The Shape, Multiplicity, and Evolution of Superclusters in LambdaCDM Cosmology

We determine the shape, multiplicity, size, and radial structure of superclusters in the LambdaCDM concordance cosmology from z = 0 to z = 2. Superclusters are defined as clusters of clusters in our large-scale cosmological simulation. We find that superclusters are triaxial in shape; many have flattened since early times to become nearly two-dimensional structures at present, with a small fraction of filamentary systems. The size and multiplicity functions are presented at different redshifts. Supercluster sizes extend to scales of ~ 100 - 200 Mpc/h. The supercluster multiplicity (richness) increases linearly with supercluster size. The density profile in superclusters is approximately isothermal (~ R^{-2}) and steepens on larger scales. These results can be used as a new test of the current cosmology when compared with upcoming observations of large-scale surveys.Comment: 33 pages, 15 figures, accepted to ApJ; minor content changes, some figures removed to shorten pape

Addiction History Associates with the Propensity to Form Habits

Learned habitual responses to environmental stimuli allow efficient interaction with the environment, freeing cognitive resources for more demanding tasks. However, when the outcome of such actions is no longer a desired goal, established stimulus-response (S-R) associations, or habits, must be overcome. Among people with substance use disorders (SUDs), difficulty in overcoming habitual responses to stimuli associated with their addiction in favor of new, goal-directed behaviors, contributes to relapse. Animal models of habit learning demonstrate that chronic self-administration of drugs of abuse promotes habitual responding beyond the domain of compulsive drug seeking. However, whether a similar propensity toward domain-general habitual responding occurs in humans with SUDs has remained unclear. To address this question, we used a visuomotor S-R learning and re-learning task, the Hidden Association Between Images Task (HABIT), which employs abstract visual stimuli and manual responses. This task allows us to measure new S-R association learning, well-learned S-R association execution, and includes a response contingency change manipulation to quantify the degree to which responding is habit-based, rather than goal-directed. We find that people with SUDs learn new S-R associations as well as healthy control subjects do. Moreover, people with an SUD history slightly outperform controls in S-R execution. In contrast, people with SUDs are specifically impaired in overcoming well-learned S-R associations; those with SUDs make a significantly greater proportion of perseverative errors during well-learned S-R replacement, indicating the more habitual nature of their responses. Thus, with equivalent training and practice, people with SUDs appear to show enhanced domain-general habit formation

Self-assembled monolayers of omega-functional silanes: A platform for understanding cellular adhesion at the molecular level

Self-assembly represents a powerful and versatile strategy to create substrates with controlled molecular-level physicochemical characteristics. As a result, self-assembled monolayers (SAMs) of silanes continue to find use in a multitude of applications in biotechnology and nanotechnology, both as model substrates to study interfacial interactions and as a strategy to chemically graft bioactive molecules. In our work, SAMs of various functional groups have been used for fundamental studies of cellular interactions with peptides and proteins. Namely, cellular adhesion was quantitatively probed to elucidate the roles of non-specific forces arising from the substrate and to study the specific interactions of cellular receptors with adsorbed extracellular matrix (ECM) proteins, such as fibronectin, and grafted arginine–glycine–aspartic acid (RGD) peptides. Measurements of the cellular detachment strength using a spinning disc apparatus demonstrated that the terminal functionality of the silane SAM used as the substrate exerted significant effects and highlighted the importance of substrate selection in biological applications. Quantitative comparison of the various cellular interactions demonstrated that non-specific interactions can be much larger in magnitude than peptide- and protein-mediated adhesion. As adhesion is the first step in a cascade of events through which cellular interaction with a material surface occurs, this finding has implications on assays of long-term cellular function as well. The insight provided by these studies should help in the development of optimized protein and peptide microarrays, or biochips, as well as better bioactive materials for biomaterial/tissue engineering applications

Monolithic simulation of convection-coupled phase-change - verification and reproducibility

Phase interfaces in melting and solidification processes are strongly affected by the presence of convection in the liquid. One way of modeling their transient evolution is to couple an incompressible flow model to an energy balance in enthalpy formulation. Two strong nonlinearities arise, which account for the viscosity variation between phases and the latent heat of fusion at the phase interface. The resulting coupled system of PDE's can be solved by a single-domain semi-phase-field, variable viscosity, finite element method with monolithic system coupling and global Newton linearization. A robust computational model for realistic phase-change regimes furthermore requires a flexible implementation based on sophisticated mesh adaptivity. In this article, we present first steps towards implementing such a computational model into a simulation tool which we call Phaseflow. Phaseflow utilizes the finite element software FEniCS, which includes a dual-weighted residual method for goal-oriented adaptive mesh refinement. Phaseflow is an open-source, dimension-independent implementation that, upon an appropriate parameter choice, reduces to classical benchmark situations including the lid-driven cavity and the Stefan problem. We present and discuss numerical results for these, an octadecane PCM convection-coupled melting benchmark, and a preliminary 3D convection-coupled melting example, demonstrating the flexible implementation. Though being preliminary, the latter is, to our knowledge, the first published 3D result for this method. In our work, we especially emphasize reproducibility and provide an easy-to-use portable software container using Docker.Comment: 20 pages, 8 figure

Single-molecule super-resolution imaging of chromosomes and in situ haplotype visualization using Oligopaint FISH probes

Fluorescence in situ hybridization (FISH) is a powerful single-cell technique for studying nuclear structure and organization. Here we report two advances in FISH-based imaging. We first describe the in situ visualization of single-copy regions of the genome using two single-molecule super-resolution methodologies. We then introduce a robust and reliable system that harnesses single-nucleotide polymorphisms (SNPs) to visually distinguish the maternal and paternal homologous chromosomes in mammalian and insect systems. Both of these new technologies are enabled by renewable, bioinformatically designed, oligonucleotide-based Oligopaint probes, which we augment with a strategy that uses secondary oligonucleotides (oligos) to produce and enhance fluorescent signals. These advances should substantially expand the capability to query parent-of-origin-specific chromosome positioning and gene expression on a cell-by-cell basis

Rab-coupling protein coordinates recycling of α5β1 integrin and EGFR1 to promote cell migration in 3D microenvironments

Here we show that blocking the adhesive function of αvβ3 integrin with soluble RGD ligands, such as osteopontin or cilengitide, promoted association of Rab-coupling protein (RCP) with α5β1 integrin and drove RCP-dependent recycling of α5β1 to the plasma membrane and its mobilization to dynamic ruffling protrusions at the cell front. These RCP-driven changes in α5β1 trafficking led to acquisition of rapid/random movement on two-dimensional substrates and to a marked increase in fibronectin-dependent migration of tumor cells into three-dimensional matrices. Recycling of α5β1 integrin did not affect its regulation or ability to form adhesive bonds with substrate fibronectin. Instead, α5β1 controlled the association of EGFR1 with RCP to promote the coordinate recycling of these two receptors. This modified signaling downstream of EGFR1 to increase its autophosphorylation and activation of the proinvasive kinase PKB/Akt. We conclude that RCP provides a scaffold that promotes the physical association and coordinate trafficking of α5β1 and EGFR1 and that this drives migration of tumor cells into three-dimensional matrices

Adhesion of MC3T3-E1 cells to RGD peptides of different flanking residues: Detachment strength and correlation with long-term cellular function

We synthesized a series of RGD peptides and immobilized them to an amine-functional self-assembled monolayer using a modified maleimide-based conjugate technique that minimizes nonspecific interactions. Using a spinning disc apparatus, a trend in the detachment strength (τ50) of RGD peptides of different flanking residues was found: RGDSPK ≻ RGDSVVYGLR ≈ RGDS ≻ RGES. Using blocking monoclonal antibodies, cellular adhesion to the peptides was shown to be primarily α√-integrin-mediated. In contrast, the τ50 value of the cells on fibronectin (Fn)-coated substrates of similar surface density was 6-7 times higher and involved both α5β1 and ανβ3 integrins. Cellular spreading was enhanced on RGD peptides after 1 h when compared to RGE and unmodified substrates. However, no significant differences were observed between the different RGD peptides. Long-term function of MC3T3-E1 cells was also evaluated by measuring alkaline phosphatase (ALP) activity and mineral deposition. Among the four peptides, RGDSPK exhibited the highest level of ALP activity after 11 days and mineralization after 15 days and reached comparable levels as Fn substrates after 15 and 24 days, respectively. These findings collectively illustrate both the advantages and limitations of enhancing cellular adhesion and function by the design of RGD peptides

Interaction between Family History of Alcoholism and Locus of Control in the Opioid Regulation of Impulsive Responding under the Influence of Alcohol

Naltrexone (NTX) is an opioid antagonist indicated for the treatment of alcoholism, which is not universally effective. Thus, identifying individual predictors of NTX’s behavioral effects is critical to optimizing its therapeutic use. Moreover, given the high rate of relapse during treatment for alcoholism, understanding NTX’s behavioral effects when combined with moderate ethanol intake is important. Our previous study of abstinent alcoholics and control subjects showed that a more internal Locus of Control score predicted increased impulsive choice on NTX (Mitchell et al., 2007). Here we tested whether this predictive relationship remains in the context of moderate alcohol intake

Physical function limitation among gay and bisexual men aged ≥55years with and without HIV: findings from the Australian Positive and Peers Longevity Evaluation Study (APPLES)

Background. As people living with HIV now have a life expectancy approaching that of the general population, clinical care focuses increasingly on the management and prevention of comorbidities and conditions associated with aging. We aimed to assess the prevalence of physical function (PF) limitation among gay and bisexual men (GBM) and determine whether HIV is associated with severe PF limitation in this population. Methods. We analysed cross-sectional data from GBM aged ≥55 years in the Australian Positive and Peers Longevity Evaluation Study who completed a self-administered survey on health and lifestyle factors. PF was measured using the Medical Outcomes Study–Physical Functioning scale. Factors associated with severe PF limitation were assessed using logistic regression. Results. The survey was completed by 381 men: 186 without HIV and 195 with HIV. Median age was 64.3 years for GBM without HIV and 62.1 years for GBM with HIV. Compared with men without HIV, those with HIV had higher proportions of severe (13.3% vs 8.1%) and moderate-to-severe (26.7% vs 24.2%) PF limitation. Severe PF limitation commonly involved difficulty with vigorous activity (95% with severe PF limitation described being limited a lot), climbing several flights of stairs (68.4% limited a lot), bending, kneeling or stooping (60.5% limited a lot), and walking 1 km (55.0% limited a lot). In a model adjusted for age, body mass index, typical duration of physical activity, psychological distress, and number of comorbidities, we found a significant association between HIV and severe PF limitation (adjusted odds ratio 3.3 vs not having HIV, 95% confidence interval 1.3–8.7). Conclusions. The biological mechanisms underlying this association require further investigation, particularly given the growing age of the HIV population and inevitable increase in the burden of PF limitation