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Detailed data on adipokines and body composition during and after pregnancy in women of different BMI categories are lacking. Furthermore, adipokine regulation during pregnancy and the factors contributing to gestational insulin resistance are not completely understood. The objective was to longitudinally determine adipokine levels, body composition, and insulin sensitivity during and after pregnancy in women of healthy weight (HW) and with obesity (OB), and identify factors associated with insulin resistance. Women (30 HW, 19 OB) underwent blood sampling and body composition examination, by air-displacement plethysmography, longitudinally during pregnancy (trimesters 1, 2, 3) and after pregnancy (6, 12, 18 months postpartum). Serum leptin, soluble leptin receptor (sOB-R), and adiponectin levels were measured and free leptin index (FLI) and homeostatic model assessment of insulin resistance (HOMA-IR) determined. Fat mass and leptin increased during pregnancy in the HW (p

We consider the benefits of dream mechanisms - that is, the ability to simulate new experiences based on past ones - in a machine learning context. Specifically, we are interested in learning for artificial agents that act in the world, and operationalize "dreaming" as a mechanism by which such an agent can use its own model of the learning environment to generate new hypotheses and training data. We first show that it is not necessarily a given that such a data-hallucination process is useful, since it can easily lead to a training set dominated by spurious imagined data until an ill-defined convergence point is reached. We then analyse a notably successful implementation of a machine learning-based dreaming mechanism by Ha and Schmidhuber (Ha, D., & Schmidhuber, J. (2018). World models. arXiv e-prints, arXiv:1803.10122). On that basis, we then develop a general framework by which an agent can generate simulated data to learn from in a manner that is beneficial to the agent. This, we argue, then forms a general method for an operationalized dream-like mechanism. We finish by demonstrating the general conditions under which such mechanisms can be useful in machine learning, wherein the implicit simulator inference and extrapolation involved in dreaming act without reinforcing inference error even when inference is incomplete. First Published January 8, 2020CC BY-NC 4.0 EC H2020 research project Dreams4Cars (no. 731593)

Factors differentiating women at highest risk of progression to type 2 diabetes mellitus (T2DM) after gestational diabetes mellitus (GDM) are incompletely known. Our aim was to characterize adipose tissue and body composition in relation to glucose metabolism in women with a history of GDM and to identify factors associated with development of T2DM. We examined glucose tolerance (OGTT), insulin sensitivity (HOMA-IR), body composition (anthropometry, air displacement plethysmography), and blood chemistry in 39 women 6 years after GDM. An adipose tissue biopsy was obtained to assess the size, number, and lipolytic activity of adipocytes, and adipokine release and density of immune cells and blood vessels in adipose tissue. Normal glucose tolerance (NGT) was identified in 31 women and impaired glucose metabolism (IGM) in 8. Women with IGM had higher BMI/fat mass, and related expected adipose tissue features, than women with NGT. Ethnicity was similar in the groups, but numerically there was a higher proportion of European women in the NGT group and a higher proportion of non-European women in the IGM group. BMI was the best discriminator of NGT versus IGM (multivariable logistic regression: OR = 1.34, P

The size distribution of adipocytes in a suspension, after collagenase digestion of adipose tissue, can be determined by computerized image analysis. Free lipid, forming droplets, in such suspensions implicates a bias since droplets present in the images may be identified as adipocytes. This problem is not always adjusted for and some reports state that distinguishing droplets and cells is a considerable problem. In addition, if the droplets originate mainly from rupture of large adipocytes, as often described, this will also bias size analysis. We here confirm that our ordinary manual means of distinguishing droplets and adipocytes in the images ensure correct and rapid identification before exclusion of the droplets. Further, in our suspensions, prepared with focus on gentle handling of tissue and cells, we find no association between the amount of free lipid and mean adipocyte size or proportion of large adipocytes.

Despite the increased usage of pearlitic compacted graphite iron (CGI) in heavy vehicle engines, poor machinability of this material remains as one of the main technical challenges as compared to conventional lamellar iron. To minimise the machining cost, it is believed that solution-strengthened CGI material with a ferritic matrix could bring an advantage. The present study focuses on the effect of solution strengthening of silicon and section thickness on tensile, microstructure and hardness properties of high-Si CGI materials. To do so, plates with thicknesses from 7 to 75 mm were cast with three different target silicon levels 3.7, 4.0 and 4.5 wt%. For all Si levels, the microstructure was ferritic with a very limited pearlite content. The highest nodularity was observed in 7 and 15 mm plate sections, respectively, however, it decreased as the plate thickness increased. Moreover, increasing Si content to 4.5 wt% resulted in substantial improvement up to 65 and 50% in proof stress and tensile strength,...

Background/Objectives: Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. Subjects/Methods: Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. Results: Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R2=0.751, P

Studying the mechanisms for the complex pathogenesis of polycystic ovary syndrome (PCOS) requires animal models with endocrine, reproductive, and metabolic features of the syndrome. Hyperandrogenism seems to be a central factor in PCOS, leading to anovulation and insulin resistance. In female rats, continuous administration of letrozole, a nonsteroidal inhibitor of P450 aromatase, at 400 μg/d starting before puberty induces hyperandrogenemia and reproductive abnormalities similar to those in women with PCOS. However, despite high circulating testosterone levels, these rats do not develop metabolic abnormalities, perhaps because of their supraphysiological testosterone concentrations or because estrogen synthesis is completely blocked in insulin-sensitive tissues. To test the hypothesis that continuous administration of lower doses of letrozole starting before puberty would result in both metabolic and reproductive phenotypes of PCOS, we performed a 12-wk dose-response study. At 21 d of age, 46 female Wistar rats were divided into two letrozole groups (100 or 200 μg/d) and a control group (placebo). Both letrozole doses resulted in increased body weight, inguinal fat accumulation, anovulation, larger ovaries with follicular atresia and multiples cysts, endogenous hyperandrogemia, and lower estrogen levels. Moreover, rats that received 200 μg/d had insulin resistance and enlarged adipocytes in inguinal and mesenteric fat depots, increased circulating levels of LH, decreased levels of FSH, and increased ovarian expression of Cyp17a1 mRNA. Thus, continuous administration of letrozole, 200 μg/d, to female rats for 90 d starting before puberty results in a PCOS model with reproductive and metabolic features of the syndrome.

The microstructure of a trial martensitic chromium steel containing a high content of boron (250 ppm) was characterized in detail in the as-tempered and aged conditions. This steel has a similar composition and heat treatment as the TAF steel that still is unsurpassed in creep strength among all 9 to 12 pct chromium steels. Characterization was performed by using scanning electron microscopy, energy-filtered transmission electron microscopy, secondary ion mass spectroscopy, and atom probe tomography. Focus was placed on investigating different types of precipitates that play a key role in improving the creep resistance of these steels. The low tempering temperature of 963 K (690 °C) is enough for the precipitation of the full volume fraction of both MX and M23C6. A high boron content, more than 1 at. pct, was found in M23C6 precipitates and they grow slowly during aging. The high boron level in the steel results in metal borides rather than BN with the approximate formula (Mo0.66Cr0.34)2(Fe0.75V0.25)B2. Two families of MX precipitates were found, one at lath boundaries about 35 nm in size and one dense inside the laths, only 5 to 15 nm in size.

The matrix structure formation of cast irons is strongly affected by the casting process where different alloying elements and cooling conditions are methods used to achieve the desired structure and performance of the material. In the presented study, six pearlitic grey cast irons have been analysed regarding how the pearlitic structure formation might be controlled. Different amounts of copper and chromium were added, ranging from 0.07 to 1.11 wt% and 0.08 to 0.60 wt%, respectively. Three different section sizes (Ø20, Ø45 and Ø85 mm) and three different cooling conditions through the eutectoid transformation were used to control the matrix structure formation. The three different cooling conditions were achieved by shake-out at 950°C and cooling in air or furnace, or by keeping the casting in the mould. The present paper focuses on the pearlite appearance, since it strongly affects the mechanical properties. The analysis shows that the refining effect of Cr is much stronger than that of Cu. Comparing the low alloyed base melt with the ones alloyed with Cu and Cr, it is seen that additions of 0.75 wt% Cu refines the pearlite by approximately 10%. Keeping this Cu level constant and adding Cr, it is observed that an addition of ~0.6 wt% refines the pearlite by another 20%. The most potent refining effect of Cr is achieved by additions up to 0.35 wt%. Keeping the Cr constant at 0.35% and changing the Cu content (0.35 to 1.10 wt%), almost no variation is observed in the overall interlamellar spacing. The eutectoid cooling rate most strongly affects the interlamellar spacing down to cooling rates of about -0.75 °C/s. At higher (i.e. lower value) cooling rates the interlamellar spacing is fairly constant. In addition to studying the interlamellar spacing, the graphite structure has also been analysed and evaluated concerning effects from the different casting variables.

In this experimental study, six pearlitic grey cast irons with different Cu and Cr content, different section thicknesses and different eutectoid cooling rates have been examined. The eutectoid cooling rate was approximated by casting simulation analysis. The purpose of the experiments was to study the effect of the matrix structure on the overall mechanical properties. An emphasis is put on the pearlite interlamellar spacing because this controls the resulting mechanical properties to a large extent. By keeping the graphite structure constant, the effect of the matrix structure was able to be studied. This was achieved by shake-out at temperatures above the eutectoid transformation range followed by subsequent cooling in air, mould or in a furnace. The pearlite interlamellar spacing ranged from 90 to 330 nm for the matrices studied. Comparing the strength of the fine structured and coarse structured materials, the tensile and yield strength was reduced by almost 50%. Regarding the elastic deformation, a weak increase in the tangent modulus with increasing alloying content was observed. It was also observed that lower cooling rate decreased the tangent modulus. The tangent modulus ranged between 70 and 110 GPa. Analysing the plastic deformation of the materials, in terms of strain hardening exponent, n, and strength coefficient, K, a strong dependence on the pearlite coarseness was observed. It was concluded that the effect of graphite particle length on tensile strength was negligible and the major improvement on the strength was due to refinement of the pearlite.

The purpose of the investigation was to study the mechanisms improving oxide scale adherence in Pt-free and Pt-rich beta-NiAl materials during high temperature oxidation. Theoretical density-functional theory (DFT) calculations were used to calculate the work of separation of the beta-NiAl(111)/alpha-Al(2)O(3)(0001) metal-oxide interfaces, in pure NiAl and Pt-rich NiAl materials. The experimental work was focused on the studies of the metal-oxide interface, its development and morphology. Based on the theoretical and experimental results a complementary picture is presented for a better understanding of the Pt effect on the oxidation and oxide adhesion. It is shown that the interfacial bonding is decreased with addition of Pt to beta-NiAl. The beneficial effect of Pt on the adhesion energy is attributed to the enhancement of contact areas between the oxide and the metal. The influence of Pt on the diffusion of Al and the formation of interfacial voids is also discussed.

The present investigation concerns the formation and healing of voids at the metal-oxide interface in beta-NiAl alloys. It is shown that transient cavities form at the metal-oxide interface during the initial stage of isothermal oxidation at 1,050 A degrees C. These voids disappear after a few hours of oxidation, due to their filling with oxide. It is proposed that the filling of the transient voids occurs through cracks in the outer oxide scale. This allows for an oxygen transport into the cavities where a new oxide is created and grows outwards from the metal surface. Pt-containing beta-NiAl alloys that have better resistance to oxide spallation show suppressed formation of cavities and/or a faster filling of voids. This is explained by the enhanced diffusion of Al in these materials.

Several simulation theories have been proposed as an explanation for how humans and other agents internalize an "inner world" that allows them to simulate interactions with the external real world - prospectively and retrospectively. Such internal simulation of interaction with the environment has been argued to be a key mechanism behind mentalizing and planning. In the present work, we study internal simulations in a robot acting in a simulated human environment. A model of sensory-motor interactions with the environment is generated from human demonstrations, and tested on a Robosoft Kompai robot. The model is used as a controller for the robot, reproducing the demonstrated behavior. Information from several different demonstrations is mixed, allowing the robot to produce novel paths through the environment, towards a goal specified by top-down contextual information. The robot model is also used in a covert mode, where actions are inhibited and perceptions are generated by a forward model. As a result, the robot generates an internal simulation of the sensory-motor interactions with the environment. Similar to the overt mode, the model is able to reproduce the demonstrated behavior as internal simulations. When experiences from several demonstrations are combined with a top-down goal signal, the system produces internal simulations of novel paths through the environment. These results can be understood as the robot imagining an "inner world" generated from previous experience, allowing it to try out different possible futures without executing actions overtly. We found that the success rate in terms of reaching the specified goal was higher during internal simulation, compared to overt action. These results are linked to a reduction in prediction errors generated during covert action. Despite the fact that the model is quite successful in terms of generating covert behavior towards specified goals, internal simulations display different temporal distributions compared to their overt counterparts. Links to human cognition and specifically mental imagery are discussed. CC BY 4.0Correspondence: Erik A. Billing, erik.billing@his.se

Three commercial Pt-modified coatings (RT22, SS82A and MDC150L) and one aluminide diffusion coating without Pt (PWA73) applied on a Ni-based single crystal superalloy (CMSX4), were investigated after isothermal oxidation in laboratory air at 1050 °C for 1 h, using X-ray diffraction, scanning electron microscopy and transmission electron microscopy (TEM). TEM investigations reveal the presence of the metastable γ-Al 2 O 3 phase on all the investigated coatings. The amount of the observed α-Al 2 O 3 phase formed seems to depend on the Al and Pt contents in the coating. A high Al content in the coatings promotes formation of α-Al 2 O 3 . A continuous layer of α-Al 2 O 3 grains was found at the coating/oxide interface of the coating containing 55 at.% Al. On the coating with a low Al content (≈40 at.%) and with low amount of Pt (4 at.%), no α-Al 2 O 3 phase was observed while on the coating with a similar Al content but with much higher Pt level (16 at.%), grains of α-Al 2 O 3 phase were detected.

Four commercial aluminide diffusion coatings (one Pt-free) and four polycrystalline NiAl model materials, isothermally oxidised in laboratory air at 1050°C for 1 hour, have been investigated. The coatings were deposited on a single crystal Ni-based superalloy, CMSX-4. Two of the model materials are binary alloys containing different Al amounts. The two other have the same Ni/Al ratio as the binary alloys but were alloyed with 4 at% Pt. In order to control the surface roughness, all materials were polished prior to oxidation. Microstructural studies have been conducted using X-ray diffraction and scanning electron microscopy. To get a deeper insight on the platinum influence on the oxide structure, two commercial coatings (one Pt free and the other modified with Pt) were also investigated using transmission electron microscopy. The results obtained are discussed according to the influence of Al and Pt contents in the materials.

Factor H (FH) and factor H-like protein 1 (FHL-1) regulate complement activation through the alternative pathway. Several extracellular bacterial pathogens, prime targets for the complement system, bind FH and FHL-1, thereby acquiring a potential mechanism for minimizing complement deposition on their surface. For group A streptococci (GAS), surface-bound antiphagocytic M proteins mediate the interaction. To study the role of the FH–FHL-1 interaction for complement deposition and opsonophagocytosis of GAS, we first constructed a set of truncated M5 protein variants and expressed them on the surface of a homologous M-negative GAS strain. Binding experiments with the resulting strains demonstrated that the major FH–FHL-1 binding is located in a 42-amino-acid region within the N-terminal third of M5. Measurement of bacteria-bound complement factor C3 after incubation in plasma showed that the presence of this region had little impact upon complement deposition through the alternative pathway. Moreover, streptococci expressing M5 proteins lacking the major FH and FHL-1 binding sequence resisted phagocytosis in human blood as efficiently as bacteria expressing the wild-type protein. Consequently, the data suggest that the binding of the regulators of the alternative pathway is of limited importance for GAS phagocytosis resistance.

Heat treatment of cast ductile iron (DI) to ausferritic ductile iron (ADI) is known to increase fatigue properties. However, the surface roughness of the cast material is also of significant importance. In this investigation, test rods with seven different surface qualities were cast from the same melt i.e. with same chemical composition. The surfaces of the test rods were varied by a number of parameters; grain size of the moulding sand, coated or non-coated mould surfaces, as-cast or machined and polished, shot peened or not. In addition, a reference material in conventional DI was cast and tested. All eight series were subjected to high-cycle fatigue bending tests. The results show that surface defects, such as micro porosity and minor inclusions drastically decrease the fatigue properties. For some ADI materials the stress amplitude limit was actually lower compared to the non-heat treated DI. The machined, polished and shot-peened material demonstrated the best fatigue properties, which is as expected.

Human high molecular mass kininogen (HK) participates as nonenzymatic cofactor in the contact system. Here, we show that recombinant domain D5 of HK (rD5) prolongs the clotting time of the intrinsic pathway of coagulation and attenuates the generation of bradykinin. Further studies indicate that a correct fold of domain D5 within HK is required for the activation of the contact system. The folding of rD5 seems to be modulated by the metal ions Zn2+, Ni2+, and Cu2+ as a specific antibody directed against the zinc-binding site in HK binds to HK and rD5 in a metal ion concentration dependent manner. The finding that these three metal ions specifically affect contact activation suggests that they regulate the accessibility of rD5 for negatively charged surfaces. Support for the assumption that the observed phenomena are due to conformational changes was obtained by fluorescence spectroscopy of rD5, demonstrating that its fluorescence spectrum was changed in the presence of ZnCl2. Moreover, negative staining electron microscopy experiments suggest that the zinc-induced changes in D5 also affect the conformation of the entire HK protein. The present data emphasize the role of zinc and other metal ions in the regulation of contact activation.

Existing Ig-binding proteins all suffer from limitations in their binding spectrum. In the pursuit of the ultimate, non-restricted, Ig-binding protein, we have constructed the hybrid protein LA, by fusing four of the Ig kappa light-chain-binding domains of peptostreptococcal protein L with four of the IgGFc- and Fab-binding regions of staphylococcal protein A. Ligand-blot experiments demonstrated that the L and the A components were both functional in the hybrid, as the protein was shown to bind purified kappa light chains and IgGFc. Protein LA bound human Ig of different classes and IgG from a wide range of mammalian species. IgG, IgM and IgA were purified from human serum and saliva by affinity chromatography on protein LA agarose. Similarly, single-chain Fv (scFv) antibodies carrying the kappa light-chain variable domain or expressing the V(H)III (variable domain of the heavy chain of Ig) determinant, were efficiently purified on immobilized protein LA. As judged by surface plasmon resonance (SPR), protein LA showed enhanced affinity for all tested ligands, including several scFv antibodies, compared with proteins L and A alone. SPR analysis also demonstrated that binding of a ligand to one of the components in protein LA did not affect the ability of the hybrid protein to interact simultaneously with a ligand for the other component. The antigen-binding capacity of a kappa-expressing scFv antibody was unaffected by the interaction with protein LA, whereas the binding of a V(H)III-expressing scFv antibody to its antigen was, unexpectedly, blocked by protein A and protein LA. Together, these data demonstrate that protein LA represents a highly versatile Ig-binding molecule.

Background Adipose tissue (AT) contributes to metabolic dysfunction through imbalanced production of adipokines, including cytokines. Visceral AT in particular is associated with metabolic disorders, indicating a specific secretory status. The relative significance of different human AT depots in adipokine release is not fully known. Further, previous in vitro systems usually included medium containing bovine serum albumin (BSA), which may induce cytokine release. Our aim was to compare release of a number of adipokines/cytokines – all implicated in insulin resistance – from human subcutaneous and visceral AT in a short-term incubation system minimizing cytokine induction and including repeated measurements during 24 h. A prerequisite was to evaluate a potential alternative to BSA in the incubation medium. Methods Subcutaneous and/or visceral AT from 17 patients (age 20–68 years; BMI 22.6–56.7 kg/m2) undergoing elective surgery was incubated for 2, 4, 6, 8, and 24 h in medium with or without 1% BSA or human serum albumin (HSA). Medium concentrations of adiponectin, chemerin, nine cytokines, dipeptidyl peptidase 4 (DPP4), and omentin were analyzed by multiplex immunoassay or ELISA. Adipocyte size, AT macrophage density, and medium concentrations of endotoxin were determined. Results Cytokine release was induced by BSA but not by HSA. In evaluation of the final incubation protocol including 1% HSA, and as expected, adiponectin release was higher from subcutaneous biopsies of nonobese than of obese subjects and inversely associated with adipocyte size; omentin was released almost exclusively from visceral AT. Exploratory incubations revealed more abundant release of chemerin, cytokines (except IL-6), and DPP4 from the visceral depot, while adiponectin release was higher from subcutaneous than visceral AT. Release was linear for a maximum of 2–6 h. Macrophage density was higher in visceral than subcutaneous AT. Levels of endotoxin in the medium were negligible. Conclusions Adiponectin, chemerin, many cytokines, and DPP4 are released from human AT in a depot-dependent manner. These results highlight functional differences between visceral and subcutaneous AT, and a mechanistic link between regional fat accumulation and metabolic disorders. Supplementation of human AT incubation medium with HSA rather than BSA is recommended to minimize induction of cytokine release.