Associations between health-related quality of life, physical function and fear of falling in older fallers receiving home care

Falls and injuries in older adults have significant consequences and costs, both personal and to society. Although having a high incidence of falls, high prevalence of fear of falling and a lower quality of life, older adults receiving home care are underrepresented in research on older fallers. The objective of this study is to determine the associations between health-related quality of life (HRQOL), fear of falling and physical function in older fallers receiving home care

Puzzles of Dark Matter - More Light on Dark Atoms?

Positive results of dark matter searches in experiments DAMA/NaI and DAMA/LIBRA confronted with results of other groups can imply nontrivial particle physics solutions for cosmological dark matter. Stable particles with charge -2, bound with primordial helium in O-helium "atoms" (OHe), represent a specific nuclear-interacting form of dark matter. Slowed down in the terrestrial matter, OHe is elusive for direct methods of underground Dark matter detection using its nuclear recoil. However, low energy binding of OHe with sodium nuclei can lead to annual variations of energy release from OHe radiative capture in the interval of energy 2-4 keV in DAMA/NaI and DAMA/LIBRA experiments. At nuclear parameters, reproducing DAMA results, the energy release predicted for detectors with chemical content other than NaI differ in the most cases from the one in DAMA detector. Moreover there is no bound systems of OHe with light and heavy nuclei, so that there is no radiative capture of OHe in detectors with xenon or helium content. Due to dipole Coulomb barrier, transitions to more energetic levels of Na+OHe system with much higher energy release are suppressed in the correspondence with the results of DAMA experiments. The proposed explanation inevitably leads to prediction of abundance of anomalous Na, corresponding to the signal, observed by DAMA.Comment: Contribution to Proceedings of XIII Bled Workshop "What Comes beyond the Standard Model?

Exactly Marginal Deformations and Global Symmetries

We study the problem of finding exactly marginal deformations of N=1 superconformal field theories in four dimensions. We find that the only way a marginal chiral operator can become not exactly marginal is for it to combine with a conserved current multiplet. Additionally, we find that the space of exactly marginal deformations, also called the "conformal manifold," is the quotient of the space of marginal couplings by the complexified continuous global symmetry group. This fact explains why exactly marginal deformations are ubiquitous in N=1 theories. Our method turns the problem of enumerating exactly marginal operators into a problem in group theory, and substantially extends and simplifies the previous analysis by Leigh and Strassler. We also briefly discuss how to apply our analysis to N=2 theories in three dimensions.Comment: 23 pages, 2 figure

Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

An early warning method for agricultural products price spike based on artificial neural networks prediction

In general, the agricultural producing sector is affected by the diversity in supply, mostly from small companies, in addition to the rigidity of the demand, the territorial dispersion, the seasonality or the generation of employment related to the rural environment. These characteristics differentiate the agricultural sector from other economic sectors. On the other hand, the volatility of prices payed by producers, the high cost of raw materials, and the instability of both domestic and international markets are factors which have eroded the competitiveness and profitability of the agricultural sector. Because of the advance in technology, applications have been developed based on Artificial Neural Networks (ANN) which have helped the development of sales forecast on consumer products, improving the accuracy of traditional forecasting systems. This research uses the RNA to develop an early warning system for facing the increase in agricultural products, considering macro and micro economic variables and factors related to the seasons of the year

Upregulated sirtuin 1 by miRNA-34a is required for smooth muscle cell differentiation from pluripotent stem cells

© 2015 Macmillan Publishers Limited. All rights reserved. microRNA-34a (miR-34a) and sirtuin 1 (SirT1) have been extensively studied in tumour biology and longevityaging, but little is known about their functional roles in smooth muscle cell (SMC) differentiation from pluripotent stem cells. Using well-established SMC differentiation models, we have demonstrated that miR-34a has an important role in SMC differentiation from murine and human embryonic stem cells. Surprisingly, deacetylase sirtuin 1 (SirT1), one of the top predicted targets, was positively regulated by miR-34a during SMC differentiation. Mechanistically, we demonstrated that miR-34a promoted differentiating stem cells' arrest at G0G1 phase and observed a significantly decreased incorporation of miR-34a and SirT1 RNA into Ago2-RISC complex upon SMC differentiation. Importantly, we have identified SirT1 as a transcriptional activator in the regulation of SMC gene programme. Finally, our data showed that SirT1 modulated the enrichment of H3K9 tri-methylation around the SMC gene-promoter regions. Taken together, our data reveal a specific regulatory pathway that miR-34a positively regulates its target gene SirT1 in a cellular context-dependent and sequence-specific manner and suggest a functional role for this pathway in SMC differentiation from stem cells in vitro and in vivo

Critical change in the Fermi surface of iron arsenic superconductors at the onset of superconductivity

The phase diagram of a correlated material is the result of a complex interplay between several degrees of freedom, providing a map of the material's behavior. One can understand (and ultimately control) the material's ground state by associating features and regions of the phase diagram, with specific physical events or underlying quantum mechanical properties. The phase diagram of the newly discovered iron arsenic high temperature superconductors is particularly rich and interesting. In the AE(Fe1-xTx)2As2 class (AE being Ca, Sr, Ba, T being transition metals), the simultaneous structural/magnetic phase transition that occurs at elevated temperature in the undoped material, splits and is suppressed by carrier doping, the suppression being complete around optimal doping. A dome of superconductivity exists with apparent equal ease in the orthorhombic / antiferromagnetic (AFM) state as well as in the tetragonal state with no long range magnetic order. The question then is what determines the critical doping at which superconductivity emerges, if the AFM order is fully suppressed only at higher doping values. Here we report evidence from angle resolved photoemission spectroscopy (ARPES) that critical changes in the Fermi surface (FS) occur at the doping level that marks the onset of superconductivity. The presence of the AFM order leads to a reconstruction of the electronic structure, most significantly the appearance of the small hole pockets at the Fermi level. These hole pockets vanish, i. e. undergo a Lifshitz transition, at the onset of superconductivity. Superconductivity and magnetism are competing states in the iron arsenic superconductors. In the presence of the hole pockets superconductivity is fully suppressed, while in their absence the two states can coexist.Comment: Updated version accepted in Nature Physic

Mitochondrial DNA Copy Number Is Associated with Breast Cancer Risk

Mitochondrial DNA (mtDNA) copy number in peripheral blood is associated with increased risk of several cancers. However, data from prospective studies on mtDNA copy number and breast cancer risk are lacking. We evaluated the association between mtDNA copy number in peripheral blood and breast cancer risk in a nested case-control study of 183 breast cancer cases with pre-diagnostic blood samples and 529 individually matched controls among participants of the Singapore Chinese Health Study. The mtDNA copy number was measured using real time PCR. Conditional logistic regression analyses showed that there was an overall positive association between mtDNA copy number and breast cancer risk (Ptrend = 0.01). The elevated risk for higher mtDNA copy numbers was primarily seen for women with <3 years between blood draw and cancer diagnosis; ORs (95% CIs) for 2nd, 3rd, 4th, and 5th quintile of mtDNA copy number were 1.52 (0.61, 3.82), 2.52 (1.03, 6.12), 3.12 (1.31, 7.43), and 3.06 (1.25, 7.47), respectively, compared with the 1st quintile (Ptrend = 0.004). There was no association between mtDNA copy number and breast cancer risk among women who donated a blood sample ≥3 years before breast cancer diagnosis (Ptrend = 0.41). This study supports a prospective association between increased mtDNA copy number and breast cancer risk that is dependent on the time interval between blood collection and breast cancer diagnosis. Future studies are warranted to confirm these findings and to elucidate the biological role of mtDNA copy number in breast cancer risk. © 2013 Thyagarajan et al

Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo

Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). SHP-2 inhibition impaired capillary-like structure formation (p < 0.01; n = 8) in vitro as well as new vessel growth ex vivo (p < 0.05; n = 10) and in vivo in the chicken chorioallantoic membrane (p < 0.01, n = 4). Additionally, SHP-2 knock-down abrogated fibroblast growth factor 2 (FGF-2)-dependent endothelial proliferation measured by MTT reduction ( p ! 0.01; n = 12). The inhibitory effect of SHP-2 knock-down on vessel growth was mediated by increased endothelial apoptosis ( annexin V staining, p ! 0.05, n = 9), which was associated with reduced FGF-2-induced phosphorylation of phosphatidylinositol 3-kinase (PI3-K), Akt and extracellular regulated kinase 1/2 (ERK1/2) and involved diminished ERK1/2 phosphorylation after PI3-K inhibition (n=3). These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. Thus, SHP-2 exhibits a pivotal role in angiogenesis and may represent an interesting target for therapeutic approaches controlling vessel growth. Copyright (C) 2007 S. Karger AG, Basel

Compact conformal manifolds

This work was partly supported by the U.S. Department of Energy under grants DOE-SC0010008, DOE-ARRA-SC0003883 and DOE-DE-SC0007897