Efficient siRNA selection using hybridization thermodynamics

Small interfering RNA (siRNA) are widely used to infer gene function. Here, insights in the equilibrium of siRNA-target hybridization are used for selection of efficient siRNA. The accessibilities of siRNA and target mRNA for hybridization, as measured by folding free energy change, are shown to be significantly correlated with efficacy. For this study, a partition function calculation that considers all possible secondary structures is used to predict target site accessibility; a significant improvement over calculations that consider only the predicted lowest free energy structure or a set of low free energy structures. The predicted thermodynamic features, in addition to siRNA sequence features, are used as input for a support vector machine that selects functional siRNA. The method works well for predicting efficient siRNA (efficacy >70%) in a large siRNA data set from Novartis. The positive predictive value (percentage of sites predicted to be efficient for silencing that are) is as high as 87.6%. The sensitivity and specificity are 22.7 and 96.5%, respectively. When tested on data from different sources, the positive predictive value increased 8.1% by adding equilibrium terms to 25 local sequence features. Prediction of hybridization affinity using partition functions is now available in the RNAstructure software package

The effects of social norms on motivation crowding: experimental evidence from the Tibetan Plateau

A growing literature examines conditions under which financial incentives for behavior change can undermine "crowd out" or reinforce ("crowd in") other sources of motivation for the behavior in question. Some of this literature points to a potential role of social norms, but it has not attempted to quantify that role. We present an interdisciplinary model from economics and communication science that measures the effects of financial incentives on social norms and their joint effects on behavior, including after incentives have ended. In a framed field experiment with Tibetan herders in Qinghai, China, we find that a temporary payment for participation in a patrol against illegal wildlife trapping reinforces a perceived injunctive norm that this conservation behavior meets with social approval. This norm remains heightened even after the payment has ended, continuing to positively influence the decision to participate in anti-trapping patrols in the experiment. This finding suggests that, under certain circumstances, a carefully framed incentive for conservation behavior can support injunctive norms in favor of conservation behavior.USDA National Institute of Food and Agriculture, Hatch project [MICL02244, MICL02173, MICL02362]; National Science Foundation [SMA-1328503]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

ZX-Calculus: Cyclotomic Supplementarity and Incompleteness for Clifford+T quantum mechanics

The ZX-Calculus is a powerful graphical language for quantum mechanics and quantum information processing. The completeness of the language -- i.e. the ability to derive any true equation -- is a crucial question. In the quest of a complete ZX-calculus, supplementarity has been recently proved to be necessary for quantum diagram reasoning (MFCS 2016). Roughly speaking, supplementarity consists in merging two subdiagrams when they are parameterized by antipodal angles. We introduce a generalised supplementarity -- called cyclotomic supplementarity -- which consists in merging n subdiagrams at once, when the n angles divide the circle into equal parts. We show that when n is an odd prime number, the cyclotomic supplementarity cannot be derived, leading to a countable family of new axioms for diagrammatic quantum reasoning.We exhibit another new simple axiom that cannot be derived from the existing rules of the ZX-Calculus, implying in particular the incompleteness of the language for the so-called Clifford+T quantum mechanics. We end up with a new axiomatisation of an extended ZX-Calculus, including an axiom schema for the cyclotomic supplementarity.Comment: Mathematical Foundations of Computer Science, Aug 2017, Aalborg, Denmar

Pervasive and dynamic protein binding sites of the mRNA transcriptome in Saccharomyces cerevisiae

Abstract Background Protein-RNA interactions are integral components of nearly every aspect of biology, including regulation of gene expression, assembly of cellular architectures, and pathogenesis of human diseases. However, studies in the past few decades have only uncovered a small fraction of the vast landscape of the protein-RNA interactome in any organism, and even less is known about the dynamics of protein-RNA interactions under changing developmental and environmental conditions. Results Here, we describe the gPAR-CLIP (global photoactivatable-ribonucleoside-enhanced crosslinking and immunopurification) approach for capturing regions of the untranslated, polyadenylated transcriptome bound by RNA-binding proteins (RBPs) in budding yeast. We report over 13,000 RBP crosslinking sites in untranslated regions (UTRs) covering 72% of protein-coding transcripts encoded in the genome, confirming 3' UTRs as major sites for RBP interaction. Comparative genomic analyses reveal that RBP crosslinking sites are highly conserved, and RNA folding predictions indicate that secondary structural elements are constrained by protein binding and may serve as generalizable modes of RNA recognition. Finally, 38% of 3' UTR crosslinking sites show changes in RBP occupancy upon glucose or nitrogen deprivation, with major impacts on metabolic pathways as well as mitochondrial and ribosomal gene expression. Conclusions Our study offers an unprecedented view of the pervasiveness and dynamics of protein-RNA interactions in vivo.http://deepblue.lib.umich.edu/bitstream/2027.42/112318/1/13059_2012_Article_3050.pd

On-chip optical diode based on silicon photonic crystal heterojunctions

Optical isolation is a long pursued object with fundamental difficulty in integrated photonics. As a step towards this goal, we demonstrate the design, fabrication, and characterization of on-chip wavelength-scale optical diodes that are made from the heterojunction between two different silicon two-dimensional square-lattice photonic crystal slabs with directional bandgap mismatch and different mode transitions. The measured transmission spectra show considerable unidirectional transmission behavior, in good agreement with numerical simulations. The experimental realization of on-chip optical diodes using all-dielectric, passive, and linear silicon photonic crystal structures may help to construct on-chip optical logical devices without nonlinearity or magnetism, and would open up a road towards photonic computers.Comment: 14 pages, 5 figure

Systematic Identification of Synergistic Drug Pairs Targeting HIV

The systematic identification of effective drug combinations has been hindered by the unavailability of methods that can explore the large combinatorial search space of drug interactions. Here we present a multiplex screening method named MuSIC (Multiplex Screening for Interacting Compounds), which expedites the comprehensive assessment of pair-wise compound interactions. We examined ~500,000 drug pairs from 1000 FDA-approved or clinically tested drugs and identified drugs that synergize to inhibit HIV replication. Our analysis reveals an enrichment of anti-inflammatory drugs in drug combinations that synergize against HIV, indicating HIV benefits from inflammation that accompanies its infection. Multiple drug pairs identified in this study, including glucocorticoid and nitazoxanide, synergize by targeting different steps of the HIV life cycle. As inflammation accompanies HIV infection, our findings indicate that inhibiting inflammation could curb HIV propagation. MuSIC can be applied to a wide variety of disease-relevant screens to facilitate efficient identification of compound combinations

A new crystal: Layer-structured rhombohedral In3Se4

A new layer-structured rhombohedral In3Se4 crystal was synthesized by a facile and mild solvothermal method. Detailed structural and chemical characterizations using transmission electron microscopy, coupled with synchrotron X-ray diffraction analysis and Rietveld refinement, indicate that In3Se4 crystallizes in a layered rhombohedral structure with lattice parameters of a = 3.964 ± 0.002 Å and c = 39.59 ± 0.02 Å, a space group of R3m, and with a layer composition of Se-In-Se-In-Se-In-Se. The theoretical modeling and experimental measurements indicate that the In3Se4 is a self-doped n-type semiconductor. This study not only enriches the understanding on crystallography of indium selenide crystals, but also paves a way in the search for new semiconducting compounds. This journal i

In vitro expression and analysis of the 826 human G protein-coupled receptors

ABSTRACT G protein-coupled receptors (GPCRs) are involved in all human physiological systems where they are responsible for transducing extracellular signals into cells. GPCRs signal in response to a diverse array of stimuli including light, hormones, and lipids, where these signals affect downstream cascades to impact both health and disease states. Yet, despite their importance as therapeutic targets, detailed molecular structures of only 30 GPCRs have been determined to date. A key challenge to their structure determination is adequate protein expression. Here we report the quantification of protein expression in an insect cell expression system for all 826 human GPCRs using two different fusion constructs. Expression characteristics are analyzed in aggregate and among each of the five distinct subfamilies. These data can be used to identify trends related to GPCR expression between different fusion constructs and between different GPCR families, and to prioritize lead candidates for future structure determination feasibility