The effect of problem complexity on the efficiency of intuitive and analytic processes

Some investigators have suggested that when material becomes more complex, an individual is forced to use an intuitive process, while others suggest that increasing complexity forces analysis. This study was an attempt to resolve this question by manipulating rate of presentation and instructions. No effect was found due to these manipulations or due to complexity. The reason is not clear, but may be due to a combination of factors which inclined the experiment in the direction of the intuitive process

Fluorescent silica manoparticles with well-separated intensity distributions from batch reactions

Silica chemistry provides pathways to uniquely tunable nanoparticle platforms for biological imaging. It has been a long-standing problem to synthesize fluorescent silica nanoparticles (SNPs) in batch reactions with high and low fluorescence intensity levels for reliable use as an intensity barcode, which would greatly increase the number of molecular species that could be tagged intracellularly and simultaneously observed in conventional fluorescence microscopy. Here, employing an amino-acid catalyzed growth, highly fluorescent SNP probes were synthesized with sizes <40 nm and well-separated intensity distributions, as mapped by single-particle imaging techniques. A seeded growth approach was used to minimize the rate of secondary particle formation. Organic fluorescent dye affinity for the SNP during shell growth was tuned using specifics of the organosilane linker chemistry. This work highlights design considerations in the development of fluorescent probes with well-separated intensity distributions synthesized in batch reactions for single-particle imaging and sensing applications, where heterogeneities across the nanoparticle ensemble are critical factors in probe performance

Fluorescent silica manoparticles with well-separated intensity distributions from batch reactions

Silica chemistry provides pathways to uniquely tunable nanoparticle platforms for biological imaging. It has been a long-standing problem to synthesize fluorescent silica nanoparticles (SNPs) in batch reactions with high and low fluorescence intensity levels for reliable use as an intensity barcode, which would greatly increase the number of molecular species that could be tagged intracellularly and simultaneously observed in conventional fluorescence microscopy. Here, employing an amino-acid catalyzed growth, highly fluorescent SNP probes were synthesized with sizes <40 nm and well-separated intensity distributions, as mapped by single-particle imaging techniques. A seeded growth approach was used to minimize the rate of secondary particle formation. Organic fluorescent dye affinity for the SNP during shell growth was tuned using specifics of the organosilane linker chemistry. This work highlights design considerations in the development of fluorescent probes with well-separated intensity distributions synthesized in batch reactions for single-particle imaging and sensing applications, where heterogeneities across the nanoparticle ensemble are critical factors in probe performance

Mycobacterium bovis genomics reveals transmission of infection between cattle and deer in Ireland

Control of bovine tuberculosis (bTB), caused by Mycobacterium bovis, in the Republic of Ireland costs €84 million each year. Badgers are recognised as being a wildlife source for M. bovis infection of cattle. Deer are thought to act as spillover hosts for infection; however, population density is recognised as an important driver in shifting their epidemiological role, and deer populations across the country have been increasing in density and range. County Wicklow represents one specific area in the Republic of Ireland that has had consistently high bTB prevalence for over a decade, despite control operations in both cattle and badgers. The area is also known to have a high density of deer. Our research used whole genome sequencing of M. bovis sourced from infected cattle, deer, and badgers in County Wicklow to evaluate whether the epidemiological role of deer could have shifted from spillover host to source. Our analyses reveal that cattle and deer share highly similar M. bovis strains suggesting that transmission between these species is occurring in the area. In addition, the high level of diversity observed in the sampled deer population suggests deer may be acting as a source of infection for local cattle populations. These findings have important implications for the control and ultimate eradication of bTB in Ireland

Ultrasmall inorganic cages directed by surfactant micelles

Functional silica nanoparticles have become highly relevant materials in the fields of biology and medicine. Ultrasmall fluorescent silica nanoparticles developed in our group (Cdots) have now reached phase 2 of clinical trials for cancer diagnostics. Nevertheless, modern nanomedicine techniques and their increasing complexity today are still in demand for more efficient and multifunctional tools for advanced applications such as theranostics. To this end, important developments have been made in order for these nanoparticles to achieve their full potential, including chemical modification of their matrix to improve their optical properties, and new synthetic strategies for multifunctional nanoparticles via a surface modification approach with various functional groups. In parallel, new alternative particle geometries have been investigated for targeted drug delivery applications. In this contribution, we will review some of the recent progress made in our group that ultimately led to the discovery of highly symmetrical dodecahedral silica nanocages, or ‘silicages’ [1]. Ultrasmall (< 10 nm) silica nanoparticles with tunable geometries can be obtained through their templating with surfactant micelles. The self-assembly of silica clusters on these micelles gives rise to unique and well defined structures. The dodecahedral cage structure in particular is of great fundamental importance. It is the simplest of a set of Voronoi polyhedra suggested to form the smallest structural units of multiple forms of mesoporous silica, yet such highly symmetrical silica cages had never been isolated before. In order to resolve the actual structure of these ultrasmall objects, single-particle 3D reconstruction from tens of thousands of cryo-electron microscopy images was performed using a custom-built ‘Hetero’ machine learning algorithm. We will finally show that cage formation is not limited to silica, but has been observed for other materials including metals and transition metal oxides. The chemical and practical value of this polyhedral structure may prove immense. Given the versatility of silica surface chemistry one can readily conceive of cage derivatives of many kinds, which may exhibit unusual properties and be useful in applications ranging from catalysis to drug delivery. For example, given recent success in the clinical translation of ultrasmall fluorescent silica nanoparticles with similar particle sizes and surface properties to these cages, one can envisage a range of new diagnostic and therapeutic probes with drugs hidden inside the cages. Reference: [1] K. Ma, Y. Gong, T. Aubert, M. Z. Turker, T. Kao, P. C. Doerschuk, U. Wiesner, Nature 2018, DOI: 10.1038/s41586-018-0221-0

The in-plane paraconductivity in La_{2-x}Sr_xCuO_4 thin film superconductors at high reduced-temperatures: Independence of the normal-state pseudogap

The in-plane resistivity has been measured in $La_{2-x}Sr_xCuO_4$ (LSxCO) superconducting thin films of underdoped ($x=0.10,0.12$), optimally-doped ($x=0.15$) and overdoped ($x=0.20,0.25$) compositions. These films were grown on (100)SrTiO$_3$ substrates, and have about 150 nm thickness. The in-plane conductivity induced by superconducting fluctuations above the superconducting transition (the so-called in-plane paraconductivity, $\Delta\sigma_{ab}$) was extracted from these data in the reduced-temperature range 10^{-2}\lsim\epsilon\equiv\ln(T/\Tc)\lsim1. Such a $\Delta\sigma_{ab}(\epsilon)$ was then analyzed in terms of the mean-field--like Gaussian-Ginzburg-Landau (GGL) approach extended to the high-$\epsilon$ region by means of the introduction of a total-energy cutoff, which takes into account both the kinetic energy and the quantum localization energy of each fluctuating mode. Our results strongly suggest that at all temperatures above Tc, including the high reduced-temperature region, the doping mainly affects in LSxCO thin films the normal-state properties and that its influence on the superconducting fluctuations is relatively moderate: Even in the high-$\epsilon$ region, the in-plane paraconductivity is found to be independent of the opening of a pseudogap in the normal state of the underdoped films.Comment: 35 pages including 10 figures and 1 tabl

A Genome-Wide Map of Conserved MicroRNA Targets in C. elegans

SummaryBackgroundMetazoan miRNAs regulate protein-coding genes by binding the 3′ UTR of cognate mRNAs. Identifying targets for the 115 known C. elegans miRNAs is essential for understanding their function.ResultsBy using a new version of PicTar and sequence alignments of three nematodes, we predict that miRNAs regulate at least 10% of C. elegans genes through conserved interactions. We have developed a new experimental pipeline to assay 3′ UTR-mediated posttranscriptional gene regulation via an endogenous reporter expression system amenable to high-throughput cloning, demonstrating the utility of this system using one of the most intensely studied miRNAs, let-7. Our expression analyses uncover several new potential let-7 targets and suggest a new let-7 activity in head muscle and neurons. To explore genome-wide trends in miRNA function, we analyzed functional categories of predicted target genes, finding that one-third of C. elegans miRNAs target gene sets are enriched for specific functional annotations. We have also integrated miRNA target predictions with other functional genomic data from C. elegans.ConclusionsAt least 10% of C. elegans genes are predicted miRNA targets, and a number of nematode miRNAs seem to regulate biological processes by targeting functionally related genes. We have also developed and successfully utilized an in vivo system for testing miRNA target predictions in likely endogenous expression domains. The thousands of genome-wide miRNA target predictions for nematodes, humans, and flies are available from the PicTar website and are linked to an accessible graphical network-browsing tool allowing exploration of miRNA target predictions in the context of various functional genomic data resources