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The failure of metabolic tissues to appropriately respond to insulin (“insulin resistance”) is an early marker in the pathogenesis of type 2 diabetes. Protein phosphorylation is central to the adipocyte insulin response, but how adipocyte signaling networks are dysregulated upon insulin resistance is unknown. Here we employed phosphoproteomics to delineate insulin signal transduction in adipocyte cells and adipose tissue. Across a range of insults triggering insulin resistance, we observed marked rewiring of the insulin signaling network. This included both attenuated insulin-responsive phosphorylation, and the emergence of phosphorylation uniquely insulin-regulated in insulin resistance. Identifying signaling changes common to multiple insults revealed subnetworks likely containing causal drivers of insulin resistance. Focusing on defective GSK3 signaling initially observed in a relatively small subset of well-characterized substrates, we employed a pipeline for identifying context-specific kinase substrates. This facilitated robust identification of widespread dysregulated GSK3 signaling. Pharmacological inhibition of GSK3 partially reversed insulin resistance in cells and tissue explants. These data highlight that insulin resistance is a multi-nodal signaling defect that encompasses dysregulated GSK3 activity.

Skeletal muscle and adipose tissue insulin resistance are major drivers of metabolic disease. To uncover pathways involved in insulin resistance, specifically in these tissues, we leveraged the metabolic diversity of different dietary exposures and discrete inbred mouse strains. This revealed that muscle insulin resistance was driven by gene-by-environment interactions and was strongly correlated with hyperinsulinemia and decreased levels of ten key glycolytic enzymes. Remarkably, there was no relationship between muscle and adipose tissue insulin action. Adipocyte size profoundly varied across strains and diets, and this was strongly correlated with adipose tissue insulin resistance. The A/J strain, in particular, exhibited marked adipocyte insulin resistance and hypertrophy despite robust muscle insulin responsiveness, challenging the role of adipocyte hypertrophy per se in systemic insulin resistance. These data demonstrate that muscle and adipose tissue insulin resistance can occur independently and underscore the need for tissue-specific interrogation to understand metabolic disease.

The pattern of weight loss and regain, termed "weight cycling," is common in overweight individuals. It is unclear whether the well-established benefits of weight loss persist following weight regain or whether weight cycling is harmful. Human studies of weight cycling have conflicting results reflecting limitations of the observational designs of these studies. By controlling the macronutrient content of diets in animal studies, weight cycling can be studied in a highly controlled manner, thereby overcoming the limitations of human studies. We conducted a systematic review and meta-analysis of animal studies which assessed the health consequences of weight cycling. Studies were classified into those which compared weight cycling to lifelong obesity and those which compared weight cycling to later onset obesity. There were no differences in health outcomes between weight cycled animals and those with lifelong obesity, highlighting that weight regain reverses health benefits achieved by weight loss. In comparison with animals with later onset obesity, weight cycled animals had higher fasting glucose levels and more impaired glucose tolerance following weight regain. Our review of animal studies suggests that health benefits of diet-induced weight loss do not persist after weight regain and weight cycling results in adverse metabolic outcomes.

White adipose tissue is deposited mainly as subcutaneous adipose tissue (SAT), often associated with metabolic protection, and abdominal/visceral adipose tissue (VAT), which contributes to metabolic disease. To investigate the molecular underpinnings of these differences, we conducted comprehensive proteomics profiling of whole tissue and isolated adipocytes from these two depots across two diets from C57Bl/6J mice. The adipocyte proteomes from lean mice were highly conserved between depots, with the major depot-specific differences encoded by just 3% of the proteome. Adipocytes from SAT (SAdi) were enriched in pathways related to mitochondrial complex I and beiging, whereas visceral adipocytes (VAdi) were enriched in structural proteins and positive regulators of mTOR presumably to promote nutrient storage and cellular expansion. This indicates that SAdi are geared toward higher catabolic activity, while VAdi are more suited for lipid storage.By comparing adipocytes from mice fed chow or Western diet (WD), we define a core adaptive proteomics signature consisting of increased extracellular matrix proteins and decreased fatty acid metabolism and mitochondrial Coenzyme Q biosynthesis. Relative to SAdi, VAdi displayed greater changes with WD including a pronounced decrease in mitochondrial proteins concomitant with upregulation of apoptotic signaling and decreased mitophagy, indicating pervasive mitochondrial stress. Furthermore, WD caused reduction in lipid handling and glucose uptake pathways particularly in VAdi, consistent with adipocyte de-differentiation. By overlaying the proteomics changes with diet in whole adipose tissue and isolated adipocytes, we uncovered concordance between adipocytes and tissue only in the VAT, indicating a unique tissue-specific adaptation to sustained WD in SAT.Finally, an in-depth comparison of isolated adipocytes and 3T3-L1 proteomes revealed a high degree of overlap, supporting the utility of the 3T3-L1 adipocyte model. These deep proteomes provide an invaluable resource highlighting differences between white adipose depots that may fine-tune their unique functions and adaptation to an obesogenic environment.

This paper investigates the applicability of numerical and semi-empirical heat flow models for calculating average fluid temperatures in groups of quadratic, precast pile heat exchangers. A 3D finite element model (FEM), verified with experimental data, is extended to account for multiple pile heat exchangers. Semi-empirical dimensionless temperature g-functions for multiple piles are developed by utilising single pile 3D FEM heat transport simulations with temporal and spatial superposition techniques to account for the thermal interaction between piles. The multiple pile g-functions, yet less accurate for short times, yield fluid temperatures similar to those obtained with full 3D modelling (with 7% of largest deviation), at minimal computational cost.

This paper applies previously validated multiple pile g-functions, for estimating operational average fluid temperatures in an actual energy pile foundation in Rosborg, Denmark. We find that the multiple pile g-functions yield fluid temperatures similar to what is observed, at minimal computational cost. The temperature model is then utilised in an optimisation algorithm that yields the minimum number of energy piles required by simultaneously maximising the pile spacing and taking into consideration the thermal load of the building. The optimisation shows that the thermal needs of the building can be fully supplied by 148 rearranged energy piles, instead of the current 219. The optimisation tool is also applied to a full-factorial design sweep which shows a large sensitivity of the number of energy piles on the thermal conductivity of the ground.

Upconversion of sunlight with energy below the band gap of a solar cell is a promising technique for enhancing the cell efficiency, simply by utilizing a larger part of the solar spectrum. The present topical review addresses this concept and discusses the material properties needed for an efficient upconversion process with focus on both silicon and organic solar cells. To design efficient upconverters, insight into topics such as quantum-optics, nano-optics, numerical modeling, optimization, material fabrication, and material characterization is paramount, and the necessary concepts are introduced throughout the review. Upconversion modeling is done using rate equations, while optical modeling is done by solving Maxwell's equations using the finite element method. Topology optimization is introduced and used to generate geometries of gold nanoparticles capable of greatly enhancing the upconversion yield. Fabrication and experimental characterization methods are discussed. Some recent results are presented and finally the possibility of designing upconverting materials capable of increasing the short-circuit current in a solar cell is discussed.

Understanding migratory behavior, mortality, and physiology is essential for conservation of many species, particularly anadromous fish. In this study, freshwater and marine migrations of the endangered salmonid North Sea houting (Coregonus oxyrinchus (Linnaeus, 1758)) were investigated using telemetry. Furthermore, physiological samples were collected from North Sea houting and from resident and anadromous populations of the closely related European whitefish (Coregonus lavaretus (Linnaeus, 1758)) to compare hypo-osmotic tolerances. On average, North Sea houting spent 193 days at sea where the mortality was 36%. Most fish returned from sea in the autumn, and river entry correlated inversely with river temperature and positively with discharge. Fish spent an average of 49 days in the estuarine area. Artificial lakes negatively affected migration speeds. Migration speeds did not differ consistently between individuals (i.e., not a repeatable trait) but correlated positively with water temperature. Fish arrived at spawning areas in November. In the post-spawning state, Na+/K+-ATPase activities were elevated in North Sea houting and anadromous whitefish compared with resident whitefish, while osmolality was elevated only in North Sea houting. Our study provides important information for conservation planning related to the Habitat Directive of the European Union that lists the North Sea houting as critically endangered.

Topology optimization is applied in an idealized structural fire safety model, where the minimum compliance problem is constrained by temperature-controlled structural degradation. The constraint ensures a certain structural stiffness after a prescribed time. As this time period is extended, resulting optimized topologies tend to become thicker or introduce redundant members that can take over when structural parts near the origin of the fire lose their load carrying capability. Hence, the structural degradation model acts as an erosion operator on the topology and indirectly enforces a minimum length scale on the final designs.

Upconversion of sub-band-gap photons constitutes a promising way for improving the efficiency of silicon-based solar cells beyond the Shockley-Queisser limit. 1500 to 980 nm upconversion by trivalent erbium ions is well-suited for this purpose, but the small absorption cross section hinders real-world applications. We employ tailored gold nanostructures to vastly improve the upconversion efficiency in erbium-doped TiO$_2$ thin films. The nanostructures are found using topology optimization and parameter optimization and fabricated by electron beam lithography. In qualitative agreement with a theoretical model, the samples show substantial electric-field enhancements inside the upconverting films for excitation at 1500 nm for both s- and p-polarization under a wide range of incidence angles and excitation intensities. An unprecedented upconversion enhancement of 913(51) is observed at an excitation intensity of 1.7 Wcm$^{-2}$. We derive a semi-empirical expression for the photonically enhanced upconversion efficiency, valid for all excitation intensities. This allows us to determine the upconversion properties needed to achieve significant improvements in real-world solar-cell devices through photonic-enhanced upconversion., Comment: 9 pages (main text), 4 figures, 1 supporting information of 15 pages

A new method for dose regularization in optimization-based proximity-effect-correction is proposed. In contrast to the commonly adopted approach of adding penalty terms to the objective function, a modified scheme is demonstrated where dose regularization is achieved via filtering and projection techniques. The resulting dose patterns are simple and two-toned, and can thus readily be applied in production. Furthermore, existing extensions developed in the context of topology optimization that build on top of the filtering framework, such as robust optimization and strict length scale control, can be adopted directly. The validity of the scheme is assessed in experiments, where the resolvable feature size of the considered 30 kV electron-beam lithography system is decreased from around 100 nm to a few tens of nm. A Python implementation of the scheme is made freely available.

Photovoltaics is amongst the most important technologies for renewable energy sources, and plays a key role in the development of a society with a smaller environmental footprint. Key parameters for solar cells are their energy conversion efficiency, their operating lifetime, and the cost of the energy obtained from a photovoltaic system compared to other sources. The optimization of these aspects involves the exploitation of new materials and development of novel solar cell concepts and designs. Both theoretical modeling and characterization of such devices require a comprehensive view including all scales from the atomic to the macroscopic and industrial scale. The different length scales of the electronic and optical degrees of freedoms specifically lead to an intrinsic need for multiscale simulation, which is accentuated in many advanced photovoltaics concepts including nanostructured regions. Therefore, multiscale modeling has found particular interest in the photovoltaics community, as a tool to advance the field beyond its current limits. In this article, we review the field of multiscale techniques applied to photovoltaics, and we discuss opportunities and remaining challenges. © T. Abu Hamed et al., published by EDP Sciences, 2018., European Cooperation in Science and Technology: MP1406, The authors are grateful for the financial support by the COST Action MP1406 “MultiscaleSolar.”

This paper describes a systematic design study of periodic gold-nanostrip arrays placed on a thin film aimed at enhancing the electric field inside the film when irradiated by light. Based on the study, a "selection rule" is proposed, which provides optimization-based design methods with an a priori choice between field-enhancement dominated by coupling to guided modes, by plasmonic near-field enhancement or by a mix hereof. An appropriate choice of wavelength and grating period is shown to selectively suppress or include waveguiding effects for the optimized designs. The validity of the selection rule is demonstrated through a numerical topology optimization study in which gold nanostrips are optimized for electric-field enhancement in an erbium-doped TiO2 thin film, targeting increased spectral upconversion in the erbium ions. The obtained designs exhibit waveguide excitation within the predicted intervals and, for light polarized perpendicularly to the strips, plasmonic response outside.

Spectral conversion of the sunlight has been proposed as a method for enhancing the efficiency of photovoltaicvdevices, which are limited in current production by the mismatch between the solar spectrum and the wavelength range for efficient carrier generation. For example, the photo current can be increased by conversion of two low-energy photons (below the band gap of the absorber) to one higher-energy photon (i.e. upconversion). In this paper, we will review our ongoing activities aimed at enhancing such spectral-conversion processes by employing appropriately designed plasmonic nanoparticles. The nanoparticles serve as light-concentrating elements in order to enhance the non-linear upconversion process. From the theoretical side, we approach the optimization of nanoparticles by finite-element modelling of the plasmonic near fields in combination with topological optimization of the particle geometries. Experimentally, the nanostructures are formed by electronbeam lithography on thin films of Er3+-containing transparent materials, foremost TiO2 made by radio-frequency magnetron sputtering, and layers of chemically synthesized NaYF4 nanoparticles. The properties of theupconverter are measured using a variety of optical methods, including time-resolved luminescence spectroscopy on erbium transitions and spectrally resolved upconversion-yield measurements at ∼1500-nm-light excitation.The calculated near-field enhancements are validated using a technique of near-field-enhanced ablation by tunable, ultrashort laser pulses.

Quantitative measurements of the electric near-field distribution of star-shaped gold nanoparticles have been performed by femtosecond laser ablation. Measurements were carried out on and off the plasmon resonance. A detailed comparison with numerical simulations of the electric fields is presented. Semi-quantitative agreement is found, with slight systematic differences between experimentally observed and simulated near-field patterns close to strong electric-field gradients. The deviations are attributed to carrier transport preceding ablation.

We propose a simplified rate-equation model for the 1500 nm to 980 nm upconversion in Er$^{3+}$. The simplifications, based on typical experimental conditions as well as on conclusions based on previously published more advanced models, enable an analytical solution of the rate equations, which reproduces known properties of upconversion. We have compared the model predictions with intensity-dependent measurements on four samples with different optical properties, such as upconversion-luminescence yield and the characteristic lifetime of the $^4I_{13/2}$ state. The saturation of the upconversion is in all cases well-described by the model over several orders of magnitude in excitation intensities. Finally, the model provides a new measure for the quality of upconverter systems based on Er$^{3+}$ -- the saturation intensity. This parameter provides valuable information on upconversion parameters such as the rates of energy-transfer upconversion and cross-relaxation. In the present investigation, we used the saturation intensity to conclude that the differences in upconversion performance of the investigated samples are mainly due to differences in the non-radiative relaxation rates., Comment: 8 pages, 6 figures, to be submitted to PRB

Nicotinamide adenine dinucleotide (NAD

A two-particle model is proposed which enables the assessment of particle-particle interactions in large, sparse arrays of randomly distributed plasmonic metal nanoparticles of arbitrary geometry in inhomogeneous environments. The two-particle model predicts experimentally observed peak splittings in the extinction cross section spectrum for randomly distributed gold nanocones on a TiO2:Er3+ thin film with average center-to-center spacings of 3-5 diameters. The main physical mechanism responsible is found to be interference between the incident field and the far-field component of the single-particle scattered field which is guided along the film.

Pile heat exchangers are traditional foundation piles with built in heat exchangers. As such, the footing of the building both serves as a structural component and a heating/cooling supply element. The existing geotechnical design standards do not consider the nature of thermo-active foundations and, therefore, there is a need to develop guidelines to design them properly. This paper contributes by studying the thermo-mechanical behavior of the precast piles which are 15-meter long and have a quadratic cross section and a W-shape pipe heat exchanger. This article aims to numerically assess the additional changes in the pile load transfer generated by its heating and cooling. In addressing this objective, a preliminary multi-physical finite element analysis is conducted which serves as a tool for exploring: i) the thermally induced mechanical stresses within the concrete and on the pile-soil axial and shaft resistances; ii) the maximum upward/downward displacements. A one-year time span is considered under operational and extreme thermal boundary conditions. The results show that a typical geothermal utilization of the energy foundation does not generate significant structural implications on the geotechnical capacity of a single energy pile. However, ground thermal loads need to be considered in the design phase to account for potential extreme temperature changes, which could generate thermal stresses that equalize the mechanically generated ones.

The large energy-density enhancements, associated with the near-field of plasmonic metal nanoparticles (MNPs), can potentially be utilized to increase the efficiency of nonlinear processes such as upconversion (UC). A drawback of employing metallic structures for UC applications is luminescence quenching, i.e. the transfer of energy from the upconverter material to the metal, where it is dissipated as heat. In this study, a rate-equation model is applied to study the interplay between near-field enhancement and luminescence quenching for a range of different geometries. It is found that while shapes that incorporate pointy features and/or narrow gaps support stronger near-field enhancements, they also suffer more severely from luminescence quenching. Due to the strong correlation between the two effects, the predicted enhancement in UC luminescence is similar across all considered geometries ranging from 1 to 3. Our results indicate that the near-field of plasmonic MNPs might not be suitable for increasing UC efficiency.

Two-phase flow and heat transfer, such as boiling and condensing flows, are complicated physical phenomena that generally prohibit an exact solution and even pose severe challenges for numerical approaches. If numerical solution time is also an issue the challenge increases even further. We present here a numerical implementation and novel study of a fully distributed dynamic one-dimensional model of two-phase flow in a tube, including pressure drop, heat transfer, and variations in tube cross-section. The model is based on a homogeneous formulation of the governing equations, discretized by a high resolution finite difference scheme due to Kurganov and Tadmore.The homogeneous formulation requires a set of thermodynamic relations to cover the entire range from liquid to gas state. This leads a number of numerical challenges since these relations introduce discontinuities in the derivative of the variables and are usually very slow to evaluate. To overcome these challenges, we use an interpolation scheme with local refinement.The simulations show that the method handles crossing of the saturation lines for both liquid to two-phase and two-phase to gas regions. Furthermore, a novel result obtained in this work, the method is stable towards dynamic transitions of the inlet/outlet boundaries across the saturation lines. Results for these cases are presented along with a numerical demonstration of conservation of mass under dynamically varying boundary conditions. Finally we present results for the stability of the code in a case of a tube with a narrow section.

A detailed comparison of continuum and valence force field strain calculations in quantum-dot structures is presented with particular emphasis to boundary conditions, their implementation in the finite-element method, and associated implications for electronic states. The first part of this work provides the equation framework for the elastic continuum model including piezoelectric effects in crystal structures as well as detailing the Keating model equations used in the atomistic valence force field calculations. Given the variety of possible structure shapes, a choice of pyramidal, spherical and cubic-dot shapes is made having in mind their pronounced shape differences and practical relevance. In this part boundary conditions are also considered; in particular the relevance of imposing different types of boundary conditions is highlighted and discussed.

The topic of fluxons in Josephson junctions appears often and in many contexts within superconductivity. The potential applications and the appearance of high-T c superconductivity are some of the reasons for this recently increased interest. Several comprehensive reviews of fluxons (solitons) in long Josephson junctions [8], [2], [10], [9] exist, of which particularly the most recent [9] gives an excellent overview of the state of the art for low- T c niobium-type long Josephson junctions. In recent years the properties of long Josephson junctions stacked on top of each other has been studied quite intensively. This is because such systems model existing low-T c superconducting multilayers. In addition these models have revealed surprising dynamical properties. The appearance of high-T c ceramic superconductors has also had quite an impact on the topic of fluxons in superconductors, in particular stacked long Josephson junctions. Here the fluxons play a very important role, for example, in the BSCCO type of material with a layered structure and big anisotropy. Dynamic properties of fluxons are also relevant for the material properties such as the bulk current density and the behaviour near the transition temperature. Some of these high-T c phenomena we will try to include in our description below.

We compare continuum and atomistic models for the electromechanical fields in wurtzite GaN/AlN quantum dots and their relative impact on the electronic band structure. Qualitative agreement between atomistic strain calculations and continuum elastic models for a wurtzite hexagonal quantum-dot structure is demonstrated; however, significant quantitative discrepancies of up to 100 meV are observed. A smaller difference of approximately 15 meV is found between fully coupled and semi-coupled continuum models.

We consider THz emission due to fluxon dynamics in a stack of inductively coupled long Josephson junctions connected electrically to a resonant cavity. By comparing to experiments on Josephson junction parametric amplifiers we consider the role of a negative resistance in connection with THz emission experiments. We suggest that indeed the negative resistance has a big influence on the experimental results.

The performance of three different functions (penalty, Lagrange–Newton, and projection) used in combination with three different Newton-based optimization algorithms for solving large-scale constrained optimizations is investigated. The test cases correspond to locating minima on seams between two force field energy functions, which can be used to model transitions structures in chemical reactions. The Lagrange–Newton function used in combination with a standard Newton–Raphson optimization is found to be the most efficient for systems up to ∼500 atoms, while an iterative algorithm becomes preferable for larger systems.

The BSCCO type intrinsic Josephson junction has been modeled as a stack of inductively coupled long Josephson junctions, which were described by a system of coupled sine-Gordon equations. In a system of 10 long Josephson junctions coupled to a linear cavity, we numerically investigate how the cavity perturbs fluxon motion in the junctions. Fluxons in neighboring junctions are repulsive leading to anti-phase motion. The cavity provides a force which perturbs this anti-phase motion, and may even force the fluxons to build a square lattice, i.e. to perform in-phase motion. For different values of the inductive coupling strength, we investigate the cavity current, fluxon phase difference, and current–voltage characteristic. The stack-cavity system with in-phase fluxon motion may be utilized as a THz oscillator.

A stack of inductively coupled long Josephson junctions are modeled as a system of coupled sine-Gordon equations. One boundary of the stack is coupled electrically to a resonant cavity. With one fluxon in each Josephson junction, the inter-junction fluxon forces are repulsive. We look at a possible transition, induced by the cavity, to a bunched state.

Background. Immunosuppressive therapies have been associated with gastrointestinal (GI) side effects, which may impair health-related quality of life (HRQoL). Methods. In this survey, 4,232 renal transplant recipients from Denmark, Finland, Nor-way, and Sweden completed the Short-Form 36 (SF-36) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). SF-36 scores were compared with country norm values. Multiple logistic regression analysis was used to identify immunosuppressants associated with GI symptoms. Results. The prevalence of troublesome GI symptoms (GSRS > 1) was 83% for indigestion, 69% for abdominal pain, 58% for constipation, 53% for diarrhea, 47% for reflux, and 92% for any GI symptom. Compared with the general population, HRQoL was most commonly meaningfully impaired in the general health dimension (53% of patients). The presence and severity of GI symptoms were associated with worse HRQoL. Tacrolimus showed a significant association with diarrhea (odds ratio [OR]: 1.7; 95% confidence interval [CI]: 1.4-2.0) and constipation (OR: 1.3; 95% Cl: 1.1-1.6), and sirolimus with indigestion (OR: 2.9; 95% Cl: 1.0-8.1) and abdominal pain (OR: 2.2; 95% Cl: 1.1-4.4). Conclusions. GI symptoms are associated with impaired HRQoL in the renal transplant population. Managing GI symptoms by careful choice of immunosuppressants should be a focus for improving HRQoL in renal transplant recipients (Less)

The focus of this paper is the validation and comparison of simplified numerical models of the mechanical rolling process used in tube to tubesheet joints. The investigated models is an axisymmetric model and planar models with plane strain and stress. There are different pros and cons for the different simplified models and therefore they are compared to an experiment where all the geometries are measured before and after expansion. This comparison gives an insight into when the different models are valid. The models investigated is an axisymmetric model, a simple 2D expansion model with both plane strain and stress assumptions. Therefore, it is desirable to investigate how close these simplified models can predict the geometry changes after expansion measured in the experiment. The conclusion of the paper is that a planer model with plane strain is the best model at predicting the actual deformation after expansion. The focus of this paper is the validation and comparison of simplified numerical models of the mechanical rolling process used in tube to tubesheet joints. The investigated models is an axisymmetric model and planar models with plane strain and stress. There are different pros and cons for the different simplified models and therefore they are compared to an experiment where all geometries are measured before and after expansion. This comparison gives an insight into when the different models are valid. The models investigated is an axisymmetric model, a simple 2D expansion model with both plane strain and stress assumptions. Therefore, it is desirable to investigate how close these simplified models can predict the geometry changes after expansion measured in the experiment. The conclusion of the paper is that a planer model with plane strain is the best model at predicting the actual deformation after expansion.

Using large monopod bucket foundations as an alternative to monopiles for offshore wind turbines offers the potential for large cost savings compared to typical piled foundations. In this paper, numerical simulations are carried out to assess the risk of structural buckling during installation of large-diameter bucket foundations. Since shell structures are generally sensitive to initially imperfect geometries, eigenmode-affine imperfections are introduced in a nonlinear finite-element analysis. The influence of modelling the real lid structure compared to classic boundary conditions is investigated. The effects of including soil restraint and soil–structure interaction on the buckling analysis are also addressed.

The focus of this paper is a numerical investigation of tubesheet deformation in tube-tubesheet joints used in tube bank heat exchangers. To increase the thermal performance of a cooler the tubes can be moved closer together to increase turbulence and the heat transfer coefficient. Reducing the tube spacing is an alternative to using finned tubes to increase thermal performance. Finned tubes is more susceptible to fouling and therefore the small tube spacing can be an attractive alternative in some cases. From a manufacturing point of view, there are some problems with small tube spacing. When the tube spacing is reduced the deformation of the tube sheet increases. The relation between the tube spacing and tubesheet deformation is of great interest to the thermal designers of heat exchangers since it sets a limit for the tube spacing. The limit depends on how much tube sheet deformation is acceptable in the design. In most cases, the tubes are joined to the tube sheet by an expansive cold forming process. The expansion process that is investigated in this paper is the mechanical rolling expansion process. The tube is plastically deformed by a series of hardened steel rollers that roll across the inner tube surface while being pushed outwards. This results in a residual contact pressure between the tube and tube sheet after relaxation/springback. The expansion process is modeled using finite elements, the model used is a 2D plane-strain model that is capable of capturing the effect of adjacent holes. This approach is new compared to previous research done in the field of mechanical roll expansion where the most commonly used model is an axisymmetric model. It is however not possible to investigate tube sheet deformation versus tube spacing with the axisymmetric model since it doesn’t include the effect of adjacent holes. The material used in the analysis is a typical stainless steel, the material is modeled using a bilinear isotropic hardening model. At some point, the deformation of the tube sheet will exponentially increase with reduced tube spacing. This effect can only be investigated using numerical tools. Too much tube sheet deformation is not desirable since it will cause the tube sheet to permanently change shape and in some cases, adjacent tube-tubesheet joints will be compromised due to the nearby expansion. The results of this paper is the relation between the tube spacing and the amount of tubesheet deformation for a given amount of apparent tube wall reduction. This relation is used to set up limits for the amount of expansion and the minimum tube spacing for the given material combination.Copyright © 2015 by ASME

The Josephson fluxon behaviour in layered BSCCO-type single crystals is modelled by coupled long Josephson junctions described by coupled sine?Gordon equations. Among all the possible solutions, particularly interesting are the so-called in-phase fluxon solutions with coherent motion of all the fluxons. Recently, generation of electromagnetic waves at almost terahertz (THz) frequencies in BSCCO single crystals was reported. In order to maximize the power of such generation, these in-phase fluxon solutions are essential. Two different avenues to obtain in-phase fluxon motion have been suggested, i.e.?either using the interaction with a cavity to phase lock the fluxon motion or applying a large magnetic field to create in-phase flux flow solutions. We have numerically considered both mechanisms. The results provide an understanding of the system and a guidance to experimentalists looking for THz generation in BSCCO.

Josephson vortex flux flow states in stacked Josephson junctions are investigated numerically. The aim of the work is to understand the mechanisms behind the formation of triangular (anti-phase) and square (in-phase) vortex lattices, and is motivated by recent experiments on layered BSCCO type high- T c superconductors in a magnetic field. In order to keep the problem as simple as possible we consider in detail only the case with two junctions in the stack.

Renal transplantation is associated with an increased risk for premature cardiovascular disease. We analyzed the data in the placebo arm of Assessment of Lescol in Renal Transplantation (ALERT) to improve our understanding of the relationship between cardiovascular risk factors and outcomes in this unique population.We performed Cox survival analysis for myocardial infarction, cardiac death, and noncardiac death in 1,052 patients recruited to the placebo arm of ALERT. These subjects were aged 30 to 75 years, had stable graft function at least 6 months after transplantation, had a serum total cholesterol level between 155 and 348 mg/dL (4 and 9 mmol/L), and were receiving cyclosporine-based immunosuppression.The results confirm previous studies. In multivariate analysis, preexisting coronary heart disease (hazard ratio [HR], 3.69; P0.001), total cholesterol level (HR, 1.55 per 50 mg/dL; P = 0.0045), and prior acute rejection (HR, 2.36; P = 0.0023) were independent risk factors. Conversely, independent risk factors for cardiac death were age (HR, 1.58 per decade; P = 0.0033), diabetes (HR, 3.35; P = 0.0002), ST-T changes on the ECG (HR, 3.17; P = 0.0004), and serum creatinine level (HR, 2.65 per milligram per deciliter; P0.0001).This analysis confirms that renal transplant recipients share risk factors for myocardial infarction and cardiac death with the general population. However, the pattern of risk factors and their relationship with outcomes is atypical, highlighting the unique nature of cardiovascular risk in transplant recipients.

We look for domain wall and textured vortex solutions in a two-component Ginzburg–Landau model inspired by two-band superconductivity. The two-dimensional two-component model, with equal coherence lengths and no magnetic field, shows some interesting properties. In the absence of a Josephson type coupling between the two order parameters a “textured vortex” is found by analytical and numerical solution of the Ginzburg–Landau equations. With a Josephson type coupling between the two order parameters we find the system to split up in two domains separated by a domain wall, where the order parameter is depressed to zero.

Effect of fluvastatin on renal end points in the Assessment of Lescol in Renal Transplant (ALERT) trial.BackgroundHyperlipidemia is a risk factor for long-term renal transplant dysfunction, but no prospective clinical trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effect of fluvastatin on long-term renal transplant function and development of chronic allograft nephropathy in the ALERT (Assessment of Lescol in Renal Transplantation) study.MethodsALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 mg and 80 mg daily, in renal transplant recipients. Patients were randomized to receive either fluvastatin (N = 1050) or placebo (N = 1052) and followed for five to six years. Renal end points included graft loss or doubling of serum creatinine or death; glomerular filtration rate (GFR) was also measured during follow-up in a subset of patients (N = 439).ResultsThere were 283 patients (13.5%) with graft loss, mainly due to chronic rejection (82%), yielding an annual rate of 2.4%. Fluvastatin treatment significantly lowered mean low-density lipoprotein (LDL)-cholesterol levels by 32% (95% CI -33 to -30) compared with placebo, but had no significant effect on the incidence of renal graft loss or doubling of serum creatinine, or decline in GFR throughout follow-up in the whole study population. Neither was any treatment effect by fluvastatin found in any of the subgroups analyzed.ConclusionFluvastatin treatment significantly improves lipid values in renal transplant recipients but has no effect on graft loss or doubling of serum creatinine.

The electrical behavior of anisotropic BSCCO single crystals is modeled by mutually coupled long Josephson junctions. We show that although the fluxons in the different layers do not a priori prefer the in-phase motion desired for many potential applications it is possible to induce such behavior by coupling the system to a high-Q resonator with a resonance frequency corresponding to fluxon in-phase motion. The resulting model is a set of coupled non-linear partial differential equations. By direct numerical simulations we have demonstrated that the qualitative behavior of the combined stacked long Josephson junctions and cavity system can be understood on the basis of the general concepts of nonlinear oscillators interacting with a resonator. For some region of the parameter space it is possible to reach the desired synchronous state, making the system potentially suitable for applications. We also look at the different dynamical states defined by different fluxon dynamical states in combination with different cavity properties.

We show how to construct fluxon modes from plasma modes in the inductively coupled stacked Josephson junctions, and consider some special cases of these fluxon modes analytically. In some cases we can find exact analytical solutions when we choose the bias current in a special way. We also consider numerically what happens to these modes when the bias current is chosen to be equal in all junctions, which is the natural way of having the bias current in an experimental setup.

We consider a system of stacked Josephson junctions and investigate the different fluxon modes. Some of these modes can be used to construct an oscillator with a frequency in the range 200 GHz–1 THz. We discuss the output that can be expected from the different fluxon modes, and we calculate the theoretical maximum output numerically.

This letter presents a topology optimization study of metal nanostructures optimized for electric-field enhancement in the infrared spectrum. Coupling of such nanostructures with suitable ions allows for an increased photon-upconversion yield, with one application being an increased solar-cell efficiency by exploiting the long-wavelength part of the solar spectrum. In this work, topology optimization is used to design a periodic array of two-dimensional gold nanostrips for electric-field enhancements in a thin film doped with upconverting erbium ions. The infrared absorption band of erbium is utilized by simultaneously optimizing for two polarizations, up to three wavelengths, and three incident angles. Geometric robustness towards manufacturing variations is implemented considering three different design realizations simultaneously in the optimization. The polarization-averaged field enhancement for each design is evaluated over an 80 nm wavelength range and a ±15-degree incident angle span. The highest polarization-averaged field enhancement is 42.2 varying by maximally 2% under ±5 nm near-uniform design perturbations at three different wavelengths (1480 nm, 1520 nm, and 1560 nm). The proposed method is generally applicable to many optical systems and is therefore not limited to enhancing photon upconversion.

Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ('statins') reduces morbidity and mortality from coronary heart disease in diverse patient populations.The aim of the present ALERT (Assessment of Lescol in Renal Transplantation) study is to determine whether renal transplant recipients would also benefit from statin therapy. ALERT is a multicentre, randomized, double-blind, placebo-controlled trial to assess the effect of fluvastatin in renal transplant recipients with mild-to-moderate hypercholesterolaemia. The primary objective is to investigate the effects of fluvastatin on major adverse cardiac events (MACE). In addition, the effects on cardiovascular and all-cause mortality, as well as renal function, will be addressed.The study population contains patients with functioning renal allografts of more than 6 months' duration, recruited from 75 centres in Northern Europe and Canada. Patients of both sexes, aged 30-75 years, with a total cholesterol level of 4.0-9.0 mmol/l (155-348 mg/dl) were included, except for those with a history of myocardial infarction, where the upper limit for inclusion was 7.0 mmol/l (270 mg/dl).A total of 2100 patients were recruited by the end of October 1997 and will be followed for up to 6 years. This report presents the design features of the study (recruitment, follow-up, sample size, data analysis and study organization), along with baseline results. ALERT is the first large-scale prospective, randomized, double-blind study to address the prevention of cardiovascular mortality in renal transplant patients receiving an HMGCoA reductase inhibitor.

The case history of a hypoparathyroid female with short bowel syndrome and long-standing therapy-resistant symptomatic hypocalcemia is reported. During treatment with massive doses of the potent vitamin D analog, 1 alpha-hydroxyvitamin D3(1 alpha(OH)D3), normocalcemia was re-established and clinical symptoms of hypocalcemia were relieved. Furthermore, significant improvement of t of intestinal calcium absorption and bone mineral content was observed after three months of treatment with 1 alpha(OH)D3. The data suggest that 1 alpha(OH)D3 may be of therapeutical value in patients with hypoparathyroidism and intestinal malabsorption.

We discuss non-spectroscopic (astrometric) ways to determine radial velocities and their potentials in future astrometric missions. Radial-velocity accuracies are presented, based on Hipparcos parallax and proper motion data for several open clusters.