Hysteretic vortex matching effects in high-TcT_c superconductors with nanoscale periodic pinning landscapes fabricated by He ion beam projection technique

Square arrays of sub-micrometer columnar defects in thin YBa$_{2}$Cu$_{3}$O$_{7-\delta}$ (YBCO) films with spacings down to 300 nm have been fabricated by a He ion beam projection technique. Pronounced peaks in the critical current and corresponding minima in the resistance demonstrate the commensurate arrangement of flux quanta with the artificial pinning landscape, despite the strong intrinsic pinning in epitaxial YBCO films. Whereas these vortex matching signatures are exactly at predicted values in field-cooled experiments, they are displaced in zero-field cooled, magnetic-field ramped experiments, conserving the equidistance of the matching peaks and minima. These observations reveal an unconventional critical state in a cuprate superconductor with an artificial, periodic pinning array. The long-term stability of such out-of-equilibrium vortex arrangements paves the way for electronic applications employing fluxons.Comment: 9 pages, 6 figures, to be published in Physical Review Applie

The effect of dietary fish oil on weight gain and insulin sensitivity is dependent on APOE genotype in humanized targeted replacement mice

We investigated the independent and interactive impact of the common APOE genotype and marine n-3 polyunsaturated fatty acids (PUFA) on the development of obesity and associated cardiometabolic dysfunction in a murine model. Human APOE3 and APOE4 targeted replacement mice were fed either a high-fat control diet (HFD) or a HFD supplemented with 3% n-3 PUFA from fish oil (HFD + FO) for 8 wk. We established the impact of intervention on food intake, bodyweight, and visceral adipose tissue (VAT) mass; plasma, lipids (cholesterol and triglycerides), liver enzymes, and adipokines; glucose and insulin during an intraperitoneal glucose tolerance test; and Glut4 and ApoE expression in VAT. HFD feeding induced more weight gain and higher plasma lipids in APOE3 compared to APOE4 mice (P < 0.05), along with a 2-fold higher insulin and impaired glucose tolerance. Supplementing APOE3, but not APOE4, animals with dietary n-3 PUFA decreased bodyweight gain, plasma lipids, and insulin (P < 0.05) and improved glucose tolerance, which was associated with increased VAT Glut4 mRNA levels (P < 0.05). Our findings demonstrate that an APOE3 genotype predisposes mice to develop obesity and its metabolic complications, which was attenuated by n-3 PUFA supplementation.—Slim, K. E., Vauzour, D., Tejera, N., Voshol, P. J., Cassidy, A., Minihane, A. M. The effect of dietary fish oil on weight gain and insulin sensitivity is dependent on APOE genotype in humanized targeted replacement mice

Early-life adversity selectively impairs α2-GABAA receptor expression in the mouse nucleus accumbens and influences the behavioral effects of cocaine

Haplotypes of the Gabra2 gene encoding the α2 subunit of the GABAA receptor (GABAAR) are associated with drug abuse, suggesting that α2-GABAARs may play an important role in the circuitry underlying drug misuse. The genetic association of Gabra2 haplotypes with cocaine addiction appears to be evident primarily in individuals who had experienced childhood trauma. Given this association of childhood trauma, cocaine abuse and the Gabra2 haplotypes, we have explored in a mouse model of early life adversity (ELA) whether such events influence the behavioral effects of cocaine and if, as suggested by the human studies, α2-GABAARs in the nucleus accumbens (NAc) are involved in these perturbed behaviors. In adult mice prior ELA caused a selective decrease of accumbal α2-subunit mRNA, resulting in a selective decrease in the number and size of the α2-subunit (but not the α1-subunit) immunoreactive clusters in NAc core medium spiny neurons (MSNs). Functionally, in adult MSNs ELA decreased the amplitude and frequency of GABAAR-mediated miniature inhibitory postsynaptic currents (mIPSCs), a profile similar to that of α2 "knock-out" (α2-/-) mice. Behaviorally, adult male ELA and α2-/- mice exhibited an enhanced locomotor response to acute cocaine and blunted sensitization upon repeated cocaine administration, when compared to their appropriate controls. Collectively, these findings reveal a neurobiological mechanism which may relate to the clinical observation that early trauma increases the risk for substance abuse disorder (SAD) in individuals harbouring haplotypic variations in the Gabra2 gene.</p

Stability of Terrestrial Planets in the Habitable Zone of Gl 777 A, HD 72659, Gl 614, 47 Uma and HD 4208

We have undertaken a thorough dynamical investigation of five extrasolar planetary systems using extensive numerical experiments. The systems Gl 777 A, HD 72659, Gl 614, 47 Uma and HD 4208 were examined concerning the question of whether they could host terrestrial like planets in their habitable zones (=HZ). First we investigated the mean motion resonances between fictitious terrestrial planets and the existing gas giants in these five extrasolar systems. Then a fine grid of initial conditions for a potential terrestrial planet within the HZ was chosen for each system, from which the stability of orbits was then assessed by direct integrations over a time interval of 1 million years. The computations were carried out using a Lie-series integration method with an adaptive step size control. This integration method achieves machine precision accuracy in a highly efficient and robust way, requiring no special adjustments when the orbits have large eccentricities. The stability of orbits was examined with a determination of the Renyi entropy, estimated from recurrence plots, and with a more straight forward method based on the maximum eccentricity achieved by the planet over the 1 million year integration. Additionally, the eccentricity is an indication of the habitability of a terrestrial planet in the HZ; any value of e>0.2 produces a significant temperature difference on a planet's surface between apoapse and periapse. The results for possible stable orbits for terrestrial planets in habitable zones for the five systems are summarized as follows: for Gl 777 A nearly the entire HZ is stable, for 47 Uma, HD 72659 and HD 4208 terrestrial planets can survive for a sufficiently long time, while for Gl 614 our results exclude terrestrial planets moving in stable orbits within the HZ.Comment: 14 pages, 18 figures submitted to A&

High-Level Expression of Various Apolipoprotein (a) Isoforms by "Transferrinfection". The Role of Kringle IV Sequences in the Extracellular Association with Low-Density Lipoprotein

Characterization of the assembly of lipoprotein(a) [Lp(a)] is of fundamental importance to understanding the biosynthesis and metabolism of this atherogenic lipoprotein. Since no established cell lines exist that express Lp(a) or apolipoprotein(a) [apo(a)], a "transferrinfection" system for apo(a) was developed utilizing adenovirus receptor- and transferrin receptor-mediated DNA uptake into cells. Using this method, different apo(a) cDNA constructions of variable length, due to the presence of 3, 5, 7, 9, 15, or 18 internal kringle IV sequences, were expressed in cos-7 cells or CHO cells. All constructions contained kringle IV-36, which includes the only unpaired cysteine residue (Cys-4057) in apo(a). r-Apo(a) was synthesized as a precursor and secreted as mature apolipoprotein into the medium. When medium containing r-apo(a) with 9, 15, or 18 kringle IV repeats was mixed with normal human plasma LDL, stable complexes formed that had a bouyant density typical of Lp(a). Association was substantially decreased if Cys-4057 on r-apo(a) was replaced by Arg by site-directed mutagenesis or if Cys-4057 was chemically modified. Lack of association was also observed with r-apo(a) containing only 3, 5, or 7 kringle IV repeats without "unique kringle IV sequences", although Cys-4057 was present in all of these constructions. Synthesis and secretion of r-apo(a) was not dependent on its sialic acid content. r-Apo(a) was expressed even more efficiently in sialylation-defective CHO cells than in wild-type CHO cells. In transfected CHO cells defective in the addition of N-acetylglucosamine, apo(a) secretion was found to be decreased by 50%. Extracellular association with LDL was not affected by the carbohydrate moiety of r-apo(a), indicating a protein-protein interaction between r-apo(a) and apoB. These results show that, besides kringle IV-36, other kringle IV sequences are necessary for the extracellular association of r-apo(a) with LDL. Changes in the carbohydrate moiety of apo(a), however, do not affect complex formation

Negotiating care in the context of Finnish and Italian elder care policies

Negotiation is an integral part of all elder care, which by definition involves a relation between at least two people. In this article we analyse negotiations concerning elder care in the context of Finnish and Italian elder care policies. At the macro level negotiations on elder care are shaped by elder care policies and at the micro level by individual skills and resources. Our focus is on the negotiations on eligibility that take place when elders attempt to access care. The data consist of qualitative interviews with Finnish and Italian elders in need of care. The analysis of individual experiences of care negotiations reflects the implementation of elder care policies. The results indicate that the most negotiated eligibility criteria when seeking access to elder care are need, money and social relations. These criteria are negotiated when seeking eligibility to different sources of care: informal care, grey market, market-based, non-profit and public services. In Italy, negotiation is particularly crucial when accessing grey market care. Cash as the main Italian elder care policy tool tends to enhance the role of and need for negotiation. In Finland, a greater part of elder care is provided by the public sector and therefore the process of negotiation is more standardized than in Italy

How residual stresses affect the fracture properties of layered thin films

The continued miniaturization effort has revealed exciting new material behavior at small length scales, where pronounced size effects come into play and material properties are subject to change. This has led to the development of miniaturized testing techniques to determine local plastic properties. So far, however, only few efforts regarding the determination of residual stresses and fracture properties in miniaturized systems were made. In this presentation, we will focus on recent developments regarding the measurement of residual stresses and miniaturized fracture properties using FIB based sample preparation and in situ SEM experiments. The depth resolved residual film stresses are determined by an improved stepwise beam layer removal method [1]. From the same film systems, beams are FIB fabricated for miniaturized fracture testing in the SEM [2]. We will discuss the general possibilities, challenges, and benefits of these approaches by examining the internal stresses and fracture properties of single layer and multilayer thin films in the immiscible system Cu-W. Particular emphasis is placed on the effect of residual stresses on the fracture properties. Moreover, possible limitations of commonly used data analysis approaches are addressed, and related improvements using finite element modelling to determine crack-driving forces in the presence of interfaces and residual stresses are presented [3]. Notably, the required material input data in terms of flow behavior for this modeling approach was determined using spherical nanoindentation experiments on single and multilayer films. Finally, the possibility of further miniaturization of such experiments by using in situ TEM is demonstrated [4]

Macrophage Glucose-6-Phosphate Dehydrogenase Stimulates Proinflammatory Responses with Oxidative Stress

Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that regulates cellular redox potential. In this study, we demonstrate that macrophage G6PD plays an important role in the modulation of proinflammatory responses and oxidative stress. The G6PD levels in macrophages in the adipose tissue of obese animals were elevated, and G6PD mRNA levels positively correlated with those of proinflammatory genes. Lipopolysaccharide (LPS) and free fatty acids, which initiate proinflammatory signals, stimulated macrophage G6PD. Overexpression of macrophage G6PD potentiated the expression of proinflammatory and prooxidative genes responsible for the aggravation of insulin sensitivity in adipocytes. In contrast, when macrophage G6PD was inhibited or suppressed via chemical inhibitors or small interfering RNA (siRNA), respectively, basal and LPS-induced proinflammatory gene expression was attenuated. Furthermore, macrophage G6PD increased activation of the p38 mitogen-activated protein kinase (MAPK) and NF-??B pathways, which may lead to a vicious cycle of oxidative stress and proinflammatory cascade. Together, these data suggest that an abnormal increase of G6PD in macrophages promotes oxidative stress and inflammatory responses in the adipose tissue of obese animals.open5

Cell-free gene expression dynamics in synthetic cell populations

The ability to build synthetic cellular populations from the bottom-up provides the groundwork to realize minimal living tissues comprising single cells which can communicate and bridge scales into multicellular systems. Engineered systems made of synthetic micron-sized compartments and integrated reaction networks coupled with mathematical modeling can facilitate the design and construction of complex and multiscale chemical systems from the bottom-up. Toward this goal, we generated populations of monodisperse liposomes encapsulating cell-free expression systems (CFESs) using double-emulsion microfluidics and quantified transcription and translation dynamics within individual synthetic cells of the population using a fluorescent Broccoli RNA aptamer and mCherry protein reporter. CFE dynamics in bulk reactions were used to test different coarse-grained resource-limited gene expression models using model selection to obtain transcription and translation rate parameters by likelihood-based parameter estimation. The selected model was then applied to quantify cell-free gene expression dynamics in populations of synthetic cells. In combination, our experimental and theoretical approaches provide a statistically robust analysis of CFE dynamics in bulk and monodisperse synthetic cell populations. We demonstrate that compartmentalization of CFESs leads to different transcription and translation rates compared to bulk CFE and show that this is due to the semipermeable lipid membrane that allows the exchange of materials between the synthetic cells and the external environment

A hypomorphic Cbx3 allele causes prenatal growth restriction and perinatal energy homeostasis defects

Mammals have three HP1 protein isotypes HP1β (CBX1), HP1γ (CBX3) and HP1α (CBX5) that are encoded by the corresponding genes Cbx1, Cbx3 and Cbx5. Recent work has shown that reduction of CBX3 protein in homozygotes for a hypomorphic allele (Cbx3 hypo) causes a severe postnatal mortality with around 99% of the homozygotes dying before weaning. It is not known what the causes of the postnatal mortality are. Here we show that Cbx3 hypo/hypo conceptuses are significantly reduced in size and the placentas exhibit a haplo-insufficiency. Late gestation Cbx3 hypo/hypo placentas have reduced mRNA transcripts for genes involved in growth regulation, amino acid and glucose transport. Blood vessels within the Cbx3 hypo/hypo placental labyrinth are narrower than wild-type. Newborn Cbx3 hypo/hypo pups are hypoglycemic, the livers are depleted of glycogen reserves and there is almost complete loss of stored lipid in brown adipose tissue (BAT). There is a 10-fold reduction in expression of the BAT-specific Ucp1 gene, whose product is responsible for non-shivering themogenesis. We suggest that it is the small size of the Cbx3 hypo/hypo neonates, a likely consequence of placental growth and transport defects, combined with a possible inability to thermoregulate that causes the severe postnatal mortality