual National Prevalence Measurement of Quality of Care (LPZ). SETTING: The National Prevalence Measurement of Quality of Care was conducted in Nursing Homes in The Netherlands. PARTICIPANTS: Participants were nursing home residents age 65 or older and admitted to psychogeriatric- or somatic wards. MEASUREMENTS: The measurements were taken by trained nurses from the participating nursing homes. Anthropometric measurements and unintended weight loss (%) were assessed to determine nutritional status (malnutrition). OD was assessed by means of a standardized questionnaire assessing clinically relevant symptoms of OD such as swallowing problems or sneezing/coughing while swallowing. Cox regression was applied to assess the association between malnutrition and clinically relevant symptoms of OD in older Dutch nursing home residents. RESULTS: Approximately 12% of the residents suffered from swallowing problems and 7% sneezed/coughed while swallowing liquids or solid foods. Approximately 10% of the residents was malnourished. Residents with OD symptoms were more often malnourished compared to residents without OD symptoms. Approximately 17% of the problematic swallowers were concurrently malnourished. Increased risk for malnutrition was found in residents suffering from swallowing problems (PR 1.5, 95%CI 1.2-1.9), as well as in residents that sneezed/coughed while swallowing (PR 1.3, 95%CI 1.0-1.7). Stratification based on wards revealed that problematic swallowers from somatic wards were at a high risk of malnutrition (PR 1.9, 95%CI 1.3-2.8). CONCLUSION: Clinically relevant symptoms of oropharyngeal dysphagia, such as swallowing problems and sneezing/coughing while swallowing are associated with increased risk of malnutrition in psychogeriatric and somatic Dutch nursing home residents.

Atomic resolution imaging of beryl: an investigation of the nano-channel occupation.

Beryl in different varieties (emerald, aquamarine, heliodor etc.) displays a wide range of colours that have fascinated humans throughout history. Beryl is a hexagonal cyclo-silicate (ring-silicate) with channels going through the crystal along the c-axis. The channels are about 0.5 nm in diameter and can be occupied by water and alkali ions. Pure beryl (Be3 Al2 Si6 O18 ) is colourless (variety goshenite). The characteristic colours are believed to be mainly generated through substitutions with metal atoms in the lattice. Which atoms that are substituted is still debated it has been proposed that metal ions may also be enclosed in the channels and that this can also contribute to the crystal colouring. So far spectroscopy studies have not been able to fully answer this. Here we present the first experiments using atomic resolution scanning transmission electron microscope imaging (STEM) to investigate the channel occupation in beryl. We present images of a natural beryl crystal (variety heliodor) from the Bin Thuan Province in Vietnam. The channel occupation can be visualized. Based on the image contrast in combination with ex situ element analysis we suggest that some or all of the atoms that are visible in the channels are Fe ions.

Effect of V/III ratio on the structural and optical properties of self-catalysed GaAs nanowires.

The performance of GaAs nanowire (NW) devices depends critically on the presence of crystallographic defects in the NWs such as twinning planes and stacking faults, and considerable effort has been devoted to understanding and preventing the occurrence of these. For self-catalysed GaAs NWs grown by molecular beam epitaxy (MBE) in particular, there are in addition other types of defects that may be just as important for NW-based optoelectronic devices. These are the point defects such as the As vacancy and the Ga antisite occurring due to the inherently Ga-rich conditions of the self-catalysed growth. Here we demonstrate experimentally the effects of these point defects on the optical properties of GaAs/AlGaAs core-shell NWs grown by self-catalysed MBE. The present results enable insight into the role of the point defects both on their own and in conjunction with crystallographic planar defects.

In situ electronic probing of semiconducting nanowires in an electron microscope.

For the development of electronic nanoscale structures, feedback on its electronic properties is crucial, but challenging. Here, we present a comparison of various in situ methods for electronically probing single, p-doped GaAs nanowires inside a scanning electron microscope. The methods used include (i) directly probing individual as-grown nanowires with a sharp nano-manipulator, (ii) contacting dispersed nanowires with two metal contacts and (iii) contacting dispersed nanowires with four metal contacts. For the last two cases, we compare the results obtained using conventional ex situ litho-graphy contacting techniques and by in situ, direct-write electron beam induced deposition of a metal (Pt). The comparison shows that 2-probe measurements gives consistent results also with contacts made by electron beam induced deposition, but that for 4-probe, stray deposition can be a problem for shorter nanowires. This comparative study demonstrates that the preferred in situ method depends on the required throughput and reliability.

Position-controlled uniform GaAs nanowires on silicon using nanoimprint lithography.

We report on the epitaxial growth of large-area position-controlled self-catalyzed GaAs nanowires (NWs) directly on Si by molecular beam epitaxy (MBE). Nanohole patterns are defined in a SiO2 mask on 2 in. Si wafers using nanoimprint lithography (NIL) for the growth of positioned GaAs NWs. To optimize the yield of vertical NWs the MBE growth parameter space is tuned, including Ga predeposition time, Ga and As fluxes, growth temperature, and annealing treatment prior to NW growth. In addition, a non-negligible radial growth is observed with increasing growth time and is found to be independent of the As species (i.e., As2 or As4) and the growth temperatures studied. Cross-sectional transmission electron microscopy analysis of the GaAs NW/Si substrate heterointerface reveals an epitaxial growth where NW base fills the oxide hole opening and eventually extends over the oxide mask. These findings have important implications for NW-based device designs with axial and radial p-n junctions. Finally, NIL positioned GaAs/AlGaAs core-shell heterostructured NWs are grown on Si to study the optical properties of the NWs. Room-temperature photoluminescence spectroscopy of ensembles of as-grown core-shell NWs reveals uniform and high optical quality, as required for the subsequent device applications. The combination of NIL and MBE thereby demonstrates the successful heterogeneous integration of highly uniform GaAs NWs on Si, important for fabricating high throughput, large-area position-controlled NW arrays for various optoelectronic device applications.

Rapid EPA and DHA incorporation and reduced PGE2 levels after one week intervention with a medical food in cancer patients receiving radiotherapy, a randomized trial.

BACKGROUND & AIMS: In cancer patients, metabolic alterations, reduced immune competence and anti-cancer treatment can increase the risk of infections. A rapid-acting nutritional intervention might reduce this risk and support overall treatment. The present study investigated whether one week of intervention with a specific medical food led to fatty acid incorporation and functional immunological changes. METHODS: In a randomized, double-blind study, 38 cancer patients receiving radiotherapy consumed daily for one week 400 ml of specific medical food, which is high in protein and leucine, and enriched with fish oil and specific oligosaccharides (Active group), or iso-caloric/iso-nitrogenous product (Control group). Blood samples were taken at day 0 (baseline) and day 7. RESULTS: After one week of intervention, the incorporation of EPA and DHA in white blood cells was significantly higher in the Active group (2.6% and 2.6% of total fatty acids) compared to the Control group (1.0% and 2.2% of total fatty acids) (p < 0.001 and p < 0.05). Serum PGE2 levels decreased in the Active group and increased in the Control group (p < 0.01). No differences were observed on cytokine production in LPS-stimulated whole blood cultures. CONCLUSIONS: In cancer patients receiving radiotherapy, nutritional intervention with a specific medical food rapidly increased the percentage EPA and DHA in white blood cell phospholipids and reduced serum levels of the inflammatory mediator PGE2 within one week. CLINICAL REGISTRATION NUMBER: NTR2121.

Compositional characterization of GaAs/GaAsSb nanowires by quantitative HAADF-STEM.

The Sb concentration in axial GaAs(1-x)Sb(x) inserts of otherwise pure GaAs nanowires has been investigated with quantitative high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). The Sb concentration was quantified by comparing the experimental image intensities normalized to the incident beam intensity with intensities simulated with a frozen lattice multislice approach. Including static atomic displacements in the simulations was found to be crucial for correct compositional analysis of GaAs(1-x)Sb(x). HAADF intensities of individual nanowires were analysed both across the nanowires, exploiting their hexagonal cross-sectional shape, and along the evenly thick central part of the nanowires. From the cross-sectional intensity profiles, a decrease in the Sb concentration towards the nanowire outer surfaces was found. The longitudinal intensity profiles revealed a gradual build-up of Sb in the insert. The decrease of the Sb concentration towards the upper interface was either gradual or abrupt, depending on the growth routine chosen. The compositional analysis with quantitative HAADF-STEM was verified by energy dispersive X-ray spectroscopy.

Controlling crystal phases in GaAs nanowires grown by Au-assisted molecular beam epitaxy.

Control of the crystal phases of GaAs nanowires (NWs) is essential to eliminate the formation of stacking faults which deteriorate the optical and electronic properties of the NWs. In addition, the ability to control the crystal phase of NWs provides an opportunity to engineer the band gap without changing the crystal material. We show that the crystal phase of GaAs NWs grown on GaAs(111)B substrates by molecular beam epitaxy using the Au-assisted vapor-liquid-solid growth mechanism can be tuned between wurtzite (WZ) and zinc blende (ZB) by changing the V/III flux ratio. As an example we demonstrate the realization of WZ GaAs NWs with a ZB GaAs insert that has been grown without changing the substrate temperature.

Correlated micro-photoluminescence and electron microscopy studies of the same individual heterostructured semiconductor nanowires.

To correlate optical properties to structural characteristics, we developed a robust strategy for characterizing the same individual heterostructured semiconductor nanowires (NWs) by alternating low temperature micro-photoluminescence (µ-PL), low voltage scanning (transmission) electron microscopy and conventional transmission electron microscopy. The NWs used in this work were wurtzite GaAs core with zinc blende GaAsSb axial insert and AlGaAs radial shell grown by molecular beam epitaxy. The series of experiments demonstrated that high energy (200 kV) electrons are detrimental for the optical properties, whereas medium energy (5-30 kV) electrons do not affect the PL response. Thus, such medium energy electrons can be used to select NWs for correlated optical-structural studies prior to µ-PL or in NW device processing. The correlation between the three main µ-PL bands and crystal phases of different compositions, present in this heterostructure, is demonstrated for selected NWs. The positions where a NW fractures during specimen preparation can considerably affect the PL spectra of the NW. The effects of crystal-phase variations and lattice defects on the optical properties are discussed. The established strategy can be applied to other nanosized electro-optical materials, and other characterization tools can be incorporated into this routine.

Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice.

Cancer cachexia, which is characterized by muscle wasting, is associated with increased morbidity and mortality. Because muscle protein synthesis may be increased and protein breakdown reduced by leucine supplementation, we used the C26 tumor-bearing cachectic mouse model to assess the effects of dietary supplementation with leucine on muscle weight and the markers of muscle protein breakdown (mRNA of atrogin and murf). Male CD2F1 mice were subcutaneously inoculated with tumor cells (tumor-bearing mice; TB) or were sham injected (control; C). They were fed standard diets or diets supplemented with leucine [1 gr (TB1Leu) or 8 gr (TB8Leu) supplemented leucine per kg feed]; TB and C received 8.7% Leu/g protein, TB1Leu received 9.6% Leu/g protein and TB8Leu received 14.6 Leu/g protein. After 21 days, the following were determined: body weights, plasma amino-acid concentrations, tumor size and muscle mass of the gastrocnemius (mG), tibialis anterior (mTA), extensor digitorum longus (mEDL) and soleus (mS) muscles. In tumor-bearing (TB) mice, carcass and skeletal muscle masses decreased, and levels of atrogin and murf mRNA in the mEDL increased. Muscle-mass loss was counteracted dose-dependently by leucine supplementation: relative to TB, the mass of the mG was +23% in TB8Leu, and +22% in mTA (p<0.05). However, leucine supplementation did not change atrogin and murf mRNA levels. Total plasma amino acid concentrations increased in TB, especially for taurine, lysine, arginine and alanine (p<0.05). Leucine supplementation attenuated the increase in total plasma amino-acid concentrations (p<0.05). Irrespective of changes in muscle protein breakdown markers, leucine supplementation reduced muscle wasting in tumor-bearing cachectic mice and attenuated changes in plasma amino acids.

Wurtzite GaAs/AlGaAs core-shell nanowires grown by molecular beam epitaxy.

We report the growth of GaAs/AlGaAs core-shell nanowires (NWs) on GaAs(111)B substrates by Au-assisted molecular beam epitaxy. Electron microscopy shows the formation of a wurtzite AlGaAs shell structure both in the radial and the axial directions outside a wurtzite GaAs core. With higher Al content, a lower axial and a higher radial growth rate of the AlGaAs shell were observed. Room temperature and low temperature (4.4 K) micro-photoluminescence measurements show a much higher radiative efficiency from the GaAs core after the NW is overgrown with a radial AlGaAs shell.

Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice.

Cancer cachexia is characterised by metabolic alterations leading to loss of adipose tissue and lean body mass and directly compromises physical performance and the quality of life of cancer patients. In a murine cancer cachectic model, the effects of dietary supplementation with a specific combination of high protein, leucine and fish oil on weight loss, muscle function and physical activity were investigated. Male CD2F1 mice, 6-7 weeks old, were divided into body weight-matched groups: (1) control, (2) tumour-bearing, and (3) tumour-bearing receiving experimental diets. Tumours were induced by s.c. inoculation with murine colon adenocarcinoma (C26) cells. Food intake, body mass, tumour size and 24 h-activity were monitored. Then, 20 days after tumour/vehicle inoculation, the animals were killed and muscle function was tested ex vivo. Tumour-bearing mice showed reduced carcass, muscle and fat mass compared with controls. EDL muscle performance and total daily activity were impaired in the tumour-bearing mice. Addition of single nutrients resulted in no or modest effects. However, supplementation of the diet with the all-in combination of high protein, leucine and fish oil significantly reduced loss of carcass, muscle and fat mass (loss in mass 45, 52 and 65% of TB-con, respectively (P<0.02)) and improved muscle performance (loss of max force reduced to 55-64% of TB-con (P<0.05)). Moreover, total daily activity normalised after intervention with the specific nutritional combination (50% of the reduction in activity of TB-con (P<0.05)). In conclusion, a nutritional combination of high protein, leucine and fish oil reduced cachectic symptoms and improved functional performance in cancer cachectic mice. Comparison of the nutritional combination with its individual modules revealed additive effects of the single components provided.

Direct effects of doxorubicin on skeletal muscle contribute to fatigue.

Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin induced impaired ex vivo skeletal muscle relaxation followed in time by contraction impediment, which could be explained by DOX-induced changes in Ca(2+) responses of myotubes in vitro. The Ca(2+) responses in skeletal muscle, however, could not be explained by oxidative stress.

Beneficial immune modulatory effects of a specific nutritional combination in a murine model for cancer cachexia.

The majority of patients with advanced cancer are recognised by impaired immune competence influenced by several factors, including the type and stage of the tumour and the presence of cachexia. Recently, a specific nutritional combination containing fish oil, specific oligosaccharide mixture, high protein content and leucine has been developed aimed to support the immune system of cancer patients in order to reduce the frequency and severity of (infectious) complications. In a recently modified animal model cachexia is induced by inoculation of C26 tumour cells in mice. In a pre-cachectic state, no effect was observed on contact hypersensitivity, a validated in vivo method to measure Th1-mediated immune function, after adding the individual nutritional ingredients to the diet of tumour-bearing mice. However, the complete mixture resulted in significantly improved Th1 immunity. Moreover, in a cachectic state, the complete mixture reduced plasma levels of pro-inflammatory cytokines and beneficially affected ex vivo immune function. Accordingly, the combination of the nutritional ingredients is required to obtain a synergistic effect, leading to a reduced inflammatory state and improved immune competence. From this, it can be concluded that the specific nutritional combination has potential as immune-supporting nutritional intervention to reduce the risk of (infectious) complications in cancer patients.

Zinc blende GaAsSb nanowires grown by molecular beam epitaxy.

We report the growth of GaAsSb nanowires (NWs) on GaAs(111)B substrates by Au-assisted molecular beam epitaxy. The structural characteristics of the GaAsSb NWs have been investigated in detail. Their Sb mole fraction was found to be about 25%. Their crystal structure was found to be pure zinc blende (ZB), in contrast to the wurtzite structure observed in GaAs NWs grown under similar conditions. The ZB GaAsSb NWs exhibit rotational twins around their [111]B growth axis, with twin-free segments as long as 500 nm. The total volumes of GaAsSb segments with twinned and un-twinned orientations, respectively, were found to be equal by x-ray diffraction analysis of NW ensembles.

Functional food ingredients against colorectal cancer. An example project integrating functional genomics, nutrition and health.

Functional Food Ingredients Against Colorectal Cancer is one of the first European Union funded Research Projects at the cross-road of functional genomics [comprising transcriptomics, the measurement of the expression of all messengers RNA (mRNAs) and proteomics, the measurement of expression/state of all proteins], nutrition and human health. The goal of Functional Food Ingredients Against Colorectal Cancer is to develop a colon epithelial cell line-based screening assay for nutrients with presumed anti-colorectal carcinogenic properties. Genes involved in colon carcinogenesis are identified at the RNA and protein level, using a variety of methods (subtractive hybridisation, DNA microarray, proteomics) in combination with models for colorectal cancer development (human biopsies, rat model for colorectal carcinogenesis, colorectal cancer epithelial cell lines). Secondly, colorectal cancer epithelial cell lines are selected, in terms of their capacity to undergo gene/protein expression changes representing different phases in the colorectal carcinogenesis. Thirdly, these cell lines are used to determine the effects of nutrients with presumed anti-carcinogenic properties (e.g. resveratrol, flavonoids) on functional genomics-derived endpoints. Once validated against the effects of these nutrients in in vivo animal models and classical biomarkers for colorectal carcinogenesis, these cell line models combined with functional genomics represent useful tools to study colorectal carcinogenesis and screen for nutrients with anti-carcinogenic properties.