The importance of the weak: Interaction modifiers in artificial spin ices

The modification of geometry and interactions in two-dimensional magnetic nanosystems has enabled a range of studies addressing the magnetic order, collective low-energy dynamics, and emergent magnetic properties, in e.g. artificial spin ice structures. The common denominator of all these investigations is the use of Ising-like mesospins as building blocks, in the form of elongated magnetic islands. Here we introduce a new approach: single interaction modifiers, using slave-mesospins in the form of discs, within which the mesospin is free to rotate in the disc plane. We show that by placing these on the vertices of square artificial spin ice arrays and varying their diameter, it is possible to tailor the strength and the ratio of the interaction energies. We demonstrate the existence of degenerate ice-rule obeying states in square artificial spin ice structures, enabling the exploration of thermal dynamics in a spin liquid manifold. Furthermore, we even observe the emergence of flux lattices on larger length-scales, when the energy landscape of the vertices is reversed. The work highlights the potential of a design strategy for two-dimensional magnetic nano-architectures, through which mixed dimensionality of mesospins can be used to promote thermally emergent mesoscale magnetic states.Comment: 17 pages, including methods, 4 figures. Supplementary information contains 16 pages and 15 figure

Human Mesenchymal Stem Cells Prolong Survival and Ameliorate Motor Deficit through Trophic Support in Huntington's Disease Mouse Models

We investigated the therapeutic potential of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in Huntington's disease (HD) mouse models. Ten weeks after intrastriatal injection of quinolinic acid (QA), mice that received hBM-MSC transplantation showed a significant reduction in motor function impairment and increased survival rate. Transplanted hBM-MSCs were capable of survival, and inducing neural proliferation and differentiation in the QA-lesioned striatum. In addition, the transplanted hBM-MSCs induced microglia, neuroblasts and bone marrow-derived cells to migrate into the QA-lesioned region. Similar results were obtained in R6/2-J2, a genetically-modified animal model of HD, except for the improvement of motor function. After hBM-MSC transplantation, the transplanted hBM-MSCs may integrate with the host cells and increase the levels of laminin, Von Willebrand Factor (VWF), stromal cell-derived factor-1 (SDF-1), and the SDF-1 receptor Cxcr4. The p-Erk1/2 expression was increased while Bax and caspase-3 levels were decreased after hBM-MSC transplantation suggesting that the reduced level of apoptosis after hBM-MSC transplantation was of benefit to the QA-lesioned mice. Our data suggest that hBM-MSCs have neural differentiation improvement potential, neurotrophic support capability and an anti-apoptotic effect, and may be a feasible candidate for HD therapy

Design of bio-nanosystems for oral delivery of functional compounds

Nanotechnology has been referred to as one of the most interesting topics in food technology due to the potentialities of its use by food industry. This calls for studying the behavior of nanosystems as carriers of biological and functional compounds aiming at their utilization for delivery, controlled release and protection of such compounds during food processing and oral ingestion. This review highlights the principles of design and production of bio-nanosystems for oral delivery and their behavior within the human gastrointestinal (GI) tract, while providing an insight into the application of reverse engineering approach to the design of those bio-nanosystems. Nanocapsules, nanohydrogels, lipid-based and multilayer nanosystems are discussed (in terms of their main ingredients, production techniques, predominant forces and properties) and some examples of possible food applications are given. Phenomena occurring in in vitro digestion models are presented, mainly using examples related to the utilization of lipid-based nanosystems and their physicochemical behavior throughout the GI tract. Furthermore, it is shown how a reverse engineering approach, through two main steps, can be used to design bio-nanosystems for food applications, and finally a last section is presented to discuss future trends and consumer perception on food nanotechnology.Miguel A. Cerqueira, Ana C. Pinheiro, Helder D. Silva, Philippe E. Ramos, Ana I. Bourbon, Oscar L. Ramos (SFRH/BPD/72753/2010, SFRH/BD/48120/2008, SFRH/BD/81288/2011, SFRH/BD/80800/2011, SFRH/BD/73178/2010 and SFRH/BPD/80766/2011, respectively) are the recipients of a fellowship from the Fundacao para a Ciencia e Tecnologia (FCT, POPH-QREN and FSE Portugal). Maria L. Flores-Lopez thanks Mexican Science and Technology Council (CONACYT, Mexico) for PhD fellowship support (CONACYT Grant number: 215499/310847). The support of EU Cost Actions FA0904 and FA1001 is gratefully acknowledged

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations

Ultrasound for Distal Forearm Fracture:A Systematic Review and Diagnostic Meta-Analysis

STUDY OBJECTIVE:To determine the diagnostic accuracy of ultrasound for detecting distal forearm fractures. METHODS:A systematic review and diagnostic meta-analysis was performed according to the PRISMA statement. We searched MEDLINE, Web of Science and the Cochrane Library from inception to September 2015. All prospective studies of the diagnostic accuracy of ultrasound versus radiography as the reference standard were included. We excluded studies with a retrospective design and those with evidence of verification bias. We assessed the methodological quality of the included studies with the QUADAS-2 tool. We performed a meta-analysis of studies evaluating ultrasound to calculate the pooled sensitivity and specificity with 95% confidence intervals (CI95%) using a bivariate model with random effects. Subgroup and sensitivity analysis were used to examine the effect of methodological differences and other study characteristics. RESULTS:Out of 867 publications we included 16 studies with 1,204 patients and 641 fractures. The pooled test characteristics for ultrasound were: sensitivity 97% (CI95% 93-99%), specificity 95% (CI95% 89-98%), positive likelihood ratio (LR) 20.0 (8.5-47.2) and negative LR 0.03 (0.01-0.08). The corresponding pooled diagnostic odds ratio (DOR) was 667 (142-3,133). Apparent differences were shown for method of viewing, with the 6-view method showing higher specificity, positive LR, and DOR, compared to the 4-view method. CONCLUSION:The present meta-analysis showed that ultrasound has a high accuracy for the diagnosis of distal forearm fractures in children when used by proper viewing method. Based on this, ultrasound should be considered a reliable alternative, which has the advantages of being radiation free