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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.

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.

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

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.

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.

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.

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.