Unidirectional Movement Fibres from A Proprioceptive Organ of the Crab, Carcinus Maenas

1. The proprioceptive organ of the shore crab Carcinus maenas, which signals all proprioceptive sensation from the joint between propodite and dactylopodite, has been shown to contain sense cells receptive to position as well as to movement. 2. Certain cells of the organ increase their discharge frequency in response to greater degrees of flexion, while other endings respond to greater degrees of extension. Movement has little effect on the frequency of the position fibres. 3. Cells responding to movement in one direction only are present, certain ones signalling fiexion and others extension. The most sensitive undirectional movement fibres are almost completely independent of position and velocity. They provide the crab with an extremely sensitive movement sense not as yet reported in other proprioceptive mechanisms. 4. Both position-sensitive and movement-sensitive cells show a wide range of thresholds. 5. Cells which cannot be strictly classified as either position or movement sensitive have also been found. 6. By tracing the origin of the signals to the cell bodies, it appears that movement fibres have on the whole larger cell bodies than position fibres and are more proximally located. 7. Flexor and extensor movement cells appear to lie on different sides of elastic strand. 8. The question of how unidirectional sensitivity may be achieved is discussed

Reproducible and User-Controlled Software Environments in HPC with Guix

Support teams of high-performance computing (HPC) systems often find themselves between a rock and a hard place: on one hand, they understandably administrate these large systems in a conservative way, but on the other hand, they try to satisfy their users by deploying up-to-date tool chains as well as libraries and scientific software. HPC system users often have no guarantee that they will be able to reproduce results at a later point in time, even on the same system-software may have been upgraded, removed, or recompiled under their feet, and they have little hope of being able to reproduce the same software environment elsewhere. We present GNU Guix and the functional package management paradigm and show how it can improve reproducibility and sharing among researchers with representative use cases.Comment: 2nd International Workshop on Reproducibility in Parallel Computing (RepPar), Aug 2015, Vienne, Austria. http://reppar.org

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

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

Running Experiments with Confidence and Sanity

Analyzing data from large experimental suites is a daily task for anyone doing experimental algorithmics. In this paper we report on several approaches we tried for this seemingly mundane task in a similarity search setting, reflecting on the challenges it poses. We conclude by proposing a workflow, which can be implemented using several tools, that allows to analyze experimental data with confidence. The extended version of this paper and the support code are provided at https://github.com/Cecca/running-experiments

Ovarian Cycle Effects on Immediate Reward Selection Bias in Humans: A Role for Estradiol

A variety of evidence suggests that, among humans, the individual tendency to choose immediate rewards (“Now”) over larger, delayed rewards (“Later”), or Now bias, varies with frontal dopamine (DA) levels. As cyclic elevations in estradiol (E+) modulate other frontal DA-dependent behaviors, we tested ovarian cycle effects on Now bias, and whether any such effects are E+ mediated. To do so, we quantified Now/Later choice behavior in naturally cycling adult females (n = 87; ages 18–40 years) during both the menstrual phase (MP; cycle day 1–2; low E+), and the follicular phase (FP; cycle day 11–12; high E+). Now bias decreased an average of 3.6% from MP to FP (p = 0.006). Measures of salivary E+ levels at each visit were available in a subsample of participants (n = 34). Participants with a verified E+ rise from MP to FP showed significantly greater decreases in Now bias at mid-cycle (n = 23) than those without a rise (n = 11; p = 0.03); Now bias decreased an average of 10.2% in the E+ rise group but increased an average of 7.9% in the no E+ rise group. The change in Now bias from MP to FP inversely correlated with the change in E+ (ρ = −0.39; p = 0.023), an effect driven by individuals with putatively lower frontal DA based on genotype at the Val158Met polymorphism in the COMT gene. This is the first demonstration that intertemporal choice varies across the ovarian cycle, with Now bias declining at mid-cycle, when fertility peaks. Moreover, our data suggest that the interacting effects of estradiol and frontal DA mediate this cycle effect on decision making

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

Acute phenylalanine/tyrosine depletion of phasic dopamine in the rat brain

Dopamine plays a critical role in striatal and cortical function, and depletion of the dopamine precursors phenylalanine and tyrosine is used in humans to temporarily reduce dopamine and probe the role of dopamine in behavior. This method has been shown to alter addiction-related behaviors and cognitive functioning presumably by reducing dopamine transmission, but it is unclear what specific aspects of dopamine transmission are altered

Immediate Reward Bias in Humans: Fronto-Parietal Networks and a Role for the Catechol-O-Methyltransferase 158Val/Val Genotype

The tendency to choose lesser immediate benefits over greater long-term benefits characterizes alcoholism and other addictive disorders. However, despite its medical and socioeconomic importance, little is known about its neurobiological mechanisms. Brain regions that are activated when deciding between immediate or delayed rewards have been identified